Bisphosphonate holiday may help to reduce atypical femur fracture risk

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Women who take a 3- to 5-year break from bisphosphonates after 3-5 years on treatment could significantly reduce their risk of atypical femur fractures, according to a study of more than 150,000 Southern California health plan members presented at the annual meeting of the American Society for Bone and Mineral Research in Montreal.

Dr. Annette L. Adams

A second study in the same group of women found that higher bone mineral density levels before bisphosphonate treatment may put women at greater risk for these fractures.

“Our findings suggest really strongly that among women who have achieved some level of bisphosphonate exposure a drug holiday is certainly a reasonable approach to trying to balance the risk of these atypical fractures versus the benefit of preventing more typical, or classic, hip fractures,” said presenter Annette L. Adams, PhD, MPH, a research scientist with Kaiser Permanente Southern California, who was an author on both studies.

Atypical femur fractures (AFFs) occur below the trochanters in the femoral shaft area, around mid-thigh, Dr. Adams said. They appear different from other fractures, usually breaking in just two pieces transversely through the center of the bone, and occur with minimal to no trauma, she said.

“We’ve heard stories of women that are just sitting in a chair, and they stand up and their femur fractures,” Dr. Adams said. “Or they’re out in the garden on their knees, and they try to stand up and it fractures. These are not necessarily fall-related like many traditional hip fractures.”

The researchers observed a 44% reduction in women’s risk of AFFs in the first year of a so-called drug holiday, or discontinuation of bisphosphonates, after 3-5 years on treatment when compared with those who stayed on the medications (hazard ratio = 0.56; 95% confidence interval, 0.38-0.82). During the first to fourth years after discontinuation, AFF risk was decreased by 80% (HR = 0.20; 95% CI, 0.10-0.37), and after 4 years, AFF risk was reduced by 78% (HR = 0.22; 95% CI, 0.08-0.59) in comparison to bisphosphonate users.

Dr. Adams and her colleagues reviewed records from 152,934 women aged 50 or older who were members of Kaiser Permanente Southern California between Jan. 1, 2007, and Sept. 30, 2015. There were 185 AFFs overall (incidence rate 1.70 per 10,000 person-years).

The cohort included women who used a bisphosphonate and had at least one available pretreatment bone mineral density (BMD) total hip scan. AFFs were identified and verified by physician review of x-ray images for fractures occurring during the study period with ICD-9 codes for subtrochanteric or femoral shaft fractures. Women were considered to have discontinued bisphosphonates if there was a gap of over 3 months between the last bisphosphonate use and cohort entry anniversaries. Researchers included information on potential confounders of the association between discontinuation time and AFF such as age, race/ethnicity, smoking status, fracture history, duration of bisphosphonate use, discontinuation of glucocorticoid use, and pretreatment total hip T-score.

A second study in the same cohort consistently showed that women with higher pretreatment BMD had a larger risk of AFFs.


Researchers assessed the relationship of bisphosphonate duration to AFF risk before and after treatment, including pretreatment BMD in multivariate Cox models. In a multivariate model without pretreatment BMD, those with longer bisphosphonate duration had higher AFF risk. Compared to those taking the drug for less than 1 year, the relative hazard (RH) for 1-4 years of bisphosphonate use was 3 (95% CI, 1.4-7.3), for 4-8 years of bisphosphonate use was 15 (95% CI, 7-33), and for over 8 years was 37 (95% CI, 16-83).

Pretreatment BMD, when added to the model, did not attenuate the relationship of bisphosphonate duration and AFF risk. However, it showed those with higher BMD had a 40% increase in AFF risk per standard deviation of BMD increase (HR = 1.4; 95% CI, 1.2-1.7).

In those with normal pretreatment BMD (T-score greater than –1), the RH for 4-8 years of bisphosphonate use (versus less than 1 year) was 35, compared with 15 in those with osteopenic BMD (T-score –1 to –2.5) and 6 in those with osteoporotic BMD (T-score less than –2.5).

If confirmed in other studies, the results suggest that pretreatment BMD could impact clinical decisions around patient selection for bisphosphonate initiation and drug holidays, Dr. Adams said.

She reported receiving grant and research support from Merck.

SOURCES: Adams A et al. ASBMR 2018 Abstract 1005, and Black D et al. ASBMR 2018 Abstract 1007

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Women who take a 3- to 5-year break from bisphosphonates after 3-5 years on treatment could significantly reduce their risk of atypical femur fractures, according to a study of more than 150,000 Southern California health plan members presented at the annual meeting of the American Society for Bone and Mineral Research in Montreal.

Dr. Annette L. Adams

A second study in the same group of women found that higher bone mineral density levels before bisphosphonate treatment may put women at greater risk for these fractures.

“Our findings suggest really strongly that among women who have achieved some level of bisphosphonate exposure a drug holiday is certainly a reasonable approach to trying to balance the risk of these atypical fractures versus the benefit of preventing more typical, or classic, hip fractures,” said presenter Annette L. Adams, PhD, MPH, a research scientist with Kaiser Permanente Southern California, who was an author on both studies.

Atypical femur fractures (AFFs) occur below the trochanters in the femoral shaft area, around mid-thigh, Dr. Adams said. They appear different from other fractures, usually breaking in just two pieces transversely through the center of the bone, and occur with minimal to no trauma, she said.

“We’ve heard stories of women that are just sitting in a chair, and they stand up and their femur fractures,” Dr. Adams said. “Or they’re out in the garden on their knees, and they try to stand up and it fractures. These are not necessarily fall-related like many traditional hip fractures.”

The researchers observed a 44% reduction in women’s risk of AFFs in the first year of a so-called drug holiday, or discontinuation of bisphosphonates, after 3-5 years on treatment when compared with those who stayed on the medications (hazard ratio = 0.56; 95% confidence interval, 0.38-0.82). During the first to fourth years after discontinuation, AFF risk was decreased by 80% (HR = 0.20; 95% CI, 0.10-0.37), and after 4 years, AFF risk was reduced by 78% (HR = 0.22; 95% CI, 0.08-0.59) in comparison to bisphosphonate users.

Dr. Adams and her colleagues reviewed records from 152,934 women aged 50 or older who were members of Kaiser Permanente Southern California between Jan. 1, 2007, and Sept. 30, 2015. There were 185 AFFs overall (incidence rate 1.70 per 10,000 person-years).

The cohort included women who used a bisphosphonate and had at least one available pretreatment bone mineral density (BMD) total hip scan. AFFs were identified and verified by physician review of x-ray images for fractures occurring during the study period with ICD-9 codes for subtrochanteric or femoral shaft fractures. Women were considered to have discontinued bisphosphonates if there was a gap of over 3 months between the last bisphosphonate use and cohort entry anniversaries. Researchers included information on potential confounders of the association between discontinuation time and AFF such as age, race/ethnicity, smoking status, fracture history, duration of bisphosphonate use, discontinuation of glucocorticoid use, and pretreatment total hip T-score.

A second study in the same cohort consistently showed that women with higher pretreatment BMD had a larger risk of AFFs.


Researchers assessed the relationship of bisphosphonate duration to AFF risk before and after treatment, including pretreatment BMD in multivariate Cox models. In a multivariate model without pretreatment BMD, those with longer bisphosphonate duration had higher AFF risk. Compared to those taking the drug for less than 1 year, the relative hazard (RH) for 1-4 years of bisphosphonate use was 3 (95% CI, 1.4-7.3), for 4-8 years of bisphosphonate use was 15 (95% CI, 7-33), and for over 8 years was 37 (95% CI, 16-83).

Pretreatment BMD, when added to the model, did not attenuate the relationship of bisphosphonate duration and AFF risk. However, it showed those with higher BMD had a 40% increase in AFF risk per standard deviation of BMD increase (HR = 1.4; 95% CI, 1.2-1.7).

In those with normal pretreatment BMD (T-score greater than –1), the RH for 4-8 years of bisphosphonate use (versus less than 1 year) was 35, compared with 15 in those with osteopenic BMD (T-score –1 to –2.5) and 6 in those with osteoporotic BMD (T-score less than –2.5).

If confirmed in other studies, the results suggest that pretreatment BMD could impact clinical decisions around patient selection for bisphosphonate initiation and drug holidays, Dr. Adams said.

She reported receiving grant and research support from Merck.

SOURCES: Adams A et al. ASBMR 2018 Abstract 1005, and Black D et al. ASBMR 2018 Abstract 1007

Women who take a 3- to 5-year break from bisphosphonates after 3-5 years on treatment could significantly reduce their risk of atypical femur fractures, according to a study of more than 150,000 Southern California health plan members presented at the annual meeting of the American Society for Bone and Mineral Research in Montreal.

Dr. Annette L. Adams

A second study in the same group of women found that higher bone mineral density levels before bisphosphonate treatment may put women at greater risk for these fractures.

“Our findings suggest really strongly that among women who have achieved some level of bisphosphonate exposure a drug holiday is certainly a reasonable approach to trying to balance the risk of these atypical fractures versus the benefit of preventing more typical, or classic, hip fractures,” said presenter Annette L. Adams, PhD, MPH, a research scientist with Kaiser Permanente Southern California, who was an author on both studies.

Atypical femur fractures (AFFs) occur below the trochanters in the femoral shaft area, around mid-thigh, Dr. Adams said. They appear different from other fractures, usually breaking in just two pieces transversely through the center of the bone, and occur with minimal to no trauma, she said.

“We’ve heard stories of women that are just sitting in a chair, and they stand up and their femur fractures,” Dr. Adams said. “Or they’re out in the garden on their knees, and they try to stand up and it fractures. These are not necessarily fall-related like many traditional hip fractures.”

The researchers observed a 44% reduction in women’s risk of AFFs in the first year of a so-called drug holiday, or discontinuation of bisphosphonates, after 3-5 years on treatment when compared with those who stayed on the medications (hazard ratio = 0.56; 95% confidence interval, 0.38-0.82). During the first to fourth years after discontinuation, AFF risk was decreased by 80% (HR = 0.20; 95% CI, 0.10-0.37), and after 4 years, AFF risk was reduced by 78% (HR = 0.22; 95% CI, 0.08-0.59) in comparison to bisphosphonate users.

Dr. Adams and her colleagues reviewed records from 152,934 women aged 50 or older who were members of Kaiser Permanente Southern California between Jan. 1, 2007, and Sept. 30, 2015. There were 185 AFFs overall (incidence rate 1.70 per 10,000 person-years).

The cohort included women who used a bisphosphonate and had at least one available pretreatment bone mineral density (BMD) total hip scan. AFFs were identified and verified by physician review of x-ray images for fractures occurring during the study period with ICD-9 codes for subtrochanteric or femoral shaft fractures. Women were considered to have discontinued bisphosphonates if there was a gap of over 3 months between the last bisphosphonate use and cohort entry anniversaries. Researchers included information on potential confounders of the association between discontinuation time and AFF such as age, race/ethnicity, smoking status, fracture history, duration of bisphosphonate use, discontinuation of glucocorticoid use, and pretreatment total hip T-score.

A second study in the same cohort consistently showed that women with higher pretreatment BMD had a larger risk of AFFs.


Researchers assessed the relationship of bisphosphonate duration to AFF risk before and after treatment, including pretreatment BMD in multivariate Cox models. In a multivariate model without pretreatment BMD, those with longer bisphosphonate duration had higher AFF risk. Compared to those taking the drug for less than 1 year, the relative hazard (RH) for 1-4 years of bisphosphonate use was 3 (95% CI, 1.4-7.3), for 4-8 years of bisphosphonate use was 15 (95% CI, 7-33), and for over 8 years was 37 (95% CI, 16-83).

Pretreatment BMD, when added to the model, did not attenuate the relationship of bisphosphonate duration and AFF risk. However, it showed those with higher BMD had a 40% increase in AFF risk per standard deviation of BMD increase (HR = 1.4; 95% CI, 1.2-1.7).

In those with normal pretreatment BMD (T-score greater than –1), the RH for 4-8 years of bisphosphonate use (versus less than 1 year) was 35, compared with 15 in those with osteopenic BMD (T-score –1 to –2.5) and 6 in those with osteoporotic BMD (T-score less than –2.5).

If confirmed in other studies, the results suggest that pretreatment BMD could impact clinical decisions around patient selection for bisphosphonate initiation and drug holidays, Dr. Adams said.

She reported receiving grant and research support from Merck.

SOURCES: Adams A et al. ASBMR 2018 Abstract 1005, and Black D et al. ASBMR 2018 Abstract 1007

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New secondary fracture–prevention recommendations carry simple messages

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Ensuring that older adults who have experienced a hip or vertebral fracture understand they likely have osteoporosis, and offering prompt drug treatment for the condition, are among five fundamental recommendations put together by a coalition of U.S. and international bone health experts and health care organizations to help prevent secondary fractures.

The recommendations were announced at the annual meeting of the American Society for Bone and Mineral Research (ASBMR) in Montreal. The 40-member group that developed the recommendations, called the ASBMR Secondary Fracture Prevention Initiative Coalition, includes the American Association of Clinical Endocrinologists/American College of Endocrinology, the Endocrine Society, the American College of Rheumatology, the American College of Physicians, the American Geriatrics Society, the American Academy of Physical Medicine and Rehabilitation, and the American Academy of Orthopaedic Surgeons.

Additional fundamental recommendations from the Coalition advised ensuring that patients’ primary health care providers are aware of the fracture, regularly assessing the risk of falls, and routinely reevaluating patients who are being treated for osteoporosis. These suggestions were developed in response to growing evidence of a rising trend in osteoporosis patients not being prescribed appropriate medications or not taking them, the ASBMR said.

Dr. Sundeep Khosla

“The very simple message is if you’ve got somebody who has had a hip fracture or a vertebral fracture, that needs secondary prevention just like somebody who’s had an MI needs to be on a statin and a beta blocker,” said coalition cochair Sundeep Khosla, MD, a past president of the ASBMR and director of the Center for Clinical and Translational Science at the Mayo Clinic, Rochester, Minn. “You can’t ignore the fracture because it’s not immediately life-threatening. Down the road they’re going to have another hip fracture if nothing is done.”

Only 23% of elderly patients who have a hip fracture receive osteoporosis medication to reduce future fracture risk, according to the ASBMR. A 30-year downward trend in the number of hip fractures in the United States has recently plateaued, raising concerns this may have been caused by doctors and patients not following diagnostic and treatment guidelines, the organization noted.

The reasons for the plateau are uncertain, Dr. Khosla said, but could include a reluctance by patients to take bisphosphonates following some reports of relatively rare side effects, such as atypical femoral fractures and osteonecrosis of the jaw. In addition, he said, reimbursement for dual-energy x-ray absorptiometry (DEXA) scans to measure bone mineral density has gone down, which has led to fewer osteoporosis diagnoses. But fracture prevention is important, he said. Of the 300,000 hip fractures in the United States each year, one of every two patients never regains their previous functioning. In addition, one of every four hip fracture patients ends up in a nursing home or dies within a year, according to the ASBMR.

The recommendations and more data about osteoporosis treatment are available on the coalition’s website, www.secondaryfractures.org. An action plan for clinicians should be added to the site sometime this fall, Dr. Khosla said.

There are five fundamental recommendations:

First, communicate three simple messages to patients and their family/caregivers throughout the fracture care and healing process. These include: Their broken bone likely means they have osteoporosis and are at high risk for breaking more bones; breaking bones means they may have to use a walker, cane, or wheelchair or move from their home to a residential facility and will be at higher risk for premature death; and there are actions they can take to reduce their risk.

Dr. Douglas P. Kiel

This is key, said coalition cochair Douglas P. Kiel, MD, a past president of ASBMR, the director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston, and a professor of medicine at Harvard Medical School, also in Boston.

“If you talk to people who have had a broken bone, they view this as an accident and not that they have anything wrong with them,” he said. “The communication should be that if you broke something, it is not a random, chance event. You have osteoporosis, and if you don’t do anything about it, you’re going to be at great risk of a life-threatening, independence-threatening fracture in the future.”

Second, ensure the patient’s primary health care provider is made aware of the occurrence of the fracture. Take action to be sure the communication is made.

Third, regularly assess the risk of falling in women and men age 65 years or older who have had a hip or vertebral fracture. At minimum, take a history of falls within the last year, minimize the use of medications associated with increased risk for falls, evaluate patients for conditions associated with an increased risk for falls, and strongly consider referring patients to physical and/or occupational therapy or a physiatrist for evaluation and interventions to improve impairments in mobility, gait, and balance to reduce the risk for falls.

Fourth, reduce the risk of additional fractures by offering pharmacologic therapy for osteoporosis to women and men age 65 years or older who have had a hip or vertebral fracture. This can begin in the hospital and be included in discharge orders. Do not delay initiation of therapy for bone mineral density (BMD) testing. Consider patients’ oral health before starting therapy with bisphosphonates or denosumab (Prolia).

Most hip fracture patients leave the hospital without osteoporosis medications, Dr. Kiel said. It could be that hospital-based physicians are concerned patients are still unsteady such that they may not want to start patients on a new medication when they’re discharging them. Physicians in rehabilitation units may not prescribe these medications because they feel they have the patients for a short time, so by the time the patient returns to their primary care provider, the patient may have the same mistaken impression the fracture was an accident.



“We’re advocating not to delay treatment for any of these care transitions or because you think they need a BMD test,” Dr. Kiel said. “Just get them treated like they do with heart attacks.”

Finally, follow and reevaluate women and men age 65 years or older who have had a hip or vertebral fracture and are being treated for osteoporosis because it is a life-long chronic condition. This can help reinforce key messages about osteoporosis and associated fractures, identify any barriers to treatment adherence, assess the risk of falls, evaluate the effectiveness of a treatment plan, monitor for adverse effects, and determine whether any changes in treatment should be made, including whether any osteoporosis pharmacotherapy should be changed or discontinued.

Ideally, patients should be managed in the context of a multidisciplinary clinical system that includes case management, such as a fracture liaison service, according to the recommendations.

Besides the fundamental five recommendations, the documents lists another seven that deal with referring patients, prescribing vitamin D, counseling on lifestyle and diet, discussing pharmacotherapy benefits and risks, weighing first-line therapy options, and determining the duration of pharmacotherapy.

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Ensuring that older adults who have experienced a hip or vertebral fracture understand they likely have osteoporosis, and offering prompt drug treatment for the condition, are among five fundamental recommendations put together by a coalition of U.S. and international bone health experts and health care organizations to help prevent secondary fractures.

The recommendations were announced at the annual meeting of the American Society for Bone and Mineral Research (ASBMR) in Montreal. The 40-member group that developed the recommendations, called the ASBMR Secondary Fracture Prevention Initiative Coalition, includes the American Association of Clinical Endocrinologists/American College of Endocrinology, the Endocrine Society, the American College of Rheumatology, the American College of Physicians, the American Geriatrics Society, the American Academy of Physical Medicine and Rehabilitation, and the American Academy of Orthopaedic Surgeons.

Additional fundamental recommendations from the Coalition advised ensuring that patients’ primary health care providers are aware of the fracture, regularly assessing the risk of falls, and routinely reevaluating patients who are being treated for osteoporosis. These suggestions were developed in response to growing evidence of a rising trend in osteoporosis patients not being prescribed appropriate medications or not taking them, the ASBMR said.

Dr. Sundeep Khosla

“The very simple message is if you’ve got somebody who has had a hip fracture or a vertebral fracture, that needs secondary prevention just like somebody who’s had an MI needs to be on a statin and a beta blocker,” said coalition cochair Sundeep Khosla, MD, a past president of the ASBMR and director of the Center for Clinical and Translational Science at the Mayo Clinic, Rochester, Minn. “You can’t ignore the fracture because it’s not immediately life-threatening. Down the road they’re going to have another hip fracture if nothing is done.”

Only 23% of elderly patients who have a hip fracture receive osteoporosis medication to reduce future fracture risk, according to the ASBMR. A 30-year downward trend in the number of hip fractures in the United States has recently plateaued, raising concerns this may have been caused by doctors and patients not following diagnostic and treatment guidelines, the organization noted.

The reasons for the plateau are uncertain, Dr. Khosla said, but could include a reluctance by patients to take bisphosphonates following some reports of relatively rare side effects, such as atypical femoral fractures and osteonecrosis of the jaw. In addition, he said, reimbursement for dual-energy x-ray absorptiometry (DEXA) scans to measure bone mineral density has gone down, which has led to fewer osteoporosis diagnoses. But fracture prevention is important, he said. Of the 300,000 hip fractures in the United States each year, one of every two patients never regains their previous functioning. In addition, one of every four hip fracture patients ends up in a nursing home or dies within a year, according to the ASBMR.

The recommendations and more data about osteoporosis treatment are available on the coalition’s website, www.secondaryfractures.org. An action plan for clinicians should be added to the site sometime this fall, Dr. Khosla said.

There are five fundamental recommendations:

First, communicate three simple messages to patients and their family/caregivers throughout the fracture care and healing process. These include: Their broken bone likely means they have osteoporosis and are at high risk for breaking more bones; breaking bones means they may have to use a walker, cane, or wheelchair or move from their home to a residential facility and will be at higher risk for premature death; and there are actions they can take to reduce their risk.

Dr. Douglas P. Kiel

This is key, said coalition cochair Douglas P. Kiel, MD, a past president of ASBMR, the director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston, and a professor of medicine at Harvard Medical School, also in Boston.

“If you talk to people who have had a broken bone, they view this as an accident and not that they have anything wrong with them,” he said. “The communication should be that if you broke something, it is not a random, chance event. You have osteoporosis, and if you don’t do anything about it, you’re going to be at great risk of a life-threatening, independence-threatening fracture in the future.”

Second, ensure the patient’s primary health care provider is made aware of the occurrence of the fracture. Take action to be sure the communication is made.

Third, regularly assess the risk of falling in women and men age 65 years or older who have had a hip or vertebral fracture. At minimum, take a history of falls within the last year, minimize the use of medications associated with increased risk for falls, evaluate patients for conditions associated with an increased risk for falls, and strongly consider referring patients to physical and/or occupational therapy or a physiatrist for evaluation and interventions to improve impairments in mobility, gait, and balance to reduce the risk for falls.

Fourth, reduce the risk of additional fractures by offering pharmacologic therapy for osteoporosis to women and men age 65 years or older who have had a hip or vertebral fracture. This can begin in the hospital and be included in discharge orders. Do not delay initiation of therapy for bone mineral density (BMD) testing. Consider patients’ oral health before starting therapy with bisphosphonates or denosumab (Prolia).

Most hip fracture patients leave the hospital without osteoporosis medications, Dr. Kiel said. It could be that hospital-based physicians are concerned patients are still unsteady such that they may not want to start patients on a new medication when they’re discharging them. Physicians in rehabilitation units may not prescribe these medications because they feel they have the patients for a short time, so by the time the patient returns to their primary care provider, the patient may have the same mistaken impression the fracture was an accident.



“We’re advocating not to delay treatment for any of these care transitions or because you think they need a BMD test,” Dr. Kiel said. “Just get them treated like they do with heart attacks.”

Finally, follow and reevaluate women and men age 65 years or older who have had a hip or vertebral fracture and are being treated for osteoporosis because it is a life-long chronic condition. This can help reinforce key messages about osteoporosis and associated fractures, identify any barriers to treatment adherence, assess the risk of falls, evaluate the effectiveness of a treatment plan, monitor for adverse effects, and determine whether any changes in treatment should be made, including whether any osteoporosis pharmacotherapy should be changed or discontinued.

Ideally, patients should be managed in the context of a multidisciplinary clinical system that includes case management, such as a fracture liaison service, according to the recommendations.

Besides the fundamental five recommendations, the documents lists another seven that deal with referring patients, prescribing vitamin D, counseling on lifestyle and diet, discussing pharmacotherapy benefits and risks, weighing first-line therapy options, and determining the duration of pharmacotherapy.

 

Ensuring that older adults who have experienced a hip or vertebral fracture understand they likely have osteoporosis, and offering prompt drug treatment for the condition, are among five fundamental recommendations put together by a coalition of U.S. and international bone health experts and health care organizations to help prevent secondary fractures.

The recommendations were announced at the annual meeting of the American Society for Bone and Mineral Research (ASBMR) in Montreal. The 40-member group that developed the recommendations, called the ASBMR Secondary Fracture Prevention Initiative Coalition, includes the American Association of Clinical Endocrinologists/American College of Endocrinology, the Endocrine Society, the American College of Rheumatology, the American College of Physicians, the American Geriatrics Society, the American Academy of Physical Medicine and Rehabilitation, and the American Academy of Orthopaedic Surgeons.

Additional fundamental recommendations from the Coalition advised ensuring that patients’ primary health care providers are aware of the fracture, regularly assessing the risk of falls, and routinely reevaluating patients who are being treated for osteoporosis. These suggestions were developed in response to growing evidence of a rising trend in osteoporosis patients not being prescribed appropriate medications or not taking them, the ASBMR said.

Dr. Sundeep Khosla

“The very simple message is if you’ve got somebody who has had a hip fracture or a vertebral fracture, that needs secondary prevention just like somebody who’s had an MI needs to be on a statin and a beta blocker,” said coalition cochair Sundeep Khosla, MD, a past president of the ASBMR and director of the Center for Clinical and Translational Science at the Mayo Clinic, Rochester, Minn. “You can’t ignore the fracture because it’s not immediately life-threatening. Down the road they’re going to have another hip fracture if nothing is done.”

Only 23% of elderly patients who have a hip fracture receive osteoporosis medication to reduce future fracture risk, according to the ASBMR. A 30-year downward trend in the number of hip fractures in the United States has recently plateaued, raising concerns this may have been caused by doctors and patients not following diagnostic and treatment guidelines, the organization noted.

The reasons for the plateau are uncertain, Dr. Khosla said, but could include a reluctance by patients to take bisphosphonates following some reports of relatively rare side effects, such as atypical femoral fractures and osteonecrosis of the jaw. In addition, he said, reimbursement for dual-energy x-ray absorptiometry (DEXA) scans to measure bone mineral density has gone down, which has led to fewer osteoporosis diagnoses. But fracture prevention is important, he said. Of the 300,000 hip fractures in the United States each year, one of every two patients never regains their previous functioning. In addition, one of every four hip fracture patients ends up in a nursing home or dies within a year, according to the ASBMR.

The recommendations and more data about osteoporosis treatment are available on the coalition’s website, www.secondaryfractures.org. An action plan for clinicians should be added to the site sometime this fall, Dr. Khosla said.

There are five fundamental recommendations:

First, communicate three simple messages to patients and their family/caregivers throughout the fracture care and healing process. These include: Their broken bone likely means they have osteoporosis and are at high risk for breaking more bones; breaking bones means they may have to use a walker, cane, or wheelchair or move from their home to a residential facility and will be at higher risk for premature death; and there are actions they can take to reduce their risk.

Dr. Douglas P. Kiel

This is key, said coalition cochair Douglas P. Kiel, MD, a past president of ASBMR, the director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston, and a professor of medicine at Harvard Medical School, also in Boston.

“If you talk to people who have had a broken bone, they view this as an accident and not that they have anything wrong with them,” he said. “The communication should be that if you broke something, it is not a random, chance event. You have osteoporosis, and if you don’t do anything about it, you’re going to be at great risk of a life-threatening, independence-threatening fracture in the future.”

Second, ensure the patient’s primary health care provider is made aware of the occurrence of the fracture. Take action to be sure the communication is made.

Third, regularly assess the risk of falling in women and men age 65 years or older who have had a hip or vertebral fracture. At minimum, take a history of falls within the last year, minimize the use of medications associated with increased risk for falls, evaluate patients for conditions associated with an increased risk for falls, and strongly consider referring patients to physical and/or occupational therapy or a physiatrist for evaluation and interventions to improve impairments in mobility, gait, and balance to reduce the risk for falls.

Fourth, reduce the risk of additional fractures by offering pharmacologic therapy for osteoporosis to women and men age 65 years or older who have had a hip or vertebral fracture. This can begin in the hospital and be included in discharge orders. Do not delay initiation of therapy for bone mineral density (BMD) testing. Consider patients’ oral health before starting therapy with bisphosphonates or denosumab (Prolia).

Most hip fracture patients leave the hospital without osteoporosis medications, Dr. Kiel said. It could be that hospital-based physicians are concerned patients are still unsteady such that they may not want to start patients on a new medication when they’re discharging them. Physicians in rehabilitation units may not prescribe these medications because they feel they have the patients for a short time, so by the time the patient returns to their primary care provider, the patient may have the same mistaken impression the fracture was an accident.



“We’re advocating not to delay treatment for any of these care transitions or because you think they need a BMD test,” Dr. Kiel said. “Just get them treated like they do with heart attacks.”

Finally, follow and reevaluate women and men age 65 years or older who have had a hip or vertebral fracture and are being treated for osteoporosis because it is a life-long chronic condition. This can help reinforce key messages about osteoporosis and associated fractures, identify any barriers to treatment adherence, assess the risk of falls, evaluate the effectiveness of a treatment plan, monitor for adverse effects, and determine whether any changes in treatment should be made, including whether any osteoporosis pharmacotherapy should be changed or discontinued.

Ideally, patients should be managed in the context of a multidisciplinary clinical system that includes case management, such as a fracture liaison service, according to the recommendations.

Besides the fundamental five recommendations, the documents lists another seven that deal with referring patients, prescribing vitamin D, counseling on lifestyle and diet, discussing pharmacotherapy benefits and risks, weighing first-line therapy options, and determining the duration of pharmacotherapy.

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Secondary fractures in older men spike soon after first, but exercise may help

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Older men have a higher risk than women of sustaining secondary fractures within a few years of their first fracture, but moderate physical activity may improve bone strength, potentially reducing their risk of fractures, according to two studies presented at the annual meeting of the American Society for Bone and Mineral Research in Montreal.

Dr. Suzanne N. Morin

The first study, a matched historical cohort of 57,783 people aged 50 or older (40,062 women and 17,721 men) in Manitoba, Canada, found that men had a threefold higher risk of sustaining a secondary major osteoporotic fracture (MOF) within 1 year of a first fracture, compared with healthy controls. The risk for women, by comparison, was 1.8 times higher than in age-matched controls who did not experience a fracture. These risks declined over time but remained elevated even as much as 15-25 years after the index fracture, according to primary investigator Suzanne N. Morin, MD, of the department of medicine at McGill University in Montreal.

“Often, men and clinicians don’t think men have skeletal fragility – everybody thinks it’s a women’s disease,” Dr. Morin said. “It’s true that it’s more frequent in women, but men do have osteoporosis, and often when they have it, they tend to have more serious complications following the fractures.” This includes higher risk of subsequent fractures and higher mortality, she said. “If you see an older gentleman with a fracture, it really should be some kind of an alarm signal.”

Using administrative health care databases, Dr. Morin and her colleagues reviewed records of patients who had an index MOF between 1989 and 2006. They compared rates of subsequent MOFs until 2016 with those of age- and sex-matched controls (n = 165,965), allowing for between 10 and 25 years of follow-up.

Researchers identified 29,694 index MOF cases (11,028 to the wrist, 9,313 to the hip, 5,799 to the humerus, and 3,554 to the spine). The annual crude rate of subsequent MOFs per 1,000 person-years was 18.5 in men (95% confidence interval, 17.3-19.8) and 29.6 in women (95% CI, 28.8-30.4). The cumulative incidence of subsequent MOFs up to 25 years later was higher in cases versus controls for both sexes and across all ages except those over 80.

Hazard ratios for subsequent MOFs were higher in men than women, particularly in the first year following the index fracture and remained very high for men during the first 3 years of follow-up. Across all follow-up years, men who had fractures were 2.5 times more likely to experience a secondary MOF (95% CI, 2.3-2.7) and women who had fractures were 1.6 times more likely to experience a secondary MOF (95% CI, 1.6-1.7), compared with controls.

To prevent fractures, clinicians should consider gait or balance training for older men and women, especially those who already have experienced a fracture, Dr. Morin said. Physicians also should note any medications such as sedatives that put patients at higher risk for falls and consider medications like bisphosphonates to reduce fracture risk. Additionally, they should ensure there are no underlying causes for skeletal fragility, such as severe vitamin D deficiency or a hormonal imbalance, she said.
 

 

 

Physical activity could reduce risk

In a second, unrelated study, researchers found that moderate physical activity may have a modest effect on bone strength in older men, accounting for up to a 20% lower fracture risk, according to Lisa Langsetmo, PhD, primary investigator and a senior research associate at the University of Minnesota, Minneapolis. She and her colleagues studied physical activity and bone strength in 994 older men (mean age 83.9) participating in the Osteoporotic Fractures in Men (MrOS) Study, a longitudinal, observational study of musculoskeletal health in older American men that initially enrolled about 6,000 participants.

Dr. Lisa Langsetmo

Participants wore armband activity monitors for 5 days during their year-7 and year-14 assessments; investigators averaged their physical activity over the two time points and used armband data along with factors like height, weight, and smoking status to estimate total energy expenditure (TEE), total steps per day, and level of activity, from sedentary to at least moderate. The men also underwent bone microarchitecture assessments of the distal radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT), a technique that produces detailed pictures of the bones. Investigators used mathematical models to predict failure load, or the force required to break a bone – a predictor of osteoporotic fractures in men. They also computed total, cortical, and trabecular volumetric bone mineral density (BMD).

Overall, researchers found that time spent doing at least moderate activity versus time spent in sedentary activity was related to better bone strength at both sites, whereas time spent in light activity was not. The results suggest that at least moderate physical activity such as vigorous walking averaged over a period of time may have a modest effect on bone strength among older men, Dr. Langsetmo said.

“This is important for older men,” she said. “They may not be able to jog any more but they may be able to do more moderate activity.” Physicians should ask older male patients about their activity levels and any barriers to activity, or consider a referral to a physical therapist to keep them active, she said.

Higher TEE, step count, and peak 30-minute cadence (P30MC), a measure of vigorous activity, were each associated with higher failure load of the distal radius (effect size 0.08-0.13) but not higher volumetric or compartment-specific BMD. These measures also were associated with higher failure load of the distal tibia (effect size 0.19-0.21), higher volumetric BMD (effect size 0.08-0.15), higher trabecular BMD (effect size 0.07-0.11), and higher cortical BMD (0.09-0.13).

The first study was funded internally; Manitoba Health provided the data. The second study was funded by the National Institutes of Health. Dr. Morin and Dr. Langsetmo reported no relevant financial disclosures.

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Older men have a higher risk than women of sustaining secondary fractures within a few years of their first fracture, but moderate physical activity may improve bone strength, potentially reducing their risk of fractures, according to two studies presented at the annual meeting of the American Society for Bone and Mineral Research in Montreal.

Dr. Suzanne N. Morin

The first study, a matched historical cohort of 57,783 people aged 50 or older (40,062 women and 17,721 men) in Manitoba, Canada, found that men had a threefold higher risk of sustaining a secondary major osteoporotic fracture (MOF) within 1 year of a first fracture, compared with healthy controls. The risk for women, by comparison, was 1.8 times higher than in age-matched controls who did not experience a fracture. These risks declined over time but remained elevated even as much as 15-25 years after the index fracture, according to primary investigator Suzanne N. Morin, MD, of the department of medicine at McGill University in Montreal.

“Often, men and clinicians don’t think men have skeletal fragility – everybody thinks it’s a women’s disease,” Dr. Morin said. “It’s true that it’s more frequent in women, but men do have osteoporosis, and often when they have it, they tend to have more serious complications following the fractures.” This includes higher risk of subsequent fractures and higher mortality, she said. “If you see an older gentleman with a fracture, it really should be some kind of an alarm signal.”

Using administrative health care databases, Dr. Morin and her colleagues reviewed records of patients who had an index MOF between 1989 and 2006. They compared rates of subsequent MOFs until 2016 with those of age- and sex-matched controls (n = 165,965), allowing for between 10 and 25 years of follow-up.

Researchers identified 29,694 index MOF cases (11,028 to the wrist, 9,313 to the hip, 5,799 to the humerus, and 3,554 to the spine). The annual crude rate of subsequent MOFs per 1,000 person-years was 18.5 in men (95% confidence interval, 17.3-19.8) and 29.6 in women (95% CI, 28.8-30.4). The cumulative incidence of subsequent MOFs up to 25 years later was higher in cases versus controls for both sexes and across all ages except those over 80.

Hazard ratios for subsequent MOFs were higher in men than women, particularly in the first year following the index fracture and remained very high for men during the first 3 years of follow-up. Across all follow-up years, men who had fractures were 2.5 times more likely to experience a secondary MOF (95% CI, 2.3-2.7) and women who had fractures were 1.6 times more likely to experience a secondary MOF (95% CI, 1.6-1.7), compared with controls.

To prevent fractures, clinicians should consider gait or balance training for older men and women, especially those who already have experienced a fracture, Dr. Morin said. Physicians also should note any medications such as sedatives that put patients at higher risk for falls and consider medications like bisphosphonates to reduce fracture risk. Additionally, they should ensure there are no underlying causes for skeletal fragility, such as severe vitamin D deficiency or a hormonal imbalance, she said.
 

 

 

Physical activity could reduce risk

In a second, unrelated study, researchers found that moderate physical activity may have a modest effect on bone strength in older men, accounting for up to a 20% lower fracture risk, according to Lisa Langsetmo, PhD, primary investigator and a senior research associate at the University of Minnesota, Minneapolis. She and her colleagues studied physical activity and bone strength in 994 older men (mean age 83.9) participating in the Osteoporotic Fractures in Men (MrOS) Study, a longitudinal, observational study of musculoskeletal health in older American men that initially enrolled about 6,000 participants.

Dr. Lisa Langsetmo

Participants wore armband activity monitors for 5 days during their year-7 and year-14 assessments; investigators averaged their physical activity over the two time points and used armband data along with factors like height, weight, and smoking status to estimate total energy expenditure (TEE), total steps per day, and level of activity, from sedentary to at least moderate. The men also underwent bone microarchitecture assessments of the distal radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT), a technique that produces detailed pictures of the bones. Investigators used mathematical models to predict failure load, or the force required to break a bone – a predictor of osteoporotic fractures in men. They also computed total, cortical, and trabecular volumetric bone mineral density (BMD).

Overall, researchers found that time spent doing at least moderate activity versus time spent in sedentary activity was related to better bone strength at both sites, whereas time spent in light activity was not. The results suggest that at least moderate physical activity such as vigorous walking averaged over a period of time may have a modest effect on bone strength among older men, Dr. Langsetmo said.

“This is important for older men,” she said. “They may not be able to jog any more but they may be able to do more moderate activity.” Physicians should ask older male patients about their activity levels and any barriers to activity, or consider a referral to a physical therapist to keep them active, she said.

Higher TEE, step count, and peak 30-minute cadence (P30MC), a measure of vigorous activity, were each associated with higher failure load of the distal radius (effect size 0.08-0.13) but not higher volumetric or compartment-specific BMD. These measures also were associated with higher failure load of the distal tibia (effect size 0.19-0.21), higher volumetric BMD (effect size 0.08-0.15), higher trabecular BMD (effect size 0.07-0.11), and higher cortical BMD (0.09-0.13).

The first study was funded internally; Manitoba Health provided the data. The second study was funded by the National Institutes of Health. Dr. Morin and Dr. Langsetmo reported no relevant financial disclosures.

Older men have a higher risk than women of sustaining secondary fractures within a few years of their first fracture, but moderate physical activity may improve bone strength, potentially reducing their risk of fractures, according to two studies presented at the annual meeting of the American Society for Bone and Mineral Research in Montreal.

Dr. Suzanne N. Morin

The first study, a matched historical cohort of 57,783 people aged 50 or older (40,062 women and 17,721 men) in Manitoba, Canada, found that men had a threefold higher risk of sustaining a secondary major osteoporotic fracture (MOF) within 1 year of a first fracture, compared with healthy controls. The risk for women, by comparison, was 1.8 times higher than in age-matched controls who did not experience a fracture. These risks declined over time but remained elevated even as much as 15-25 years after the index fracture, according to primary investigator Suzanne N. Morin, MD, of the department of medicine at McGill University in Montreal.

“Often, men and clinicians don’t think men have skeletal fragility – everybody thinks it’s a women’s disease,” Dr. Morin said. “It’s true that it’s more frequent in women, but men do have osteoporosis, and often when they have it, they tend to have more serious complications following the fractures.” This includes higher risk of subsequent fractures and higher mortality, she said. “If you see an older gentleman with a fracture, it really should be some kind of an alarm signal.”

Using administrative health care databases, Dr. Morin and her colleagues reviewed records of patients who had an index MOF between 1989 and 2006. They compared rates of subsequent MOFs until 2016 with those of age- and sex-matched controls (n = 165,965), allowing for between 10 and 25 years of follow-up.

Researchers identified 29,694 index MOF cases (11,028 to the wrist, 9,313 to the hip, 5,799 to the humerus, and 3,554 to the spine). The annual crude rate of subsequent MOFs per 1,000 person-years was 18.5 in men (95% confidence interval, 17.3-19.8) and 29.6 in women (95% CI, 28.8-30.4). The cumulative incidence of subsequent MOFs up to 25 years later was higher in cases versus controls for both sexes and across all ages except those over 80.

Hazard ratios for subsequent MOFs were higher in men than women, particularly in the first year following the index fracture and remained very high for men during the first 3 years of follow-up. Across all follow-up years, men who had fractures were 2.5 times more likely to experience a secondary MOF (95% CI, 2.3-2.7) and women who had fractures were 1.6 times more likely to experience a secondary MOF (95% CI, 1.6-1.7), compared with controls.

To prevent fractures, clinicians should consider gait or balance training for older men and women, especially those who already have experienced a fracture, Dr. Morin said. Physicians also should note any medications such as sedatives that put patients at higher risk for falls and consider medications like bisphosphonates to reduce fracture risk. Additionally, they should ensure there are no underlying causes for skeletal fragility, such as severe vitamin D deficiency or a hormonal imbalance, she said.
 

 

 

Physical activity could reduce risk

In a second, unrelated study, researchers found that moderate physical activity may have a modest effect on bone strength in older men, accounting for up to a 20% lower fracture risk, according to Lisa Langsetmo, PhD, primary investigator and a senior research associate at the University of Minnesota, Minneapolis. She and her colleagues studied physical activity and bone strength in 994 older men (mean age 83.9) participating in the Osteoporotic Fractures in Men (MrOS) Study, a longitudinal, observational study of musculoskeletal health in older American men that initially enrolled about 6,000 participants.

Dr. Lisa Langsetmo

Participants wore armband activity monitors for 5 days during their year-7 and year-14 assessments; investigators averaged their physical activity over the two time points and used armband data along with factors like height, weight, and smoking status to estimate total energy expenditure (TEE), total steps per day, and level of activity, from sedentary to at least moderate. The men also underwent bone microarchitecture assessments of the distal radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT), a technique that produces detailed pictures of the bones. Investigators used mathematical models to predict failure load, or the force required to break a bone – a predictor of osteoporotic fractures in men. They also computed total, cortical, and trabecular volumetric bone mineral density (BMD).

Overall, researchers found that time spent doing at least moderate activity versus time spent in sedentary activity was related to better bone strength at both sites, whereas time spent in light activity was not. The results suggest that at least moderate physical activity such as vigorous walking averaged over a period of time may have a modest effect on bone strength among older men, Dr. Langsetmo said.

“This is important for older men,” she said. “They may not be able to jog any more but they may be able to do more moderate activity.” Physicians should ask older male patients about their activity levels and any barriers to activity, or consider a referral to a physical therapist to keep them active, she said.

Higher TEE, step count, and peak 30-minute cadence (P30MC), a measure of vigorous activity, were each associated with higher failure load of the distal radius (effect size 0.08-0.13) but not higher volumetric or compartment-specific BMD. These measures also were associated with higher failure load of the distal tibia (effect size 0.19-0.21), higher volumetric BMD (effect size 0.08-0.15), higher trabecular BMD (effect size 0.07-0.11), and higher cortical BMD (0.09-0.13).

The first study was funded internally; Manitoba Health provided the data. The second study was funded by the National Institutes of Health. Dr. Morin and Dr. Langsetmo reported no relevant financial disclosures.

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Zoledronate reduces fracture risk in elderly women with osteopenia

Look beyond bone mineral density
Article Type
Changed
Fri, 01/18/2019 - 17:59

Intravenous zoledronate therapy given once every 18 months, with minimal use of calcium supplements, was associated with an increase in bone mass and significantly reduced the risk of vertebral and nonvertebral fractures in postmenopausal women, compared with a placebo, based on data from a 6-year trial of 2,000 ambulatory women aged 65 and older with osteopenia.

The findings were presented at the annual meeting of the American Society for Bone and Mineral Research and published simultaneously in the New England Journal of Medicine.

Bisphosphonates have been shown to prevent fractures in osteoporosis patients, but their effectiveness has not been well studied in patients with osteopenia alone, noted Ian R. Reid, MD, of the University of Auckland, New Zealand, and his colleagues. “Many patients at high risk for fracture do not have T scores of less than –2.5 but rather have osteopenia in combination with other risk factors such as age.”

The researchers randomized 2,000 women aged 65 years and older with osteopenia to receive four infusions of zoledronate or a saline placebo every 18 months. A dietary intake of 1 g of calcium per day was advised, but calcium supplements were not provided; 2% of the women took supplements. Those not taking vitamin D before the trial were given a single 2.5-mg dose of cholecalciferol and a monthly 1.25-mg dose during the trial. Trial participants were followed for 6 years.

Courtesy Dr. Ian Reid
Dr. Ian Reid


Demographic characteristics were similar between the groups, and their T scores ranged from –1.0 to –2.5 at the total hip or femoral neck. The primary endpoint was the time to a first fragility fracture, defined as nonvertebral fractures and vertebral fractures confirmed by radiography.

Overall, 122 women in the zoledronate group experienced 131 fractures, and 190 women in the placebo group experienced 227 fractures (hazard ratio 0.63, P less than .001). Differences in bone mineral density between the two groups were observed by 3 years.

The number needed to treat to prevent a single fragility fracture was 10; the number needed to treat to prevent a symptomatic fracture was 20.

The findings were consistent with data on reduced fracture risk in osteoporosis patients treated with zoledronate. The study differed from other similar trials in its use of 18-month dosing intervals and low use of calcium supplements (2%), they noted.

The data were limited by the older age of the study individuals, so the results should not be extrapolated to younger women or individuals with normal bone mineral density, the researchers said. The results suggest that annual zoledronate dosing may be unnecessary, but further research is needed to explore longer dose intervals.

Dr. Reid disclosed grants from Health Research Council of New Zealand, nonfinancial support from Novartis during the study, and financial relationships with Amgen, Merck, Novartis, and Eli Lilly unrelated to the study.

SOURCE: Reid I et al. N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMoa1808082.

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This trial reminds us that risk assessment and treatment decisions go well beyond bone mineral density and should focus particularly on age and a history of fractures.

Osteoporosis is defined as a T score below –2.5, but several longitudinal studies have shown that most fractures among postmenopausal women occur in those with osteopenia. Further, alendronate therapy did not reduce the risk of fractures among women with osteopenia which contributed to a treatment gap for women with osteopenic T scores but strong risk factors for an osteoporotic fracture.

In the current study, zoledronate was associated with a greater increase in bone mass and a lower fracture risk compared with placebo. Plus, zoledronate prevented fractures among women with an average T score of –1.27 at the total hip and –1.64 at the femoral neck. The positive data, coupled with the low number of adverse events over the 6-year study period, support the addition of zoledronate to the treatment options for osteoporosis. However, the average age of the patients in the current study was 3.5 years older than that of patients in previous alendronate studies. As a result, the findings should not be extrapolated to postmenopausal women under the age of 65 years with osteopenia.

Clifford J. Rosen, MD, is affiliated with the Maine Medical Center Research Institute, Scarborough, and serves as an associate editor at the New England Journal of Medicine. He made his remarks in an accompanying editorial (N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMe1812434). Dr. Rosen had no relevant financial conflicts to disclose.

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Body

 

This trial reminds us that risk assessment and treatment decisions go well beyond bone mineral density and should focus particularly on age and a history of fractures.

Osteoporosis is defined as a T score below –2.5, but several longitudinal studies have shown that most fractures among postmenopausal women occur in those with osteopenia. Further, alendronate therapy did not reduce the risk of fractures among women with osteopenia which contributed to a treatment gap for women with osteopenic T scores but strong risk factors for an osteoporotic fracture.

In the current study, zoledronate was associated with a greater increase in bone mass and a lower fracture risk compared with placebo. Plus, zoledronate prevented fractures among women with an average T score of –1.27 at the total hip and –1.64 at the femoral neck. The positive data, coupled with the low number of adverse events over the 6-year study period, support the addition of zoledronate to the treatment options for osteoporosis. However, the average age of the patients in the current study was 3.5 years older than that of patients in previous alendronate studies. As a result, the findings should not be extrapolated to postmenopausal women under the age of 65 years with osteopenia.

Clifford J. Rosen, MD, is affiliated with the Maine Medical Center Research Institute, Scarborough, and serves as an associate editor at the New England Journal of Medicine. He made his remarks in an accompanying editorial (N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMe1812434). Dr. Rosen had no relevant financial conflicts to disclose.

Body

 

This trial reminds us that risk assessment and treatment decisions go well beyond bone mineral density and should focus particularly on age and a history of fractures.

Osteoporosis is defined as a T score below –2.5, but several longitudinal studies have shown that most fractures among postmenopausal women occur in those with osteopenia. Further, alendronate therapy did not reduce the risk of fractures among women with osteopenia which contributed to a treatment gap for women with osteopenic T scores but strong risk factors for an osteoporotic fracture.

In the current study, zoledronate was associated with a greater increase in bone mass and a lower fracture risk compared with placebo. Plus, zoledronate prevented fractures among women with an average T score of –1.27 at the total hip and –1.64 at the femoral neck. The positive data, coupled with the low number of adverse events over the 6-year study period, support the addition of zoledronate to the treatment options for osteoporosis. However, the average age of the patients in the current study was 3.5 years older than that of patients in previous alendronate studies. As a result, the findings should not be extrapolated to postmenopausal women under the age of 65 years with osteopenia.

Clifford J. Rosen, MD, is affiliated with the Maine Medical Center Research Institute, Scarborough, and serves as an associate editor at the New England Journal of Medicine. He made his remarks in an accompanying editorial (N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMe1812434). Dr. Rosen had no relevant financial conflicts to disclose.

Title
Look beyond bone mineral density
Look beyond bone mineral density

Intravenous zoledronate therapy given once every 18 months, with minimal use of calcium supplements, was associated with an increase in bone mass and significantly reduced the risk of vertebral and nonvertebral fractures in postmenopausal women, compared with a placebo, based on data from a 6-year trial of 2,000 ambulatory women aged 65 and older with osteopenia.

The findings were presented at the annual meeting of the American Society for Bone and Mineral Research and published simultaneously in the New England Journal of Medicine.

Bisphosphonates have been shown to prevent fractures in osteoporosis patients, but their effectiveness has not been well studied in patients with osteopenia alone, noted Ian R. Reid, MD, of the University of Auckland, New Zealand, and his colleagues. “Many patients at high risk for fracture do not have T scores of less than –2.5 but rather have osteopenia in combination with other risk factors such as age.”

The researchers randomized 2,000 women aged 65 years and older with osteopenia to receive four infusions of zoledronate or a saline placebo every 18 months. A dietary intake of 1 g of calcium per day was advised, but calcium supplements were not provided; 2% of the women took supplements. Those not taking vitamin D before the trial were given a single 2.5-mg dose of cholecalciferol and a monthly 1.25-mg dose during the trial. Trial participants were followed for 6 years.

Courtesy Dr. Ian Reid
Dr. Ian Reid


Demographic characteristics were similar between the groups, and their T scores ranged from –1.0 to –2.5 at the total hip or femoral neck. The primary endpoint was the time to a first fragility fracture, defined as nonvertebral fractures and vertebral fractures confirmed by radiography.

Overall, 122 women in the zoledronate group experienced 131 fractures, and 190 women in the placebo group experienced 227 fractures (hazard ratio 0.63, P less than .001). Differences in bone mineral density between the two groups were observed by 3 years.

The number needed to treat to prevent a single fragility fracture was 10; the number needed to treat to prevent a symptomatic fracture was 20.

The findings were consistent with data on reduced fracture risk in osteoporosis patients treated with zoledronate. The study differed from other similar trials in its use of 18-month dosing intervals and low use of calcium supplements (2%), they noted.

The data were limited by the older age of the study individuals, so the results should not be extrapolated to younger women or individuals with normal bone mineral density, the researchers said. The results suggest that annual zoledronate dosing may be unnecessary, but further research is needed to explore longer dose intervals.

Dr. Reid disclosed grants from Health Research Council of New Zealand, nonfinancial support from Novartis during the study, and financial relationships with Amgen, Merck, Novartis, and Eli Lilly unrelated to the study.

SOURCE: Reid I et al. N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMoa1808082.

Intravenous zoledronate therapy given once every 18 months, with minimal use of calcium supplements, was associated with an increase in bone mass and significantly reduced the risk of vertebral and nonvertebral fractures in postmenopausal women, compared with a placebo, based on data from a 6-year trial of 2,000 ambulatory women aged 65 and older with osteopenia.

The findings were presented at the annual meeting of the American Society for Bone and Mineral Research and published simultaneously in the New England Journal of Medicine.

Bisphosphonates have been shown to prevent fractures in osteoporosis patients, but their effectiveness has not been well studied in patients with osteopenia alone, noted Ian R. Reid, MD, of the University of Auckland, New Zealand, and his colleagues. “Many patients at high risk for fracture do not have T scores of less than –2.5 but rather have osteopenia in combination with other risk factors such as age.”

The researchers randomized 2,000 women aged 65 years and older with osteopenia to receive four infusions of zoledronate or a saline placebo every 18 months. A dietary intake of 1 g of calcium per day was advised, but calcium supplements were not provided; 2% of the women took supplements. Those not taking vitamin D before the trial were given a single 2.5-mg dose of cholecalciferol and a monthly 1.25-mg dose during the trial. Trial participants were followed for 6 years.

Courtesy Dr. Ian Reid
Dr. Ian Reid


Demographic characteristics were similar between the groups, and their T scores ranged from –1.0 to –2.5 at the total hip or femoral neck. The primary endpoint was the time to a first fragility fracture, defined as nonvertebral fractures and vertebral fractures confirmed by radiography.

Overall, 122 women in the zoledronate group experienced 131 fractures, and 190 women in the placebo group experienced 227 fractures (hazard ratio 0.63, P less than .001). Differences in bone mineral density between the two groups were observed by 3 years.

The number needed to treat to prevent a single fragility fracture was 10; the number needed to treat to prevent a symptomatic fracture was 20.

The findings were consistent with data on reduced fracture risk in osteoporosis patients treated with zoledronate. The study differed from other similar trials in its use of 18-month dosing intervals and low use of calcium supplements (2%), they noted.

The data were limited by the older age of the study individuals, so the results should not be extrapolated to younger women or individuals with normal bone mineral density, the researchers said. The results suggest that annual zoledronate dosing may be unnecessary, but further research is needed to explore longer dose intervals.

Dr. Reid disclosed grants from Health Research Council of New Zealand, nonfinancial support from Novartis during the study, and financial relationships with Amgen, Merck, Novartis, and Eli Lilly unrelated to the study.

SOURCE: Reid I et al. N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMoa1808082.

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Key clinical point: Vertebral and nonvertebral fracture risk was significantly lower in osteopenic women who received zoledronate, compared with those who received a placebo.

Major finding: Fragility fractures occurred in 122 women in a zoledronate group and 190 women in a placebo group. The number needed to treat to prevent a single fragility fracture was 10; the number needed to treat to prevent a symptomatic fracture was 20.

Study details: A 6-year randomized, double-blind trial of 2,000 women aged 65 years and older with osteopenia.

Disclosures: The study was supported in part by grants from the Health Research Council of New Zealand; Novartis provided the medication. Dr. Reid disclosed grants from Health Research Council of New Zealand, nonfinancial support from Novartis during the study, and financial relationships with Amgen, Merck, Novartis, and Eli Lilly unrelated to the study.

Source: Reid I et al. N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMoa1808082.

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