Osteoporosis

People with subclinical hyperthyroidism are at 34% greater risk of experiencing a fracture compared with those with normal thyroid function, new research shows.

The finding, from a study of nearly 11,000 middle-aged men and women followed for a median of 2 decades, “highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease,” the researchers wrote.

Primary care physicians “should be more aware of the risks for fracture among persons with subclinical hyperthyroidism in the ambulatory setting,” Natalie R. Daya, a PhD student in epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, and first author of the study, told this news organization.

Ms. Daya and her colleagues published their findings in JAMA Network Open.

 

Building on earlier findings

The results agree with previous work, including a meta-analysis of 13 prospective cohort studies of 70,289 primarily White individuals with an average age of 64 years, which found that subclinical hyperthyroidism was associated with a modestly increased risk for fractures, the researchers noted.

“Our study extends these findings to a younger, community-based cohort that included both Black and White participants, included extensive adjustment for potential confounders, and had a longer follow-up period (median follow-up of 21 years vs. 12 years),” they wrote.

The study included 10,946 participants in the Atherosclerosis Risk in Communities Study who were recruited in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis.

Baseline thyroid function was measured in blood samples collected during the second visit, which occurred between 1990 and 1992. No participants in the new analysis took thyroid medications or had a history of hospitalization for fractures at baseline, and all identified as Black or White. The mean age was 57 years, 24% were Black, and 54.3% were female.

Subclinical hyperthyroidism was defined as a thyrotropin level less than 0.56 mIU/L; subclinical hypothyroidism as a thyrotropin level greater than 5.1 mIU/L; and normal thyroid function as a thyrotropin level between 0.56 and 5.1 mIU/L, with normal free thyroxine levels of 0.85-1.4 ng/dL.

The vast majority (93%) of participants had normal thyroid function, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism, according to the researchers.

Median follow-up was 21 years. The researchers identified 3,556 incident fractures, detected with hospitalization discharge codes through 2019 and inpatient and Medicare claims data through 2018, for a rate of 167.1 per 10,000 person-years.

Adjusted hazard ratios for fracture were 1.34 (95% confidence interval [CI], 1.09-1.65) for people with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism, compared with those with normal thyroid function.

Most fractures occurred in either the hip (14.1%) or spine (13.8%), according to the researchers.

Limitations included a lack of thyroid function data during the follow-up period and lack of data on bone mineral density, the researchers wrote.
 

‘An important risk factor’

Endocrinologist Michael McClung, MD, founding and emeritus director of the Oregon Osteoporosis Center, Portland, who was not involved in the study, pointed out that both subclinical hypothyroidism and subclinical hyperthyroidism have been linked to greater risk for cardiovascular disease as well as fracture.

The new paper underscores that subclinical hyperthyroidism “should be included as an important risk factor” for fracture as well as cardiovascular risk, Dr. McClung said in an interview. In considering whether to treat osteoporosis, subclinical hyperthyroidism “may be enough to tip the balance in favor of pharmacological therapy,” he added.

Thyroid-stimulating hormone (TSH) tests to assess thyroid function are typically ordered only if a patient has symptoms of hyperthyroidism or hypothyroidism, Ms. Daya said. Depending on the cause and severity of a low TSH level, a physician may prescribe methimazole or radioactive iodine therapy to reduce the production of thyroxine, she said.

However, well-designed studies are needed to evaluate whether treatment of subclinical thyroid dysfunction reduces the risk for fracture or cardiovascular problems and assess downsides such as side effects, costs, and psychological harm, Dr. McClung noted.

The U.S. Preventive Services Task Force concluded in 2015 that the data were insufficient to recommend screening for thyroid dysfunction in adults without symptoms. As of a year ago, no new evidence has emerged to support an update, according to the task force’s website.

“Until those studies are available, selective screening of thyroid function should be considered in all patients undergoing risk assessment for cardiovascular disease or skeletal health,” Dr. McClung said.

The Atherosclerosis Risk in Communities Study has been funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) and the U.S. Department of Health and Human Services. Ms. Daya and four study authors reported receiving NIH grants during the study period. Dr. McClung reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

People with subclinical hyperthyroidism are at 34% greater risk of experiencing a fracture compared with those with normal thyroid function, new research shows.

The finding, from a study of nearly 11,000 middle-aged men and women followed for a median of 2 decades, “highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease,” the researchers wrote.

Primary care physicians “should be more aware of the risks for fracture among persons with subclinical hyperthyroidism in the ambulatory setting,” Natalie R. Daya, a PhD student in epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, and first author of the study, told this news organization.

Ms. Daya and her colleagues published their findings in JAMA Network Open.

 

Building on earlier findings

The results agree with previous work, including a meta-analysis of 13 prospective cohort studies of 70,289 primarily White individuals with an average age of 64 years, which found that subclinical hyperthyroidism was associated with a modestly increased risk for fractures, the researchers noted.

“Our study extends these findings to a younger, community-based cohort that included both Black and White participants, included extensive adjustment for potential confounders, and had a longer follow-up period (median follow-up of 21 years vs. 12 years),” they wrote.

The study included 10,946 participants in the Atherosclerosis Risk in Communities Study who were recruited in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis.

Baseline thyroid function was measured in blood samples collected during the second visit, which occurred between 1990 and 1992. No participants in the new analysis took thyroid medications or had a history of hospitalization for fractures at baseline, and all identified as Black or White. The mean age was 57 years, 24% were Black, and 54.3% were female.

Subclinical hyperthyroidism was defined as a thyrotropin level less than 0.56 mIU/L; subclinical hypothyroidism as a thyrotropin level greater than 5.1 mIU/L; and normal thyroid function as a thyrotropin level between 0.56 and 5.1 mIU/L, with normal free thyroxine levels of 0.85-1.4 ng/dL.

The vast majority (93%) of participants had normal thyroid function, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism, according to the researchers.

Median follow-up was 21 years. The researchers identified 3,556 incident fractures, detected with hospitalization discharge codes through 2019 and inpatient and Medicare claims data through 2018, for a rate of 167.1 per 10,000 person-years.

Adjusted hazard ratios for fracture were 1.34 (95% confidence interval [CI], 1.09-1.65) for people with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism, compared with those with normal thyroid function.

Most fractures occurred in either the hip (14.1%) or spine (13.8%), according to the researchers.

Limitations included a lack of thyroid function data during the follow-up period and lack of data on bone mineral density, the researchers wrote.
 

‘An important risk factor’

Endocrinologist Michael McClung, MD, founding and emeritus director of the Oregon Osteoporosis Center, Portland, who was not involved in the study, pointed out that both subclinical hypothyroidism and subclinical hyperthyroidism have been linked to greater risk for cardiovascular disease as well as fracture.

The new paper underscores that subclinical hyperthyroidism “should be included as an important risk factor” for fracture as well as cardiovascular risk, Dr. McClung said in an interview. In considering whether to treat osteoporosis, subclinical hyperthyroidism “may be enough to tip the balance in favor of pharmacological therapy,” he added.

Thyroid-stimulating hormone (TSH) tests to assess thyroid function are typically ordered only if a patient has symptoms of hyperthyroidism or hypothyroidism, Ms. Daya said. Depending on the cause and severity of a low TSH level, a physician may prescribe methimazole or radioactive iodine therapy to reduce the production of thyroxine, she said.

However, well-designed studies are needed to evaluate whether treatment of subclinical thyroid dysfunction reduces the risk for fracture or cardiovascular problems and assess downsides such as side effects, costs, and psychological harm, Dr. McClung noted.

The U.S. Preventive Services Task Force concluded in 2015 that the data were insufficient to recommend screening for thyroid dysfunction in adults without symptoms. As of a year ago, no new evidence has emerged to support an update, according to the task force’s website.

“Until those studies are available, selective screening of thyroid function should be considered in all patients undergoing risk assessment for cardiovascular disease or skeletal health,” Dr. McClung said.

The Atherosclerosis Risk in Communities Study has been funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) and the U.S. Department of Health and Human Services. Ms. Daya and four study authors reported receiving NIH grants during the study period. Dr. McClung reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

People with subclinical hyperthyroidism are at 34% greater risk of experiencing a fracture compared with those with normal thyroid function, new research shows.

The finding, from a study of nearly 11,000 middle-aged men and women followed for a median of 2 decades, “highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease,” the researchers wrote.

Primary care physicians “should be more aware of the risks for fracture among persons with subclinical hyperthyroidism in the ambulatory setting,” Natalie R. Daya, a PhD student in epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, and first author of the study, told this news organization.

Ms. Daya and her colleagues published their findings in JAMA Network Open.

 

Building on earlier findings

The results agree with previous work, including a meta-analysis of 13 prospective cohort studies of 70,289 primarily White individuals with an average age of 64 years, which found that subclinical hyperthyroidism was associated with a modestly increased risk for fractures, the researchers noted.

“Our study extends these findings to a younger, community-based cohort that included both Black and White participants, included extensive adjustment for potential confounders, and had a longer follow-up period (median follow-up of 21 years vs. 12 years),” they wrote.

The study included 10,946 participants in the Atherosclerosis Risk in Communities Study who were recruited in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis.

Baseline thyroid function was measured in blood samples collected during the second visit, which occurred between 1990 and 1992. No participants in the new analysis took thyroid medications or had a history of hospitalization for fractures at baseline, and all identified as Black or White. The mean age was 57 years, 24% were Black, and 54.3% were female.

Subclinical hyperthyroidism was defined as a thyrotropin level less than 0.56 mIU/L; subclinical hypothyroidism as a thyrotropin level greater than 5.1 mIU/L; and normal thyroid function as a thyrotropin level between 0.56 and 5.1 mIU/L, with normal free thyroxine levels of 0.85-1.4 ng/dL.

The vast majority (93%) of participants had normal thyroid function, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism, according to the researchers.

Median follow-up was 21 years. The researchers identified 3,556 incident fractures, detected with hospitalization discharge codes through 2019 and inpatient and Medicare claims data through 2018, for a rate of 167.1 per 10,000 person-years.

Adjusted hazard ratios for fracture were 1.34 (95% confidence interval [CI], 1.09-1.65) for people with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism, compared with those with normal thyroid function.

Most fractures occurred in either the hip (14.1%) or spine (13.8%), according to the researchers.

Limitations included a lack of thyroid function data during the follow-up period and lack of data on bone mineral density, the researchers wrote.
 

‘An important risk factor’

Endocrinologist Michael McClung, MD, founding and emeritus director of the Oregon Osteoporosis Center, Portland, who was not involved in the study, pointed out that both subclinical hypothyroidism and subclinical hyperthyroidism have been linked to greater risk for cardiovascular disease as well as fracture.

The new paper underscores that subclinical hyperthyroidism “should be included as an important risk factor” for fracture as well as cardiovascular risk, Dr. McClung said in an interview. In considering whether to treat osteoporosis, subclinical hyperthyroidism “may be enough to tip the balance in favor of pharmacological therapy,” he added.

Thyroid-stimulating hormone (TSH) tests to assess thyroid function are typically ordered only if a patient has symptoms of hyperthyroidism or hypothyroidism, Ms. Daya said. Depending on the cause and severity of a low TSH level, a physician may prescribe methimazole or radioactive iodine therapy to reduce the production of thyroxine, she said.

However, well-designed studies are needed to evaluate whether treatment of subclinical thyroid dysfunction reduces the risk for fracture or cardiovascular problems and assess downsides such as side effects, costs, and psychological harm, Dr. McClung noted.

The U.S. Preventive Services Task Force concluded in 2015 that the data were insufficient to recommend screening for thyroid dysfunction in adults without symptoms. As of a year ago, no new evidence has emerged to support an update, according to the task force’s website.

“Until those studies are available, selective screening of thyroid function should be considered in all patients undergoing risk assessment for cardiovascular disease or skeletal health,” Dr. McClung said.

The Atherosclerosis Risk in Communities Study has been funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) and the U.S. Department of Health and Human Services. Ms. Daya and four study authors reported receiving NIH grants during the study period. Dr. McClung reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

Knee and hip replacements can improve how well patients get around and can significantly increase their quality of life. But if a bone near the new joint breaks, the injury can be a major setback for the patient’s mobility, and the consequences can be life-threatening.

The proportion of patients who experience a periprosthetic fracture within 5 years of total hip arthroplasty is 0.9%. After total knee arthroplasty (TKA), the proportion is 0.6%, research shows.

Those rates might seem low. But given that more than a million of these joint replacement surgeries are performed each year in the United States – they are the most common inpatient surgical procedures among people aged 65 and older – thousands of revision surgeries due to periprosthetic fractures occur each year.

Primary care physicians, surgeons, and researchers are trying to identify risk factors, medication regimens, and nondrug approaches to avoid these complications. Primary care clinicians who make their patients’ bone health a priority early on – years before surgery, ideally – may help patients enjoy the benefits of new joints long term.

At the 2022 annual Santa Fe Bone Symposium this summer, Susan V. Bukata, MD, professor and chair of orthopedics at the University of California, San Diego, showed an image of “what we’re trying to avoid” – a patient with a broken bone and infection. Unfortunately, Dr. Bukata said, the patient’s clinicians had not adequately addressed her skeletal health before the injury.

“This is a complete disaster for this person who went in having a total hip to improve their function and now will probably never walk normally on that leg,” Dr. Bukata said at the meeting.

The patient eventually underwent total femur replacement. Five surgeries were required to clear the infection.

Medical and surgical advances have allowed more people – including older patients and those with other medical conditions – to undergo joint replacement surgery, including replacement of knees, hips, and shoulders.

The surgeries often are performed for adults whose bones are thinning. Sometimes surgeons don’t realize just how thin a patient’s bone is until they are operating.
 

Prioritizing bone health

In patients with osteoporosis, the bone surrounding the new joint is weaker than the metal of the prosthesis, and the metal can rip out of the bone, Dr. Bukata told this news organization. A periprosthetic fracture should be recognized as an osteoporotic fracture, too, although these fractures have not typically been categorized that way, she said.

People live with total joints in place for as long as 40 years, and fractures around the implants are “one of the fastest growing injuries that we are seeing in older patients,” Dr. Bukata said. “People don’t think of those as osteoporotic fractures. But a 90-year-old who falls and breaks next to their total knee, if they didn’t have that total knee in place, everybody would be, like, ‘Oh, that’s an osteoporotic fracture.’ ”

Periprosthetic fractures tend not to occur right after surgery but rather after the bone continues to lose density as the patient ages, Dr. Bukata said.
 

Missed chances

One approach to preventing periprosthetic fractures could involve prioritizing bone health earlier in life and diagnosing and treating osteoporosis well before a patient is scheduled for surgery.

A patient’s initial visit to their primary care doctor because of joint pain is an opportunity to check on and promote their bone health, given that they might be a candidate for surgery in the future, Dr. Bukata said.

Ahead of a scheduled surgery, patients can see endocrinologists or rheumatologists to receive medication to try to strengthen bones. Doctors may be limited in how much of a difference they can make in a matter of several weeks or months with these drugs, however. These patients still likely will need to be treated as if they have osteoporosis, Dr. Bukata said.

When surgeons realize that a patient has weaker bones while they are in the middle of an operation, they should emphasize the importance of bone health after the procedure, Dr. Bukata said.

Strengthening, maintaining, and protecting bone should be seen as a long-term investment in the patient’s success after a joint replacement. That said, “There is no clear evidence or protocol for us to follow,” she said. “The mantra at UCSD now is, let’s keep it simple. Get the patient on track. And then we can always refine things as we continue to treat the patient.”

Health systems should establish routines in which bone health is discussed before surgery in the way patient education programs address smoking cessation, nutrition, and weight management, Dr. Bukata said. Another step in the right direction could involve setting electronic medical records to automatically order assessments of bone health when a surgeon books a case.

Linda A. Russell, MD, rheumatologist and director of perioperative medicine at the Hospital for Special Surgery in New York, said periprosthetic fractures are a “complication we fear.”

“It’s a big deal to try to repair it,” Dr. Russell said. “Sometimes you need to revise the joint, or sometimes you need to put lots more hardware in.” Surgeons increasingly appreciate the need to pay attention to the quality of the bone before they operate, she said.

Nevertheless, Dr. Russell does not necessarily say that such cases call for alarm or particularly aggressive treatment regimens – just regular bone health evaluations before and after surgery to see whether patients have osteoporosis and are candidates for treatment.
 

Lifelong effort

In some ways, to address bone health at the time of surgery may be too late.

Bone health “is not something that you can have as an afterthought when you’re 75 years old,” said Elizabeth Matzkin, MD, chief of women’s sports medicine at Brigham and Women’s Hospital, in Boston.

The chance of being able to rebuild bone mass at that age is slim. If patients maximize bone density when they are young, they can afford to lose some bone mass each year as they age.

To that end, a healthy diet, exercise, not smoking, and cutting back on alcohol can help, she said.

For Dr. Matzkin, a fragility fracture is a red flag that the patient’s bone density is probably not optimal. In such cases, she prepares for various scenarios during surgery, such as a screw not holding in a low-density bone.

Recently published research reflects that prior fragility fractures are a significant risk factor for complications after surgery, including periprosthetic fractures.

Edward J. Testa, MD, of Brown University, Providence, R.I., and colleagues analyzed insurance claims to compare outcomes for 24,398 patients who had experienced a fragility fracture – that is, a break caused by low-velocity trauma such as a fall – during the 3 years before their TKA procedure and a matched group of patients who were similar in many respects but who had not had a fragility fracture in the 3 years before surgery.

Dr. Testa’s group found that a history of fragility fracture was associated with higher rates of complications in the year after surgery, including hospital readmissions (hazard ratio = 1.30; 95% CI, 1.22-1.38), periprosthetic fractures (odds ratio = 2.72; 95% CI, 1.89-3.99), and secondary fragility fractures (OR = 4.62; 95% CI, 4.19-5.12). Patients who had previously experienced fragility fractures also experienced dislocated prostheses (OR = 1.76; 95% CI, 1.22-2.56) and periprosthetic infections (OR = 1.49; 95% CI, 1.29-1.71) at higher rates.

The rates of complications were similar regardless of whether patients had filled a prescription for medications used to treat osteoporosis, including bisphosphonates, vitamin D replacement, raloxifene, and denosumab, the researchers reported.

The lack of a clear association between these treatments and patient outcomes could be related to an insufficient duration of pharmacotherapy before or after TKA, poor medication adherence, or small sample sizes, Dr. Testa said.

Given the findings, which were published online in the Journal of Arthroplasty, “patients with a history of fragility fracture should be identified and counseled appropriately for a possible increased risk of the aforementioned complications, and optimized when possible, prior to undergoing TKA,” Dr. Testa told this news organization. “Ultimately, the decision to move forward with surgery is far more complex than the identification of this sole, yet important, risk factor for certain postoperative, implant-related complications.”
 

Treatment gaps

Prior research has shown that women aged 70 years and older are at higher risk for periprosthetic fractures. Many women in this age group who could receive treatment for osteoporosis do not, and major treatment gaps exist worldwide, noted Neil Binkley, MD, with the University of Wisconsin–Madison, in a separate talk at the Santa Fe Bone Symposium.

Ensuring adequate protein intake and addressing the risk of falling are other measures that clinicians can take to promote healthy bones, apart from prescribing drugs, he said.

Unpublished data from one group show that nearly 90% of periprosthetic fractures may result from falls, while about 8% may be spontaneous. “We need to be thinking about falls,” Dr. Binkley said.

Dr. Bukata has consulted for Amgen, Radius, and Solarea Bio and has served on a speakers bureau for Radius. She also is a board member for the Orthopaedic Research Society and the American Academy of Orthopaedic Surgeons Board of Specialty Societies. Dr. Binkley has received research support from Radius and has consulted for Amgen.

A version of this article first appeared on Medscape.com.

Knee and hip replacements can improve how well patients get around and can significantly increase their quality of life. But if a bone near the new joint breaks, the injury can be a major setback for the patient’s mobility, and the consequences can be life-threatening.

The proportion of patients who experience a periprosthetic fracture within 5 years of total hip arthroplasty is 0.9%. After total knee arthroplasty (TKA), the proportion is 0.6%, research shows.

Those rates might seem low. But given that more than a million of these joint replacement surgeries are performed each year in the United States – they are the most common inpatient surgical procedures among people aged 65 and older – thousands of revision surgeries due to periprosthetic fractures occur each year.

Primary care physicians, surgeons, and researchers are trying to identify risk factors, medication regimens, and nondrug approaches to avoid these complications. Primary care clinicians who make their patients’ bone health a priority early on – years before surgery, ideally – may help patients enjoy the benefits of new joints long term.

At the 2022 annual Santa Fe Bone Symposium this summer, Susan V. Bukata, MD, professor and chair of orthopedics at the University of California, San Diego, showed an image of “what we’re trying to avoid” – a patient with a broken bone and infection. Unfortunately, Dr. Bukata said, the patient’s clinicians had not adequately addressed her skeletal health before the injury.

“This is a complete disaster for this person who went in having a total hip to improve their function and now will probably never walk normally on that leg,” Dr. Bukata said at the meeting.

The patient eventually underwent total femur replacement. Five surgeries were required to clear the infection.

Medical and surgical advances have allowed more people – including older patients and those with other medical conditions – to undergo joint replacement surgery, including replacement of knees, hips, and shoulders.

The surgeries often are performed for adults whose bones are thinning. Sometimes surgeons don’t realize just how thin a patient’s bone is until they are operating.
 

Prioritizing bone health

In patients with osteoporosis, the bone surrounding the new joint is weaker than the metal of the prosthesis, and the metal can rip out of the bone, Dr. Bukata told this news organization. A periprosthetic fracture should be recognized as an osteoporotic fracture, too, although these fractures have not typically been categorized that way, she said.

People live with total joints in place for as long as 40 years, and fractures around the implants are “one of the fastest growing injuries that we are seeing in older patients,” Dr. Bukata said. “People don’t think of those as osteoporotic fractures. But a 90-year-old who falls and breaks next to their total knee, if they didn’t have that total knee in place, everybody would be, like, ‘Oh, that’s an osteoporotic fracture.’ ”

Periprosthetic fractures tend not to occur right after surgery but rather after the bone continues to lose density as the patient ages, Dr. Bukata said.
 

Missed chances

One approach to preventing periprosthetic fractures could involve prioritizing bone health earlier in life and diagnosing and treating osteoporosis well before a patient is scheduled for surgery.

A patient’s initial visit to their primary care doctor because of joint pain is an opportunity to check on and promote their bone health, given that they might be a candidate for surgery in the future, Dr. Bukata said.

Ahead of a scheduled surgery, patients can see endocrinologists or rheumatologists to receive medication to try to strengthen bones. Doctors may be limited in how much of a difference they can make in a matter of several weeks or months with these drugs, however. These patients still likely will need to be treated as if they have osteoporosis, Dr. Bukata said.

When surgeons realize that a patient has weaker bones while they are in the middle of an operation, they should emphasize the importance of bone health after the procedure, Dr. Bukata said.

Strengthening, maintaining, and protecting bone should be seen as a long-term investment in the patient’s success after a joint replacement. That said, “There is no clear evidence or protocol for us to follow,” she said. “The mantra at UCSD now is, let’s keep it simple. Get the patient on track. And then we can always refine things as we continue to treat the patient.”

Health systems should establish routines in which bone health is discussed before surgery in the way patient education programs address smoking cessation, nutrition, and weight management, Dr. Bukata said. Another step in the right direction could involve setting electronic medical records to automatically order assessments of bone health when a surgeon books a case.

Linda A. Russell, MD, rheumatologist and director of perioperative medicine at the Hospital for Special Surgery in New York, said periprosthetic fractures are a “complication we fear.”

“It’s a big deal to try to repair it,” Dr. Russell said. “Sometimes you need to revise the joint, or sometimes you need to put lots more hardware in.” Surgeons increasingly appreciate the need to pay attention to the quality of the bone before they operate, she said.

Nevertheless, Dr. Russell does not necessarily say that such cases call for alarm or particularly aggressive treatment regimens – just regular bone health evaluations before and after surgery to see whether patients have osteoporosis and are candidates for treatment.
 

Lifelong effort

In some ways, to address bone health at the time of surgery may be too late.

Bone health “is not something that you can have as an afterthought when you’re 75 years old,” said Elizabeth Matzkin, MD, chief of women’s sports medicine at Brigham and Women’s Hospital, in Boston.

The chance of being able to rebuild bone mass at that age is slim. If patients maximize bone density when they are young, they can afford to lose some bone mass each year as they age.

To that end, a healthy diet, exercise, not smoking, and cutting back on alcohol can help, she said.

For Dr. Matzkin, a fragility fracture is a red flag that the patient’s bone density is probably not optimal. In such cases, she prepares for various scenarios during surgery, such as a screw not holding in a low-density bone.

Recently published research reflects that prior fragility fractures are a significant risk factor for complications after surgery, including periprosthetic fractures.

Edward J. Testa, MD, of Brown University, Providence, R.I., and colleagues analyzed insurance claims to compare outcomes for 24,398 patients who had experienced a fragility fracture – that is, a break caused by low-velocity trauma such as a fall – during the 3 years before their TKA procedure and a matched group of patients who were similar in many respects but who had not had a fragility fracture in the 3 years before surgery.

Dr. Testa’s group found that a history of fragility fracture was associated with higher rates of complications in the year after surgery, including hospital readmissions (hazard ratio = 1.30; 95% CI, 1.22-1.38), periprosthetic fractures (odds ratio = 2.72; 95% CI, 1.89-3.99), and secondary fragility fractures (OR = 4.62; 95% CI, 4.19-5.12). Patients who had previously experienced fragility fractures also experienced dislocated prostheses (OR = 1.76; 95% CI, 1.22-2.56) and periprosthetic infections (OR = 1.49; 95% CI, 1.29-1.71) at higher rates.

The rates of complications were similar regardless of whether patients had filled a prescription for medications used to treat osteoporosis, including bisphosphonates, vitamin D replacement, raloxifene, and denosumab, the researchers reported.

The lack of a clear association between these treatments and patient outcomes could be related to an insufficient duration of pharmacotherapy before or after TKA, poor medication adherence, or small sample sizes, Dr. Testa said.

Given the findings, which were published online in the Journal of Arthroplasty, “patients with a history of fragility fracture should be identified and counseled appropriately for a possible increased risk of the aforementioned complications, and optimized when possible, prior to undergoing TKA,” Dr. Testa told this news organization. “Ultimately, the decision to move forward with surgery is far more complex than the identification of this sole, yet important, risk factor for certain postoperative, implant-related complications.”
 

Treatment gaps

Prior research has shown that women aged 70 years and older are at higher risk for periprosthetic fractures. Many women in this age group who could receive treatment for osteoporosis do not, and major treatment gaps exist worldwide, noted Neil Binkley, MD, with the University of Wisconsin–Madison, in a separate talk at the Santa Fe Bone Symposium.

Ensuring adequate protein intake and addressing the risk of falling are other measures that clinicians can take to promote healthy bones, apart from prescribing drugs, he said.

Unpublished data from one group show that nearly 90% of periprosthetic fractures may result from falls, while about 8% may be spontaneous. “We need to be thinking about falls,” Dr. Binkley said.

Dr. Bukata has consulted for Amgen, Radius, and Solarea Bio and has served on a speakers bureau for Radius. She also is a board member for the Orthopaedic Research Society and the American Academy of Orthopaedic Surgeons Board of Specialty Societies. Dr. Binkley has received research support from Radius and has consulted for Amgen.

A version of this article first appeared on Medscape.com.

Knee and hip replacements can improve how well patients get around and can significantly increase their quality of life. But if a bone near the new joint breaks, the injury can be a major setback for the patient’s mobility, and the consequences can be life-threatening.

The proportion of patients who experience a periprosthetic fracture within 5 years of total hip arthroplasty is 0.9%. After total knee arthroplasty (TKA), the proportion is 0.6%, research shows.

Those rates might seem low. But given that more than a million of these joint replacement surgeries are performed each year in the United States – they are the most common inpatient surgical procedures among people aged 65 and older – thousands of revision surgeries due to periprosthetic fractures occur each year.

Primary care physicians, surgeons, and researchers are trying to identify risk factors, medication regimens, and nondrug approaches to avoid these complications. Primary care clinicians who make their patients’ bone health a priority early on – years before surgery, ideally – may help patients enjoy the benefits of new joints long term.

At the 2022 annual Santa Fe Bone Symposium this summer, Susan V. Bukata, MD, professor and chair of orthopedics at the University of California, San Diego, showed an image of “what we’re trying to avoid” – a patient with a broken bone and infection. Unfortunately, Dr. Bukata said, the patient’s clinicians had not adequately addressed her skeletal health before the injury.

“This is a complete disaster for this person who went in having a total hip to improve their function and now will probably never walk normally on that leg,” Dr. Bukata said at the meeting.

The patient eventually underwent total femur replacement. Five surgeries were required to clear the infection.

Medical and surgical advances have allowed more people – including older patients and those with other medical conditions – to undergo joint replacement surgery, including replacement of knees, hips, and shoulders.

The surgeries often are performed for adults whose bones are thinning. Sometimes surgeons don’t realize just how thin a patient’s bone is until they are operating.
 

Prioritizing bone health

In patients with osteoporosis, the bone surrounding the new joint is weaker than the metal of the prosthesis, and the metal can rip out of the bone, Dr. Bukata told this news organization. A periprosthetic fracture should be recognized as an osteoporotic fracture, too, although these fractures have not typically been categorized that way, she said.

People live with total joints in place for as long as 40 years, and fractures around the implants are “one of the fastest growing injuries that we are seeing in older patients,” Dr. Bukata said. “People don’t think of those as osteoporotic fractures. But a 90-year-old who falls and breaks next to their total knee, if they didn’t have that total knee in place, everybody would be, like, ‘Oh, that’s an osteoporotic fracture.’ ”

Periprosthetic fractures tend not to occur right after surgery but rather after the bone continues to lose density as the patient ages, Dr. Bukata said.
 

Missed chances

One approach to preventing periprosthetic fractures could involve prioritizing bone health earlier in life and diagnosing and treating osteoporosis well before a patient is scheduled for surgery.

A patient’s initial visit to their primary care doctor because of joint pain is an opportunity to check on and promote their bone health, given that they might be a candidate for surgery in the future, Dr. Bukata said.

Ahead of a scheduled surgery, patients can see endocrinologists or rheumatologists to receive medication to try to strengthen bones. Doctors may be limited in how much of a difference they can make in a matter of several weeks or months with these drugs, however. These patients still likely will need to be treated as if they have osteoporosis, Dr. Bukata said.

When surgeons realize that a patient has weaker bones while they are in the middle of an operation, they should emphasize the importance of bone health after the procedure, Dr. Bukata said.

Strengthening, maintaining, and protecting bone should be seen as a long-term investment in the patient’s success after a joint replacement. That said, “There is no clear evidence or protocol for us to follow,” she said. “The mantra at UCSD now is, let’s keep it simple. Get the patient on track. And then we can always refine things as we continue to treat the patient.”

Health systems should establish routines in which bone health is discussed before surgery in the way patient education programs address smoking cessation, nutrition, and weight management, Dr. Bukata said. Another step in the right direction could involve setting electronic medical records to automatically order assessments of bone health when a surgeon books a case.

Linda A. Russell, MD, rheumatologist and director of perioperative medicine at the Hospital for Special Surgery in New York, said periprosthetic fractures are a “complication we fear.”

“It’s a big deal to try to repair it,” Dr. Russell said. “Sometimes you need to revise the joint, or sometimes you need to put lots more hardware in.” Surgeons increasingly appreciate the need to pay attention to the quality of the bone before they operate, she said.

Nevertheless, Dr. Russell does not necessarily say that such cases call for alarm or particularly aggressive treatment regimens – just regular bone health evaluations before and after surgery to see whether patients have osteoporosis and are candidates for treatment.
 

Lifelong effort

In some ways, to address bone health at the time of surgery may be too late.

Bone health “is not something that you can have as an afterthought when you’re 75 years old,” said Elizabeth Matzkin, MD, chief of women’s sports medicine at Brigham and Women’s Hospital, in Boston.

The chance of being able to rebuild bone mass at that age is slim. If patients maximize bone density when they are young, they can afford to lose some bone mass each year as they age.

To that end, a healthy diet, exercise, not smoking, and cutting back on alcohol can help, she said.

For Dr. Matzkin, a fragility fracture is a red flag that the patient’s bone density is probably not optimal. In such cases, she prepares for various scenarios during surgery, such as a screw not holding in a low-density bone.

Recently published research reflects that prior fragility fractures are a significant risk factor for complications after surgery, including periprosthetic fractures.

Edward J. Testa, MD, of Brown University, Providence, R.I., and colleagues analyzed insurance claims to compare outcomes for 24,398 patients who had experienced a fragility fracture – that is, a break caused by low-velocity trauma such as a fall – during the 3 years before their TKA procedure and a matched group of patients who were similar in many respects but who had not had a fragility fracture in the 3 years before surgery.

Dr. Testa’s group found that a history of fragility fracture was associated with higher rates of complications in the year after surgery, including hospital readmissions (hazard ratio = 1.30; 95% CI, 1.22-1.38), periprosthetic fractures (odds ratio = 2.72; 95% CI, 1.89-3.99), and secondary fragility fractures (OR = 4.62; 95% CI, 4.19-5.12). Patients who had previously experienced fragility fractures also experienced dislocated prostheses (OR = 1.76; 95% CI, 1.22-2.56) and periprosthetic infections (OR = 1.49; 95% CI, 1.29-1.71) at higher rates.

The rates of complications were similar regardless of whether patients had filled a prescription for medications used to treat osteoporosis, including bisphosphonates, vitamin D replacement, raloxifene, and denosumab, the researchers reported.

The lack of a clear association between these treatments and patient outcomes could be related to an insufficient duration of pharmacotherapy before or after TKA, poor medication adherence, or small sample sizes, Dr. Testa said.

Given the findings, which were published online in the Journal of Arthroplasty, “patients with a history of fragility fracture should be identified and counseled appropriately for a possible increased risk of the aforementioned complications, and optimized when possible, prior to undergoing TKA,” Dr. Testa told this news organization. “Ultimately, the decision to move forward with surgery is far more complex than the identification of this sole, yet important, risk factor for certain postoperative, implant-related complications.”
 

Treatment gaps

Prior research has shown that women aged 70 years and older are at higher risk for periprosthetic fractures. Many women in this age group who could receive treatment for osteoporosis do not, and major treatment gaps exist worldwide, noted Neil Binkley, MD, with the University of Wisconsin–Madison, in a separate talk at the Santa Fe Bone Symposium.

Ensuring adequate protein intake and addressing the risk of falling are other measures that clinicians can take to promote healthy bones, apart from prescribing drugs, he said.

Unpublished data from one group show that nearly 90% of periprosthetic fractures may result from falls, while about 8% may be spontaneous. “We need to be thinking about falls,” Dr. Binkley said.

Dr. Bukata has consulted for Amgen, Radius, and Solarea Bio and has served on a speakers bureau for Radius. She also is a board member for the Orthopaedic Research Society and the American Academy of Orthopaedic Surgeons Board of Specialty Societies. Dr. Binkley has received research support from Radius and has consulted for Amgen.

A version of this article first appeared on Medscape.com.

The U.S. Preventive Services Task Force moved forward their recommendations for using hormone therapy to prevent chronic conditions in postmenopausal women by keeping them the same.

The central message of the new recommendations, released on Nov. 1 as a statement published in JAMA, remains unchanged from the last update in 2017.

The message also remains simple: Don’t use hormone therapy for preventing chronic conditions, such as cardiovascular disease, cancer, and osteoporosis, or bone fracture.

The USPSTF summarized its recommendations in two brief statements: the group “recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons” and “recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy.”

This wording is identical to that used in the 2017 guidance (except it now refers to postmenopausal persons instead of specifically women). The recommendation against use of estrogen and progestin for prevention of chronic conditions in postmenopausal women was first made by the USPSTF in 2002.

An editorial accompanying the 2022 revision notes that the evidence cited by the USPSTF includes “only two additional, modest-sized trials” (that focused on the effects of hormone therapy on cognition and brain structure) compared with 2017, “as well as ancillary analyses of previous trials.”
 

A standard 5-year update

The 2022 revision and revisiting of the evidence base by the Task Force regarding the benefits and risks of postmenopausal hormone therapy occurred “as part of the Task Force’s standard approach, which includes updating each recommendation approximately every 5 years,” explained Carol M. Mangione, MD, who is USPSTF chair and chief of the division of general internal medicine and health services research at the University of California, Los Angeles.

“In our review we again found that while hormone therapy may reduce the risk of some conditions, it can also lead to serious harms such as an increase in the risk of blood clots and stroke,” Dr. Mangione said in an interview. “The harms cancel out any potential benefits overall.”

This new statement only applies to using menopausal hormone treatment for preventing chronic conditions in asymptomatic people but does not speak to using this treatment in managing people with perimenopausal symptoms such as hot flashes or vaginal dryness or treating people with premature or surgical menopause, Dr. Mangione highlighted.
 

No review for treating menopausal symptoms

“The Task Force encourages people who are experiencing symptoms of menopause to talk with their health care professional about the best treatment for them,” explained Dr. Mangione. “The Task Force did not review the evidence on the use of hormone therapy to treat symptoms of menopause.”

Osteoporosis and increased risk for bone fracture were among the conditions that accompany menopause reviewed by the USPSTF. The Task Force concluded that while “hormone therapy was associated with decreased risk of fractures,” after weighing the benefits and harms for preventing this condition, “there is no net benefit at the population level.”

This conclusion seems to contrast with the 2022 hormone therapy position statement of the North American Menopause Society (NAMS), released in July, which states: “For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for treatment of bothersome vasomotor symptoms and prevention of bone loss.”
 

USPSTF, NAMS are ‘completely consistent’

However, Stephanie S. Faubion, MD, medical director of NAMS and director of the women’s health clinic at Mayo Clinic, Rochester, Minn., said the new USPSTF recommendations “are completely consistent” with the recent NAMS statement.

“We are entirely aligned with the recommendation to use hormone therapy for management of menopausal symptoms and not for chronic disease prevention or as an anti-aging strategy,” Dr. Faubion commented in an interview.

Dr. Faubion also stressed that “menopausal hormone therapy remains the most effective treatment for menopausal symptoms,” and that “women should not be reflexively directed to other pharmacologic therapies for management of menopausal symptoms.”

The distinction the USPSTF makes between its recommendations against using hormone therapy to prevent chronic conditions and its deferral of comment on use of the same treatment to manage perimenopausal symptoms is often forgotten, note Alison J. Huang, MD, and Deborah Grady, MD, in their editorial.
 

A problem of conflation

“Many patients and clinicians conflate these two different indications,” they write.

The notion that the net harms of menopausal hormone therapy outweigh the benefits “is now widely adopted as a rationale for foregoing menopausal hormone therapy for symptomatic treatment,” even though “nonhormonal treatments that are as effective as menopausal hormone therapy have not yet been identified,” say Dr. Huang and Dr. Grady, both physicians at the University of California, San Francisco.

In addition, alternative, nonhormonal options for treating perimenopausal symptoms have not received the same level of scrutiny as hormonal treatment, they say.

“It is arguably problematic to avoid menopausal hormone therapy and favor potentially less effective treatments, when the longer-term implications of those treatments for health have not been evaluated,” Dr. Huang and Dr. Grady write in their editorial.

In short, during menopause, people are at risk of being “frightened away from considering using menopausal hormone therapy for distressing symptoms,” they say.

“We can’t speak to whether or how often clinicians might be conflating the role of hormone therapy in treating symptoms and preventing chronic conditions,” answered Dr. Mangione.

“We hope to ensure that health professionals know that hormone therapy is not a beneficial way to reduce the risk of chronic conditions such as heart disease, cancer, and strokes,” she added. The new recommendations are an effort to “raise awareness about the value of considering other safe and effective ways for people to reduce their risk of chronic health problems as they age.”
 

The issue of timing

Another critique offered by Dr. Huang and Dr. Grady in their editorial is that “the scientific and medical community should let go of the past,” and should no longer invest additional resources in “trying to parse out subsets of menopausal patients who may derive some preventive benefit from menopausal hormone therapy for a limited amount of time.”

But Dr. Mangione disagreed.

The USPSTF “calls for more research that can help us understand whether health outcomes – both benefits and harms – differ depending on a person’s age or when they started hormone therapy related to when they went through menopause,” she said.

Dr. Mangione also highlighted the need for additional research on whether the benefits and risks of menopausal hormone therapy vary across racial and ethnic groups.

USPSTF receives no commercial funding. Dr. Mangione, Dr. Huang, and Dr. Grady have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.S. Preventive Services Task Force moved forward their recommendations for using hormone therapy to prevent chronic conditions in postmenopausal women by keeping them the same.

The central message of the new recommendations, released on Nov. 1 as a statement published in JAMA, remains unchanged from the last update in 2017.

The message also remains simple: Don’t use hormone therapy for preventing chronic conditions, such as cardiovascular disease, cancer, and osteoporosis, or bone fracture.

The USPSTF summarized its recommendations in two brief statements: the group “recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons” and “recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy.”

This wording is identical to that used in the 2017 guidance (except it now refers to postmenopausal persons instead of specifically women). The recommendation against use of estrogen and progestin for prevention of chronic conditions in postmenopausal women was first made by the USPSTF in 2002.

An editorial accompanying the 2022 revision notes that the evidence cited by the USPSTF includes “only two additional, modest-sized trials” (that focused on the effects of hormone therapy on cognition and brain structure) compared with 2017, “as well as ancillary analyses of previous trials.”
 

A standard 5-year update

The 2022 revision and revisiting of the evidence base by the Task Force regarding the benefits and risks of postmenopausal hormone therapy occurred “as part of the Task Force’s standard approach, which includes updating each recommendation approximately every 5 years,” explained Carol M. Mangione, MD, who is USPSTF chair and chief of the division of general internal medicine and health services research at the University of California, Los Angeles.

“In our review we again found that while hormone therapy may reduce the risk of some conditions, it can also lead to serious harms such as an increase in the risk of blood clots and stroke,” Dr. Mangione said in an interview. “The harms cancel out any potential benefits overall.”

This new statement only applies to using menopausal hormone treatment for preventing chronic conditions in asymptomatic people but does not speak to using this treatment in managing people with perimenopausal symptoms such as hot flashes or vaginal dryness or treating people with premature or surgical menopause, Dr. Mangione highlighted.
 

No review for treating menopausal symptoms

“The Task Force encourages people who are experiencing symptoms of menopause to talk with their health care professional about the best treatment for them,” explained Dr. Mangione. “The Task Force did not review the evidence on the use of hormone therapy to treat symptoms of menopause.”

Osteoporosis and increased risk for bone fracture were among the conditions that accompany menopause reviewed by the USPSTF. The Task Force concluded that while “hormone therapy was associated with decreased risk of fractures,” after weighing the benefits and harms for preventing this condition, “there is no net benefit at the population level.”

This conclusion seems to contrast with the 2022 hormone therapy position statement of the North American Menopause Society (NAMS), released in July, which states: “For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for treatment of bothersome vasomotor symptoms and prevention of bone loss.”
 

USPSTF, NAMS are ‘completely consistent’

However, Stephanie S. Faubion, MD, medical director of NAMS and director of the women’s health clinic at Mayo Clinic, Rochester, Minn., said the new USPSTF recommendations “are completely consistent” with the recent NAMS statement.

“We are entirely aligned with the recommendation to use hormone therapy for management of menopausal symptoms and not for chronic disease prevention or as an anti-aging strategy,” Dr. Faubion commented in an interview.

Dr. Faubion also stressed that “menopausal hormone therapy remains the most effective treatment for menopausal symptoms,” and that “women should not be reflexively directed to other pharmacologic therapies for management of menopausal symptoms.”

The distinction the USPSTF makes between its recommendations against using hormone therapy to prevent chronic conditions and its deferral of comment on use of the same treatment to manage perimenopausal symptoms is often forgotten, note Alison J. Huang, MD, and Deborah Grady, MD, in their editorial.
 

A problem of conflation

“Many patients and clinicians conflate these two different indications,” they write.

The notion that the net harms of menopausal hormone therapy outweigh the benefits “is now widely adopted as a rationale for foregoing menopausal hormone therapy for symptomatic treatment,” even though “nonhormonal treatments that are as effective as menopausal hormone therapy have not yet been identified,” say Dr. Huang and Dr. Grady, both physicians at the University of California, San Francisco.

In addition, alternative, nonhormonal options for treating perimenopausal symptoms have not received the same level of scrutiny as hormonal treatment, they say.

“It is arguably problematic to avoid menopausal hormone therapy and favor potentially less effective treatments, when the longer-term implications of those treatments for health have not been evaluated,” Dr. Huang and Dr. Grady write in their editorial.

In short, during menopause, people are at risk of being “frightened away from considering using menopausal hormone therapy for distressing symptoms,” they say.

“We can’t speak to whether or how often clinicians might be conflating the role of hormone therapy in treating symptoms and preventing chronic conditions,” answered Dr. Mangione.

“We hope to ensure that health professionals know that hormone therapy is not a beneficial way to reduce the risk of chronic conditions such as heart disease, cancer, and strokes,” she added. The new recommendations are an effort to “raise awareness about the value of considering other safe and effective ways for people to reduce their risk of chronic health problems as they age.”
 

The issue of timing

Another critique offered by Dr. Huang and Dr. Grady in their editorial is that “the scientific and medical community should let go of the past,” and should no longer invest additional resources in “trying to parse out subsets of menopausal patients who may derive some preventive benefit from menopausal hormone therapy for a limited amount of time.”

But Dr. Mangione disagreed.

The USPSTF “calls for more research that can help us understand whether health outcomes – both benefits and harms – differ depending on a person’s age or when they started hormone therapy related to when they went through menopause,” she said.

Dr. Mangione also highlighted the need for additional research on whether the benefits and risks of menopausal hormone therapy vary across racial and ethnic groups.

USPSTF receives no commercial funding. Dr. Mangione, Dr. Huang, and Dr. Grady have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.S. Preventive Services Task Force moved forward their recommendations for using hormone therapy to prevent chronic conditions in postmenopausal women by keeping them the same.

The central message of the new recommendations, released on Nov. 1 as a statement published in JAMA, remains unchanged from the last update in 2017.

The message also remains simple: Don’t use hormone therapy for preventing chronic conditions, such as cardiovascular disease, cancer, and osteoporosis, or bone fracture.

The USPSTF summarized its recommendations in two brief statements: the group “recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons” and “recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy.”

This wording is identical to that used in the 2017 guidance (except it now refers to postmenopausal persons instead of specifically women). The recommendation against use of estrogen and progestin for prevention of chronic conditions in postmenopausal women was first made by the USPSTF in 2002.

An editorial accompanying the 2022 revision notes that the evidence cited by the USPSTF includes “only two additional, modest-sized trials” (that focused on the effects of hormone therapy on cognition and brain structure) compared with 2017, “as well as ancillary analyses of previous trials.”
 

A standard 5-year update

The 2022 revision and revisiting of the evidence base by the Task Force regarding the benefits and risks of postmenopausal hormone therapy occurred “as part of the Task Force’s standard approach, which includes updating each recommendation approximately every 5 years,” explained Carol M. Mangione, MD, who is USPSTF chair and chief of the division of general internal medicine and health services research at the University of California, Los Angeles.

“In our review we again found that while hormone therapy may reduce the risk of some conditions, it can also lead to serious harms such as an increase in the risk of blood clots and stroke,” Dr. Mangione said in an interview. “The harms cancel out any potential benefits overall.”

This new statement only applies to using menopausal hormone treatment for preventing chronic conditions in asymptomatic people but does not speak to using this treatment in managing people with perimenopausal symptoms such as hot flashes or vaginal dryness or treating people with premature or surgical menopause, Dr. Mangione highlighted.
 

No review for treating menopausal symptoms

“The Task Force encourages people who are experiencing symptoms of menopause to talk with their health care professional about the best treatment for them,” explained Dr. Mangione. “The Task Force did not review the evidence on the use of hormone therapy to treat symptoms of menopause.”

Osteoporosis and increased risk for bone fracture were among the conditions that accompany menopause reviewed by the USPSTF. The Task Force concluded that while “hormone therapy was associated with decreased risk of fractures,” after weighing the benefits and harms for preventing this condition, “there is no net benefit at the population level.”

This conclusion seems to contrast with the 2022 hormone therapy position statement of the North American Menopause Society (NAMS), released in July, which states: “For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for treatment of bothersome vasomotor symptoms and prevention of bone loss.”
 

USPSTF, NAMS are ‘completely consistent’

However, Stephanie S. Faubion, MD, medical director of NAMS and director of the women’s health clinic at Mayo Clinic, Rochester, Minn., said the new USPSTF recommendations “are completely consistent” with the recent NAMS statement.

“We are entirely aligned with the recommendation to use hormone therapy for management of menopausal symptoms and not for chronic disease prevention or as an anti-aging strategy,” Dr. Faubion commented in an interview.

Dr. Faubion also stressed that “menopausal hormone therapy remains the most effective treatment for menopausal symptoms,” and that “women should not be reflexively directed to other pharmacologic therapies for management of menopausal symptoms.”

The distinction the USPSTF makes between its recommendations against using hormone therapy to prevent chronic conditions and its deferral of comment on use of the same treatment to manage perimenopausal symptoms is often forgotten, note Alison J. Huang, MD, and Deborah Grady, MD, in their editorial.
 

A problem of conflation

“Many patients and clinicians conflate these two different indications,” they write.

The notion that the net harms of menopausal hormone therapy outweigh the benefits “is now widely adopted as a rationale for foregoing menopausal hormone therapy for symptomatic treatment,” even though “nonhormonal treatments that are as effective as menopausal hormone therapy have not yet been identified,” say Dr. Huang and Dr. Grady, both physicians at the University of California, San Francisco.

In addition, alternative, nonhormonal options for treating perimenopausal symptoms have not received the same level of scrutiny as hormonal treatment, they say.

“It is arguably problematic to avoid menopausal hormone therapy and favor potentially less effective treatments, when the longer-term implications of those treatments for health have not been evaluated,” Dr. Huang and Dr. Grady write in their editorial.

In short, during menopause, people are at risk of being “frightened away from considering using menopausal hormone therapy for distressing symptoms,” they say.

“We can’t speak to whether or how often clinicians might be conflating the role of hormone therapy in treating symptoms and preventing chronic conditions,” answered Dr. Mangione.

“We hope to ensure that health professionals know that hormone therapy is not a beneficial way to reduce the risk of chronic conditions such as heart disease, cancer, and strokes,” she added. The new recommendations are an effort to “raise awareness about the value of considering other safe and effective ways for people to reduce their risk of chronic health problems as they age.”
 

The issue of timing

Another critique offered by Dr. Huang and Dr. Grady in their editorial is that “the scientific and medical community should let go of the past,” and should no longer invest additional resources in “trying to parse out subsets of menopausal patients who may derive some preventive benefit from menopausal hormone therapy for a limited amount of time.”

But Dr. Mangione disagreed.

The USPSTF “calls for more research that can help us understand whether health outcomes – both benefits and harms – differ depending on a person’s age or when they started hormone therapy related to when they went through menopause,” she said.

Dr. Mangione also highlighted the need for additional research on whether the benefits and risks of menopausal hormone therapy vary across racial and ethnic groups.

USPSTF receives no commercial funding. Dr. Mangione, Dr. Huang, and Dr. Grady have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Vitamin D deficiency increases mortality risk and raising levels even slightly could decrease the risk, researchers examining data from the UK Biobank have found.

They used a Mendelian randomization approach, which uses genetic variants as “proxy indicators” for external factors that affect vitamin D levels, such as sun exposure or dietary intake. It allows for analysis of the relationship between deficiency and outcomes including mortality, which can’t be done in randomized clinical trials for ethical reasons.

Using this method, nutritionist Joshua P. Sutherland, PhD, of the Australian Centre for Precision Health, Adelaide, and colleagues found an association between genetically predicted vitamin D levels [25-(OH)D] and mortality from several major causes, with evidence of causality among people with measured concentrations below, but not above, 50 nmol/L. The findings were published online in Annals of Internal Medicine.

Genetic approach reveals causal relationship

The investigators analyzed data from 307,601 individuals in the UK Biobank, a prospective cohort of people recruited from England, Scotland, and Wales during March 2006 and July 2010. Most were of White European ancestry and were aged 37-73 years at baseline.

Genetically predicted vitamin D levels were estimated using 35 confirmed 25-(OH)D variants. Participants were followed for outcomes up to June 2020.

The average baseline measured 25-(OH)D concentration was 45.2 nmol/L, and 11.7% (n = 36,009) of participants had levels between 10.0  and 24.9 nmol/L. Higher levels were seen in people living in southern areas and nonsmokers as well as those with a higher level of physical activity, less socioeconomic deprivation, and lower body mass index.

During follow-up, 6.1% of participants died (n = 18,700). After adjustment for variables, odds ratios for all causes of mortality were highest among people with 25-(OH)D levels below 25 nmol/L and appeared to plateau between 50 and 75 nmol/L, with no further reduction in mortality at values of 75-125 nmol/L.
 

Mortality 36% higher in those deficient in vitamin D

The risk for mortality was a significant 36% higher for participants with 25-(OH)D 25 nmol/L compared with 50 nmol/L.

With the Mendelian randomization, there was an L-shaped association between genetically predicted 25-(OH)D level and all-cause mortality (P for nonlinearity < .001) and for mortality because of cancer and cardiovascular disease (P for nonlinearity ≤ .033).

Again, the strongest association with those outcomes and genetically predicted 25-(OH)D was found at levels below 25 nmol/L and a plateau was seen by 50 nmol/L.

Compared with a measured 25-(OH)D concentration of 50 nmol/L, investigators estimated that the genetically predicted odds of all-cause mortality would increase sixfold (odds ratio, 6.00) for participants at 10 nmol/L and by 25% (OR, 1.25) for those at 25 nmol/L.

And, compared with a measured 25-(OH)D concentration of 50 nmol/L, those with 10 nmol/L had genetically predicted odds ratios of 5.98 for cardiovascular mortality, 3.37 for cancer mortality, and 12.44 for respiratory mortality.

Comparing measured 25-(OH)D concentrations of 25 nmol/L versus 50 nmol/L, odds ratios for those outcomes were 1.25, 1.16, and 1.96 (95% confidence interval, 1.88-4.67), respectively. All were statistically significant.

Consistent results supportive of a causal effect of genetically predicted 25-(OH)D on all-cause mortality in those with low measured vitamin D concentrations were also found in a sensitivity analysis of 20,837 people of non-White ethnic origin.

The study was funded by the Australian National Health and Medical Research Council. Dr. Sutherland’s studentship is funded by an Australian Research Training Program Scholarship.

A version of this article first appeared on Medscape.com.  

Vitamin D deficiency increases mortality risk and raising levels even slightly could decrease the risk, researchers examining data from the UK Biobank have found.

They used a Mendelian randomization approach, which uses genetic variants as “proxy indicators” for external factors that affect vitamin D levels, such as sun exposure or dietary intake. It allows for analysis of the relationship between deficiency and outcomes including mortality, which can’t be done in randomized clinical trials for ethical reasons.

Using this method, nutritionist Joshua P. Sutherland, PhD, of the Australian Centre for Precision Health, Adelaide, and colleagues found an association between genetically predicted vitamin D levels [25-(OH)D] and mortality from several major causes, with evidence of causality among people with measured concentrations below, but not above, 50 nmol/L. The findings were published online in Annals of Internal Medicine.

Genetic approach reveals causal relationship

The investigators analyzed data from 307,601 individuals in the UK Biobank, a prospective cohort of people recruited from England, Scotland, and Wales during March 2006 and July 2010. Most were of White European ancestry and were aged 37-73 years at baseline.

Genetically predicted vitamin D levels were estimated using 35 confirmed 25-(OH)D variants. Participants were followed for outcomes up to June 2020.

The average baseline measured 25-(OH)D concentration was 45.2 nmol/L, and 11.7% (n = 36,009) of participants had levels between 10.0  and 24.9 nmol/L. Higher levels were seen in people living in southern areas and nonsmokers as well as those with a higher level of physical activity, less socioeconomic deprivation, and lower body mass index.

During follow-up, 6.1% of participants died (n = 18,700). After adjustment for variables, odds ratios for all causes of mortality were highest among people with 25-(OH)D levels below 25 nmol/L and appeared to plateau between 50 and 75 nmol/L, with no further reduction in mortality at values of 75-125 nmol/L.
 

Mortality 36% higher in those deficient in vitamin D

The risk for mortality was a significant 36% higher for participants with 25-(OH)D 25 nmol/L compared with 50 nmol/L.

With the Mendelian randomization, there was an L-shaped association between genetically predicted 25-(OH)D level and all-cause mortality (P for nonlinearity < .001) and for mortality because of cancer and cardiovascular disease (P for nonlinearity ≤ .033).

Again, the strongest association with those outcomes and genetically predicted 25-(OH)D was found at levels below 25 nmol/L and a plateau was seen by 50 nmol/L.

Compared with a measured 25-(OH)D concentration of 50 nmol/L, investigators estimated that the genetically predicted odds of all-cause mortality would increase sixfold (odds ratio, 6.00) for participants at 10 nmol/L and by 25% (OR, 1.25) for those at 25 nmol/L.

And, compared with a measured 25-(OH)D concentration of 50 nmol/L, those with 10 nmol/L had genetically predicted odds ratios of 5.98 for cardiovascular mortality, 3.37 for cancer mortality, and 12.44 for respiratory mortality.

Comparing measured 25-(OH)D concentrations of 25 nmol/L versus 50 nmol/L, odds ratios for those outcomes were 1.25, 1.16, and 1.96 (95% confidence interval, 1.88-4.67), respectively. All were statistically significant.

Consistent results supportive of a causal effect of genetically predicted 25-(OH)D on all-cause mortality in those with low measured vitamin D concentrations were also found in a sensitivity analysis of 20,837 people of non-White ethnic origin.

The study was funded by the Australian National Health and Medical Research Council. Dr. Sutherland’s studentship is funded by an Australian Research Training Program Scholarship.

A version of this article first appeared on Medscape.com.  

Vitamin D deficiency increases mortality risk and raising levels even slightly could decrease the risk, researchers examining data from the UK Biobank have found.

They used a Mendelian randomization approach, which uses genetic variants as “proxy indicators” for external factors that affect vitamin D levels, such as sun exposure or dietary intake. It allows for analysis of the relationship between deficiency and outcomes including mortality, which can’t be done in randomized clinical trials for ethical reasons.

Using this method, nutritionist Joshua P. Sutherland, PhD, of the Australian Centre for Precision Health, Adelaide, and colleagues found an association between genetically predicted vitamin D levels [25-(OH)D] and mortality from several major causes, with evidence of causality among people with measured concentrations below, but not above, 50 nmol/L. The findings were published online in Annals of Internal Medicine.

Genetic approach reveals causal relationship

The investigators analyzed data from 307,601 individuals in the UK Biobank, a prospective cohort of people recruited from England, Scotland, and Wales during March 2006 and July 2010. Most were of White European ancestry and were aged 37-73 years at baseline.

Genetically predicted vitamin D levels were estimated using 35 confirmed 25-(OH)D variants. Participants were followed for outcomes up to June 2020.

The average baseline measured 25-(OH)D concentration was 45.2 nmol/L, and 11.7% (n = 36,009) of participants had levels between 10.0  and 24.9 nmol/L. Higher levels were seen in people living in southern areas and nonsmokers as well as those with a higher level of physical activity, less socioeconomic deprivation, and lower body mass index.

During follow-up, 6.1% of participants died (n = 18,700). After adjustment for variables, odds ratios for all causes of mortality were highest among people with 25-(OH)D levels below 25 nmol/L and appeared to plateau between 50 and 75 nmol/L, with no further reduction in mortality at values of 75-125 nmol/L.
 

Mortality 36% higher in those deficient in vitamin D

The risk for mortality was a significant 36% higher for participants with 25-(OH)D 25 nmol/L compared with 50 nmol/L.

With the Mendelian randomization, there was an L-shaped association between genetically predicted 25-(OH)D level and all-cause mortality (P for nonlinearity < .001) and for mortality because of cancer and cardiovascular disease (P for nonlinearity ≤ .033).

Again, the strongest association with those outcomes and genetically predicted 25-(OH)D was found at levels below 25 nmol/L and a plateau was seen by 50 nmol/L.

Compared with a measured 25-(OH)D concentration of 50 nmol/L, investigators estimated that the genetically predicted odds of all-cause mortality would increase sixfold (odds ratio, 6.00) for participants at 10 nmol/L and by 25% (OR, 1.25) for those at 25 nmol/L.

And, compared with a measured 25-(OH)D concentration of 50 nmol/L, those with 10 nmol/L had genetically predicted odds ratios of 5.98 for cardiovascular mortality, 3.37 for cancer mortality, and 12.44 for respiratory mortality.

Comparing measured 25-(OH)D concentrations of 25 nmol/L versus 50 nmol/L, odds ratios for those outcomes were 1.25, 1.16, and 1.96 (95% confidence interval, 1.88-4.67), respectively. All were statistically significant.

Consistent results supportive of a causal effect of genetically predicted 25-(OH)D on all-cause mortality in those with low measured vitamin D concentrations were also found in a sensitivity analysis of 20,837 people of non-White ethnic origin.

The study was funded by the Australian National Health and Medical Research Council. Dr. Sutherland’s studentship is funded by an Australian Research Training Program Scholarship.

A version of this article first appeared on Medscape.com.  

Doctors caring for patients taking steroids now have broader flexibility for which drugs to use to prevent osteoporosis associated with the medications.

The American College of Rheumatology (ACR) has released an updated guideline that advises treatment providers on when and how long to prescribe therapies that prevent or treat glucocorticoid-induced osteoporosis (GIOP). Since the ACR last updated the guideline in 2017, the Food and Drug Administration has approved new treatments for osteoporosis, which are now included in the recommendations.

The new guideline also advises physicians that they may need to transition patients to a second treatment after concluding a first course – so-called sequential therapy – to better protect them against bone loss and fracture. It also offers detailed instructions for which drugs to use, when, and how long these medications should be administered for patients taking glucocorticoids over a long period of time.

The guideline’s inclusion of sequential therapy is significant and will be helpful to practicing clinicians, according to S.B. Tanner IV, MD, director of the Osteoporosis Clinic at Vanderbilt Health, Nashville, Tenn.

“For the first time, the ACR has offered guidance for starting and stopping treatments,” Dr. Tanner said. “This guideline supports awareness that osteoporosis is lifelong – something that will consistently need monitoring.”

An estimated 2.5 million Americans use glucocorticoids, according to a 2013 study in Arthritis Care & Research. Meanwhile, a 2019 study of residents in Denmark found 3% of people in the country were prescribed glucocorticoids annually. That study estimated 54% of glucocorticoid users were female and found the percentage of people taking glucocorticoids increased with age.

Glucocorticoids are used to treat a variety of inflammatory conditions, from multiple sclerosis to lupus, and often are prescribed to transplant patients to prevent their immune systems from rejecting new organs. When taken over time these medications can cause osteoporosis, which in turn raises the risk of fracture.

More than 10% of patients who receive long-term glucocorticoid treatment are diagnosed with clinical fractures. In addition, even low-dose glucocorticoid therapy is associated with a bone loss rate of 10% per year for a patient.

Osteoporosis prevention

After stopping some prevention therapies for GIOP, a high risk of bone loss or fracture still persists, according to Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center for the Hospital for Special Surgery, New York, and co-principal investigator of the new guideline.

“We wanted to be sure the need for sequential treatment is adequately communicated, including to patients who might not know they need to start a second medication,” Dr. Russell said.

Physicians and patients must be aware that when completing a course of one GIOP treatment, another drug for the condition should be started, as specified in the guideline.

“Early intervention can prevent glucocorticoid-induced fractures that can lead to substantial morbidity and increased mortality,” said Mary Beth Humphrey, MD, PhD, interim vice president for research at the University of Oklahoma Health Sciences Center in Oklahoma City and co-principal investigator of the ACR guideline.

Anyone can fracture

While age and other risk factors, including menopause, increase the risk of developing GIOP, bone loss can occur rapidly for a patient of any age.

Even a glucocorticoid dose as low as 2.5 mg will increase the risk of vertebral fractures, with some occurring as soon as 3 months after treatment starts, Dr. Humphrey said. For patients taking up to 7.5 mg daily, the risk of vertebral fracture doubles. Doses greater than 10 mg daily for more than 3 months raise the likelihood of a vertebral fracture by a factor of 14, and result in a 300% increase in the likelihood of hip fractures, according to Dr. Humphrey.

“When on steroids, even patients with high bone density scores can fracture,” Dr. Tanner said. “The 2017 guideline was almost too elaborate in its effort to calculate risk. The updated guideline acknowledges moderate risk and suggests that this is a group of patients who need treatment.”
 

Rank ordering adds flexibility

The updated ACR guideline no longer ranks medications based on patient fracture data, side effects, cost care, and whether the drug is provided through injection, pill, or IV.

All of the preventive treatments the panel recommends reduce the risk of steroid-induced bone loss, Dr. Humphrey said.

“We thought the 2017 guideline was too restrictive,” Dr. Russell said. “We’re giving physicians and patients more leeway to choose a medication based on their preferences.”

Patient preference of delivery mechanism – such as a desire for pills only – can now be weighed more heavily into drug treatment decisions.

“In the exam room, there are three dynamics going on: What the patient wants, what the doctor knows is most effective, and what the insurer will pay,” Dr. Tanner said. “Doing away with rank ordering opens up the conversation beyond cost to consider all those factors.”

The guideline team conducted a systematic literature review for clinical questions on nonpharmacologic and pharmacologic treatment addressed in the 2017 guideline, and for questions on new pharmacologic treatments, discontinuation of medications, and sequential and combination therapy. The voting panel consisted of two patient representatives and 13 experts representing adult and pediatric rheumatology and endocrinology, nephrology, and gastroenterology.

A full manuscript has been submitted for publication in Arthritis & Rheumatology and Arthritis Care and Research for peer review, and is expected to publish in early 2023.

Dr. Humphrey and Dr. Russell, the co-principal investigators for the guideline, and Dr. Rubin have disclosed no relevant financial relationships. Dr. Tanner reported a current research grant funded by Amgen through the University of Alabama at Birmingham and being a paid course instructor for the International Society for Clinical Densitometry bone density course, Osteoporosis Essentials.

A version of this article first appeared on Medscape.com.

Doctors caring for patients taking steroids now have broader flexibility for which drugs to use to prevent osteoporosis associated with the medications.

The American College of Rheumatology (ACR) has released an updated guideline that advises treatment providers on when and how long to prescribe therapies that prevent or treat glucocorticoid-induced osteoporosis (GIOP). Since the ACR last updated the guideline in 2017, the Food and Drug Administration has approved new treatments for osteoporosis, which are now included in the recommendations.

The new guideline also advises physicians that they may need to transition patients to a second treatment after concluding a first course – so-called sequential therapy – to better protect them against bone loss and fracture. It also offers detailed instructions for which drugs to use, when, and how long these medications should be administered for patients taking glucocorticoids over a long period of time.

The guideline’s inclusion of sequential therapy is significant and will be helpful to practicing clinicians, according to S.B. Tanner IV, MD, director of the Osteoporosis Clinic at Vanderbilt Health, Nashville, Tenn.

“For the first time, the ACR has offered guidance for starting and stopping treatments,” Dr. Tanner said. “This guideline supports awareness that osteoporosis is lifelong – something that will consistently need monitoring.”

An estimated 2.5 million Americans use glucocorticoids, according to a 2013 study in Arthritis Care & Research. Meanwhile, a 2019 study of residents in Denmark found 3% of people in the country were prescribed glucocorticoids annually. That study estimated 54% of glucocorticoid users were female and found the percentage of people taking glucocorticoids increased with age.

Glucocorticoids are used to treat a variety of inflammatory conditions, from multiple sclerosis to lupus, and often are prescribed to transplant patients to prevent their immune systems from rejecting new organs. When taken over time these medications can cause osteoporosis, which in turn raises the risk of fracture.

More than 10% of patients who receive long-term glucocorticoid treatment are diagnosed with clinical fractures. In addition, even low-dose glucocorticoid therapy is associated with a bone loss rate of 10% per year for a patient.

Osteoporosis prevention

After stopping some prevention therapies for GIOP, a high risk of bone loss or fracture still persists, according to Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center for the Hospital for Special Surgery, New York, and co-principal investigator of the new guideline.

“We wanted to be sure the need for sequential treatment is adequately communicated, including to patients who might not know they need to start a second medication,” Dr. Russell said.

Physicians and patients must be aware that when completing a course of one GIOP treatment, another drug for the condition should be started, as specified in the guideline.

“Early intervention can prevent glucocorticoid-induced fractures that can lead to substantial morbidity and increased mortality,” said Mary Beth Humphrey, MD, PhD, interim vice president for research at the University of Oklahoma Health Sciences Center in Oklahoma City and co-principal investigator of the ACR guideline.

Anyone can fracture

While age and other risk factors, including menopause, increase the risk of developing GIOP, bone loss can occur rapidly for a patient of any age.

Even a glucocorticoid dose as low as 2.5 mg will increase the risk of vertebral fractures, with some occurring as soon as 3 months after treatment starts, Dr. Humphrey said. For patients taking up to 7.5 mg daily, the risk of vertebral fracture doubles. Doses greater than 10 mg daily for more than 3 months raise the likelihood of a vertebral fracture by a factor of 14, and result in a 300% increase in the likelihood of hip fractures, according to Dr. Humphrey.

“When on steroids, even patients with high bone density scores can fracture,” Dr. Tanner said. “The 2017 guideline was almost too elaborate in its effort to calculate risk. The updated guideline acknowledges moderate risk and suggests that this is a group of patients who need treatment.”
 

Rank ordering adds flexibility

The updated ACR guideline no longer ranks medications based on patient fracture data, side effects, cost care, and whether the drug is provided through injection, pill, or IV.

All of the preventive treatments the panel recommends reduce the risk of steroid-induced bone loss, Dr. Humphrey said.

“We thought the 2017 guideline was too restrictive,” Dr. Russell said. “We’re giving physicians and patients more leeway to choose a medication based on their preferences.”

Patient preference of delivery mechanism – such as a desire for pills only – can now be weighed more heavily into drug treatment decisions.

“In the exam room, there are three dynamics going on: What the patient wants, what the doctor knows is most effective, and what the insurer will pay,” Dr. Tanner said. “Doing away with rank ordering opens up the conversation beyond cost to consider all those factors.”

The guideline team conducted a systematic literature review for clinical questions on nonpharmacologic and pharmacologic treatment addressed in the 2017 guideline, and for questions on new pharmacologic treatments, discontinuation of medications, and sequential and combination therapy. The voting panel consisted of two patient representatives and 13 experts representing adult and pediatric rheumatology and endocrinology, nephrology, and gastroenterology.

A full manuscript has been submitted for publication in Arthritis & Rheumatology and Arthritis Care and Research for peer review, and is expected to publish in early 2023.

Dr. Humphrey and Dr. Russell, the co-principal investigators for the guideline, and Dr. Rubin have disclosed no relevant financial relationships. Dr. Tanner reported a current research grant funded by Amgen through the University of Alabama at Birmingham and being a paid course instructor for the International Society for Clinical Densitometry bone density course, Osteoporosis Essentials.

A version of this article first appeared on Medscape.com.

Doctors caring for patients taking steroids now have broader flexibility for which drugs to use to prevent osteoporosis associated with the medications.

The American College of Rheumatology (ACR) has released an updated guideline that advises treatment providers on when and how long to prescribe therapies that prevent or treat glucocorticoid-induced osteoporosis (GIOP). Since the ACR last updated the guideline in 2017, the Food and Drug Administration has approved new treatments for osteoporosis, which are now included in the recommendations.

The new guideline also advises physicians that they may need to transition patients to a second treatment after concluding a first course – so-called sequential therapy – to better protect them against bone loss and fracture. It also offers detailed instructions for which drugs to use, when, and how long these medications should be administered for patients taking glucocorticoids over a long period of time.

The guideline’s inclusion of sequential therapy is significant and will be helpful to practicing clinicians, according to S.B. Tanner IV, MD, director of the Osteoporosis Clinic at Vanderbilt Health, Nashville, Tenn.

“For the first time, the ACR has offered guidance for starting and stopping treatments,” Dr. Tanner said. “This guideline supports awareness that osteoporosis is lifelong – something that will consistently need monitoring.”

An estimated 2.5 million Americans use glucocorticoids, according to a 2013 study in Arthritis Care & Research. Meanwhile, a 2019 study of residents in Denmark found 3% of people in the country were prescribed glucocorticoids annually. That study estimated 54% of glucocorticoid users were female and found the percentage of people taking glucocorticoids increased with age.

Glucocorticoids are used to treat a variety of inflammatory conditions, from multiple sclerosis to lupus, and often are prescribed to transplant patients to prevent their immune systems from rejecting new organs. When taken over time these medications can cause osteoporosis, which in turn raises the risk of fracture.

More than 10% of patients who receive long-term glucocorticoid treatment are diagnosed with clinical fractures. In addition, even low-dose glucocorticoid therapy is associated with a bone loss rate of 10% per year for a patient.

Osteoporosis prevention

After stopping some prevention therapies for GIOP, a high risk of bone loss or fracture still persists, according to Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center for the Hospital for Special Surgery, New York, and co-principal investigator of the new guideline.

“We wanted to be sure the need for sequential treatment is adequately communicated, including to patients who might not know they need to start a second medication,” Dr. Russell said.

Physicians and patients must be aware that when completing a course of one GIOP treatment, another drug for the condition should be started, as specified in the guideline.

“Early intervention can prevent glucocorticoid-induced fractures that can lead to substantial morbidity and increased mortality,” said Mary Beth Humphrey, MD, PhD, interim vice president for research at the University of Oklahoma Health Sciences Center in Oklahoma City and co-principal investigator of the ACR guideline.

Anyone can fracture

While age and other risk factors, including menopause, increase the risk of developing GIOP, bone loss can occur rapidly for a patient of any age.

Even a glucocorticoid dose as low as 2.5 mg will increase the risk of vertebral fractures, with some occurring as soon as 3 months after treatment starts, Dr. Humphrey said. For patients taking up to 7.5 mg daily, the risk of vertebral fracture doubles. Doses greater than 10 mg daily for more than 3 months raise the likelihood of a vertebral fracture by a factor of 14, and result in a 300% increase in the likelihood of hip fractures, according to Dr. Humphrey.

“When on steroids, even patients with high bone density scores can fracture,” Dr. Tanner said. “The 2017 guideline was almost too elaborate in its effort to calculate risk. The updated guideline acknowledges moderate risk and suggests that this is a group of patients who need treatment.”
 

Rank ordering adds flexibility

The updated ACR guideline no longer ranks medications based on patient fracture data, side effects, cost care, and whether the drug is provided through injection, pill, or IV.

All of the preventive treatments the panel recommends reduce the risk of steroid-induced bone loss, Dr. Humphrey said.

“We thought the 2017 guideline was too restrictive,” Dr. Russell said. “We’re giving physicians and patients more leeway to choose a medication based on their preferences.”

Patient preference of delivery mechanism – such as a desire for pills only – can now be weighed more heavily into drug treatment decisions.

“In the exam room, there are three dynamics going on: What the patient wants, what the doctor knows is most effective, and what the insurer will pay,” Dr. Tanner said. “Doing away with rank ordering opens up the conversation beyond cost to consider all those factors.”

The guideline team conducted a systematic literature review for clinical questions on nonpharmacologic and pharmacologic treatment addressed in the 2017 guideline, and for questions on new pharmacologic treatments, discontinuation of medications, and sequential and combination therapy. The voting panel consisted of two patient representatives and 13 experts representing adult and pediatric rheumatology and endocrinology, nephrology, and gastroenterology.

A full manuscript has been submitted for publication in Arthritis & Rheumatology and Arthritis Care and Research for peer review, and is expected to publish in early 2023.

Dr. Humphrey and Dr. Russell, the co-principal investigators for the guideline, and Dr. Rubin have disclosed no relevant financial relationships. Dr. Tanner reported a current research grant funded by Amgen through the University of Alabama at Birmingham and being a paid course instructor for the International Society for Clinical Densitometry bone density course, Osteoporosis Essentials.

A version of this article first appeared on Medscape.com.

Patients with iron overload – serum ferritin greater than 1,000 mcg/L or a diagnosis of hemochromatosis or thalassemia – were 60% more likely to have an osteoporotic fracture during an up to 10-year follow-up than matched control patients, in a large study.

Compared with control patients, those with iron overload had a roughly twofold increased risk of a vertebral fracture, as well as an increased risk of a hip or humerus fracture, but not a forearm fracture.

The increased risk of fracture in men with iron overload (compared with other matched men) was greater than the increased risk of fracture in women with iron overload (compared with other matched women).

Andrea Burden, PhD, presented the findings during a late-breaking clinical science session at the annual meeting of the American Society of Bone and Mineral Research.
 

‘We should worry about the bones as well as the liver’

Based on these results, clinicians should probably do earlier bone mineral density (BMD) determinations to screen for osteoporosis and perhaps consider prophylaxis with vitamin D and calcium, said Dr. Burden, assistant professor, Institute of Pharmaceutical Sciences, ETH Zürich.

“However, I say that with a bunch of caution,” she added, “because we actually don’t have much evidence of the impact of these treatment differences on fracture risk.”

“This is the first large population study on this topic,” although there have been a few case reports, Dr. Burden explained in an interview.

However, “the high iron overload of greater than 1,000 mcg/L is not common, and hereditary hemochromatosis or thalassemia also are very rare,” she noted.

“The study shows that, once patients have an iron overload of more than 1,000 mcg/L, we need to be doing regular checks for their BMD and figuring how to best minimize their fracture risk,” she said.

“A twofold risk for a vertebral fracture” in patients with iron overload “is really high,” she noted. It is known that men with iron overload have loss of testosterone, but it may be less well known that they have an increased fracture risk.

“We worry about the liver,” she said, “not so much about the bones, and this shows us that we really should.”

Session comoderator Michael J. Econs, MD, who was not involved with the research, agreed. “Iron overload does occur, and it is a clinically important problem and can lead to hemochromatosis, which can lead to a whole host of diseases, but the most common is liver disease,” he told this news organization.

“So, it is a clinically important problem, not only in people who are genetically predisposed but in people who get frequent transfusion,” said Dr. Econs, distinguished professor of medicine and medical and molecular genetics at Indiana University, Indianapolis.

Now this new study has found an increase in fractures in such people, he noted.
 

Large case-control study used U.K. database

Using data from the IQVIA Medical Research Database, researchers identified 21,166 iron overload patients aged 18 years and older who saw a general practitioner in the United Kingdom between 2010 and 2020 and had a serum ferritin level above 1,000 mcg/L or a diagnostic code for hemochromatosis or nonanemic thalassemia.

They matched each iron overload patient with up to 10 control patients based on age, sex, year, and general practitioner, for a total of 198,037 control patients.

Patients were a mean age of 59 years and 59% were men.

During follow-up there were 777 fractures in the iron-overload patients (9.61 fractures per 1,000 patient-years) and 4,344 fractures in the control group (4.68 fractures per 1,000 patient-years).

In adjusted hazard ratio models, researchers adjusted for age, sex, body mass index, alcohol, smoking, history of fractures earlier than 365 days prior to study entry, hypogonadism, osteoporosis, medications, and comorbidities.

Overall, patients in the iron overload group had a 60% higher risk of an osteoporotic fracture (aHR, 1.60).

Among women, the incidence of osteoporotic fracture was 12.63 per 1,000 patient-years in the iron overload group and 7.09 per 1,000 patient-years in the control group.

Women with iron overload had a 48% higher risk of osteoporotic fracture, compared with other women (aHR, 1.48).

Among men, the incidence of osteoporotic fracture was 6.71 per 1,000 patient-years in the iron overload group and 3.01 per 1,000 patient-years in the control group.

Men with iron overload therefore had an 82% higher risk of osteoporotic fracture, compared with other men (aHR, 1.82).

Compared with patients without iron overload, patients with iron overload had an increased risk of a vertebral (aHR, 2.18), hip (aHR, 1.60), and humerus (aHR, 1.82) fracture but not a forearm fracture.

The researchers acknowledge that study limitations include they did not look at phlebotomy or changes in ferritin levels, and they excluded patients with hereditary hemochromatosis diagnosed before age 18.

The work was funded by the German Research Foundation. One of the researchers has reported receiving an independent grant from Pharmacosmos. The other researchers as well as Dr. Econs have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with iron overload – serum ferritin greater than 1,000 mcg/L or a diagnosis of hemochromatosis or thalassemia – were 60% more likely to have an osteoporotic fracture during an up to 10-year follow-up than matched control patients, in a large study.

Compared with control patients, those with iron overload had a roughly twofold increased risk of a vertebral fracture, as well as an increased risk of a hip or humerus fracture, but not a forearm fracture.

The increased risk of fracture in men with iron overload (compared with other matched men) was greater than the increased risk of fracture in women with iron overload (compared with other matched women).

Andrea Burden, PhD, presented the findings during a late-breaking clinical science session at the annual meeting of the American Society of Bone and Mineral Research.
 

‘We should worry about the bones as well as the liver’

Based on these results, clinicians should probably do earlier bone mineral density (BMD) determinations to screen for osteoporosis and perhaps consider prophylaxis with vitamin D and calcium, said Dr. Burden, assistant professor, Institute of Pharmaceutical Sciences, ETH Zürich.

“However, I say that with a bunch of caution,” she added, “because we actually don’t have much evidence of the impact of these treatment differences on fracture risk.”

“This is the first large population study on this topic,” although there have been a few case reports, Dr. Burden explained in an interview.

However, “the high iron overload of greater than 1,000 mcg/L is not common, and hereditary hemochromatosis or thalassemia also are very rare,” she noted.

“The study shows that, once patients have an iron overload of more than 1,000 mcg/L, we need to be doing regular checks for their BMD and figuring how to best minimize their fracture risk,” she said.

“A twofold risk for a vertebral fracture” in patients with iron overload “is really high,” she noted. It is known that men with iron overload have loss of testosterone, but it may be less well known that they have an increased fracture risk.

“We worry about the liver,” she said, “not so much about the bones, and this shows us that we really should.”

Session comoderator Michael J. Econs, MD, who was not involved with the research, agreed. “Iron overload does occur, and it is a clinically important problem and can lead to hemochromatosis, which can lead to a whole host of diseases, but the most common is liver disease,” he told this news organization.

“So, it is a clinically important problem, not only in people who are genetically predisposed but in people who get frequent transfusion,” said Dr. Econs, distinguished professor of medicine and medical and molecular genetics at Indiana University, Indianapolis.

Now this new study has found an increase in fractures in such people, he noted.
 

Large case-control study used U.K. database

Using data from the IQVIA Medical Research Database, researchers identified 21,166 iron overload patients aged 18 years and older who saw a general practitioner in the United Kingdom between 2010 and 2020 and had a serum ferritin level above 1,000 mcg/L or a diagnostic code for hemochromatosis or nonanemic thalassemia.

They matched each iron overload patient with up to 10 control patients based on age, sex, year, and general practitioner, for a total of 198,037 control patients.

Patients were a mean age of 59 years and 59% were men.

During follow-up there were 777 fractures in the iron-overload patients (9.61 fractures per 1,000 patient-years) and 4,344 fractures in the control group (4.68 fractures per 1,000 patient-years).

In adjusted hazard ratio models, researchers adjusted for age, sex, body mass index, alcohol, smoking, history of fractures earlier than 365 days prior to study entry, hypogonadism, osteoporosis, medications, and comorbidities.

Overall, patients in the iron overload group had a 60% higher risk of an osteoporotic fracture (aHR, 1.60).

Among women, the incidence of osteoporotic fracture was 12.63 per 1,000 patient-years in the iron overload group and 7.09 per 1,000 patient-years in the control group.

Women with iron overload had a 48% higher risk of osteoporotic fracture, compared with other women (aHR, 1.48).

Among men, the incidence of osteoporotic fracture was 6.71 per 1,000 patient-years in the iron overload group and 3.01 per 1,000 patient-years in the control group.

Men with iron overload therefore had an 82% higher risk of osteoporotic fracture, compared with other men (aHR, 1.82).

Compared with patients without iron overload, patients with iron overload had an increased risk of a vertebral (aHR, 2.18), hip (aHR, 1.60), and humerus (aHR, 1.82) fracture but not a forearm fracture.

The researchers acknowledge that study limitations include they did not look at phlebotomy or changes in ferritin levels, and they excluded patients with hereditary hemochromatosis diagnosed before age 18.

The work was funded by the German Research Foundation. One of the researchers has reported receiving an independent grant from Pharmacosmos. The other researchers as well as Dr. Econs have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with iron overload – serum ferritin greater than 1,000 mcg/L or a diagnosis of hemochromatosis or thalassemia – were 60% more likely to have an osteoporotic fracture during an up to 10-year follow-up than matched control patients, in a large study.

Compared with control patients, those with iron overload had a roughly twofold increased risk of a vertebral fracture, as well as an increased risk of a hip or humerus fracture, but not a forearm fracture.

The increased risk of fracture in men with iron overload (compared with other matched men) was greater than the increased risk of fracture in women with iron overload (compared with other matched women).

Andrea Burden, PhD, presented the findings during a late-breaking clinical science session at the annual meeting of the American Society of Bone and Mineral Research.
 

‘We should worry about the bones as well as the liver’

Based on these results, clinicians should probably do earlier bone mineral density (BMD) determinations to screen for osteoporosis and perhaps consider prophylaxis with vitamin D and calcium, said Dr. Burden, assistant professor, Institute of Pharmaceutical Sciences, ETH Zürich.

“However, I say that with a bunch of caution,” she added, “because we actually don’t have much evidence of the impact of these treatment differences on fracture risk.”

“This is the first large population study on this topic,” although there have been a few case reports, Dr. Burden explained in an interview.

However, “the high iron overload of greater than 1,000 mcg/L is not common, and hereditary hemochromatosis or thalassemia also are very rare,” she noted.

“The study shows that, once patients have an iron overload of more than 1,000 mcg/L, we need to be doing regular checks for their BMD and figuring how to best minimize their fracture risk,” she said.

“A twofold risk for a vertebral fracture” in patients with iron overload “is really high,” she noted. It is known that men with iron overload have loss of testosterone, but it may be less well known that they have an increased fracture risk.

“We worry about the liver,” she said, “not so much about the bones, and this shows us that we really should.”

Session comoderator Michael J. Econs, MD, who was not involved with the research, agreed. “Iron overload does occur, and it is a clinically important problem and can lead to hemochromatosis, which can lead to a whole host of diseases, but the most common is liver disease,” he told this news organization.

“So, it is a clinically important problem, not only in people who are genetically predisposed but in people who get frequent transfusion,” said Dr. Econs, distinguished professor of medicine and medical and molecular genetics at Indiana University, Indianapolis.

Now this new study has found an increase in fractures in such people, he noted.
 

Large case-control study used U.K. database

Using data from the IQVIA Medical Research Database, researchers identified 21,166 iron overload patients aged 18 years and older who saw a general practitioner in the United Kingdom between 2010 and 2020 and had a serum ferritin level above 1,000 mcg/L or a diagnostic code for hemochromatosis or nonanemic thalassemia.

They matched each iron overload patient with up to 10 control patients based on age, sex, year, and general practitioner, for a total of 198,037 control patients.

Patients were a mean age of 59 years and 59% were men.

During follow-up there were 777 fractures in the iron-overload patients (9.61 fractures per 1,000 patient-years) and 4,344 fractures in the control group (4.68 fractures per 1,000 patient-years).

In adjusted hazard ratio models, researchers adjusted for age, sex, body mass index, alcohol, smoking, history of fractures earlier than 365 days prior to study entry, hypogonadism, osteoporosis, medications, and comorbidities.

Overall, patients in the iron overload group had a 60% higher risk of an osteoporotic fracture (aHR, 1.60).

Among women, the incidence of osteoporotic fracture was 12.63 per 1,000 patient-years in the iron overload group and 7.09 per 1,000 patient-years in the control group.

Women with iron overload had a 48% higher risk of osteoporotic fracture, compared with other women (aHR, 1.48).

Among men, the incidence of osteoporotic fracture was 6.71 per 1,000 patient-years in the iron overload group and 3.01 per 1,000 patient-years in the control group.

Men with iron overload therefore had an 82% higher risk of osteoporotic fracture, compared with other men (aHR, 1.82).

Compared with patients without iron overload, patients with iron overload had an increased risk of a vertebral (aHR, 2.18), hip (aHR, 1.60), and humerus (aHR, 1.82) fracture but not a forearm fracture.

The researchers acknowledge that study limitations include they did not look at phlebotomy or changes in ferritin levels, and they excluded patients with hereditary hemochromatosis diagnosed before age 18.

The work was funded by the German Research Foundation. One of the researchers has reported receiving an independent grant from Pharmacosmos. The other researchers as well as Dr. Econs have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Omega-3 supplements did not reduce fractures during a median 5.3-year follow-up in the more than 25,000 generally healthy men and women (≥ age 50 and ≥ age 55, respectively) in the Vitamin D and Omega-3 Trial (VITAL).

The large randomized controlled trial tested whether omega-3 fatty acid or vitamin D supplements prevented cardiovascular disease or cancer in a representative sample of midlife and older adults from 50 U.S. states – which they did not. In a further analysis of VITAL, vitamin D supplements (cholecalciferol, 2,000 IU/day) did not lower the risk of incident total, nonvertebral, and hip fractures, compared with placebo.

Dmitriy Danilchenko/Shutterstock

Now this new analysis shows that omega-3 fatty acid supplements (1 g/day of fish oil) did not reduce the risk of such fractures in the VITAL population either. Meryl S. LeBoff, MD, presented the latest findings during an oral session at the annual meeting of the American Society for Bone and Mineral Research.

“In this, the largest randomized controlled trial in the world, we did not find an effect of omega-3 fatty acid supplements on fractures,” Dr. LeBoff, from Brigham and Women’s Hospital and Harvard Medical School, both in Boston, told this news organization.

The current analysis did “unexpectedly” show that among participants who received the omega-3 fatty acid supplements, there was an increase in fractures in men, and fracture risk was higher in people with a normal or low body mass index and lower in people with higher BMI.

However, these subgroup findings need to be interpreted with caution and may be caused by chance, Dr. LeBoff warned. The researchers will be investigating these findings in further analyses.
 

Should patients take omega-3 supplements or not?

Asked whether, in the meantime, patients should start or keep taking fish oil supplements for possible health benefits, she noted that certain individuals might benefit.

For example, in VITAL, participants who ate less than 1.5 servings of fish per week and received omega-3 fatty acid supplements had a decrease in the combined cardiovascular endpoint, and Black participants who took fish oil supplements had a substantially reduced risk of the outcome, regardless of fish intake.

“I think everybody needs to review [the study findings] with clinicians and make a decision in terms of what would be best for them,” she said.

Session comoderator Bente Langdahl, MD, PhD, commented that “many people take omega-3 because they think it will help” knee, hip, or other joint pain.

Perhaps men are more prone to joint pain because of osteoarthritis and the supplements lessen the pain, so these men became more physically active and more prone to fractures, she speculated.

The current study shows that, “so far, we haven’t been able to demonstrate a reduced rate of fractures with fish oil supplements in clinical randomized trials” conducted in relatively healthy and not the oldest patients, she summarized. “We’re not talking about 80-year-olds.”

In this “well-conducted study, they were not able to see any difference” with omega-3 fatty acid supplements versus placebo, but apparently, there are no harms associated with taking these supplements, she said.

To patients who ask her about such supplements, Dr. Langdahl advised: “Try it out for 3 months. If it really helps you, if it takes away your joint pain or whatever, then that might work for you. But then remember to stop again because it might just be a temporary effect.”
 

Could fish oil supplements protect against fractures?

An estimated 22% of U.S. adults aged 60 and older take omega-3 fatty acid supplements, Dr. LeBoff noted.

Preclinical studies have shown that omega-3 fatty acids reduce bone resorption and have anti-inflammatory effects, but observational studies have reported conflicting findings.

The researchers conducted this ancillary study of VITAL to fill these knowledge gaps.

VITAL enrolled a national sample of 25,871 U.S. men and women, including 5,106 Black participants, with a mean age of 67 and a mean BMI of 28 kg/m2.

Importantly, participants were not recruited by low bone density, fractures, or vitamin D deficiency. Prior to entry, participants were required to stop taking omega-3 supplements and limit nonstudy vitamin D and calcium supplements.

The omega-3 fatty acid supplements used in the study contained eicosapentaenoic acid and docosahexaenoic acid in a 1.2:1 ratio.

VITAL had a 2x2 factorial design whereby 6,463 participants were randomized to receive the omega-3 fatty acid supplement and 6,474 were randomized to placebo. (Remaining participants were randomized to receive vitamin D or placebo.)

Participants in the omega-3 fatty acid and placebo groups had similar baseline characteristics. For example, about half (50.5%) were women, and on average, they ate 1.1 servings of dark-meat fish (such as salmon) per week.

Participants completed detailed questionnaires at baseline and each year.

Plasma omega-3 levels were measured at baseline and, in 1,583 participants, at 1 year of follow-up. The mean omega-3 index rose 54.7% in the omega-3 fatty acid group and changed less than 2% in the placebo group at 1 year.

Study pill adherence was 87.0% at 2 years and 85.7% at 5 years.

Fractures were self-reported on annual questionnaires and centrally adjudicated in medical record review.
 

No clinically meaningful effect of omega-3 fatty acids on fractures

During a median 5.3-year follow-up, researchers adjudicated 2,133 total fractures and confirmed 1,991 fractures (93%) in 1551 participants.

Incidences of total, nonvertebral, and hip fractures were similar in both groups.

Compared with placebo, omega-3 fatty acid supplements had no significant effect on risk of total fractures (hazard ratio, 1.02; 95% confidence interval, 0.92-1.13), nonvertebral fractures (HR, 1.01; 95% CI, 0.91-1.12), or hip fractures (HR, 0.89; 95% CI, 0.61-1.30), all adjusted for age, sex, and race.

The “confidence intervals were narrow, likely excluding a clinically meaningful effect,” Dr. LeBoff noted.

Among men, those who received fish oil supplements had a greater risk of fracture than those who received placebo (HR, 1.27; 95% CI, 1.07-1.51), but this result “was not corrected for multiple hypothesis testing,” Dr. LeBoff cautioned.

In the overall population, participants with a BMI less than 25 who received fish oil versus placebo had an increased risk of fracture, and those with a BMI of at least 30 who received fish oil versus placebo had a decreased risk of fracture, but the limits of the confidence intervals crossed 1.00.

After excluding digit, skull, and pathologic fractures, there was no significant reduction in total fractures (HR, 1.02; 95% CI, 0.92-1.14), nonvertebral fractures (HR, 1.02; 95% CI, 0.92-1.14), or hip fractures (HR, 0.90; 95% CI, 0.61-1.33), with omega-3 supplements versus placebo.

Similarly, there was no significant reduction in risk of major osteoporotic fractures (hip, wrist, humerus, and clinical spine fractures) or wrist fractures with omega-3 supplements versus placebo.

VITAL only studied one dose of omega-3 fatty acid supplements, and results may not be generalizable to younger adults, or older adults living in residential communities, Dr. LeBoff noted.

The study was supported by grants from the National Institute of Arthritis Musculoskeletal and Skin Diseases. VITAL was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute. Dr. LeBoff and Dr. Langdahl have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Omega-3 supplements did not reduce fractures during a median 5.3-year follow-up in the more than 25,000 generally healthy men and women (≥ age 50 and ≥ age 55, respectively) in the Vitamin D and Omega-3 Trial (VITAL).

The large randomized controlled trial tested whether omega-3 fatty acid or vitamin D supplements prevented cardiovascular disease or cancer in a representative sample of midlife and older adults from 50 U.S. states – which they did not. In a further analysis of VITAL, vitamin D supplements (cholecalciferol, 2,000 IU/day) did not lower the risk of incident total, nonvertebral, and hip fractures, compared with placebo.

Dmitriy Danilchenko/Shutterstock

Now this new analysis shows that omega-3 fatty acid supplements (1 g/day of fish oil) did not reduce the risk of such fractures in the VITAL population either. Meryl S. LeBoff, MD, presented the latest findings during an oral session at the annual meeting of the American Society for Bone and Mineral Research.

“In this, the largest randomized controlled trial in the world, we did not find an effect of omega-3 fatty acid supplements on fractures,” Dr. LeBoff, from Brigham and Women’s Hospital and Harvard Medical School, both in Boston, told this news organization.

The current analysis did “unexpectedly” show that among participants who received the omega-3 fatty acid supplements, there was an increase in fractures in men, and fracture risk was higher in people with a normal or low body mass index and lower in people with higher BMI.

However, these subgroup findings need to be interpreted with caution and may be caused by chance, Dr. LeBoff warned. The researchers will be investigating these findings in further analyses.
 

Should patients take omega-3 supplements or not?

Asked whether, in the meantime, patients should start or keep taking fish oil supplements for possible health benefits, she noted that certain individuals might benefit.

For example, in VITAL, participants who ate less than 1.5 servings of fish per week and received omega-3 fatty acid supplements had a decrease in the combined cardiovascular endpoint, and Black participants who took fish oil supplements had a substantially reduced risk of the outcome, regardless of fish intake.

“I think everybody needs to review [the study findings] with clinicians and make a decision in terms of what would be best for them,” she said.

Session comoderator Bente Langdahl, MD, PhD, commented that “many people take omega-3 because they think it will help” knee, hip, or other joint pain.

Perhaps men are more prone to joint pain because of osteoarthritis and the supplements lessen the pain, so these men became more physically active and more prone to fractures, she speculated.

The current study shows that, “so far, we haven’t been able to demonstrate a reduced rate of fractures with fish oil supplements in clinical randomized trials” conducted in relatively healthy and not the oldest patients, she summarized. “We’re not talking about 80-year-olds.”

In this “well-conducted study, they were not able to see any difference” with omega-3 fatty acid supplements versus placebo, but apparently, there are no harms associated with taking these supplements, she said.

To patients who ask her about such supplements, Dr. Langdahl advised: “Try it out for 3 months. If it really helps you, if it takes away your joint pain or whatever, then that might work for you. But then remember to stop again because it might just be a temporary effect.”
 

Could fish oil supplements protect against fractures?

An estimated 22% of U.S. adults aged 60 and older take omega-3 fatty acid supplements, Dr. LeBoff noted.

Preclinical studies have shown that omega-3 fatty acids reduce bone resorption and have anti-inflammatory effects, but observational studies have reported conflicting findings.

The researchers conducted this ancillary study of VITAL to fill these knowledge gaps.

VITAL enrolled a national sample of 25,871 U.S. men and women, including 5,106 Black participants, with a mean age of 67 and a mean BMI of 28 kg/m2.

Importantly, participants were not recruited by low bone density, fractures, or vitamin D deficiency. Prior to entry, participants were required to stop taking omega-3 supplements and limit nonstudy vitamin D and calcium supplements.

The omega-3 fatty acid supplements used in the study contained eicosapentaenoic acid and docosahexaenoic acid in a 1.2:1 ratio.

VITAL had a 2x2 factorial design whereby 6,463 participants were randomized to receive the omega-3 fatty acid supplement and 6,474 were randomized to placebo. (Remaining participants were randomized to receive vitamin D or placebo.)

Participants in the omega-3 fatty acid and placebo groups had similar baseline characteristics. For example, about half (50.5%) were women, and on average, they ate 1.1 servings of dark-meat fish (such as salmon) per week.

Participants completed detailed questionnaires at baseline and each year.

Plasma omega-3 levels were measured at baseline and, in 1,583 participants, at 1 year of follow-up. The mean omega-3 index rose 54.7% in the omega-3 fatty acid group and changed less than 2% in the placebo group at 1 year.

Study pill adherence was 87.0% at 2 years and 85.7% at 5 years.

Fractures were self-reported on annual questionnaires and centrally adjudicated in medical record review.
 

No clinically meaningful effect of omega-3 fatty acids on fractures

During a median 5.3-year follow-up, researchers adjudicated 2,133 total fractures and confirmed 1,991 fractures (93%) in 1551 participants.

Incidences of total, nonvertebral, and hip fractures were similar in both groups.

Compared with placebo, omega-3 fatty acid supplements had no significant effect on risk of total fractures (hazard ratio, 1.02; 95% confidence interval, 0.92-1.13), nonvertebral fractures (HR, 1.01; 95% CI, 0.91-1.12), or hip fractures (HR, 0.89; 95% CI, 0.61-1.30), all adjusted for age, sex, and race.

The “confidence intervals were narrow, likely excluding a clinically meaningful effect,” Dr. LeBoff noted.

Among men, those who received fish oil supplements had a greater risk of fracture than those who received placebo (HR, 1.27; 95% CI, 1.07-1.51), but this result “was not corrected for multiple hypothesis testing,” Dr. LeBoff cautioned.

In the overall population, participants with a BMI less than 25 who received fish oil versus placebo had an increased risk of fracture, and those with a BMI of at least 30 who received fish oil versus placebo had a decreased risk of fracture, but the limits of the confidence intervals crossed 1.00.

After excluding digit, skull, and pathologic fractures, there was no significant reduction in total fractures (HR, 1.02; 95% CI, 0.92-1.14), nonvertebral fractures (HR, 1.02; 95% CI, 0.92-1.14), or hip fractures (HR, 0.90; 95% CI, 0.61-1.33), with omega-3 supplements versus placebo.

Similarly, there was no significant reduction in risk of major osteoporotic fractures (hip, wrist, humerus, and clinical spine fractures) or wrist fractures with omega-3 supplements versus placebo.

VITAL only studied one dose of omega-3 fatty acid supplements, and results may not be generalizable to younger adults, or older adults living in residential communities, Dr. LeBoff noted.

The study was supported by grants from the National Institute of Arthritis Musculoskeletal and Skin Diseases. VITAL was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute. Dr. LeBoff and Dr. Langdahl have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Omega-3 supplements did not reduce fractures during a median 5.3-year follow-up in the more than 25,000 generally healthy men and women (≥ age 50 and ≥ age 55, respectively) in the Vitamin D and Omega-3 Trial (VITAL).

The large randomized controlled trial tested whether omega-3 fatty acid or vitamin D supplements prevented cardiovascular disease or cancer in a representative sample of midlife and older adults from 50 U.S. states – which they did not. In a further analysis of VITAL, vitamin D supplements (cholecalciferol, 2,000 IU/day) did not lower the risk of incident total, nonvertebral, and hip fractures, compared with placebo.

Dmitriy Danilchenko/Shutterstock

Now this new analysis shows that omega-3 fatty acid supplements (1 g/day of fish oil) did not reduce the risk of such fractures in the VITAL population either. Meryl S. LeBoff, MD, presented the latest findings during an oral session at the annual meeting of the American Society for Bone and Mineral Research.

“In this, the largest randomized controlled trial in the world, we did not find an effect of omega-3 fatty acid supplements on fractures,” Dr. LeBoff, from Brigham and Women’s Hospital and Harvard Medical School, both in Boston, told this news organization.

The current analysis did “unexpectedly” show that among participants who received the omega-3 fatty acid supplements, there was an increase in fractures in men, and fracture risk was higher in people with a normal or low body mass index and lower in people with higher BMI.

However, these subgroup findings need to be interpreted with caution and may be caused by chance, Dr. LeBoff warned. The researchers will be investigating these findings in further analyses.
 

Should patients take omega-3 supplements or not?

Asked whether, in the meantime, patients should start or keep taking fish oil supplements for possible health benefits, she noted that certain individuals might benefit.

For example, in VITAL, participants who ate less than 1.5 servings of fish per week and received omega-3 fatty acid supplements had a decrease in the combined cardiovascular endpoint, and Black participants who took fish oil supplements had a substantially reduced risk of the outcome, regardless of fish intake.

“I think everybody needs to review [the study findings] with clinicians and make a decision in terms of what would be best for them,” she said.

Session comoderator Bente Langdahl, MD, PhD, commented that “many people take omega-3 because they think it will help” knee, hip, or other joint pain.

Perhaps men are more prone to joint pain because of osteoarthritis and the supplements lessen the pain, so these men became more physically active and more prone to fractures, she speculated.

The current study shows that, “so far, we haven’t been able to demonstrate a reduced rate of fractures with fish oil supplements in clinical randomized trials” conducted in relatively healthy and not the oldest patients, she summarized. “We’re not talking about 80-year-olds.”

In this “well-conducted study, they were not able to see any difference” with omega-3 fatty acid supplements versus placebo, but apparently, there are no harms associated with taking these supplements, she said.

To patients who ask her about such supplements, Dr. Langdahl advised: “Try it out for 3 months. If it really helps you, if it takes away your joint pain or whatever, then that might work for you. But then remember to stop again because it might just be a temporary effect.”
 

Could fish oil supplements protect against fractures?

An estimated 22% of U.S. adults aged 60 and older take omega-3 fatty acid supplements, Dr. LeBoff noted.

Preclinical studies have shown that omega-3 fatty acids reduce bone resorption and have anti-inflammatory effects, but observational studies have reported conflicting findings.

The researchers conducted this ancillary study of VITAL to fill these knowledge gaps.

VITAL enrolled a national sample of 25,871 U.S. men and women, including 5,106 Black participants, with a mean age of 67 and a mean BMI of 28 kg/m2.

Importantly, participants were not recruited by low bone density, fractures, or vitamin D deficiency. Prior to entry, participants were required to stop taking omega-3 supplements and limit nonstudy vitamin D and calcium supplements.

The omega-3 fatty acid supplements used in the study contained eicosapentaenoic acid and docosahexaenoic acid in a 1.2:1 ratio.

VITAL had a 2x2 factorial design whereby 6,463 participants were randomized to receive the omega-3 fatty acid supplement and 6,474 were randomized to placebo. (Remaining participants were randomized to receive vitamin D or placebo.)

Participants in the omega-3 fatty acid and placebo groups had similar baseline characteristics. For example, about half (50.5%) were women, and on average, they ate 1.1 servings of dark-meat fish (such as salmon) per week.

Participants completed detailed questionnaires at baseline and each year.

Plasma omega-3 levels were measured at baseline and, in 1,583 participants, at 1 year of follow-up. The mean omega-3 index rose 54.7% in the omega-3 fatty acid group and changed less than 2% in the placebo group at 1 year.

Study pill adherence was 87.0% at 2 years and 85.7% at 5 years.

Fractures were self-reported on annual questionnaires and centrally adjudicated in medical record review.
 

No clinically meaningful effect of omega-3 fatty acids on fractures

During a median 5.3-year follow-up, researchers adjudicated 2,133 total fractures and confirmed 1,991 fractures (93%) in 1551 participants.

Incidences of total, nonvertebral, and hip fractures were similar in both groups.

Compared with placebo, omega-3 fatty acid supplements had no significant effect on risk of total fractures (hazard ratio, 1.02; 95% confidence interval, 0.92-1.13), nonvertebral fractures (HR, 1.01; 95% CI, 0.91-1.12), or hip fractures (HR, 0.89; 95% CI, 0.61-1.30), all adjusted for age, sex, and race.

The “confidence intervals were narrow, likely excluding a clinically meaningful effect,” Dr. LeBoff noted.

Among men, those who received fish oil supplements had a greater risk of fracture than those who received placebo (HR, 1.27; 95% CI, 1.07-1.51), but this result “was not corrected for multiple hypothesis testing,” Dr. LeBoff cautioned.

In the overall population, participants with a BMI less than 25 who received fish oil versus placebo had an increased risk of fracture, and those with a BMI of at least 30 who received fish oil versus placebo had a decreased risk of fracture, but the limits of the confidence intervals crossed 1.00.

After excluding digit, skull, and pathologic fractures, there was no significant reduction in total fractures (HR, 1.02; 95% CI, 0.92-1.14), nonvertebral fractures (HR, 1.02; 95% CI, 0.92-1.14), or hip fractures (HR, 0.90; 95% CI, 0.61-1.33), with omega-3 supplements versus placebo.

Similarly, there was no significant reduction in risk of major osteoporotic fractures (hip, wrist, humerus, and clinical spine fractures) or wrist fractures with omega-3 supplements versus placebo.

VITAL only studied one dose of omega-3 fatty acid supplements, and results may not be generalizable to younger adults, or older adults living in residential communities, Dr. LeBoff noted.

The study was supported by grants from the National Institute of Arthritis Musculoskeletal and Skin Diseases. VITAL was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute. Dr. LeBoff and Dr. Langdahl have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The annual incidence of hip fractures declined in most countries from 2005 to 2018, but this rate is projected to roughly double by 2050, according to a new study of 19 countries/regions.

The study by Chor-Wing Sing, PhD, and colleagues was presented at the annual meeting of the American Society of Bone and Mineral Research. The predicted increase in hip fractures is being driven by the aging population, with the population of those age 85 and older projected to increase 4.5-fold from 2010 to 2050, they note.

The researchers also estimate that from 2018 to 2050 the incidence of fractures will increase by 1.9-fold overall – more in men (2.4-fold) than in women (1.7-fold).

In addition, rates of use of osteoporosis drugs 1 year after a hip fracture were less than 50%, with less treatment in men. Men were also more likely than women to die within 1 year of a hip fracture.

iStock/Thinkstock

Aging will fuel rise in hip fractures; more preventive treatment needed

“Even though there is a decreasing trend of hip fracture incidence in some countries, such a percentage decrease is insufficient to offset the percentage increase in the aging population,” senior co-author Ching-Lung Cheung, PhD, associate professor in the department of pharmacology and pharmacy at the University of Hong Kong, explained to this news organization.

The takeaways from the study are that “a greater effort on fracture prevention should be made to avoid the continuous increase in the number of hip fractures,” he said.

In addition, “although initiation of anti-osteoporosis medication after hip fracture is recommended in international guidelines, the 1-year treatment rate [was] well below 50% in most of the countries and regions studied. This indicates the treatment rate is far from optimal.”

“Our study also showed that the use of anti-osteoporosis medications following a hip fracture is lower in men than in women by 30% to 67%,” he said. “Thus, more attention should be paid to preventing and treating hip fractures in men.”

“The greater increase in the projected number of hip fractures in men than in women “could be [because] osteoporosis is commonly perceived as a ‘woman’s disease,’ ” he speculated.

Invited to comment, Juliet Compston, MD, who selected the study as one of the top clinical science highlight abstracts at the ASBMR meeting, agrees that “there is substantial room for improvement” in osteoporosis treatment rates following a hip fracture “in all the regions covered by the study.”

“In addition,” she continues, “the wide variations in treatment rates can provide important lessons about the most effective models of care for people who sustain a hip fracture: for example, fracture liaison services.”

Men suffer as osteoporosis perceived to be a ‘woman’s disease’

The even lower treatment rate in men than women is “concerning and likely reflects the mistaken perception that osteoporosis is predominantly a disease affecting women,” notes Dr. Compston, emeritus professor of bone medicine, University of Cambridge, United Kingdom.  

Also invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, said that the projected doubling of hip fractures “is likely mainly due to aging of the population, with increasing lifespan for males in particular. However, increasing urbanization and decreasing weight-bearing exercise as a result are likely to also contribute in developing countries.”

“Unfortunately, despite the advances in treatments for osteoporosis over the last 25 years, osteoporosis treatment rates remain low, and osteoporosis remains undiagnosed in postmenopausal women and older men,” added Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research.

“More targeted screening for osteoporosis would help,” he said, “as would treating patients for it following other minimal trauma fractures (vertebral, distal radius, and humerus, etc.), since if left untreated, about 50% of these patients will have hip fractures later in life.”

“Some countries may be doing better because they have health quality standards for hip fracture (for example, surgery within 24 hours, investigation, and treatment for osteoporosis). In other countries like Australia, bone density tests and treatment for osteoporosis are reimbursed, increasing their uptake.”

The public health implications of this study are “substantial” according to Dr. Compston. “People who have sustained a hip fracture are at high risk of subsequent fractures if untreated. There is a range of safe, cost-effective pharmacological therapies to reduce fracture rate, and wider use of these would have a major impact on the current and future burden imposed by hip fractures in the elderly population.”

Similarly, Dr. Ebeling noted that “prevention is important to save a huge health burden for patients and costs for society.”

“Patients with minimal trauma fractures (particularly hip or spinal fractures) should be investigated and treated for osteoporosis with care pathways established in the hospitals, reaching out to the community [fracture liaison services],” he said.

Support for these is being sought under Medicare in the United States, he noted, and bone densitometry reimbursement rates also need to be higher in the United States.
 

Projections for number of hip fractures to 2050

Previous international reviews of hip fractures have been based on heterogeneous data from more than 10 to 30 years ago, the researchers note.

They performed a retrospective cohort study using a common protocol across 19 countries/regions, as described in an article about the protocol published in BMJ Open.

They analyzed data from adults aged 50 and older who were hospitalized with a hip fracture to determine 1) the annual incidence of hip fractures in 2008-2015; 2) the uptake of drugs to treat osteoporosis at 1 year after a hip fracture; and 3) all-cause mortality at 1 year after a hip fracture.

In a second step, they estimated the number of hip fractures that would occur from 2030 to 2050, using World Bank population growth projections.

The data are from 20 health care databases from 19 countries/regions: Oceania (Australia, New Zealand), Asia (Hong Kong, Japan, Singapore, South Korea, Taiwan, and Thailand), Northern Europe (Denmark, Finland, and U.K.), Western Europe (France, Germany, Italy, The Netherlands, and Spain), and North and South America (Canada, United States, and Brazil).

The population in Japan was under age 75. U.S. data are from two databases: Medicare (age ≥ 65) and Optum.

Most databases (13) covered 90%-100% of the national population, and the rest covered 5%-70% of the population.

From 2008 to 2015, the annual incidence of hip fractures declined in 11 countries/regions (Singapore, Denmark, Hong Kong, Taiwan, Finland, U.K., Italy, Spain, United States [Medicare], Canada, and New Zealand).

“One potential reason that some countries have seen relatively large declines in hip fractures is better osteoporosis management and post-fracture care,” said Dr. Sing in a press release issued by ASBMR. “Better fall-prevention programs and clearer guidelines for clinical care have likely made a difference.”

Hip fracture incidence increased in five countries (The Netherlands, South Korea, France, Germany, and Brazil) and was stable in four countries (Australia, Japan, Thailand, and United States [Optum]).

The United Kingdom had the highest rate of osteoporosis treatment at 1-year after a hip fracture (50.3%). Rates in the other countries/regions ranged from 11.5% to 37%.

Fewer men than women were receiving drugs for osteoporosis at 1 year (range 5.1% to 38.2% versus 15.0% to 54.7%).

From 2005 to 2018, rates of osteoporosis treatment at 1 year after a hip fracture declined in six countries, increased in four countries, and were stable in five countries.

All-cause mortality within 1 year of hip fracture was higher in men than in women (range 19.2% to 35.8% versus 12.1% to 25.4%).

“Among the studied countries and regions, the U.S. ranks fifth with the highest hip fracture incidence,” Dr. Cheung replied when specifically asked about this. “The risk of hip fracture is determined by multiple factors: for example, lifestyle, diet, genetics, as well as management of osteoporosis,” he noted.

“Denmark is the only country showing no projected increase, and it is because Denmark had a continuous and remarkable decrease in the incidence of hip fractures,” he added, which “can offset the number of hip fractures contributed by the population aging.”

The study was funded by Amgen. Dr. Sing and Dr. Cheung have reported no relevant financial relationships. One of the study authors is employed by Amgen.

A version of this article first appeared on Medscape.com.

The annual incidence of hip fractures declined in most countries from 2005 to 2018, but this rate is projected to roughly double by 2050, according to a new study of 19 countries/regions.

The study by Chor-Wing Sing, PhD, and colleagues was presented at the annual meeting of the American Society of Bone and Mineral Research. The predicted increase in hip fractures is being driven by the aging population, with the population of those age 85 and older projected to increase 4.5-fold from 2010 to 2050, they note.

The researchers also estimate that from 2018 to 2050 the incidence of fractures will increase by 1.9-fold overall – more in men (2.4-fold) than in women (1.7-fold).

In addition, rates of use of osteoporosis drugs 1 year after a hip fracture were less than 50%, with less treatment in men. Men were also more likely than women to die within 1 year of a hip fracture.

iStock/Thinkstock

Aging will fuel rise in hip fractures; more preventive treatment needed

“Even though there is a decreasing trend of hip fracture incidence in some countries, such a percentage decrease is insufficient to offset the percentage increase in the aging population,” senior co-author Ching-Lung Cheung, PhD, associate professor in the department of pharmacology and pharmacy at the University of Hong Kong, explained to this news organization.

The takeaways from the study are that “a greater effort on fracture prevention should be made to avoid the continuous increase in the number of hip fractures,” he said.

In addition, “although initiation of anti-osteoporosis medication after hip fracture is recommended in international guidelines, the 1-year treatment rate [was] well below 50% in most of the countries and regions studied. This indicates the treatment rate is far from optimal.”

“Our study also showed that the use of anti-osteoporosis medications following a hip fracture is lower in men than in women by 30% to 67%,” he said. “Thus, more attention should be paid to preventing and treating hip fractures in men.”

“The greater increase in the projected number of hip fractures in men than in women “could be [because] osteoporosis is commonly perceived as a ‘woman’s disease,’ ” he speculated.

Invited to comment, Juliet Compston, MD, who selected the study as one of the top clinical science highlight abstracts at the ASBMR meeting, agrees that “there is substantial room for improvement” in osteoporosis treatment rates following a hip fracture “in all the regions covered by the study.”

“In addition,” she continues, “the wide variations in treatment rates can provide important lessons about the most effective models of care for people who sustain a hip fracture: for example, fracture liaison services.”

Men suffer as osteoporosis perceived to be a ‘woman’s disease’

The even lower treatment rate in men than women is “concerning and likely reflects the mistaken perception that osteoporosis is predominantly a disease affecting women,” notes Dr. Compston, emeritus professor of bone medicine, University of Cambridge, United Kingdom.  

Also invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, said that the projected doubling of hip fractures “is likely mainly due to aging of the population, with increasing lifespan for males in particular. However, increasing urbanization and decreasing weight-bearing exercise as a result are likely to also contribute in developing countries.”

“Unfortunately, despite the advances in treatments for osteoporosis over the last 25 years, osteoporosis treatment rates remain low, and osteoporosis remains undiagnosed in postmenopausal women and older men,” added Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research.

“More targeted screening for osteoporosis would help,” he said, “as would treating patients for it following other minimal trauma fractures (vertebral, distal radius, and humerus, etc.), since if left untreated, about 50% of these patients will have hip fractures later in life.”

“Some countries may be doing better because they have health quality standards for hip fracture (for example, surgery within 24 hours, investigation, and treatment for osteoporosis). In other countries like Australia, bone density tests and treatment for osteoporosis are reimbursed, increasing their uptake.”

The public health implications of this study are “substantial” according to Dr. Compston. “People who have sustained a hip fracture are at high risk of subsequent fractures if untreated. There is a range of safe, cost-effective pharmacological therapies to reduce fracture rate, and wider use of these would have a major impact on the current and future burden imposed by hip fractures in the elderly population.”

Similarly, Dr. Ebeling noted that “prevention is important to save a huge health burden for patients and costs for society.”

“Patients with minimal trauma fractures (particularly hip or spinal fractures) should be investigated and treated for osteoporosis with care pathways established in the hospitals, reaching out to the community [fracture liaison services],” he said.

Support for these is being sought under Medicare in the United States, he noted, and bone densitometry reimbursement rates also need to be higher in the United States.
 

Projections for number of hip fractures to 2050

Previous international reviews of hip fractures have been based on heterogeneous data from more than 10 to 30 years ago, the researchers note.

They performed a retrospective cohort study using a common protocol across 19 countries/regions, as described in an article about the protocol published in BMJ Open.

They analyzed data from adults aged 50 and older who were hospitalized with a hip fracture to determine 1) the annual incidence of hip fractures in 2008-2015; 2) the uptake of drugs to treat osteoporosis at 1 year after a hip fracture; and 3) all-cause mortality at 1 year after a hip fracture.

In a second step, they estimated the number of hip fractures that would occur from 2030 to 2050, using World Bank population growth projections.

The data are from 20 health care databases from 19 countries/regions: Oceania (Australia, New Zealand), Asia (Hong Kong, Japan, Singapore, South Korea, Taiwan, and Thailand), Northern Europe (Denmark, Finland, and U.K.), Western Europe (France, Germany, Italy, The Netherlands, and Spain), and North and South America (Canada, United States, and Brazil).

The population in Japan was under age 75. U.S. data are from two databases: Medicare (age ≥ 65) and Optum.

Most databases (13) covered 90%-100% of the national population, and the rest covered 5%-70% of the population.

From 2008 to 2015, the annual incidence of hip fractures declined in 11 countries/regions (Singapore, Denmark, Hong Kong, Taiwan, Finland, U.K., Italy, Spain, United States [Medicare], Canada, and New Zealand).

“One potential reason that some countries have seen relatively large declines in hip fractures is better osteoporosis management and post-fracture care,” said Dr. Sing in a press release issued by ASBMR. “Better fall-prevention programs and clearer guidelines for clinical care have likely made a difference.”

Hip fracture incidence increased in five countries (The Netherlands, South Korea, France, Germany, and Brazil) and was stable in four countries (Australia, Japan, Thailand, and United States [Optum]).

The United Kingdom had the highest rate of osteoporosis treatment at 1-year after a hip fracture (50.3%). Rates in the other countries/regions ranged from 11.5% to 37%.

Fewer men than women were receiving drugs for osteoporosis at 1 year (range 5.1% to 38.2% versus 15.0% to 54.7%).

From 2005 to 2018, rates of osteoporosis treatment at 1 year after a hip fracture declined in six countries, increased in four countries, and were stable in five countries.

All-cause mortality within 1 year of hip fracture was higher in men than in women (range 19.2% to 35.8% versus 12.1% to 25.4%).

“Among the studied countries and regions, the U.S. ranks fifth with the highest hip fracture incidence,” Dr. Cheung replied when specifically asked about this. “The risk of hip fracture is determined by multiple factors: for example, lifestyle, diet, genetics, as well as management of osteoporosis,” he noted.

“Denmark is the only country showing no projected increase, and it is because Denmark had a continuous and remarkable decrease in the incidence of hip fractures,” he added, which “can offset the number of hip fractures contributed by the population aging.”

The study was funded by Amgen. Dr. Sing and Dr. Cheung have reported no relevant financial relationships. One of the study authors is employed by Amgen.

A version of this article first appeared on Medscape.com.

The annual incidence of hip fractures declined in most countries from 2005 to 2018, but this rate is projected to roughly double by 2050, according to a new study of 19 countries/regions.

The study by Chor-Wing Sing, PhD, and colleagues was presented at the annual meeting of the American Society of Bone and Mineral Research. The predicted increase in hip fractures is being driven by the aging population, with the population of those age 85 and older projected to increase 4.5-fold from 2010 to 2050, they note.

The researchers also estimate that from 2018 to 2050 the incidence of fractures will increase by 1.9-fold overall – more in men (2.4-fold) than in women (1.7-fold).

In addition, rates of use of osteoporosis drugs 1 year after a hip fracture were less than 50%, with less treatment in men. Men were also more likely than women to die within 1 year of a hip fracture.

iStock/Thinkstock

Aging will fuel rise in hip fractures; more preventive treatment needed

“Even though there is a decreasing trend of hip fracture incidence in some countries, such a percentage decrease is insufficient to offset the percentage increase in the aging population,” senior co-author Ching-Lung Cheung, PhD, associate professor in the department of pharmacology and pharmacy at the University of Hong Kong, explained to this news organization.

The takeaways from the study are that “a greater effort on fracture prevention should be made to avoid the continuous increase in the number of hip fractures,” he said.

In addition, “although initiation of anti-osteoporosis medication after hip fracture is recommended in international guidelines, the 1-year treatment rate [was] well below 50% in most of the countries and regions studied. This indicates the treatment rate is far from optimal.”

“Our study also showed that the use of anti-osteoporosis medications following a hip fracture is lower in men than in women by 30% to 67%,” he said. “Thus, more attention should be paid to preventing and treating hip fractures in men.”

“The greater increase in the projected number of hip fractures in men than in women “could be [because] osteoporosis is commonly perceived as a ‘woman’s disease,’ ” he speculated.

Invited to comment, Juliet Compston, MD, who selected the study as one of the top clinical science highlight abstracts at the ASBMR meeting, agrees that “there is substantial room for improvement” in osteoporosis treatment rates following a hip fracture “in all the regions covered by the study.”

“In addition,” she continues, “the wide variations in treatment rates can provide important lessons about the most effective models of care for people who sustain a hip fracture: for example, fracture liaison services.”

Men suffer as osteoporosis perceived to be a ‘woman’s disease’

The even lower treatment rate in men than women is “concerning and likely reflects the mistaken perception that osteoporosis is predominantly a disease affecting women,” notes Dr. Compston, emeritus professor of bone medicine, University of Cambridge, United Kingdom.  

Also invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, said that the projected doubling of hip fractures “is likely mainly due to aging of the population, with increasing lifespan for males in particular. However, increasing urbanization and decreasing weight-bearing exercise as a result are likely to also contribute in developing countries.”

“Unfortunately, despite the advances in treatments for osteoporosis over the last 25 years, osteoporosis treatment rates remain low, and osteoporosis remains undiagnosed in postmenopausal women and older men,” added Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research.

“More targeted screening for osteoporosis would help,” he said, “as would treating patients for it following other minimal trauma fractures (vertebral, distal radius, and humerus, etc.), since if left untreated, about 50% of these patients will have hip fractures later in life.”

“Some countries may be doing better because they have health quality standards for hip fracture (for example, surgery within 24 hours, investigation, and treatment for osteoporosis). In other countries like Australia, bone density tests and treatment for osteoporosis are reimbursed, increasing their uptake.”

The public health implications of this study are “substantial” according to Dr. Compston. “People who have sustained a hip fracture are at high risk of subsequent fractures if untreated. There is a range of safe, cost-effective pharmacological therapies to reduce fracture rate, and wider use of these would have a major impact on the current and future burden imposed by hip fractures in the elderly population.”

Similarly, Dr. Ebeling noted that “prevention is important to save a huge health burden for patients and costs for society.”

“Patients with minimal trauma fractures (particularly hip or spinal fractures) should be investigated and treated for osteoporosis with care pathways established in the hospitals, reaching out to the community [fracture liaison services],” he said.

Support for these is being sought under Medicare in the United States, he noted, and bone densitometry reimbursement rates also need to be higher in the United States.
 

Projections for number of hip fractures to 2050

Previous international reviews of hip fractures have been based on heterogeneous data from more than 10 to 30 years ago, the researchers note.

They performed a retrospective cohort study using a common protocol across 19 countries/regions, as described in an article about the protocol published in BMJ Open.

They analyzed data from adults aged 50 and older who were hospitalized with a hip fracture to determine 1) the annual incidence of hip fractures in 2008-2015; 2) the uptake of drugs to treat osteoporosis at 1 year after a hip fracture; and 3) all-cause mortality at 1 year after a hip fracture.

In a second step, they estimated the number of hip fractures that would occur from 2030 to 2050, using World Bank population growth projections.

The data are from 20 health care databases from 19 countries/regions: Oceania (Australia, New Zealand), Asia (Hong Kong, Japan, Singapore, South Korea, Taiwan, and Thailand), Northern Europe (Denmark, Finland, and U.K.), Western Europe (France, Germany, Italy, The Netherlands, and Spain), and North and South America (Canada, United States, and Brazil).

The population in Japan was under age 75. U.S. data are from two databases: Medicare (age ≥ 65) and Optum.

Most databases (13) covered 90%-100% of the national population, and the rest covered 5%-70% of the population.

From 2008 to 2015, the annual incidence of hip fractures declined in 11 countries/regions (Singapore, Denmark, Hong Kong, Taiwan, Finland, U.K., Italy, Spain, United States [Medicare], Canada, and New Zealand).

“One potential reason that some countries have seen relatively large declines in hip fractures is better osteoporosis management and post-fracture care,” said Dr. Sing in a press release issued by ASBMR. “Better fall-prevention programs and clearer guidelines for clinical care have likely made a difference.”

Hip fracture incidence increased in five countries (The Netherlands, South Korea, France, Germany, and Brazil) and was stable in four countries (Australia, Japan, Thailand, and United States [Optum]).

The United Kingdom had the highest rate of osteoporosis treatment at 1-year after a hip fracture (50.3%). Rates in the other countries/regions ranged from 11.5% to 37%.

Fewer men than women were receiving drugs for osteoporosis at 1 year (range 5.1% to 38.2% versus 15.0% to 54.7%).

From 2005 to 2018, rates of osteoporosis treatment at 1 year after a hip fracture declined in six countries, increased in four countries, and were stable in five countries.

All-cause mortality within 1 year of hip fracture was higher in men than in women (range 19.2% to 35.8% versus 12.1% to 25.4%).

“Among the studied countries and regions, the U.S. ranks fifth with the highest hip fracture incidence,” Dr. Cheung replied when specifically asked about this. “The risk of hip fracture is determined by multiple factors: for example, lifestyle, diet, genetics, as well as management of osteoporosis,” he noted.

“Denmark is the only country showing no projected increase, and it is because Denmark had a continuous and remarkable decrease in the incidence of hip fractures,” he added, which “can offset the number of hip fractures contributed by the population aging.”

The study was funded by Amgen. Dr. Sing and Dr. Cheung have reported no relevant financial relationships. One of the study authors is employed by Amgen.

A version of this article first appeared on Medscape.com.

The Crystal Bone (Amgen) novel algorithm predicted 2-year risk of osteoporotic fractures in a large dataset with an accuracy that was consistent with FRAX 10-year risk predictions, researchers report.  

The algorithm was built using machine learning and artificial intelligence to predict fracture risk based on International Classification of Diseases (ICD) codes, as described in an article published in the Journal of Medical Internet Research.

The current validation study was presented September 9 as a poster at the annual meeting of the American Society for Bone and Mineral Research.

The scientists validated the algorithm in more than 100,000 patients aged 50 and older (that is, at risk of fracture) who were part of the Reliant Medical Group dataset (a subset of Optum Care).

Importantly, the algorithm predicted increased fracture in many patients who did not have a diagnosis of osteoporosis.

The next steps are validation in other datasets to support the generalizability of Crystal Bone across U.S. health care systems, Elinor Mody, MD, Reliant Medical Group, and colleagues report.

“Implementation research, in which patients identified by Crystal Bone undergo a bone health assessment and receive ongoing management, will help inform the clinical utility of this novel algorithm,” they conclude.

At the poster session, Tina Kelley, Optum Life Sciences, explained: “It’s a screening tool that says: ‘These are your patients that maybe you should spend a little extra time with, ask a few extra questions.’ ”

However, further study is needed before it should be used in clinical practice, she emphasized to this news organization.

‘A very useful advance’ but needs further validation

Invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, noted that “many clinicians now use FRAX to calculate absolute fracture risk and select patients who should initiate anti-osteoporosis drugs.”

With FRAX, clinicians input a patient’s age, sex, weight, height, previous fracture, [history of] parent with fractured hip, current smoking status, glucocorticoids, rheumatoid arthritis, secondary osteoporosis, alcohol (3 units/day or more), and bone mineral density (by DXA at the femoral neck) into the tool, to obtain a 10-year probability of fracture.

“Crystal Bone takes a different approach,” Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research but who disclosed receiving funding from Amgen, told this news organization in an email.

The algorithm uses electronic health records (EHRs) to identify patients who are likely to have a fracture within the next 2 years, he explained, based on diagnoses and medications associated with osteoporosis and fractures. These include ICD-10 codes for fractures at various sites and secondary causes of osteoporosis (such as rheumatoid and other inflammatory arthritis, chronic obstructive pulmonary disease, asthma, celiac disease, and inflammatory bowel disease).

“This is a very useful advance,” Dr. Ebeling summarized, “in that it would alert the clinician to patients in their practice who have a high fracture risk and need to be investigated for osteoporosis and initiated on treatment. Otherwise, the patients would be missed, as currently often occurs.”

“It would need to be adaptable to other [EMR] systems and to be validated in a large separate population to be ready to enter clinical practice,” he said, “but these data look very promising with a good [positive predictive value (PPV)].”

Similarly, Juliet Compston, MD, said: “It provides a novel, fully automated approach to population-based screening for osteoporosis using EHRs to identify people at high imminent risk of fracture.”

Dr. Compston, emeritus professor of bone medicine, University of Cambridge, England, who was not involved with the research but who also disclosed being a consultant for Amgen, selected the study as one of the top clinical science highlights abstracts at the meeting.

“The algorithm looks at ICD codes for previous history of fracture, medications that have adverse effects on bone – for example glucocorticoids, aromatase inhibitors, and anti-androgens – as well as chronic diseases that increase the risk of fracture,” she explained.

“FRAX is the most commonly used tool to estimate fracture probability in clinical practice and to guide treatment decisions,” she noted. However, “currently it requires human input of data into the FRAX website and is generally only performed on individuals who are selected on the basis of clinical risk factors.”

“The Crystal Bone algorithm offers the potential for fully automated population-based screening in older adults to identify those at high risk of fracture, for whom effective therapies are available to reduce fracture risk,” she summarized.

“It needs further validation,” she noted, “and implementation into clinical practice requires the availability of high-quality EHRs.”
 

Algorithm validated in 106,328 patients aged 50 and older

Despite guidelines that recommend screening for osteoporosis in women aged 65 and older, men older than 70, and adults aged 50-79 with risk factors, real-world data suggest such screening is low, the researchers note.

The current validation study identified 106,328 patients aged 50 and older who had at least 2 years of consecutive medical history with the Reliant Medical Group from December 2014 to November 2020 as well as at least two EHR codes.

The accuracy of predicting a fracture within 2 years, expressed as area under the receiver operating characteristic (AUROC), was 0.77, where 1 is perfect, 0.5 is no better than random selection, 0.7 to 0.8 is acceptable, and 0.8 to 0.9 indicates excellent predictive accuracy.

In the entire Optum Reliant population older than 50, the risk of fracture within 2 years was 1.95%.

The algorithm identified four groups with a greater risk: 19,100 patients had a threefold higher risk of fracture within 2 years, 9,246 patients had a fourfold higher risk, 3,533 patients had a sevenfold higher risk, and 1,735 patients had a ninefold higher risk.

Many of these patients had no prior diagnosis of osteoporosis

For example, in the 19,100 patients with a threefold greater risk of fracture in 2 years, 69% of patients had not been diagnosed with osteoporosis (49% of them had no history of fracture and 20% did have a history of fracture).

The algorithm had a positive predictive value of 6%-18%, a negative predictive value of 98%-99%, a specificity of 81%-98%, and a sensitivity of 18%-59%, for the four groups.

The study was funded by Amgen. Dr. Mody and another author are Reliant Medical Group employees. Ms. Kelley and another author are Optum Life Sciences employees. One author is an employee at Landing AI. Two authors are Amgen employees and own Amgen stock. Dr. Ebeling has disclosed receiving research funding from Amgen, Sanofi, and Alexion, and his institution has received honoraria from Amgen and Kyowa Kirin. Dr. Compston has disclosed receiving speaking and consultancy fees from Amgen and UCB.

A version of this article first appeared on Medscape.com.

The Crystal Bone (Amgen) novel algorithm predicted 2-year risk of osteoporotic fractures in a large dataset with an accuracy that was consistent with FRAX 10-year risk predictions, researchers report.  

The algorithm was built using machine learning and artificial intelligence to predict fracture risk based on International Classification of Diseases (ICD) codes, as described in an article published in the Journal of Medical Internet Research.

The current validation study was presented September 9 as a poster at the annual meeting of the American Society for Bone and Mineral Research.

The scientists validated the algorithm in more than 100,000 patients aged 50 and older (that is, at risk of fracture) who were part of the Reliant Medical Group dataset (a subset of Optum Care).

Importantly, the algorithm predicted increased fracture in many patients who did not have a diagnosis of osteoporosis.

The next steps are validation in other datasets to support the generalizability of Crystal Bone across U.S. health care systems, Elinor Mody, MD, Reliant Medical Group, and colleagues report.

“Implementation research, in which patients identified by Crystal Bone undergo a bone health assessment and receive ongoing management, will help inform the clinical utility of this novel algorithm,” they conclude.

At the poster session, Tina Kelley, Optum Life Sciences, explained: “It’s a screening tool that says: ‘These are your patients that maybe you should spend a little extra time with, ask a few extra questions.’ ”

However, further study is needed before it should be used in clinical practice, she emphasized to this news organization.

‘A very useful advance’ but needs further validation

Invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, noted that “many clinicians now use FRAX to calculate absolute fracture risk and select patients who should initiate anti-osteoporosis drugs.”

With FRAX, clinicians input a patient’s age, sex, weight, height, previous fracture, [history of] parent with fractured hip, current smoking status, glucocorticoids, rheumatoid arthritis, secondary osteoporosis, alcohol (3 units/day or more), and bone mineral density (by DXA at the femoral neck) into the tool, to obtain a 10-year probability of fracture.

“Crystal Bone takes a different approach,” Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research but who disclosed receiving funding from Amgen, told this news organization in an email.

The algorithm uses electronic health records (EHRs) to identify patients who are likely to have a fracture within the next 2 years, he explained, based on diagnoses and medications associated with osteoporosis and fractures. These include ICD-10 codes for fractures at various sites and secondary causes of osteoporosis (such as rheumatoid and other inflammatory arthritis, chronic obstructive pulmonary disease, asthma, celiac disease, and inflammatory bowel disease).

“This is a very useful advance,” Dr. Ebeling summarized, “in that it would alert the clinician to patients in their practice who have a high fracture risk and need to be investigated for osteoporosis and initiated on treatment. Otherwise, the patients would be missed, as currently often occurs.”

“It would need to be adaptable to other [EMR] systems and to be validated in a large separate population to be ready to enter clinical practice,” he said, “but these data look very promising with a good [positive predictive value (PPV)].”

Similarly, Juliet Compston, MD, said: “It provides a novel, fully automated approach to population-based screening for osteoporosis using EHRs to identify people at high imminent risk of fracture.”

Dr. Compston, emeritus professor of bone medicine, University of Cambridge, England, who was not involved with the research but who also disclosed being a consultant for Amgen, selected the study as one of the top clinical science highlights abstracts at the meeting.

“The algorithm looks at ICD codes for previous history of fracture, medications that have adverse effects on bone – for example glucocorticoids, aromatase inhibitors, and anti-androgens – as well as chronic diseases that increase the risk of fracture,” she explained.

“FRAX is the most commonly used tool to estimate fracture probability in clinical practice and to guide treatment decisions,” she noted. However, “currently it requires human input of data into the FRAX website and is generally only performed on individuals who are selected on the basis of clinical risk factors.”

“The Crystal Bone algorithm offers the potential for fully automated population-based screening in older adults to identify those at high risk of fracture, for whom effective therapies are available to reduce fracture risk,” she summarized.

“It needs further validation,” she noted, “and implementation into clinical practice requires the availability of high-quality EHRs.”
 

Algorithm validated in 106,328 patients aged 50 and older

Despite guidelines that recommend screening for osteoporosis in women aged 65 and older, men older than 70, and adults aged 50-79 with risk factors, real-world data suggest such screening is low, the researchers note.

The current validation study identified 106,328 patients aged 50 and older who had at least 2 years of consecutive medical history with the Reliant Medical Group from December 2014 to November 2020 as well as at least two EHR codes.

The accuracy of predicting a fracture within 2 years, expressed as area under the receiver operating characteristic (AUROC), was 0.77, where 1 is perfect, 0.5 is no better than random selection, 0.7 to 0.8 is acceptable, and 0.8 to 0.9 indicates excellent predictive accuracy.

In the entire Optum Reliant population older than 50, the risk of fracture within 2 years was 1.95%.

The algorithm identified four groups with a greater risk: 19,100 patients had a threefold higher risk of fracture within 2 years, 9,246 patients had a fourfold higher risk, 3,533 patients had a sevenfold higher risk, and 1,735 patients had a ninefold higher risk.

Many of these patients had no prior diagnosis of osteoporosis

For example, in the 19,100 patients with a threefold greater risk of fracture in 2 years, 69% of patients had not been diagnosed with osteoporosis (49% of them had no history of fracture and 20% did have a history of fracture).

The algorithm had a positive predictive value of 6%-18%, a negative predictive value of 98%-99%, a specificity of 81%-98%, and a sensitivity of 18%-59%, for the four groups.

The study was funded by Amgen. Dr. Mody and another author are Reliant Medical Group employees. Ms. Kelley and another author are Optum Life Sciences employees. One author is an employee at Landing AI. Two authors are Amgen employees and own Amgen stock. Dr. Ebeling has disclosed receiving research funding from Amgen, Sanofi, and Alexion, and his institution has received honoraria from Amgen and Kyowa Kirin. Dr. Compston has disclosed receiving speaking and consultancy fees from Amgen and UCB.

A version of this article first appeared on Medscape.com.

The Crystal Bone (Amgen) novel algorithm predicted 2-year risk of osteoporotic fractures in a large dataset with an accuracy that was consistent with FRAX 10-year risk predictions, researchers report.  

The algorithm was built using machine learning and artificial intelligence to predict fracture risk based on International Classification of Diseases (ICD) codes, as described in an article published in the Journal of Medical Internet Research.

The current validation study was presented September 9 as a poster at the annual meeting of the American Society for Bone and Mineral Research.

The scientists validated the algorithm in more than 100,000 patients aged 50 and older (that is, at risk of fracture) who were part of the Reliant Medical Group dataset (a subset of Optum Care).

Importantly, the algorithm predicted increased fracture in many patients who did not have a diagnosis of osteoporosis.

The next steps are validation in other datasets to support the generalizability of Crystal Bone across U.S. health care systems, Elinor Mody, MD, Reliant Medical Group, and colleagues report.

“Implementation research, in which patients identified by Crystal Bone undergo a bone health assessment and receive ongoing management, will help inform the clinical utility of this novel algorithm,” they conclude.

At the poster session, Tina Kelley, Optum Life Sciences, explained: “It’s a screening tool that says: ‘These are your patients that maybe you should spend a little extra time with, ask a few extra questions.’ ”

However, further study is needed before it should be used in clinical practice, she emphasized to this news organization.

‘A very useful advance’ but needs further validation

Invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, noted that “many clinicians now use FRAX to calculate absolute fracture risk and select patients who should initiate anti-osteoporosis drugs.”

With FRAX, clinicians input a patient’s age, sex, weight, height, previous fracture, [history of] parent with fractured hip, current smoking status, glucocorticoids, rheumatoid arthritis, secondary osteoporosis, alcohol (3 units/day or more), and bone mineral density (by DXA at the femoral neck) into the tool, to obtain a 10-year probability of fracture.

“Crystal Bone takes a different approach,” Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research but who disclosed receiving funding from Amgen, told this news organization in an email.

The algorithm uses electronic health records (EHRs) to identify patients who are likely to have a fracture within the next 2 years, he explained, based on diagnoses and medications associated with osteoporosis and fractures. These include ICD-10 codes for fractures at various sites and secondary causes of osteoporosis (such as rheumatoid and other inflammatory arthritis, chronic obstructive pulmonary disease, asthma, celiac disease, and inflammatory bowel disease).

“This is a very useful advance,” Dr. Ebeling summarized, “in that it would alert the clinician to patients in their practice who have a high fracture risk and need to be investigated for osteoporosis and initiated on treatment. Otherwise, the patients would be missed, as currently often occurs.”

“It would need to be adaptable to other [EMR] systems and to be validated in a large separate population to be ready to enter clinical practice,” he said, “but these data look very promising with a good [positive predictive value (PPV)].”

Similarly, Juliet Compston, MD, said: “It provides a novel, fully automated approach to population-based screening for osteoporosis using EHRs to identify people at high imminent risk of fracture.”

Dr. Compston, emeritus professor of bone medicine, University of Cambridge, England, who was not involved with the research but who also disclosed being a consultant for Amgen, selected the study as one of the top clinical science highlights abstracts at the meeting.

“The algorithm looks at ICD codes for previous history of fracture, medications that have adverse effects on bone – for example glucocorticoids, aromatase inhibitors, and anti-androgens – as well as chronic diseases that increase the risk of fracture,” she explained.

“FRAX is the most commonly used tool to estimate fracture probability in clinical practice and to guide treatment decisions,” she noted. However, “currently it requires human input of data into the FRAX website and is generally only performed on individuals who are selected on the basis of clinical risk factors.”

“The Crystal Bone algorithm offers the potential for fully automated population-based screening in older adults to identify those at high risk of fracture, for whom effective therapies are available to reduce fracture risk,” she summarized.

“It needs further validation,” she noted, “and implementation into clinical practice requires the availability of high-quality EHRs.”
 

Algorithm validated in 106,328 patients aged 50 and older

Despite guidelines that recommend screening for osteoporosis in women aged 65 and older, men older than 70, and adults aged 50-79 with risk factors, real-world data suggest such screening is low, the researchers note.

The current validation study identified 106,328 patients aged 50 and older who had at least 2 years of consecutive medical history with the Reliant Medical Group from December 2014 to November 2020 as well as at least two EHR codes.

The accuracy of predicting a fracture within 2 years, expressed as area under the receiver operating characteristic (AUROC), was 0.77, where 1 is perfect, 0.5 is no better than random selection, 0.7 to 0.8 is acceptable, and 0.8 to 0.9 indicates excellent predictive accuracy.

In the entire Optum Reliant population older than 50, the risk of fracture within 2 years was 1.95%.

The algorithm identified four groups with a greater risk: 19,100 patients had a threefold higher risk of fracture within 2 years, 9,246 patients had a fourfold higher risk, 3,533 patients had a sevenfold higher risk, and 1,735 patients had a ninefold higher risk.

Many of these patients had no prior diagnosis of osteoporosis

For example, in the 19,100 patients with a threefold greater risk of fracture in 2 years, 69% of patients had not been diagnosed with osteoporosis (49% of them had no history of fracture and 20% did have a history of fracture).

The algorithm had a positive predictive value of 6%-18%, a negative predictive value of 98%-99%, a specificity of 81%-98%, and a sensitivity of 18%-59%, for the four groups.

The study was funded by Amgen. Dr. Mody and another author are Reliant Medical Group employees. Ms. Kelley and another author are Optum Life Sciences employees. One author is an employee at Landing AI. Two authors are Amgen employees and own Amgen stock. Dr. Ebeling has disclosed receiving research funding from Amgen, Sanofi, and Alexion, and his institution has received honoraria from Amgen and Kyowa Kirin. Dr. Compston has disclosed receiving speaking and consultancy fees from Amgen and UCB.

A version of this article first appeared on Medscape.com.

Patients with melanoma who are deficient in vitamin D have significantly worse overall survival than those with higher levels, according to research presented at the annual congress of the European Academy of Dermatology and Venereology.

Whereas the 5-year overall survival was 90% when vitamin D serum levels were above a 10 ng/mL threshold, it was 84% when levels fell below it. Notably, the gap in overall survival between those above and below the threshold appeared to widen as time went on.

The research adds to existing evidence that “vitamin D levels can play an important and independent role in patients’ survival outcomes,” study investigator Inés Gracia-Darder, MD, told this news organization. “The important application in clinical practice would be to know if vitamin D supplementation influences the survival of melanoma patients,” said Dr. Gracia-Darder, a clinical specialist in dermatology at the Hospital Universitari Son Espases, Mallorca, Spain.

Dr. Inés Gracia-Darder

Known association, but not much data

“It is not a new finding,” but there are limited data, especially in melanoma, said Julie De Smedt, MD, of KU Leuven, Belgium, who was asked to comment on the results. Other groups have shown, certainly for cancer in general, that vitamin D can have an effect on overall survival.

“Low levels of vitamin D are associated with the pathological parameters of the melanoma, such as the thickness of the tumor,” Dr. De Smedt said in an interview, indicating that it’s not just overall survival that might be affected.

“So we assume that also has an effect on melanoma-specific survival,” she added.

That assumption, however, is not supported by the data Dr. Gracia-Darder presented, as there was no difference in melanoma-specific survival among the two groups of patients that had been studied.
 

Retrospective cohort analysis

Vitamin D levels had been studied in 264 patients who were included in the retrospective cohort analysis. All had invasive melanomas, and all had been seen at the Hospital Clinic of Barcelona between January 1998 and June 2021. Their mean age was 57 years, and the median follow-up was 6.7 years.

For inclusion, all patients had to have had their vitamin D levels measured after being diagnosed with melanoma; those with a 25-hydroxyvitamin D3 serum level of less than 10 ng/mL were deemed to be vitamin D deficient, whereas those with levels of 10 ng/mL and above were deemed normal or insufficient.

A measurement less than 10 ng/mL is considered vitamin D deficiency, Dr. De Smedt said. “But there is a difference between countries, and there’s also a difference between societies,” noting the cut-off used in the lab where she works is 20 ng/mL. This makes it difficult to compare studies, she said.
 

Independent association with overall survival

Seasonal variation in vitamin D levels were considered as a possible confounding factor, but Dr. Gracia-Darder noted that there was a similar distribution of measurements taken between October to March and April to September.

Univariate and multivariate analyses established vitamin D deficiency as being independently associated with overall survival with hazard ratios of 2.34 and 2.45, respectively.

Other predictive factors were having a higher Breslow index, as well as older age and gender.
 

Time to recommend vitamin D supplementation?

So should patients with melanoma have their vitamin D levels routinely checked? And what about advising them to take vitamin D supplements?

“In our practice, we analyze the vitamin D levels of our patients,” Dr. Gracia-Darder said. Patients are told to limit their exposure to the sun because of their skin cancer, so they are very likely to become vitamin D deficient.

While dietary changes or supplements might be suggested, there’s no real evidence to support upping vitamin D levels to date, so “future prospective studies are needed,” Dr. Gracia-Darder added.

Such studies have already started, including one in Italy, one in Australia, and another study that Dr. De Smedt has been involved with for the past few years.

Called the ViDMe study, it’s a multicenter, randomized, double-blind trial in which patients are being given a high-dose oral vitamin D supplement or placebo once a month for at least 1 year. About 430 patients with a first cutaneous malignant melanoma have been included in the trial, which started in December 2012.

It is hoped that the results will show that the supplementation will have had a protective effect on the risk of relapse and that there will be a correlation between vitamin D levels in the blood and vitamin D receptor immunoreactivity in the tumor.

“The study is still blinded,” Dr. De Smedt said. “We will unblind in the coming months and then at the end of the year, maybe next year, we will have the results.”

The study reported by Dr. Gracia-Darder did not receive any specific funding. Dr. Gracia-Darder disclosed that the melanoma unit where the study was performed receives many grants and funds to carry out research. She reported no other relevant financial relationships. Dr. De Smedt had no relevant financial relationships. The ViDMe study is sponsored by the Universitaire Ziekenhuizen Leuven.

A version of this article first appeared on Medscape.com.

Patients with melanoma who are deficient in vitamin D have significantly worse overall survival than those with higher levels, according to research presented at the annual congress of the European Academy of Dermatology and Venereology.

Whereas the 5-year overall survival was 90% when vitamin D serum levels were above a 10 ng/mL threshold, it was 84% when levels fell below it. Notably, the gap in overall survival between those above and below the threshold appeared to widen as time went on.

The research adds to existing evidence that “vitamin D levels can play an important and independent role in patients’ survival outcomes,” study investigator Inés Gracia-Darder, MD, told this news organization. “The important application in clinical practice would be to know if vitamin D supplementation influences the survival of melanoma patients,” said Dr. Gracia-Darder, a clinical specialist in dermatology at the Hospital Universitari Son Espases, Mallorca, Spain.

Dr. Inés Gracia-Darder

Known association, but not much data

“It is not a new finding,” but there are limited data, especially in melanoma, said Julie De Smedt, MD, of KU Leuven, Belgium, who was asked to comment on the results. Other groups have shown, certainly for cancer in general, that vitamin D can have an effect on overall survival.

“Low levels of vitamin D are associated with the pathological parameters of the melanoma, such as the thickness of the tumor,” Dr. De Smedt said in an interview, indicating that it’s not just overall survival that might be affected.

“So we assume that also has an effect on melanoma-specific survival,” she added.

That assumption, however, is not supported by the data Dr. Gracia-Darder presented, as there was no difference in melanoma-specific survival among the two groups of patients that had been studied.
 

Retrospective cohort analysis

Vitamin D levels had been studied in 264 patients who were included in the retrospective cohort analysis. All had invasive melanomas, and all had been seen at the Hospital Clinic of Barcelona between January 1998 and June 2021. Their mean age was 57 years, and the median follow-up was 6.7 years.

For inclusion, all patients had to have had their vitamin D levels measured after being diagnosed with melanoma; those with a 25-hydroxyvitamin D3 serum level of less than 10 ng/mL were deemed to be vitamin D deficient, whereas those with levels of 10 ng/mL and above were deemed normal or insufficient.

A measurement less than 10 ng/mL is considered vitamin D deficiency, Dr. De Smedt said. “But there is a difference between countries, and there’s also a difference between societies,” noting the cut-off used in the lab where she works is 20 ng/mL. This makes it difficult to compare studies, she said.
 

Independent association with overall survival

Seasonal variation in vitamin D levels were considered as a possible confounding factor, but Dr. Gracia-Darder noted that there was a similar distribution of measurements taken between October to March and April to September.

Univariate and multivariate analyses established vitamin D deficiency as being independently associated with overall survival with hazard ratios of 2.34 and 2.45, respectively.

Other predictive factors were having a higher Breslow index, as well as older age and gender.
 

Time to recommend vitamin D supplementation?

So should patients with melanoma have their vitamin D levels routinely checked? And what about advising them to take vitamin D supplements?

“In our practice, we analyze the vitamin D levels of our patients,” Dr. Gracia-Darder said. Patients are told to limit their exposure to the sun because of their skin cancer, so they are very likely to become vitamin D deficient.

While dietary changes or supplements might be suggested, there’s no real evidence to support upping vitamin D levels to date, so “future prospective studies are needed,” Dr. Gracia-Darder added.

Such studies have already started, including one in Italy, one in Australia, and another study that Dr. De Smedt has been involved with for the past few years.

Called the ViDMe study, it’s a multicenter, randomized, double-blind trial in which patients are being given a high-dose oral vitamin D supplement or placebo once a month for at least 1 year. About 430 patients with a first cutaneous malignant melanoma have been included in the trial, which started in December 2012.

It is hoped that the results will show that the supplementation will have had a protective effect on the risk of relapse and that there will be a correlation between vitamin D levels in the blood and vitamin D receptor immunoreactivity in the tumor.

“The study is still blinded,” Dr. De Smedt said. “We will unblind in the coming months and then at the end of the year, maybe next year, we will have the results.”

The study reported by Dr. Gracia-Darder did not receive any specific funding. Dr. Gracia-Darder disclosed that the melanoma unit where the study was performed receives many grants and funds to carry out research. She reported no other relevant financial relationships. Dr. De Smedt had no relevant financial relationships. The ViDMe study is sponsored by the Universitaire Ziekenhuizen Leuven.

A version of this article first appeared on Medscape.com.

Patients with melanoma who are deficient in vitamin D have significantly worse overall survival than those with higher levels, according to research presented at the annual congress of the European Academy of Dermatology and Venereology.

Whereas the 5-year overall survival was 90% when vitamin D serum levels were above a 10 ng/mL threshold, it was 84% when levels fell below it. Notably, the gap in overall survival between those above and below the threshold appeared to widen as time went on.

The research adds to existing evidence that “vitamin D levels can play an important and independent role in patients’ survival outcomes,” study investigator Inés Gracia-Darder, MD, told this news organization. “The important application in clinical practice would be to know if vitamin D supplementation influences the survival of melanoma patients,” said Dr. Gracia-Darder, a clinical specialist in dermatology at the Hospital Universitari Son Espases, Mallorca, Spain.

Dr. Inés Gracia-Darder

Known association, but not much data

“It is not a new finding,” but there are limited data, especially in melanoma, said Julie De Smedt, MD, of KU Leuven, Belgium, who was asked to comment on the results. Other groups have shown, certainly for cancer in general, that vitamin D can have an effect on overall survival.

“Low levels of vitamin D are associated with the pathological parameters of the melanoma, such as the thickness of the tumor,” Dr. De Smedt said in an interview, indicating that it’s not just overall survival that might be affected.

“So we assume that also has an effect on melanoma-specific survival,” she added.

That assumption, however, is not supported by the data Dr. Gracia-Darder presented, as there was no difference in melanoma-specific survival among the two groups of patients that had been studied.
 

Retrospective cohort analysis

Vitamin D levels had been studied in 264 patients who were included in the retrospective cohort analysis. All had invasive melanomas, and all had been seen at the Hospital Clinic of Barcelona between January 1998 and June 2021. Their mean age was 57 years, and the median follow-up was 6.7 years.

For inclusion, all patients had to have had their vitamin D levels measured after being diagnosed with melanoma; those with a 25-hydroxyvitamin D3 serum level of less than 10 ng/mL were deemed to be vitamin D deficient, whereas those with levels of 10 ng/mL and above were deemed normal or insufficient.

A measurement less than 10 ng/mL is considered vitamin D deficiency, Dr. De Smedt said. “But there is a difference between countries, and there’s also a difference between societies,” noting the cut-off used in the lab where she works is 20 ng/mL. This makes it difficult to compare studies, she said.
 

Independent association with overall survival

Seasonal variation in vitamin D levels were considered as a possible confounding factor, but Dr. Gracia-Darder noted that there was a similar distribution of measurements taken between October to March and April to September.

Univariate and multivariate analyses established vitamin D deficiency as being independently associated with overall survival with hazard ratios of 2.34 and 2.45, respectively.

Other predictive factors were having a higher Breslow index, as well as older age and gender.
 

Time to recommend vitamin D supplementation?

So should patients with melanoma have their vitamin D levels routinely checked? And what about advising them to take vitamin D supplements?

“In our practice, we analyze the vitamin D levels of our patients,” Dr. Gracia-Darder said. Patients are told to limit their exposure to the sun because of their skin cancer, so they are very likely to become vitamin D deficient.

While dietary changes or supplements might be suggested, there’s no real evidence to support upping vitamin D levels to date, so “future prospective studies are needed,” Dr. Gracia-Darder added.

Such studies have already started, including one in Italy, one in Australia, and another study that Dr. De Smedt has been involved with for the past few years.

Called the ViDMe study, it’s a multicenter, randomized, double-blind trial in which patients are being given a high-dose oral vitamin D supplement or placebo once a month for at least 1 year. About 430 patients with a first cutaneous malignant melanoma have been included in the trial, which started in December 2012.

It is hoped that the results will show that the supplementation will have had a protective effect on the risk of relapse and that there will be a correlation between vitamin D levels in the blood and vitamin D receptor immunoreactivity in the tumor.

“The study is still blinded,” Dr. De Smedt said. “We will unblind in the coming months and then at the end of the year, maybe next year, we will have the results.”

The study reported by Dr. Gracia-Darder did not receive any specific funding. Dr. Gracia-Darder disclosed that the melanoma unit where the study was performed receives many grants and funds to carry out research. She reported no other relevant financial relationships. Dr. De Smedt had no relevant financial relationships. The ViDMe study is sponsored by the Universitaire Ziekenhuizen Leuven.

A version of this article first appeared on Medscape.com.