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A ‘one-stop shop’: New guidance on hormones and aging
The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.
The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.
“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.
During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”
The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men, diabetes treatment goals in older adults, distinguishing between age-associated changes in thyroid function and early hypothyroidism, and vitamin D supplementation in older adults.
“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.
Not designed to be read all at once
In the menopause section, for example, one “key point” is that menopausal symptoms are common, vary in degree and bother, and can be effectively treated with a variety of therapies proven effective in randomized clinical trials. Another key point is that menopausal hormone therapy is safest for women who are younger than 60 years and less than 10 years since starting menopause.
“It’s almost 20 years since the original Women’s Health Initiative, and that led to an incredible falloff of prescribing hormone therapy and a falloff in teaching of our students, residents, fellows, and practitioners about [menopausal] hormone therapy. ... Hopefully, by issuing this kind of aging statement it gets people to read, think, and learn more. And, hopefully, we can improve the education of physicians. ... Menopause is a universal experience. Clinicians should know about it,” noted Dr. Stuenkel, who chaired the menopause section writing panel.
In the type 2 diabetes section, in the bullet points it is noted that oral glucose tolerance testing may reveal abnormal glucose status in older adults that are not picked up with hemoglobin A1c or fasting glucose levels and that glycemic targets should be individualized.
Asked to comment on the statement, Michele Bellantoni, MD, said: “This was a huge undertaking because there are so many areas of expertise here. I thought they did a very good job of reviewing the literature and showing each of the different hormonal axes. ... It’s a good go-to review.”
“I thought it was a very good attempt to catalog and provide opportunities for policy, and particularly at [the National Institutes of Health], as they look at funding to show where are these gaps and to support appropriate research. I think the most important aspect to come of this is identifying research gaps for funding opportunities. I very much support that,” noted Dr. Bellantoni, who is clinical director of the division of geriatric medicine at Johns Hopkins University, Baltimore.
However, she also said that the 40-page document might be a bit much for busy clinicians, despite the bullet points at the end of each section.
“I would love to see an editorial that puts into perspective the take-home messages or a subsequent article that distills this into every day practice of care of older adults, both preventative and treatment care. ... I think that would be so useful.”
During the briefing, Dr. Cappola noted that the document need not be read all at once.
“It ended up being a large document, but you should not be intimidated by it because each section is only about 2,000 words. So, it’s really a kind of one-stop shop to be able to look across all these axes at once. We also wanted people to think about the common themes that occur across all these axes when considering what’s going on right now and for future research,” she said.
Dr. Stuenkel, Dr. Cappola, and Dr. Bellantoni reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.
The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.
“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.
During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”
The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men, diabetes treatment goals in older adults, distinguishing between age-associated changes in thyroid function and early hypothyroidism, and vitamin D supplementation in older adults.
“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.
Not designed to be read all at once
In the menopause section, for example, one “key point” is that menopausal symptoms are common, vary in degree and bother, and can be effectively treated with a variety of therapies proven effective in randomized clinical trials. Another key point is that menopausal hormone therapy is safest for women who are younger than 60 years and less than 10 years since starting menopause.
“It’s almost 20 years since the original Women’s Health Initiative, and that led to an incredible falloff of prescribing hormone therapy and a falloff in teaching of our students, residents, fellows, and practitioners about [menopausal] hormone therapy. ... Hopefully, by issuing this kind of aging statement it gets people to read, think, and learn more. And, hopefully, we can improve the education of physicians. ... Menopause is a universal experience. Clinicians should know about it,” noted Dr. Stuenkel, who chaired the menopause section writing panel.
In the type 2 diabetes section, in the bullet points it is noted that oral glucose tolerance testing may reveal abnormal glucose status in older adults that are not picked up with hemoglobin A1c or fasting glucose levels and that glycemic targets should be individualized.
Asked to comment on the statement, Michele Bellantoni, MD, said: “This was a huge undertaking because there are so many areas of expertise here. I thought they did a very good job of reviewing the literature and showing each of the different hormonal axes. ... It’s a good go-to review.”
“I thought it was a very good attempt to catalog and provide opportunities for policy, and particularly at [the National Institutes of Health], as they look at funding to show where are these gaps and to support appropriate research. I think the most important aspect to come of this is identifying research gaps for funding opportunities. I very much support that,” noted Dr. Bellantoni, who is clinical director of the division of geriatric medicine at Johns Hopkins University, Baltimore.
However, she also said that the 40-page document might be a bit much for busy clinicians, despite the bullet points at the end of each section.
“I would love to see an editorial that puts into perspective the take-home messages or a subsequent article that distills this into every day practice of care of older adults, both preventative and treatment care. ... I think that would be so useful.”
During the briefing, Dr. Cappola noted that the document need not be read all at once.
“It ended up being a large document, but you should not be intimidated by it because each section is only about 2,000 words. So, it’s really a kind of one-stop shop to be able to look across all these axes at once. We also wanted people to think about the common themes that occur across all these axes when considering what’s going on right now and for future research,” she said.
Dr. Stuenkel, Dr. Cappola, and Dr. Bellantoni reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.
The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.
“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.
During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”
The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men, diabetes treatment goals in older adults, distinguishing between age-associated changes in thyroid function and early hypothyroidism, and vitamin D supplementation in older adults.
“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.
Not designed to be read all at once
In the menopause section, for example, one “key point” is that menopausal symptoms are common, vary in degree and bother, and can be effectively treated with a variety of therapies proven effective in randomized clinical trials. Another key point is that menopausal hormone therapy is safest for women who are younger than 60 years and less than 10 years since starting menopause.
“It’s almost 20 years since the original Women’s Health Initiative, and that led to an incredible falloff of prescribing hormone therapy and a falloff in teaching of our students, residents, fellows, and practitioners about [menopausal] hormone therapy. ... Hopefully, by issuing this kind of aging statement it gets people to read, think, and learn more. And, hopefully, we can improve the education of physicians. ... Menopause is a universal experience. Clinicians should know about it,” noted Dr. Stuenkel, who chaired the menopause section writing panel.
In the type 2 diabetes section, in the bullet points it is noted that oral glucose tolerance testing may reveal abnormal glucose status in older adults that are not picked up with hemoglobin A1c or fasting glucose levels and that glycemic targets should be individualized.
Asked to comment on the statement, Michele Bellantoni, MD, said: “This was a huge undertaking because there are so many areas of expertise here. I thought they did a very good job of reviewing the literature and showing each of the different hormonal axes. ... It’s a good go-to review.”
“I thought it was a very good attempt to catalog and provide opportunities for policy, and particularly at [the National Institutes of Health], as they look at funding to show where are these gaps and to support appropriate research. I think the most important aspect to come of this is identifying research gaps for funding opportunities. I very much support that,” noted Dr. Bellantoni, who is clinical director of the division of geriatric medicine at Johns Hopkins University, Baltimore.
However, she also said that the 40-page document might be a bit much for busy clinicians, despite the bullet points at the end of each section.
“I would love to see an editorial that puts into perspective the take-home messages or a subsequent article that distills this into every day practice of care of older adults, both preventative and treatment care. ... I think that would be so useful.”
During the briefing, Dr. Cappola noted that the document need not be read all at once.
“It ended up being a large document, but you should not be intimidated by it because each section is only about 2,000 words. So, it’s really a kind of one-stop shop to be able to look across all these axes at once. We also wanted people to think about the common themes that occur across all these axes when considering what’s going on right now and for future research,” she said.
Dr. Stuenkel, Dr. Cappola, and Dr. Bellantoni reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ENDO 2023
Vitamin D deficiency: Can we improve diagnosis?
CHICAGO – , new research suggests.
The study supports previous data suggesting that a ratio cut-off of greater than 100 is associated with the development of secondary hyperparathyroidism and the need for correction with supplementation, while a level greater than 50 suggests mild to moderate deficiency, Zhinous Shahidzadeh Yazdi, MD, noted in a poster presented at the annual meeting of the Endocrine Society
Current Endocrine Society guidelines published in 2011 advise measurement of plasma circulating 25(OH)D levels to evaluate vitamin D status in patients at risk for deficiency, defined as < 20 ng/mL (50 nmol/L). Revised guidelines are due out in early 2024.
“We don’t think measuring 25 hydroxy D is optimal because of the impact of vitamin D binding protein,” Dr. Yazdi said in an interview.
“Over 99% of all metabolites are bound to vitamin D binding protein, but only the free fraction is biologically active. By measuring total plasma 25(OH)D – as we do right now in clinic – we cannot account for the impact of vitamin D binding proteins, which vary by threefold across the population,” she added.
Thus, the total 25(OH)D deficiency cut-off of < 20 mg/mL currently recommended by the Endocrine Society may signal clinically significant vitamin D deficiency in one person but not another, noted Dr. Yazdi, a postdoctoral fellow at the University of Maryland, Baltimore.
Directly measuring binding protein or the free fraction would be ideal, but “there aren’t good commercial assays for those, and it’s more difficult to do. So, as an alternative, the vitamin D metabolite ratios implicitly adjust for individual differences in vitamin D binding protein,” she explained.
The ratio that Dr. Yazdi and colleagues propose to measure is that of the vitamin D metabolites 1,25(OH)2D/24,25 (OH)2D (shortened to 1,25D/24,25D), which they say reflect the body’s homeostatic response to vitamin D levels, and which rises in the setting of deficiency. It is a measurement > 100 in this ratio that they believe means the patient should receive vitamin D supplementation.
Controversial topic, ratio proposal is “very early in the game”
The issue of vitamin D deficiency has long generated controversy, particularly since publication of findings from the VITAL study in 2022, which showed vitamin D supplements did not significantly reduce the risk of fracture among adults in midlife and older compared with placebo.
According to the senior author of the new study, Simeon I. Taylor, MD, professor of medicine at the University of Maryland, what still remains controversial after VITAL is the question: “How can you identify people who have sufficiently bad vitamin D deficiency that it’s adversely impacting their bones?”
He added that there is a suggestion that small subpopulations in VITAL really did benefit from vitamin D supplementation, but the study “wasn’t designed to look at that.”
Indeed, the authors of an editorial accompanying the publication of the VITAL study said the findings mean there is no justification for measuring 25(OH)D in the general population or for treating to a target level.
Asked to comment on Dr. Yazdi and colleagues’ ratio proposal for diagnosing vitamin D deficiency, the coauthor of the VITAL study editorial, Clifford J. Rosen, MD, said in an interview: “I do think it’s important to point out that changes in the vitamin D binding protein can have a significant impact on the level of 25 [OH] D ... People should recognize that.”
And, Dr. Rosen noted, “I like the idea that the ... [ratio] is a measure of what’s happening in the body in response to vitamin D stores. So, when you supplement, it comes back up ... In certain individuals at high risk for fractures, for example, you might want to consider a more extensive workup like they’re suggesting.”
However, Dr. Rosen, of the Rosen Musculoskeletal Laboratory at Maine Medical Center Research Institute, Scarborough, added: “If the 25[OH]D level is below 20 [ng/mL] you’re going to treat regardless. When we think about sensitivity, a 25[OH]D level less than 20 [ng/mL] is a good screen ... Those individuals need to be treated, especially if they have low bone mass or fractures.”
To validate the ratio for clinical use, Dr. Rosen said, larger numbers of individuals would need to be evaluated. Moreover, “you’d need to run a standard of vitamin D binding protein by mass spectrometry versus their assumed method using ratios. Ratios are always a little tricky to interpret. So, I think this is very early in the game.”
And measuring the ratio of 1,25D/24,25D “is quite expensive,” he added.
He also pointed out that “calcium intake is really critical. You can have a [25(OH)D] level of 18 ng/mL and not have any of those secondary changes because [you’re] taking adequate calcium ... So, that always is a consideration that has to be worked into the evaluation.”
Same 25(OH)D, different risk level
In their poster, Dr. Yazdi and colleagues explain that to assess vitamin D status “one needs to understand regulation of vitamin D metabolism.” 25(OH)D undergoes two alternative fates: 1α-hydroxylation in the kidney, generating 1,25D (the biologically active form) or 24-hydroxylation leading to 24,25D (a biologically inactive metabolite).
For their study, they analyzed pilot data from 11 otherwise healthy individuals who had total baseline plasma 25(OH)D levels < 20 ng/mL, and compared 25(OH)D, 1,25D, 24,25D, and parathyroid hormone before versus after treating them with vitamin D3 supplementation of 50,000 IU per week for 4-6 weeks, aiming for a total 25D level above 30 ng/mL.
They then modeled how the body maintains 1,25D in a normal range and calculated/compared two vitamin D metabolite ratios in vitamin D deficient versus sufficient states: 25(OH)D/1,25D and 1,25D/24,25D. They then evaluated the applicability of these ratios for assessment of vitamin D status.
They explained that suppression of 24-hydroxylase is the first line of defense to maintain 1,25D levels. Secondary hyperparathyroidism is the second line of defense and occurs in severe vitamin D deficiency when the first line is maximally deployed.
Overall, there was poor correlation between 25[OH]D and 1,25D, “consistent with previous evidence that in mild to moderate vitamin D deficiency, 1,25D is maintained in the normal range, and therefore not a useful index for assessing vitamin D status,” the researchers said in their poster.
Hence, they said, the need to add the ratio of 1,25D/24,25D.
They presented a comparison of two study participants: one with a baseline 25[OH]D of 12.3 ng/mL, the other of 11.7 ng/mL. Although both would therefore be classified as deficient according to current guidelines, their 1,25D/24,25D ratios were 20 and 110, respectively.
In the first participant, the parathyroid hormone response to vitamin D supplementation was negligible, at +5%, compared with a dramatic 34% drop in the second participant.
“We think only the one with very high 1,25D/24,25D [ratio of 110] and a significant drop in parathyroid hormone after vitamin D supplementation [-34%] was vitamin D deficient,” the researchers said.
However, Dr. Taylor noted: “The diagnostic cut-offs we describe should be viewed as tentative for the time being. Additional research will be required to fully validate the optimal diagnostic criteria.”
Dr. Yazdi and Dr. Rosen have reported no relevant financial relationships. Dr. Taylor has reported being a consultant for Ionis Pharmaceuticals.
A version of this article originally appeared on Medscape.com.
CHICAGO – , new research suggests.
The study supports previous data suggesting that a ratio cut-off of greater than 100 is associated with the development of secondary hyperparathyroidism and the need for correction with supplementation, while a level greater than 50 suggests mild to moderate deficiency, Zhinous Shahidzadeh Yazdi, MD, noted in a poster presented at the annual meeting of the Endocrine Society
Current Endocrine Society guidelines published in 2011 advise measurement of plasma circulating 25(OH)D levels to evaluate vitamin D status in patients at risk for deficiency, defined as < 20 ng/mL (50 nmol/L). Revised guidelines are due out in early 2024.
“We don’t think measuring 25 hydroxy D is optimal because of the impact of vitamin D binding protein,” Dr. Yazdi said in an interview.
“Over 99% of all metabolites are bound to vitamin D binding protein, but only the free fraction is biologically active. By measuring total plasma 25(OH)D – as we do right now in clinic – we cannot account for the impact of vitamin D binding proteins, which vary by threefold across the population,” she added.
Thus, the total 25(OH)D deficiency cut-off of < 20 mg/mL currently recommended by the Endocrine Society may signal clinically significant vitamin D deficiency in one person but not another, noted Dr. Yazdi, a postdoctoral fellow at the University of Maryland, Baltimore.
Directly measuring binding protein or the free fraction would be ideal, but “there aren’t good commercial assays for those, and it’s more difficult to do. So, as an alternative, the vitamin D metabolite ratios implicitly adjust for individual differences in vitamin D binding protein,” she explained.
The ratio that Dr. Yazdi and colleagues propose to measure is that of the vitamin D metabolites 1,25(OH)2D/24,25 (OH)2D (shortened to 1,25D/24,25D), which they say reflect the body’s homeostatic response to vitamin D levels, and which rises in the setting of deficiency. It is a measurement > 100 in this ratio that they believe means the patient should receive vitamin D supplementation.
Controversial topic, ratio proposal is “very early in the game”
The issue of vitamin D deficiency has long generated controversy, particularly since publication of findings from the VITAL study in 2022, which showed vitamin D supplements did not significantly reduce the risk of fracture among adults in midlife and older compared with placebo.
According to the senior author of the new study, Simeon I. Taylor, MD, professor of medicine at the University of Maryland, what still remains controversial after VITAL is the question: “How can you identify people who have sufficiently bad vitamin D deficiency that it’s adversely impacting their bones?”
He added that there is a suggestion that small subpopulations in VITAL really did benefit from vitamin D supplementation, but the study “wasn’t designed to look at that.”
Indeed, the authors of an editorial accompanying the publication of the VITAL study said the findings mean there is no justification for measuring 25(OH)D in the general population or for treating to a target level.
Asked to comment on Dr. Yazdi and colleagues’ ratio proposal for diagnosing vitamin D deficiency, the coauthor of the VITAL study editorial, Clifford J. Rosen, MD, said in an interview: “I do think it’s important to point out that changes in the vitamin D binding protein can have a significant impact on the level of 25 [OH] D ... People should recognize that.”
And, Dr. Rosen noted, “I like the idea that the ... [ratio] is a measure of what’s happening in the body in response to vitamin D stores. So, when you supplement, it comes back up ... In certain individuals at high risk for fractures, for example, you might want to consider a more extensive workup like they’re suggesting.”
However, Dr. Rosen, of the Rosen Musculoskeletal Laboratory at Maine Medical Center Research Institute, Scarborough, added: “If the 25[OH]D level is below 20 [ng/mL] you’re going to treat regardless. When we think about sensitivity, a 25[OH]D level less than 20 [ng/mL] is a good screen ... Those individuals need to be treated, especially if they have low bone mass or fractures.”
To validate the ratio for clinical use, Dr. Rosen said, larger numbers of individuals would need to be evaluated. Moreover, “you’d need to run a standard of vitamin D binding protein by mass spectrometry versus their assumed method using ratios. Ratios are always a little tricky to interpret. So, I think this is very early in the game.”
And measuring the ratio of 1,25D/24,25D “is quite expensive,” he added.
He also pointed out that “calcium intake is really critical. You can have a [25(OH)D] level of 18 ng/mL and not have any of those secondary changes because [you’re] taking adequate calcium ... So, that always is a consideration that has to be worked into the evaluation.”
Same 25(OH)D, different risk level
In their poster, Dr. Yazdi and colleagues explain that to assess vitamin D status “one needs to understand regulation of vitamin D metabolism.” 25(OH)D undergoes two alternative fates: 1α-hydroxylation in the kidney, generating 1,25D (the biologically active form) or 24-hydroxylation leading to 24,25D (a biologically inactive metabolite).
For their study, they analyzed pilot data from 11 otherwise healthy individuals who had total baseline plasma 25(OH)D levels < 20 ng/mL, and compared 25(OH)D, 1,25D, 24,25D, and parathyroid hormone before versus after treating them with vitamin D3 supplementation of 50,000 IU per week for 4-6 weeks, aiming for a total 25D level above 30 ng/mL.
They then modeled how the body maintains 1,25D in a normal range and calculated/compared two vitamin D metabolite ratios in vitamin D deficient versus sufficient states: 25(OH)D/1,25D and 1,25D/24,25D. They then evaluated the applicability of these ratios for assessment of vitamin D status.
They explained that suppression of 24-hydroxylase is the first line of defense to maintain 1,25D levels. Secondary hyperparathyroidism is the second line of defense and occurs in severe vitamin D deficiency when the first line is maximally deployed.
Overall, there was poor correlation between 25[OH]D and 1,25D, “consistent with previous evidence that in mild to moderate vitamin D deficiency, 1,25D is maintained in the normal range, and therefore not a useful index for assessing vitamin D status,” the researchers said in their poster.
Hence, they said, the need to add the ratio of 1,25D/24,25D.
They presented a comparison of two study participants: one with a baseline 25[OH]D of 12.3 ng/mL, the other of 11.7 ng/mL. Although both would therefore be classified as deficient according to current guidelines, their 1,25D/24,25D ratios were 20 and 110, respectively.
In the first participant, the parathyroid hormone response to vitamin D supplementation was negligible, at +5%, compared with a dramatic 34% drop in the second participant.
“We think only the one with very high 1,25D/24,25D [ratio of 110] and a significant drop in parathyroid hormone after vitamin D supplementation [-34%] was vitamin D deficient,” the researchers said.
However, Dr. Taylor noted: “The diagnostic cut-offs we describe should be viewed as tentative for the time being. Additional research will be required to fully validate the optimal diagnostic criteria.”
Dr. Yazdi and Dr. Rosen have reported no relevant financial relationships. Dr. Taylor has reported being a consultant for Ionis Pharmaceuticals.
A version of this article originally appeared on Medscape.com.
CHICAGO – , new research suggests.
The study supports previous data suggesting that a ratio cut-off of greater than 100 is associated with the development of secondary hyperparathyroidism and the need for correction with supplementation, while a level greater than 50 suggests mild to moderate deficiency, Zhinous Shahidzadeh Yazdi, MD, noted in a poster presented at the annual meeting of the Endocrine Society
Current Endocrine Society guidelines published in 2011 advise measurement of plasma circulating 25(OH)D levels to evaluate vitamin D status in patients at risk for deficiency, defined as < 20 ng/mL (50 nmol/L). Revised guidelines are due out in early 2024.
“We don’t think measuring 25 hydroxy D is optimal because of the impact of vitamin D binding protein,” Dr. Yazdi said in an interview.
“Over 99% of all metabolites are bound to vitamin D binding protein, but only the free fraction is biologically active. By measuring total plasma 25(OH)D – as we do right now in clinic – we cannot account for the impact of vitamin D binding proteins, which vary by threefold across the population,” she added.
Thus, the total 25(OH)D deficiency cut-off of < 20 mg/mL currently recommended by the Endocrine Society may signal clinically significant vitamin D deficiency in one person but not another, noted Dr. Yazdi, a postdoctoral fellow at the University of Maryland, Baltimore.
Directly measuring binding protein or the free fraction would be ideal, but “there aren’t good commercial assays for those, and it’s more difficult to do. So, as an alternative, the vitamin D metabolite ratios implicitly adjust for individual differences in vitamin D binding protein,” she explained.
The ratio that Dr. Yazdi and colleagues propose to measure is that of the vitamin D metabolites 1,25(OH)2D/24,25 (OH)2D (shortened to 1,25D/24,25D), which they say reflect the body’s homeostatic response to vitamin D levels, and which rises in the setting of deficiency. It is a measurement > 100 in this ratio that they believe means the patient should receive vitamin D supplementation.
Controversial topic, ratio proposal is “very early in the game”
The issue of vitamin D deficiency has long generated controversy, particularly since publication of findings from the VITAL study in 2022, which showed vitamin D supplements did not significantly reduce the risk of fracture among adults in midlife and older compared with placebo.
According to the senior author of the new study, Simeon I. Taylor, MD, professor of medicine at the University of Maryland, what still remains controversial after VITAL is the question: “How can you identify people who have sufficiently bad vitamin D deficiency that it’s adversely impacting their bones?”
He added that there is a suggestion that small subpopulations in VITAL really did benefit from vitamin D supplementation, but the study “wasn’t designed to look at that.”
Indeed, the authors of an editorial accompanying the publication of the VITAL study said the findings mean there is no justification for measuring 25(OH)D in the general population or for treating to a target level.
Asked to comment on Dr. Yazdi and colleagues’ ratio proposal for diagnosing vitamin D deficiency, the coauthor of the VITAL study editorial, Clifford J. Rosen, MD, said in an interview: “I do think it’s important to point out that changes in the vitamin D binding protein can have a significant impact on the level of 25 [OH] D ... People should recognize that.”
And, Dr. Rosen noted, “I like the idea that the ... [ratio] is a measure of what’s happening in the body in response to vitamin D stores. So, when you supplement, it comes back up ... In certain individuals at high risk for fractures, for example, you might want to consider a more extensive workup like they’re suggesting.”
However, Dr. Rosen, of the Rosen Musculoskeletal Laboratory at Maine Medical Center Research Institute, Scarborough, added: “If the 25[OH]D level is below 20 [ng/mL] you’re going to treat regardless. When we think about sensitivity, a 25[OH]D level less than 20 [ng/mL] is a good screen ... Those individuals need to be treated, especially if they have low bone mass or fractures.”
To validate the ratio for clinical use, Dr. Rosen said, larger numbers of individuals would need to be evaluated. Moreover, “you’d need to run a standard of vitamin D binding protein by mass spectrometry versus their assumed method using ratios. Ratios are always a little tricky to interpret. So, I think this is very early in the game.”
And measuring the ratio of 1,25D/24,25D “is quite expensive,” he added.
He also pointed out that “calcium intake is really critical. You can have a [25(OH)D] level of 18 ng/mL and not have any of those secondary changes because [you’re] taking adequate calcium ... So, that always is a consideration that has to be worked into the evaluation.”
Same 25(OH)D, different risk level
In their poster, Dr. Yazdi and colleagues explain that to assess vitamin D status “one needs to understand regulation of vitamin D metabolism.” 25(OH)D undergoes two alternative fates: 1α-hydroxylation in the kidney, generating 1,25D (the biologically active form) or 24-hydroxylation leading to 24,25D (a biologically inactive metabolite).
For their study, they analyzed pilot data from 11 otherwise healthy individuals who had total baseline plasma 25(OH)D levels < 20 ng/mL, and compared 25(OH)D, 1,25D, 24,25D, and parathyroid hormone before versus after treating them with vitamin D3 supplementation of 50,000 IU per week for 4-6 weeks, aiming for a total 25D level above 30 ng/mL.
They then modeled how the body maintains 1,25D in a normal range and calculated/compared two vitamin D metabolite ratios in vitamin D deficient versus sufficient states: 25(OH)D/1,25D and 1,25D/24,25D. They then evaluated the applicability of these ratios for assessment of vitamin D status.
They explained that suppression of 24-hydroxylase is the first line of defense to maintain 1,25D levels. Secondary hyperparathyroidism is the second line of defense and occurs in severe vitamin D deficiency when the first line is maximally deployed.
Overall, there was poor correlation between 25[OH]D and 1,25D, “consistent with previous evidence that in mild to moderate vitamin D deficiency, 1,25D is maintained in the normal range, and therefore not a useful index for assessing vitamin D status,” the researchers said in their poster.
Hence, they said, the need to add the ratio of 1,25D/24,25D.
They presented a comparison of two study participants: one with a baseline 25[OH]D of 12.3 ng/mL, the other of 11.7 ng/mL. Although both would therefore be classified as deficient according to current guidelines, their 1,25D/24,25D ratios were 20 and 110, respectively.
In the first participant, the parathyroid hormone response to vitamin D supplementation was negligible, at +5%, compared with a dramatic 34% drop in the second participant.
“We think only the one with very high 1,25D/24,25D [ratio of 110] and a significant drop in parathyroid hormone after vitamin D supplementation [-34%] was vitamin D deficient,” the researchers said.
However, Dr. Taylor noted: “The diagnostic cut-offs we describe should be viewed as tentative for the time being. Additional research will be required to fully validate the optimal diagnostic criteria.”
Dr. Yazdi and Dr. Rosen have reported no relevant financial relationships. Dr. Taylor has reported being a consultant for Ionis Pharmaceuticals.
A version of this article originally appeared on Medscape.com.
AT ENDO 2023
Does weight loss surgery up the risk for bone fractures?
Currently, the two most common types of weight loss surgery performed include sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB). Sleeve gastrectomy involves removing a large portion of the stomach so that its capacity is significantly decreased (to about 20%), reducing the ability to consume large quantities of food. Also, the procedure leads to marked reductions in ghrelin (an appetite-stimulating hormone), and some studies have reported increases in glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), hormones that induce satiety. Gastric bypass involves creating a small stomach pouch and rerouting the small intestine so that it bypasses much of the stomach and also the upper portion of the small intestine. This reduces the amount of food that can be consumed at any time, increases levels of GLP-1 and PYY, and reduces absorption of nutrients with resultant weight loss. Less common bariatric surgeries include gastric banding and biliopancreatic diversion with duodenal switch (BPD-DS). Gastric banding involves placing a ring in the upper portion of the stomach, and the size of the pouch created can be altered by injecting more or less saline through a port inserted under the skin. BPD-DS includes sleeve gastrectomy, resection of a large section of the small intestine, and diversion of the pancreatic and biliary duct to a point below the junction of the ends of the resected gut.
Weight loss surgery is currently recommended for people who have a body mass index greater than or equal to 35 regardless of obesity-related complication and may be considered for those with a BMI greater than or equal to 30. BMI is calculated by dividing the weight (in kilograms) by the height (in meters). In children and adolescents, weight loss surgery should be considered in those with a BMI greater than 120% of the 95th percentile and with a major comorbidity or in those with a BMI greater than 140% of the 95th percentile.
What impact does weight loss surgery have on bone?
Multiple studies in both adults and teenagers have demonstrated that sleeve gastrectomy, RYGB, and BPD-DS (but not gastric banding) are associated with a decrease in bone density, impaired bone structure, and reduced strength estimates over time (Beavers et al; Gagnon, Schafer; Misra, Bredella). The relative risk for fracture after RYGB and BPD-DS is reported to be 1.2-2.3 (that is, 20%-130% more than normal), whereas fracture risk after sleeve gastrectomy is still under study with some conflicting results. Fracture risk starts to increase 2-3 years after surgery and peaks at 5-plus years after surgery. Most of the data for fractures come from studies in adults. With the rising use of weight loss surgery, particularly sleeve gastrectomy, in teenagers, studies are needed to determine fracture risk in this younger age group, who also seem to experience marked reductions in bone density, altered bone structure, and reduced bone strength after bariatric surgery.
What contributes to impaired bone health after weight loss surgery?
The deleterious effect of weight loss surgery on bone appears to be caused by various factors, including the massive and rapid weight loss that occurs after surgery, because body weight has a mechanical loading effect on bone and otherwise promotes bone formation. Weight loss results in mechanical unloading and thus a decrease in bone density. Further, when weight loss occurs, there is loss of both muscle and fat mass, and the reduction in muscle mass is deleterious to bone.
Other possible causes of bone density reduction include reduced absorption of certain nutrients, such as calcium and vitamin D critical for bone mineralization, and alterations in certain hormones that impact bone health. These include increases in parathyroid hormone, which increases bone loss when secreted in excess; increases in PYY (a hormone that reduces bone formation); decreases in ghrelin (a hormone that typically increases bone formation), particularly after sleeve gastrectomy; and decreases in estrone (a kind of estrogen that like other estrogens prevents bone loss). Further, age and gender may modify the bone consequences of surgery as outcomes in postmenopausal women appear to be worse than in younger women and men.
Preventing bone density loss
Given the many benefits of weight loss surgery, what can we do to prevent this decrease in bone density after surgery? It’s important for people undergoing weight loss surgery to be cognizant of this potentially negative outcome and to take appropriate precautions to mitigate this concern.
We should monitor bone density after surgery with the help of dual energy x-ray absorptiometry, starting a few years after surgery, particularly in those who are at greatest risk for fracture, so that we can be proactive about addressing any severe bone loss that warrants pharmacologic intervention.
More general recommendations include optimizing intake of calcium (1,200-1,500 mg/d), vitamin D (2,000-3,000 IUs/d), and protein (60-75 g/d) via diet and/or as supplements and engaging in weight-bearing physical activity because this exerts mechanical loading effects on the skeleton leading to increased bone formation and also increases muscle mass over time, which is beneficial to bone. A progressive resistance training program has been demonstrated to have beneficial effects on bone, and measures should be taken to reduce the risk for falls, which increases after certain kinds of weight loss surgery, such as gastric bypass.
Meeting with a dietitian can help determine any other nutrients that need to be optimized.
Though many hormonal changes after surgery have been linked to reductions in bone density, there are still no recommended hormonal therapies at this time, and more work is required to determine whether specific pharmacologic therapies might help improve bone outcomes after surgery.
Dr. Misra is chief of the division of pediatric endocrinology, Mass General for Children; associate director, Harvard Catalyst Translation and Clinical Research Center; director, Pediatric Endocrine-Sports Endocrine-Neuroendocrine Lab, Mass General Hospital; and professor, department of pediatrics, Harvard Medical School, Boston.
A version of this article originally appeared on Medscape.com.
Currently, the two most common types of weight loss surgery performed include sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB). Sleeve gastrectomy involves removing a large portion of the stomach so that its capacity is significantly decreased (to about 20%), reducing the ability to consume large quantities of food. Also, the procedure leads to marked reductions in ghrelin (an appetite-stimulating hormone), and some studies have reported increases in glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), hormones that induce satiety. Gastric bypass involves creating a small stomach pouch and rerouting the small intestine so that it bypasses much of the stomach and also the upper portion of the small intestine. This reduces the amount of food that can be consumed at any time, increases levels of GLP-1 and PYY, and reduces absorption of nutrients with resultant weight loss. Less common bariatric surgeries include gastric banding and biliopancreatic diversion with duodenal switch (BPD-DS). Gastric banding involves placing a ring in the upper portion of the stomach, and the size of the pouch created can be altered by injecting more or less saline through a port inserted under the skin. BPD-DS includes sleeve gastrectomy, resection of a large section of the small intestine, and diversion of the pancreatic and biliary duct to a point below the junction of the ends of the resected gut.
Weight loss surgery is currently recommended for people who have a body mass index greater than or equal to 35 regardless of obesity-related complication and may be considered for those with a BMI greater than or equal to 30. BMI is calculated by dividing the weight (in kilograms) by the height (in meters). In children and adolescents, weight loss surgery should be considered in those with a BMI greater than 120% of the 95th percentile and with a major comorbidity or in those with a BMI greater than 140% of the 95th percentile.
What impact does weight loss surgery have on bone?
Multiple studies in both adults and teenagers have demonstrated that sleeve gastrectomy, RYGB, and BPD-DS (but not gastric banding) are associated with a decrease in bone density, impaired bone structure, and reduced strength estimates over time (Beavers et al; Gagnon, Schafer; Misra, Bredella). The relative risk for fracture after RYGB and BPD-DS is reported to be 1.2-2.3 (that is, 20%-130% more than normal), whereas fracture risk after sleeve gastrectomy is still under study with some conflicting results. Fracture risk starts to increase 2-3 years after surgery and peaks at 5-plus years after surgery. Most of the data for fractures come from studies in adults. With the rising use of weight loss surgery, particularly sleeve gastrectomy, in teenagers, studies are needed to determine fracture risk in this younger age group, who also seem to experience marked reductions in bone density, altered bone structure, and reduced bone strength after bariatric surgery.
What contributes to impaired bone health after weight loss surgery?
The deleterious effect of weight loss surgery on bone appears to be caused by various factors, including the massive and rapid weight loss that occurs after surgery, because body weight has a mechanical loading effect on bone and otherwise promotes bone formation. Weight loss results in mechanical unloading and thus a decrease in bone density. Further, when weight loss occurs, there is loss of both muscle and fat mass, and the reduction in muscle mass is deleterious to bone.
Other possible causes of bone density reduction include reduced absorption of certain nutrients, such as calcium and vitamin D critical for bone mineralization, and alterations in certain hormones that impact bone health. These include increases in parathyroid hormone, which increases bone loss when secreted in excess; increases in PYY (a hormone that reduces bone formation); decreases in ghrelin (a hormone that typically increases bone formation), particularly after sleeve gastrectomy; and decreases in estrone (a kind of estrogen that like other estrogens prevents bone loss). Further, age and gender may modify the bone consequences of surgery as outcomes in postmenopausal women appear to be worse than in younger women and men.
Preventing bone density loss
Given the many benefits of weight loss surgery, what can we do to prevent this decrease in bone density after surgery? It’s important for people undergoing weight loss surgery to be cognizant of this potentially negative outcome and to take appropriate precautions to mitigate this concern.
We should monitor bone density after surgery with the help of dual energy x-ray absorptiometry, starting a few years after surgery, particularly in those who are at greatest risk for fracture, so that we can be proactive about addressing any severe bone loss that warrants pharmacologic intervention.
More general recommendations include optimizing intake of calcium (1,200-1,500 mg/d), vitamin D (2,000-3,000 IUs/d), and protein (60-75 g/d) via diet and/or as supplements and engaging in weight-bearing physical activity because this exerts mechanical loading effects on the skeleton leading to increased bone formation and also increases muscle mass over time, which is beneficial to bone. A progressive resistance training program has been demonstrated to have beneficial effects on bone, and measures should be taken to reduce the risk for falls, which increases after certain kinds of weight loss surgery, such as gastric bypass.
Meeting with a dietitian can help determine any other nutrients that need to be optimized.
Though many hormonal changes after surgery have been linked to reductions in bone density, there are still no recommended hormonal therapies at this time, and more work is required to determine whether specific pharmacologic therapies might help improve bone outcomes after surgery.
Dr. Misra is chief of the division of pediatric endocrinology, Mass General for Children; associate director, Harvard Catalyst Translation and Clinical Research Center; director, Pediatric Endocrine-Sports Endocrine-Neuroendocrine Lab, Mass General Hospital; and professor, department of pediatrics, Harvard Medical School, Boston.
A version of this article originally appeared on Medscape.com.
Currently, the two most common types of weight loss surgery performed include sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB). Sleeve gastrectomy involves removing a large portion of the stomach so that its capacity is significantly decreased (to about 20%), reducing the ability to consume large quantities of food. Also, the procedure leads to marked reductions in ghrelin (an appetite-stimulating hormone), and some studies have reported increases in glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), hormones that induce satiety. Gastric bypass involves creating a small stomach pouch and rerouting the small intestine so that it bypasses much of the stomach and also the upper portion of the small intestine. This reduces the amount of food that can be consumed at any time, increases levels of GLP-1 and PYY, and reduces absorption of nutrients with resultant weight loss. Less common bariatric surgeries include gastric banding and biliopancreatic diversion with duodenal switch (BPD-DS). Gastric banding involves placing a ring in the upper portion of the stomach, and the size of the pouch created can be altered by injecting more or less saline through a port inserted under the skin. BPD-DS includes sleeve gastrectomy, resection of a large section of the small intestine, and diversion of the pancreatic and biliary duct to a point below the junction of the ends of the resected gut.
Weight loss surgery is currently recommended for people who have a body mass index greater than or equal to 35 regardless of obesity-related complication and may be considered for those with a BMI greater than or equal to 30. BMI is calculated by dividing the weight (in kilograms) by the height (in meters). In children and adolescents, weight loss surgery should be considered in those with a BMI greater than 120% of the 95th percentile and with a major comorbidity or in those with a BMI greater than 140% of the 95th percentile.
What impact does weight loss surgery have on bone?
Multiple studies in both adults and teenagers have demonstrated that sleeve gastrectomy, RYGB, and BPD-DS (but not gastric banding) are associated with a decrease in bone density, impaired bone structure, and reduced strength estimates over time (Beavers et al; Gagnon, Schafer; Misra, Bredella). The relative risk for fracture after RYGB and BPD-DS is reported to be 1.2-2.3 (that is, 20%-130% more than normal), whereas fracture risk after sleeve gastrectomy is still under study with some conflicting results. Fracture risk starts to increase 2-3 years after surgery and peaks at 5-plus years after surgery. Most of the data for fractures come from studies in adults. With the rising use of weight loss surgery, particularly sleeve gastrectomy, in teenagers, studies are needed to determine fracture risk in this younger age group, who also seem to experience marked reductions in bone density, altered bone structure, and reduced bone strength after bariatric surgery.
What contributes to impaired bone health after weight loss surgery?
The deleterious effect of weight loss surgery on bone appears to be caused by various factors, including the massive and rapid weight loss that occurs after surgery, because body weight has a mechanical loading effect on bone and otherwise promotes bone formation. Weight loss results in mechanical unloading and thus a decrease in bone density. Further, when weight loss occurs, there is loss of both muscle and fat mass, and the reduction in muscle mass is deleterious to bone.
Other possible causes of bone density reduction include reduced absorption of certain nutrients, such as calcium and vitamin D critical for bone mineralization, and alterations in certain hormones that impact bone health. These include increases in parathyroid hormone, which increases bone loss when secreted in excess; increases in PYY (a hormone that reduces bone formation); decreases in ghrelin (a hormone that typically increases bone formation), particularly after sleeve gastrectomy; and decreases in estrone (a kind of estrogen that like other estrogens prevents bone loss). Further, age and gender may modify the bone consequences of surgery as outcomes in postmenopausal women appear to be worse than in younger women and men.
Preventing bone density loss
Given the many benefits of weight loss surgery, what can we do to prevent this decrease in bone density after surgery? It’s important for people undergoing weight loss surgery to be cognizant of this potentially negative outcome and to take appropriate precautions to mitigate this concern.
We should monitor bone density after surgery with the help of dual energy x-ray absorptiometry, starting a few years after surgery, particularly in those who are at greatest risk for fracture, so that we can be proactive about addressing any severe bone loss that warrants pharmacologic intervention.
More general recommendations include optimizing intake of calcium (1,200-1,500 mg/d), vitamin D (2,000-3,000 IUs/d), and protein (60-75 g/d) via diet and/or as supplements and engaging in weight-bearing physical activity because this exerts mechanical loading effects on the skeleton leading to increased bone formation and also increases muscle mass over time, which is beneficial to bone. A progressive resistance training program has been demonstrated to have beneficial effects on bone, and measures should be taken to reduce the risk for falls, which increases after certain kinds of weight loss surgery, such as gastric bypass.
Meeting with a dietitian can help determine any other nutrients that need to be optimized.
Though many hormonal changes after surgery have been linked to reductions in bone density, there are still no recommended hormonal therapies at this time, and more work is required to determine whether specific pharmacologic therapies might help improve bone outcomes after surgery.
Dr. Misra is chief of the division of pediatric endocrinology, Mass General for Children; associate director, Harvard Catalyst Translation and Clinical Research Center; director, Pediatric Endocrine-Sports Endocrine-Neuroendocrine Lab, Mass General Hospital; and professor, department of pediatrics, Harvard Medical School, Boston.
A version of this article originally appeared on Medscape.com.
Common fracture risk predictors often fail for women of any race
according to a study published in JAMA Internal Medicine.
One of the screenings, the U.S. Fracture Risk Assessment Tool (FRAX), proved relatively ineffective at identifying women who developed osteoporosis. The other screening, the Osteoporosis Self-Assessment Tool (OST), excelled at identifying osteoporosis for women in every racial and ethnic group, but also failed at identifying who was most likely to experience a fracture. Osteoporosis experts say that primary care physicians should test for the condition in anyone with any risk factor for it, even if a screening tool suggests doing so is unnecessary.
The United States Preventive Services Task Force (USPSTF) recommends routine testing of bone mineral density in women age 65 years and older to detect risk of developing osteoporosis, which in turn leads to an increased risk for fractures of the hip, spine, shoulder, or forearm. For women aged 50-64, whether bone mineral density accurately reflects who will develop osteoporosis is less clear. In this age range, the USPSTF recommends using either FRAX or OST rather than routine bone mineral density tests.
“I have the utmost respect for the United States Preventive Services Task Force, which lists both of these as valid screening tools for younger postmenopausal women. What I hope this study does is to inform the next iteration of the screening guidelines,” by maintaining the recommendation to use the OST while not keeping FRAX, said Carolyn J. Crandall, MD, MS, an internal medicine physician and health services researcher at University of California, Los Angeles, who helped conduct the research.
The U.S. version of FRAX requires identifying someone’s race, height, and weight, then answering whether they have different risk factors for a fracture such as a previous fracture, rheumatoid arthritis, or smoking. The result was thought to indicate a cumulative risk for major fracture over the next 10 years. Patients at significant risk should then undergo a bone density test.
The tool can also incorporate information about bone mineral density, if available, but the FRAX analyses in Dr. Crandall’s study did not include those data because the study aimed to test the measure’s predictive ability in the absence of a bone scan.
The OST includes only two variables – weight and age – to calculate risk for osteoporosis, and generally takes seconds to complete. It does not include race. As with FRAX, anyone deemed at significant risk for developing osteoporosis should undergo a bone density test.
“OST is really simple; that makes it very appealing,” Dr. Crandall said. “OST could probably be automatically calculated in the electronic medical record.”
Using data from the Women’s Health Initiative, Dr. Crandall and colleagues tracked more than 67,000 women aged 50-64 years for 10 years following enrollment in the study to see who experienced a fracture or developed osteoporosis over that decade. The investigators found that neither FRAX nor OST was particularly good at predicting who went on to experience a fracture.
The accuracy of FRAX at fracture prediction peaked at 65% for Asian women (area under the receiver operating curve, 0.65; 95% confidence interval, 0.58-0.71), and was lowest for Black women (AUC 0.55; 95% CI, 0.52-0.59). OST also was most accurate for Asian women, but only up to 62% (AUC 0.62; 95% CI, 0.56-0.69), and was again lowest for Black women (AUC 0.53; 95% CI, 0.50 - 0.57)
“It is just very hard to predict fractures in this age group,” Dr. Crandall said, noting that more evidence exists about risk for fracture in people older than 65.
The story diverges with predicting risk of osteoporosis in the neck. The OST did this roughly 80% of the time, for all racial groups. That figure proved better than FRAX, without including race.
Treatment gap
“This evidence supports using OST instead of FRAX” for selecting younger postmenopausal women who should undergo a bone mineral density exam, said E. Michael Lewiecki, MD, director of the New Mexico Clinical Research & Osteoporosis Center in Albuquerque.
Dr. Lewiecki, who was not involved in the new study, noted that the U.S. version of FRAX specifies race because of some clinical evidence that different races have different rates of fracture. But he and Dr. Crandall said the validity of race-based algorithms to guide clinical care is a controversial and evolving topic in medicine. Dr. Lewiecki said the Canadian version of FRAX, which is similarly applied to a diverse population as in the United States, omits race and works as well as the U.S. version. Future iterations of the instrument in the United States may not include race, Dr. Lewiecki said.
“The study is perfectly valid as far as it goes. But the big gorilla in the room is that most patients who need a bone density test are not getting it,” Dr. Lewiecki added. Sometimes a patient might break a bone in their wrist, for example, and tell their primary care provider that anyone would have broken that bone because the fall was so hard. Even if that’s true, Dr. Lewiecki said, any woman older than 45 who has broken a bone should undergo a bone density test to determine if they have osteoporosis, even if it seems like there are other possible reasons for why the break occurred.
“Most of the clinical practice guidelines that are used by physicians recommend getting a bone density test in postmenopausal women under the age of 65 who have a risk factor for fracture,” Dr. Lewiecki said, with a primary risk factor being a prior fracture. Dr. Lewiecki said he would rather that anyone who could benefit from a bone density test receive it, rather than someone foregoing a scan based on a screening tool that may be flawed.
“Most patients – men and women – who have osteoporosis are currently not being identified. Even when they are being identified, they are commonly not being treated. And when they are started on treatment, many patients discontinue treatment before they’ve taken it long enough to benefit,” Dr. Lewiecki said.
Dr. Crandall and Dr. Lewiecki report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a study published in JAMA Internal Medicine.
One of the screenings, the U.S. Fracture Risk Assessment Tool (FRAX), proved relatively ineffective at identifying women who developed osteoporosis. The other screening, the Osteoporosis Self-Assessment Tool (OST), excelled at identifying osteoporosis for women in every racial and ethnic group, but also failed at identifying who was most likely to experience a fracture. Osteoporosis experts say that primary care physicians should test for the condition in anyone with any risk factor for it, even if a screening tool suggests doing so is unnecessary.
The United States Preventive Services Task Force (USPSTF) recommends routine testing of bone mineral density in women age 65 years and older to detect risk of developing osteoporosis, which in turn leads to an increased risk for fractures of the hip, spine, shoulder, or forearm. For women aged 50-64, whether bone mineral density accurately reflects who will develop osteoporosis is less clear. In this age range, the USPSTF recommends using either FRAX or OST rather than routine bone mineral density tests.
“I have the utmost respect for the United States Preventive Services Task Force, which lists both of these as valid screening tools for younger postmenopausal women. What I hope this study does is to inform the next iteration of the screening guidelines,” by maintaining the recommendation to use the OST while not keeping FRAX, said Carolyn J. Crandall, MD, MS, an internal medicine physician and health services researcher at University of California, Los Angeles, who helped conduct the research.
The U.S. version of FRAX requires identifying someone’s race, height, and weight, then answering whether they have different risk factors for a fracture such as a previous fracture, rheumatoid arthritis, or smoking. The result was thought to indicate a cumulative risk for major fracture over the next 10 years. Patients at significant risk should then undergo a bone density test.
The tool can also incorporate information about bone mineral density, if available, but the FRAX analyses in Dr. Crandall’s study did not include those data because the study aimed to test the measure’s predictive ability in the absence of a bone scan.
The OST includes only two variables – weight and age – to calculate risk for osteoporosis, and generally takes seconds to complete. It does not include race. As with FRAX, anyone deemed at significant risk for developing osteoporosis should undergo a bone density test.
“OST is really simple; that makes it very appealing,” Dr. Crandall said. “OST could probably be automatically calculated in the electronic medical record.”
Using data from the Women’s Health Initiative, Dr. Crandall and colleagues tracked more than 67,000 women aged 50-64 years for 10 years following enrollment in the study to see who experienced a fracture or developed osteoporosis over that decade. The investigators found that neither FRAX nor OST was particularly good at predicting who went on to experience a fracture.
The accuracy of FRAX at fracture prediction peaked at 65% for Asian women (area under the receiver operating curve, 0.65; 95% confidence interval, 0.58-0.71), and was lowest for Black women (AUC 0.55; 95% CI, 0.52-0.59). OST also was most accurate for Asian women, but only up to 62% (AUC 0.62; 95% CI, 0.56-0.69), and was again lowest for Black women (AUC 0.53; 95% CI, 0.50 - 0.57)
“It is just very hard to predict fractures in this age group,” Dr. Crandall said, noting that more evidence exists about risk for fracture in people older than 65.
The story diverges with predicting risk of osteoporosis in the neck. The OST did this roughly 80% of the time, for all racial groups. That figure proved better than FRAX, without including race.
Treatment gap
“This evidence supports using OST instead of FRAX” for selecting younger postmenopausal women who should undergo a bone mineral density exam, said E. Michael Lewiecki, MD, director of the New Mexico Clinical Research & Osteoporosis Center in Albuquerque.
Dr. Lewiecki, who was not involved in the new study, noted that the U.S. version of FRAX specifies race because of some clinical evidence that different races have different rates of fracture. But he and Dr. Crandall said the validity of race-based algorithms to guide clinical care is a controversial and evolving topic in medicine. Dr. Lewiecki said the Canadian version of FRAX, which is similarly applied to a diverse population as in the United States, omits race and works as well as the U.S. version. Future iterations of the instrument in the United States may not include race, Dr. Lewiecki said.
“The study is perfectly valid as far as it goes. But the big gorilla in the room is that most patients who need a bone density test are not getting it,” Dr. Lewiecki added. Sometimes a patient might break a bone in their wrist, for example, and tell their primary care provider that anyone would have broken that bone because the fall was so hard. Even if that’s true, Dr. Lewiecki said, any woman older than 45 who has broken a bone should undergo a bone density test to determine if they have osteoporosis, even if it seems like there are other possible reasons for why the break occurred.
“Most of the clinical practice guidelines that are used by physicians recommend getting a bone density test in postmenopausal women under the age of 65 who have a risk factor for fracture,” Dr. Lewiecki said, with a primary risk factor being a prior fracture. Dr. Lewiecki said he would rather that anyone who could benefit from a bone density test receive it, rather than someone foregoing a scan based on a screening tool that may be flawed.
“Most patients – men and women – who have osteoporosis are currently not being identified. Even when they are being identified, they are commonly not being treated. And when they are started on treatment, many patients discontinue treatment before they’ve taken it long enough to benefit,” Dr. Lewiecki said.
Dr. Crandall and Dr. Lewiecki report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a study published in JAMA Internal Medicine.
One of the screenings, the U.S. Fracture Risk Assessment Tool (FRAX), proved relatively ineffective at identifying women who developed osteoporosis. The other screening, the Osteoporosis Self-Assessment Tool (OST), excelled at identifying osteoporosis for women in every racial and ethnic group, but also failed at identifying who was most likely to experience a fracture. Osteoporosis experts say that primary care physicians should test for the condition in anyone with any risk factor for it, even if a screening tool suggests doing so is unnecessary.
The United States Preventive Services Task Force (USPSTF) recommends routine testing of bone mineral density in women age 65 years and older to detect risk of developing osteoporosis, which in turn leads to an increased risk for fractures of the hip, spine, shoulder, or forearm. For women aged 50-64, whether bone mineral density accurately reflects who will develop osteoporosis is less clear. In this age range, the USPSTF recommends using either FRAX or OST rather than routine bone mineral density tests.
“I have the utmost respect for the United States Preventive Services Task Force, which lists both of these as valid screening tools for younger postmenopausal women. What I hope this study does is to inform the next iteration of the screening guidelines,” by maintaining the recommendation to use the OST while not keeping FRAX, said Carolyn J. Crandall, MD, MS, an internal medicine physician and health services researcher at University of California, Los Angeles, who helped conduct the research.
The U.S. version of FRAX requires identifying someone’s race, height, and weight, then answering whether they have different risk factors for a fracture such as a previous fracture, rheumatoid arthritis, or smoking. The result was thought to indicate a cumulative risk for major fracture over the next 10 years. Patients at significant risk should then undergo a bone density test.
The tool can also incorporate information about bone mineral density, if available, but the FRAX analyses in Dr. Crandall’s study did not include those data because the study aimed to test the measure’s predictive ability in the absence of a bone scan.
The OST includes only two variables – weight and age – to calculate risk for osteoporosis, and generally takes seconds to complete. It does not include race. As with FRAX, anyone deemed at significant risk for developing osteoporosis should undergo a bone density test.
“OST is really simple; that makes it very appealing,” Dr. Crandall said. “OST could probably be automatically calculated in the electronic medical record.”
Using data from the Women’s Health Initiative, Dr. Crandall and colleagues tracked more than 67,000 women aged 50-64 years for 10 years following enrollment in the study to see who experienced a fracture or developed osteoporosis over that decade. The investigators found that neither FRAX nor OST was particularly good at predicting who went on to experience a fracture.
The accuracy of FRAX at fracture prediction peaked at 65% for Asian women (area under the receiver operating curve, 0.65; 95% confidence interval, 0.58-0.71), and was lowest for Black women (AUC 0.55; 95% CI, 0.52-0.59). OST also was most accurate for Asian women, but only up to 62% (AUC 0.62; 95% CI, 0.56-0.69), and was again lowest for Black women (AUC 0.53; 95% CI, 0.50 - 0.57)
“It is just very hard to predict fractures in this age group,” Dr. Crandall said, noting that more evidence exists about risk for fracture in people older than 65.
The story diverges with predicting risk of osteoporosis in the neck. The OST did this roughly 80% of the time, for all racial groups. That figure proved better than FRAX, without including race.
Treatment gap
“This evidence supports using OST instead of FRAX” for selecting younger postmenopausal women who should undergo a bone mineral density exam, said E. Michael Lewiecki, MD, director of the New Mexico Clinical Research & Osteoporosis Center in Albuquerque.
Dr. Lewiecki, who was not involved in the new study, noted that the U.S. version of FRAX specifies race because of some clinical evidence that different races have different rates of fracture. But he and Dr. Crandall said the validity of race-based algorithms to guide clinical care is a controversial and evolving topic in medicine. Dr. Lewiecki said the Canadian version of FRAX, which is similarly applied to a diverse population as in the United States, omits race and works as well as the U.S. version. Future iterations of the instrument in the United States may not include race, Dr. Lewiecki said.
“The study is perfectly valid as far as it goes. But the big gorilla in the room is that most patients who need a bone density test are not getting it,” Dr. Lewiecki added. Sometimes a patient might break a bone in their wrist, for example, and tell their primary care provider that anyone would have broken that bone because the fall was so hard. Even if that’s true, Dr. Lewiecki said, any woman older than 45 who has broken a bone should undergo a bone density test to determine if they have osteoporosis, even if it seems like there are other possible reasons for why the break occurred.
“Most of the clinical practice guidelines that are used by physicians recommend getting a bone density test in postmenopausal women under the age of 65 who have a risk factor for fracture,” Dr. Lewiecki said, with a primary risk factor being a prior fracture. Dr. Lewiecki said he would rather that anyone who could benefit from a bone density test receive it, rather than someone foregoing a scan based on a screening tool that may be flawed.
“Most patients – men and women – who have osteoporosis are currently not being identified. Even when they are being identified, they are commonly not being treated. And when they are started on treatment, many patients discontinue treatment before they’ve taken it long enough to benefit,” Dr. Lewiecki said.
Dr. Crandall and Dr. Lewiecki report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA INTERNAL MEDICINE
Preventing breaks and falls in older adults
LONG BEACH, CALIF. – Ms. S had recently arrived home after a stay at a skilled nursing facility to recover from a hip fracture resulting from osteoporosis. For many patients, follow-up care would have included a DEXA scan or a prescription for a bisphosphonate from a primary care clinician not trained in geriatrics.
But the 85-year-old received care that went further and that is considered best practice for the management of geriatric fractures: A physical therapist visited her after discharge and provided education on the importance of maintaining mobility. Ms. S also underwent assessment for fall risk and gait balance, and a team of multidisciplinary clinicians managed other factors, from postural hypotension to footwear and foot problems.
Sonja Rosen, MD, professor of medicine and chief of geriatric medicine at Cedars-Sinai Medical Center, Los Angeles, talked about Ms. S as part of a panel discussion on applying the “Geriatric 5Ms” for patients with osteoporosis at the annual meeting of the American Geriatrics Society.
“You have to figure out why they are falling and help them not fall again,” Dr. Rosen said.
Approximately 10 million Americans have osteoporosis, and another 44 million have low bone density. One in two women and up to one in four men will experience a bone fracture as a result of osteoporosis, according to the Bone Health and Osteoporosis Foundation.
, which involves considering the care preferences and goals for health care outcomes of individuals.
Ms. S eventually visited a geriatrician through the Cedars-Sinai Geriatric Fracture Program, which has been shown to lower costs and shorten hospital stays. In the program, she was advised to use a walker. Initially, she saw the aid as a hindrance – she felt she should be able to walk without it, like before. But with education, she learned that it is impossible to predict falls and that the walking aid could reduce her risk of a stumble.
Dr. Rosen said clinicians should address any vision problems, prescriptions for psychotropic drugs,which can affect balance, and heart rate and rhythm abnormalities, and they should suggest modifications to the home environment, such as installing grab bars in showers and removing rugs that can easily be tripped over.
The program at Cedars-Sinai, like similar initiatives, offers a team with resources that some clinicians may not have access to, such as a care coordinator and bone-health coach. But health care providers can utilize aspects, such as making referrals to community exercise classes.
Dr. Rosen and her colleagues studied the effects of such exercise programs and found that the programs lessen loneliness and social isolation. Fear of falling decreased in 75% of participants, “which is so key to these postfracture patients in getting back out into the world and engaging in their prior level of functional status,” Dr. Rosen said.
The second ‘M’: Medication management
The second “M,” medications, can help clinicians sequence osteoporosis drugs, depending on patient characteristics and scenarios.
Cathleen Colon-Emeric, MD, MHS, chief of geriatrics at Duke University, in Durham, N.C., dived into the case history of Ms. S, who had hypertension and insomnia in addition to osteoporosis.
First-line treatment for Ms. S – and for most patients – was an oral bisphosphonate, Dr. Colon-Emeric said. Compared with placebo, the drugs decrease the risk of overall osteoporotic fractures by nearly 40% (odds ratio, 0.62). But the medications are linked to injury of the esophageal mucosa. This risk is decreased when a patient stays upright for 30 minutes after taking oral bisphosphonates. Dr. Colon-Emeric displayed a slide of a woman receiving a pedicure at a nail salon.
“The picture of the pedicure is to share the wonderful idea I got from one skilled nursing facility I was working with, who makes sure they do safe administration to prevent esophagitis in their patients by having them all go to a spa day, where they all sit up and get their nails done while they wait their 30 minutes [after taking the pill] sitting up safely,” Dr. Colon-Emeric said.
This strategy drew applause from the audience.
Dr. Colon-Emeric advised that clinicians use judgment in the interpretation of results from the Fracture Risk Assessment Tool (FRAX). Incorporating race into estimates of fracture risk has pros and cons. While there are racial and ethnic differences in average bone density, the data for race calibrations to estimate risk are dated, she said. Clinicians should compare FRAX estimates with and without race input to help patients understand a range of risks.
Some patients may be reluctant to begin taking osteoporosis drugs because of misinformation originating from inaccurate news reports or anecdotes from friends. Dr. Colon-Emeric advised clinicians to remind patients that one in five who experience a fracture will have another injury in the following 2 years.
“A major osteoporotic fracture is akin to a heart attack; it has a very similar 1-year mortality rate and a very similar rate of a subsequent secondary event,” Dr. Colon-Emeric said. “We have a class of medications that decrease both those risks by nearly a third.”
Shared decision-making can help patients understand the risks and benefits of treatment, she said.
“People are really scared about the side effects,” Michelle Keller, PhD, MPH, a research scientist at Cedars-Sinai who attended the session, said. “The idea that a “bone attack” is like a heart attack gets the message across.”
Mind and multicomplexity
Medical complexity of a patient must be considered when making decisions on treatment, according to Joshua Niznik, PharmD, PhD, assistant professor of medicine in the Center for Aging and Health at the University of North Carolina at Chapel Hill.
“Medical complexity is an acknowledgment of the entire person, the burden of their multiple chronic conditions, advanced illnesses, and also their biopsychosocial needs and how those together might augment treatment selection and decision-making,” Dr. Niznik said.
Studies by Dr. Niznik and others have shown that swallowing difficulties, severe dementia, and being older than 90 are linked with a lower likelihood of receiving treatment for osteoporosis.
But therapies for fracture prevention, especially bisphosphonates, appear to be at least as effective for adults with medical complexity as they are for people without such conditions, Dr. Niznik said. Physicians must consider the potential treatment burden and the likelihood of benefit, he said.
Dr. Niznik’s research has shown a lack of strong evidence on how clinicians can manage patients in nursing homes. In some cases, deprescribing is reasonable, such as for patients who have undergone treatment for several years and whose life expectancy is less than 2 years.
“In the absence of any of those, if they are not already treated for osteoporosis, it makes sense to initiate treatment at that time,” Dr. Niznik said.
Matters most: Patient input
Clinicians need to educate patients on how long they must undergo a treatment before they experience benefits, according to Sarah D. Berry, MD, MPH, associate professor of medicine at Harvard Medical School, in Boston.
A meta-analysis of studies that included more than 20,000 women who were randomly assigned to receive bisphosphonate or placebo found that one nonvertebral fracture was avoided during a 12-month period for every 100 persons treated. One hip fracture was avoided during a 20-month period for every 200 patients treated.
“In general, in persons with a 2-year life expectancy, time to benefit favors bisphosphonate use,” Dr. Berry said. “Anabolics may have an even quicker time to benefit.”
Dr. Berry said a shared a decision-making model can help clinicians facilitate discussions that help patients prioritize goals and compare options while considering results, benefits, and harms. And she offered a final tip: Use tools with absolute risk reduction to convey risks and benefits, as the relative risk calculations overestimate how effective treatment will be.
Dr. Rosen has disclosed no relevant financial relationships. Dr. Colon-Emeric has received grants from the National Institutes of Health and VA Health Services Research and Development Funding; has served as endpoint adjudication chair for UCB Pharma; and has received royalties from Wolters Kluwer. Dr. Niznik has received funding from the National Institute of Aging and the Centers for Disease Control and Prevention. Dr. Berry has received funding from the NIH and royalties from Wolters Kluwer.
A version of this article originally appeared on Medscape.com.
LONG BEACH, CALIF. – Ms. S had recently arrived home after a stay at a skilled nursing facility to recover from a hip fracture resulting from osteoporosis. For many patients, follow-up care would have included a DEXA scan or a prescription for a bisphosphonate from a primary care clinician not trained in geriatrics.
But the 85-year-old received care that went further and that is considered best practice for the management of geriatric fractures: A physical therapist visited her after discharge and provided education on the importance of maintaining mobility. Ms. S also underwent assessment for fall risk and gait balance, and a team of multidisciplinary clinicians managed other factors, from postural hypotension to footwear and foot problems.
Sonja Rosen, MD, professor of medicine and chief of geriatric medicine at Cedars-Sinai Medical Center, Los Angeles, talked about Ms. S as part of a panel discussion on applying the “Geriatric 5Ms” for patients with osteoporosis at the annual meeting of the American Geriatrics Society.
“You have to figure out why they are falling and help them not fall again,” Dr. Rosen said.
Approximately 10 million Americans have osteoporosis, and another 44 million have low bone density. One in two women and up to one in four men will experience a bone fracture as a result of osteoporosis, according to the Bone Health and Osteoporosis Foundation.
, which involves considering the care preferences and goals for health care outcomes of individuals.
Ms. S eventually visited a geriatrician through the Cedars-Sinai Geriatric Fracture Program, which has been shown to lower costs and shorten hospital stays. In the program, she was advised to use a walker. Initially, she saw the aid as a hindrance – she felt she should be able to walk without it, like before. But with education, she learned that it is impossible to predict falls and that the walking aid could reduce her risk of a stumble.
Dr. Rosen said clinicians should address any vision problems, prescriptions for psychotropic drugs,which can affect balance, and heart rate and rhythm abnormalities, and they should suggest modifications to the home environment, such as installing grab bars in showers and removing rugs that can easily be tripped over.
The program at Cedars-Sinai, like similar initiatives, offers a team with resources that some clinicians may not have access to, such as a care coordinator and bone-health coach. But health care providers can utilize aspects, such as making referrals to community exercise classes.
Dr. Rosen and her colleagues studied the effects of such exercise programs and found that the programs lessen loneliness and social isolation. Fear of falling decreased in 75% of participants, “which is so key to these postfracture patients in getting back out into the world and engaging in their prior level of functional status,” Dr. Rosen said.
The second ‘M’: Medication management
The second “M,” medications, can help clinicians sequence osteoporosis drugs, depending on patient characteristics and scenarios.
Cathleen Colon-Emeric, MD, MHS, chief of geriatrics at Duke University, in Durham, N.C., dived into the case history of Ms. S, who had hypertension and insomnia in addition to osteoporosis.
First-line treatment for Ms. S – and for most patients – was an oral bisphosphonate, Dr. Colon-Emeric said. Compared with placebo, the drugs decrease the risk of overall osteoporotic fractures by nearly 40% (odds ratio, 0.62). But the medications are linked to injury of the esophageal mucosa. This risk is decreased when a patient stays upright for 30 minutes after taking oral bisphosphonates. Dr. Colon-Emeric displayed a slide of a woman receiving a pedicure at a nail salon.
“The picture of the pedicure is to share the wonderful idea I got from one skilled nursing facility I was working with, who makes sure they do safe administration to prevent esophagitis in their patients by having them all go to a spa day, where they all sit up and get their nails done while they wait their 30 minutes [after taking the pill] sitting up safely,” Dr. Colon-Emeric said.
This strategy drew applause from the audience.
Dr. Colon-Emeric advised that clinicians use judgment in the interpretation of results from the Fracture Risk Assessment Tool (FRAX). Incorporating race into estimates of fracture risk has pros and cons. While there are racial and ethnic differences in average bone density, the data for race calibrations to estimate risk are dated, she said. Clinicians should compare FRAX estimates with and without race input to help patients understand a range of risks.
Some patients may be reluctant to begin taking osteoporosis drugs because of misinformation originating from inaccurate news reports or anecdotes from friends. Dr. Colon-Emeric advised clinicians to remind patients that one in five who experience a fracture will have another injury in the following 2 years.
“A major osteoporotic fracture is akin to a heart attack; it has a very similar 1-year mortality rate and a very similar rate of a subsequent secondary event,” Dr. Colon-Emeric said. “We have a class of medications that decrease both those risks by nearly a third.”
Shared decision-making can help patients understand the risks and benefits of treatment, she said.
“People are really scared about the side effects,” Michelle Keller, PhD, MPH, a research scientist at Cedars-Sinai who attended the session, said. “The idea that a “bone attack” is like a heart attack gets the message across.”
Mind and multicomplexity
Medical complexity of a patient must be considered when making decisions on treatment, according to Joshua Niznik, PharmD, PhD, assistant professor of medicine in the Center for Aging and Health at the University of North Carolina at Chapel Hill.
“Medical complexity is an acknowledgment of the entire person, the burden of their multiple chronic conditions, advanced illnesses, and also their biopsychosocial needs and how those together might augment treatment selection and decision-making,” Dr. Niznik said.
Studies by Dr. Niznik and others have shown that swallowing difficulties, severe dementia, and being older than 90 are linked with a lower likelihood of receiving treatment for osteoporosis.
But therapies for fracture prevention, especially bisphosphonates, appear to be at least as effective for adults with medical complexity as they are for people without such conditions, Dr. Niznik said. Physicians must consider the potential treatment burden and the likelihood of benefit, he said.
Dr. Niznik’s research has shown a lack of strong evidence on how clinicians can manage patients in nursing homes. In some cases, deprescribing is reasonable, such as for patients who have undergone treatment for several years and whose life expectancy is less than 2 years.
“In the absence of any of those, if they are not already treated for osteoporosis, it makes sense to initiate treatment at that time,” Dr. Niznik said.
Matters most: Patient input
Clinicians need to educate patients on how long they must undergo a treatment before they experience benefits, according to Sarah D. Berry, MD, MPH, associate professor of medicine at Harvard Medical School, in Boston.
A meta-analysis of studies that included more than 20,000 women who were randomly assigned to receive bisphosphonate or placebo found that one nonvertebral fracture was avoided during a 12-month period for every 100 persons treated. One hip fracture was avoided during a 20-month period for every 200 patients treated.
“In general, in persons with a 2-year life expectancy, time to benefit favors bisphosphonate use,” Dr. Berry said. “Anabolics may have an even quicker time to benefit.”
Dr. Berry said a shared a decision-making model can help clinicians facilitate discussions that help patients prioritize goals and compare options while considering results, benefits, and harms. And she offered a final tip: Use tools with absolute risk reduction to convey risks and benefits, as the relative risk calculations overestimate how effective treatment will be.
Dr. Rosen has disclosed no relevant financial relationships. Dr. Colon-Emeric has received grants from the National Institutes of Health and VA Health Services Research and Development Funding; has served as endpoint adjudication chair for UCB Pharma; and has received royalties from Wolters Kluwer. Dr. Niznik has received funding from the National Institute of Aging and the Centers for Disease Control and Prevention. Dr. Berry has received funding from the NIH and royalties from Wolters Kluwer.
A version of this article originally appeared on Medscape.com.
LONG BEACH, CALIF. – Ms. S had recently arrived home after a stay at a skilled nursing facility to recover from a hip fracture resulting from osteoporosis. For many patients, follow-up care would have included a DEXA scan or a prescription for a bisphosphonate from a primary care clinician not trained in geriatrics.
But the 85-year-old received care that went further and that is considered best practice for the management of geriatric fractures: A physical therapist visited her after discharge and provided education on the importance of maintaining mobility. Ms. S also underwent assessment for fall risk and gait balance, and a team of multidisciplinary clinicians managed other factors, from postural hypotension to footwear and foot problems.
Sonja Rosen, MD, professor of medicine and chief of geriatric medicine at Cedars-Sinai Medical Center, Los Angeles, talked about Ms. S as part of a panel discussion on applying the “Geriatric 5Ms” for patients with osteoporosis at the annual meeting of the American Geriatrics Society.
“You have to figure out why they are falling and help them not fall again,” Dr. Rosen said.
Approximately 10 million Americans have osteoporosis, and another 44 million have low bone density. One in two women and up to one in four men will experience a bone fracture as a result of osteoporosis, according to the Bone Health and Osteoporosis Foundation.
, which involves considering the care preferences and goals for health care outcomes of individuals.
Ms. S eventually visited a geriatrician through the Cedars-Sinai Geriatric Fracture Program, which has been shown to lower costs and shorten hospital stays. In the program, she was advised to use a walker. Initially, she saw the aid as a hindrance – she felt she should be able to walk without it, like before. But with education, she learned that it is impossible to predict falls and that the walking aid could reduce her risk of a stumble.
Dr. Rosen said clinicians should address any vision problems, prescriptions for psychotropic drugs,which can affect balance, and heart rate and rhythm abnormalities, and they should suggest modifications to the home environment, such as installing grab bars in showers and removing rugs that can easily be tripped over.
The program at Cedars-Sinai, like similar initiatives, offers a team with resources that some clinicians may not have access to, such as a care coordinator and bone-health coach. But health care providers can utilize aspects, such as making referrals to community exercise classes.
Dr. Rosen and her colleagues studied the effects of such exercise programs and found that the programs lessen loneliness and social isolation. Fear of falling decreased in 75% of participants, “which is so key to these postfracture patients in getting back out into the world and engaging in their prior level of functional status,” Dr. Rosen said.
The second ‘M’: Medication management
The second “M,” medications, can help clinicians sequence osteoporosis drugs, depending on patient characteristics and scenarios.
Cathleen Colon-Emeric, MD, MHS, chief of geriatrics at Duke University, in Durham, N.C., dived into the case history of Ms. S, who had hypertension and insomnia in addition to osteoporosis.
First-line treatment for Ms. S – and for most patients – was an oral bisphosphonate, Dr. Colon-Emeric said. Compared with placebo, the drugs decrease the risk of overall osteoporotic fractures by nearly 40% (odds ratio, 0.62). But the medications are linked to injury of the esophageal mucosa. This risk is decreased when a patient stays upright for 30 minutes after taking oral bisphosphonates. Dr. Colon-Emeric displayed a slide of a woman receiving a pedicure at a nail salon.
“The picture of the pedicure is to share the wonderful idea I got from one skilled nursing facility I was working with, who makes sure they do safe administration to prevent esophagitis in their patients by having them all go to a spa day, where they all sit up and get their nails done while they wait their 30 minutes [after taking the pill] sitting up safely,” Dr. Colon-Emeric said.
This strategy drew applause from the audience.
Dr. Colon-Emeric advised that clinicians use judgment in the interpretation of results from the Fracture Risk Assessment Tool (FRAX). Incorporating race into estimates of fracture risk has pros and cons. While there are racial and ethnic differences in average bone density, the data for race calibrations to estimate risk are dated, she said. Clinicians should compare FRAX estimates with and without race input to help patients understand a range of risks.
Some patients may be reluctant to begin taking osteoporosis drugs because of misinformation originating from inaccurate news reports or anecdotes from friends. Dr. Colon-Emeric advised clinicians to remind patients that one in five who experience a fracture will have another injury in the following 2 years.
“A major osteoporotic fracture is akin to a heart attack; it has a very similar 1-year mortality rate and a very similar rate of a subsequent secondary event,” Dr. Colon-Emeric said. “We have a class of medications that decrease both those risks by nearly a third.”
Shared decision-making can help patients understand the risks and benefits of treatment, she said.
“People are really scared about the side effects,” Michelle Keller, PhD, MPH, a research scientist at Cedars-Sinai who attended the session, said. “The idea that a “bone attack” is like a heart attack gets the message across.”
Mind and multicomplexity
Medical complexity of a patient must be considered when making decisions on treatment, according to Joshua Niznik, PharmD, PhD, assistant professor of medicine in the Center for Aging and Health at the University of North Carolina at Chapel Hill.
“Medical complexity is an acknowledgment of the entire person, the burden of their multiple chronic conditions, advanced illnesses, and also their biopsychosocial needs and how those together might augment treatment selection and decision-making,” Dr. Niznik said.
Studies by Dr. Niznik and others have shown that swallowing difficulties, severe dementia, and being older than 90 are linked with a lower likelihood of receiving treatment for osteoporosis.
But therapies for fracture prevention, especially bisphosphonates, appear to be at least as effective for adults with medical complexity as they are for people without such conditions, Dr. Niznik said. Physicians must consider the potential treatment burden and the likelihood of benefit, he said.
Dr. Niznik’s research has shown a lack of strong evidence on how clinicians can manage patients in nursing homes. In some cases, deprescribing is reasonable, such as for patients who have undergone treatment for several years and whose life expectancy is less than 2 years.
“In the absence of any of those, if they are not already treated for osteoporosis, it makes sense to initiate treatment at that time,” Dr. Niznik said.
Matters most: Patient input
Clinicians need to educate patients on how long they must undergo a treatment before they experience benefits, according to Sarah D. Berry, MD, MPH, associate professor of medicine at Harvard Medical School, in Boston.
A meta-analysis of studies that included more than 20,000 women who were randomly assigned to receive bisphosphonate or placebo found that one nonvertebral fracture was avoided during a 12-month period for every 100 persons treated. One hip fracture was avoided during a 20-month period for every 200 patients treated.
“In general, in persons with a 2-year life expectancy, time to benefit favors bisphosphonate use,” Dr. Berry said. “Anabolics may have an even quicker time to benefit.”
Dr. Berry said a shared a decision-making model can help clinicians facilitate discussions that help patients prioritize goals and compare options while considering results, benefits, and harms. And she offered a final tip: Use tools with absolute risk reduction to convey risks and benefits, as the relative risk calculations overestimate how effective treatment will be.
Dr. Rosen has disclosed no relevant financial relationships. Dr. Colon-Emeric has received grants from the National Institutes of Health and VA Health Services Research and Development Funding; has served as endpoint adjudication chair for UCB Pharma; and has received royalties from Wolters Kluwer. Dr. Niznik has received funding from the National Institute of Aging and the Centers for Disease Control and Prevention. Dr. Berry has received funding from the NIH and royalties from Wolters Kluwer.
A version of this article originally appeared on Medscape.com.
AT AGS 2023
Risk assessment first urged for fragility fracture screening
A new Canadian guideline on screening for the primary prevention of fragility fractures recommends risk assessment first, before bone mineral density (BMD) testing, for women aged 65 and older. For younger women and men aged 40 and older, screening is not recommended.
To develop the guideline, a writing group from Canadian Task Force on Preventive Health Care commissioned systematic reviews of studies on the benefits and harms of fragility fracture screenings; the predictive accuracy of current risk-assessment tools; patient acceptability; and benefits of treatment. Treatment harms were analyzed via a rapid overview of reviews.
The guideline, published online in the Canadian Medical Association Journal, is aimed at primary care practitioners for their community-dwelling patients aged 40 and older. The recommendations do not apply to people already taking preventive drugs.
Nondrug treatments were beyond the scope of the current guideline, but guidelines on the prevention of falls and other strategies are planned, Roland Grad, MD, a guideline author and associate professor at McGill University in Montreal, told this news organization.
The new guideline says that women aged 65 and older may be able to avoid fracture through screening and preventive medication. An individual’s fracture risk can be estimated with a new Fragility Fractures Decision Aid, which uses the Canadian FRAX risk-assessment tool.
“A risk assessment–first approach promotes shared decision-making with the patient, based on best medical evidence,” Dr. Grad said.
“To help clinicians, we have created an infographic with visuals to communicate the time spent on BMD vs risk assessment first.”
New evidence
“At least three things motivated this new guideline,” Dr. Grad said. “When we started work on this prior to the pandemic, we saw a need for updated guidance on screening to prevent fragility fractures. We were also aware of new evidence from the publication of screening trials in females older than 65.”
To conduct the risk assessment in older women, clinicians are advised to do the following:
- Use the decision aid (which patients can also use on their own).
- Use the 10-year absolute risk of major osteoporotic fracture to facilitate shared decision-making about possible benefits and harms of preventive pharmacotherapy.
- If pharmacotherapy is being considered, request a BMD using DXA of the femoral neck, then reestimate the fracture risk by adding the BMD T-score into the FRAX.
Potential harms associated with various treatments, with varying levels of evidence, include the following: with alendronate and denosumab, nonserious gastrointestinal adverse events; with denosumab, rash, eczema, and infections; with zoledronic acid, nonserious events, such as headache and flulike symptoms; and with alendronate and bisphosphonates, rare but serious harms of atypical femoral fracture and osteonecrosis of the jaw.
“These recommendations emphasize the importance of good clinical practice, where clinicians are alert to changes in physical health and patient well-being,” the authors wrote. “Clinicians should also be aware of the importance of secondary prevention (i.e., after fracture) and manage patients accordingly.”
“This is an important topic,” Dr. Grad said. “Fragility fractures are consequential for individuals and for our publicly funded health care system. We anticipate questions from clinicians about the time needed to screen with the risk assessment–first strategy. Our modeling work suggests time savings with [this] strategy compared to a strategy of BMD testing first. Following our recommendations may lead to a reduction in BMD testing.”
To promote the guideline, the CMAJ has recorded a podcast and will use other strategies to increase awareness, Dr. Grad said. “The Canadian Task Force has a communications strategy that includes outreach to primary care, stakeholder webinars, social media, partnerships, and other tactics. The College of Family Physicians of Canada has endorsed the guideline and will help promote to its members.”
Other at-risk groups?
Aliya Khan, MD, FRCPC, FACP, FACE, professor in the divisions of endocrinology and metabolism and geriatrics and director of the fellowship in metabolic bone diseases at McMaster University in Hamilton, Ont., told this news organization she agrees with the strategy of evaluating women aged 65 and older for fracture risk.
“The decision aid is useful, but I would like to see it expanded to other circumstances and situations,” she said.
For example, Dr. Khan would like to see recommendations for younger women and for men of all ages regarding secondary causes of osteoporosis or medications known to have a detrimental effect on bone health. By not addressing these patients, she said, “we may miss patients who would benefit from a fracture risk assessment and potentially treatment to prevent low-trauma fractures.”
A recommendation for younger postmenopausal women was included in the most recent Society of Obstetricians and Gynaecologists Canada guideline, she noted.
Overall, she said, “I believe these recommendations will reduce the excess or inappropriate use of BMD testing and that is welcome.”
Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. The task force members report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new Canadian guideline on screening for the primary prevention of fragility fractures recommends risk assessment first, before bone mineral density (BMD) testing, for women aged 65 and older. For younger women and men aged 40 and older, screening is not recommended.
To develop the guideline, a writing group from Canadian Task Force on Preventive Health Care commissioned systematic reviews of studies on the benefits and harms of fragility fracture screenings; the predictive accuracy of current risk-assessment tools; patient acceptability; and benefits of treatment. Treatment harms were analyzed via a rapid overview of reviews.
The guideline, published online in the Canadian Medical Association Journal, is aimed at primary care practitioners for their community-dwelling patients aged 40 and older. The recommendations do not apply to people already taking preventive drugs.
Nondrug treatments were beyond the scope of the current guideline, but guidelines on the prevention of falls and other strategies are planned, Roland Grad, MD, a guideline author and associate professor at McGill University in Montreal, told this news organization.
The new guideline says that women aged 65 and older may be able to avoid fracture through screening and preventive medication. An individual’s fracture risk can be estimated with a new Fragility Fractures Decision Aid, which uses the Canadian FRAX risk-assessment tool.
“A risk assessment–first approach promotes shared decision-making with the patient, based on best medical evidence,” Dr. Grad said.
“To help clinicians, we have created an infographic with visuals to communicate the time spent on BMD vs risk assessment first.”
New evidence
“At least three things motivated this new guideline,” Dr. Grad said. “When we started work on this prior to the pandemic, we saw a need for updated guidance on screening to prevent fragility fractures. We were also aware of new evidence from the publication of screening trials in females older than 65.”
To conduct the risk assessment in older women, clinicians are advised to do the following:
- Use the decision aid (which patients can also use on their own).
- Use the 10-year absolute risk of major osteoporotic fracture to facilitate shared decision-making about possible benefits and harms of preventive pharmacotherapy.
- If pharmacotherapy is being considered, request a BMD using DXA of the femoral neck, then reestimate the fracture risk by adding the BMD T-score into the FRAX.
Potential harms associated with various treatments, with varying levels of evidence, include the following: with alendronate and denosumab, nonserious gastrointestinal adverse events; with denosumab, rash, eczema, and infections; with zoledronic acid, nonserious events, such as headache and flulike symptoms; and with alendronate and bisphosphonates, rare but serious harms of atypical femoral fracture and osteonecrosis of the jaw.
“These recommendations emphasize the importance of good clinical practice, where clinicians are alert to changes in physical health and patient well-being,” the authors wrote. “Clinicians should also be aware of the importance of secondary prevention (i.e., after fracture) and manage patients accordingly.”
“This is an important topic,” Dr. Grad said. “Fragility fractures are consequential for individuals and for our publicly funded health care system. We anticipate questions from clinicians about the time needed to screen with the risk assessment–first strategy. Our modeling work suggests time savings with [this] strategy compared to a strategy of BMD testing first. Following our recommendations may lead to a reduction in BMD testing.”
To promote the guideline, the CMAJ has recorded a podcast and will use other strategies to increase awareness, Dr. Grad said. “The Canadian Task Force has a communications strategy that includes outreach to primary care, stakeholder webinars, social media, partnerships, and other tactics. The College of Family Physicians of Canada has endorsed the guideline and will help promote to its members.”
Other at-risk groups?
Aliya Khan, MD, FRCPC, FACP, FACE, professor in the divisions of endocrinology and metabolism and geriatrics and director of the fellowship in metabolic bone diseases at McMaster University in Hamilton, Ont., told this news organization she agrees with the strategy of evaluating women aged 65 and older for fracture risk.
“The decision aid is useful, but I would like to see it expanded to other circumstances and situations,” she said.
For example, Dr. Khan would like to see recommendations for younger women and for men of all ages regarding secondary causes of osteoporosis or medications known to have a detrimental effect on bone health. By not addressing these patients, she said, “we may miss patients who would benefit from a fracture risk assessment and potentially treatment to prevent low-trauma fractures.”
A recommendation for younger postmenopausal women was included in the most recent Society of Obstetricians and Gynaecologists Canada guideline, she noted.
Overall, she said, “I believe these recommendations will reduce the excess or inappropriate use of BMD testing and that is welcome.”
Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. The task force members report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new Canadian guideline on screening for the primary prevention of fragility fractures recommends risk assessment first, before bone mineral density (BMD) testing, for women aged 65 and older. For younger women and men aged 40 and older, screening is not recommended.
To develop the guideline, a writing group from Canadian Task Force on Preventive Health Care commissioned systematic reviews of studies on the benefits and harms of fragility fracture screenings; the predictive accuracy of current risk-assessment tools; patient acceptability; and benefits of treatment. Treatment harms were analyzed via a rapid overview of reviews.
The guideline, published online in the Canadian Medical Association Journal, is aimed at primary care practitioners for their community-dwelling patients aged 40 and older. The recommendations do not apply to people already taking preventive drugs.
Nondrug treatments were beyond the scope of the current guideline, but guidelines on the prevention of falls and other strategies are planned, Roland Grad, MD, a guideline author and associate professor at McGill University in Montreal, told this news organization.
The new guideline says that women aged 65 and older may be able to avoid fracture through screening and preventive medication. An individual’s fracture risk can be estimated with a new Fragility Fractures Decision Aid, which uses the Canadian FRAX risk-assessment tool.
“A risk assessment–first approach promotes shared decision-making with the patient, based on best medical evidence,” Dr. Grad said.
“To help clinicians, we have created an infographic with visuals to communicate the time spent on BMD vs risk assessment first.”
New evidence
“At least three things motivated this new guideline,” Dr. Grad said. “When we started work on this prior to the pandemic, we saw a need for updated guidance on screening to prevent fragility fractures. We were also aware of new evidence from the publication of screening trials in females older than 65.”
To conduct the risk assessment in older women, clinicians are advised to do the following:
- Use the decision aid (which patients can also use on their own).
- Use the 10-year absolute risk of major osteoporotic fracture to facilitate shared decision-making about possible benefits and harms of preventive pharmacotherapy.
- If pharmacotherapy is being considered, request a BMD using DXA of the femoral neck, then reestimate the fracture risk by adding the BMD T-score into the FRAX.
Potential harms associated with various treatments, with varying levels of evidence, include the following: with alendronate and denosumab, nonserious gastrointestinal adverse events; with denosumab, rash, eczema, and infections; with zoledronic acid, nonserious events, such as headache and flulike symptoms; and with alendronate and bisphosphonates, rare but serious harms of atypical femoral fracture and osteonecrosis of the jaw.
“These recommendations emphasize the importance of good clinical practice, where clinicians are alert to changes in physical health and patient well-being,” the authors wrote. “Clinicians should also be aware of the importance of secondary prevention (i.e., after fracture) and manage patients accordingly.”
“This is an important topic,” Dr. Grad said. “Fragility fractures are consequential for individuals and for our publicly funded health care system. We anticipate questions from clinicians about the time needed to screen with the risk assessment–first strategy. Our modeling work suggests time savings with [this] strategy compared to a strategy of BMD testing first. Following our recommendations may lead to a reduction in BMD testing.”
To promote the guideline, the CMAJ has recorded a podcast and will use other strategies to increase awareness, Dr. Grad said. “The Canadian Task Force has a communications strategy that includes outreach to primary care, stakeholder webinars, social media, partnerships, and other tactics. The College of Family Physicians of Canada has endorsed the guideline and will help promote to its members.”
Other at-risk groups?
Aliya Khan, MD, FRCPC, FACP, FACE, professor in the divisions of endocrinology and metabolism and geriatrics and director of the fellowship in metabolic bone diseases at McMaster University in Hamilton, Ont., told this news organization she agrees with the strategy of evaluating women aged 65 and older for fracture risk.
“The decision aid is useful, but I would like to see it expanded to other circumstances and situations,” she said.
For example, Dr. Khan would like to see recommendations for younger women and for men of all ages regarding secondary causes of osteoporosis or medications known to have a detrimental effect on bone health. By not addressing these patients, she said, “we may miss patients who would benefit from a fracture risk assessment and potentially treatment to prevent low-trauma fractures.”
A recommendation for younger postmenopausal women was included in the most recent Society of Obstetricians and Gynaecologists Canada guideline, she noted.
Overall, she said, “I believe these recommendations will reduce the excess or inappropriate use of BMD testing and that is welcome.”
Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. The task force members report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Osteoporosis and osteopenia: Latest treatment recommendations
This transcript has been edited for clarity.
I’m Dr. Neil Skolnik. Today’s topic is the new osteoporosis treatment guidelines issued by the American College of Physicians (ACP). The focus of the guidelines is treatment of osteoporosis. But first, I want to discuss screening.
In its 2018 statement, the U.S. Preventive Services Task Force (USPSTF) says that osteoporosis should be screened for in women older than 65 years of age, and those who are younger who are at increased risk based on a risk assessment tool (usually the FRAX tool). There is not enough evidence to weigh in for or against screening men. The other large organization that weighs in on screening is the Bone Health & Osteoporosis Foundation, which agrees with the USPSTF, but in addition says that we should be screening men over age 70 and men who are younger (age 50 to 69) who have risk factors. We should also screen anyone who has a fracture after low impact or no trauma.
Let’s now go on to the ACP treatment guidelines. Osteoporosis is defined as bone mineral density at the femoral neck or the lumbar spine, or both, with a T score less than -2.5.
For postmenopausal women with osteoporosis, you should use a bisphosphonate as first-line treatment to reduce the risk for future fractures. This is given a strong recommendation based on a high certainty of evidence. Bisphosphonates vs. placebo over 3 years leads to one fewer hip fracture per 150 patients treated and one fewer vertebral fracture per 50 people treated.
All the other recommendations in the guidelines are considered “conditional recommendations” that are correct for most people. But whether they make sense for an individual patient depends upon other details, as well as their values and preferences. For instance, treatment of osteoporosis in men is given a conditional recommendation, not because the evidence suggests that it’s not as effective, but because there is not as much evidence. Initial treatment for a man with osteoporosis is with bisphosphonates. Men do get osteoporosis and account for about 30% of hip fractures. This is not a surprise to anyone who takes care of older adults.
For postmenopausal women or men who you would want to treat but who can’t tolerate a bisphosphonate, then the recommendation is to use a RANK ligand inhibitor. Denosumab can be used as second-line treatment to reduce the risk for fractures. Remember, bisphosphonates and denosumab are antiresorptive drugs, meaning they slow the progression of osteoporosis. The anabolic drugs, on the other hand, such as the sclerostin inhibitor romosozumab and recombinant human parathyroid hormone (PTH) teriparatide, increase bone density. The anabolic agents should be used only in women with primary osteoporosis who are at very high risk for fractures, and use of these agents always needs to be followed by an antiresorptive agent, because otherwise there’s a risk for rebound osteoporosis and an increased risk for vertebral fractures.
Now, how about osteopenia? The guidelines recommend that for women over 65 with osteopenia, use an individualized approach influenced by the level of risk for fracture, including increased age, low body weight, current smoking, hip fracture in a parent, fall risk, and a personal history of fracture. The guidelines note that increasing the duration of bisphosphonate therapy beyond 3-5 years does reduce the risk for new vertebral fractures, but it doesn’t reduce the risk for other fractures and it increases the risk for osteonecrosis of the jaw and atypical hip fractures. Therefore, the guidelines say that we should use bisphosphonates only for 3-5 years unless someone is at extremely high risk. It’s also important to note that there’s a fivefold higher risk for atypical femoral fractures among Asian women.
Don’t forget about adequate vitamin D and calcium. And most importantly, don’t forget about exercise, particularly exercise aimed at improving balance and quadriceps strength, which helps prevent falls.
Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He disclosed ties with AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck, Sanofi, Sanofi Pasteur, and Teva.
A version of this article originally appeared on Medscape.com.
This transcript has been edited for clarity.
I’m Dr. Neil Skolnik. Today’s topic is the new osteoporosis treatment guidelines issued by the American College of Physicians (ACP). The focus of the guidelines is treatment of osteoporosis. But first, I want to discuss screening.
In its 2018 statement, the U.S. Preventive Services Task Force (USPSTF) says that osteoporosis should be screened for in women older than 65 years of age, and those who are younger who are at increased risk based on a risk assessment tool (usually the FRAX tool). There is not enough evidence to weigh in for or against screening men. The other large organization that weighs in on screening is the Bone Health & Osteoporosis Foundation, which agrees with the USPSTF, but in addition says that we should be screening men over age 70 and men who are younger (age 50 to 69) who have risk factors. We should also screen anyone who has a fracture after low impact or no trauma.
Let’s now go on to the ACP treatment guidelines. Osteoporosis is defined as bone mineral density at the femoral neck or the lumbar spine, or both, with a T score less than -2.5.
For postmenopausal women with osteoporosis, you should use a bisphosphonate as first-line treatment to reduce the risk for future fractures. This is given a strong recommendation based on a high certainty of evidence. Bisphosphonates vs. placebo over 3 years leads to one fewer hip fracture per 150 patients treated and one fewer vertebral fracture per 50 people treated.
All the other recommendations in the guidelines are considered “conditional recommendations” that are correct for most people. But whether they make sense for an individual patient depends upon other details, as well as their values and preferences. For instance, treatment of osteoporosis in men is given a conditional recommendation, not because the evidence suggests that it’s not as effective, but because there is not as much evidence. Initial treatment for a man with osteoporosis is with bisphosphonates. Men do get osteoporosis and account for about 30% of hip fractures. This is not a surprise to anyone who takes care of older adults.
For postmenopausal women or men who you would want to treat but who can’t tolerate a bisphosphonate, then the recommendation is to use a RANK ligand inhibitor. Denosumab can be used as second-line treatment to reduce the risk for fractures. Remember, bisphosphonates and denosumab are antiresorptive drugs, meaning they slow the progression of osteoporosis. The anabolic drugs, on the other hand, such as the sclerostin inhibitor romosozumab and recombinant human parathyroid hormone (PTH) teriparatide, increase bone density. The anabolic agents should be used only in women with primary osteoporosis who are at very high risk for fractures, and use of these agents always needs to be followed by an antiresorptive agent, because otherwise there’s a risk for rebound osteoporosis and an increased risk for vertebral fractures.
Now, how about osteopenia? The guidelines recommend that for women over 65 with osteopenia, use an individualized approach influenced by the level of risk for fracture, including increased age, low body weight, current smoking, hip fracture in a parent, fall risk, and a personal history of fracture. The guidelines note that increasing the duration of bisphosphonate therapy beyond 3-5 years does reduce the risk for new vertebral fractures, but it doesn’t reduce the risk for other fractures and it increases the risk for osteonecrosis of the jaw and atypical hip fractures. Therefore, the guidelines say that we should use bisphosphonates only for 3-5 years unless someone is at extremely high risk. It’s also important to note that there’s a fivefold higher risk for atypical femoral fractures among Asian women.
Don’t forget about adequate vitamin D and calcium. And most importantly, don’t forget about exercise, particularly exercise aimed at improving balance and quadriceps strength, which helps prevent falls.
Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He disclosed ties with AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck, Sanofi, Sanofi Pasteur, and Teva.
A version of this article originally appeared on Medscape.com.
This transcript has been edited for clarity.
I’m Dr. Neil Skolnik. Today’s topic is the new osteoporosis treatment guidelines issued by the American College of Physicians (ACP). The focus of the guidelines is treatment of osteoporosis. But first, I want to discuss screening.
In its 2018 statement, the U.S. Preventive Services Task Force (USPSTF) says that osteoporosis should be screened for in women older than 65 years of age, and those who are younger who are at increased risk based on a risk assessment tool (usually the FRAX tool). There is not enough evidence to weigh in for or against screening men. The other large organization that weighs in on screening is the Bone Health & Osteoporosis Foundation, which agrees with the USPSTF, but in addition says that we should be screening men over age 70 and men who are younger (age 50 to 69) who have risk factors. We should also screen anyone who has a fracture after low impact or no trauma.
Let’s now go on to the ACP treatment guidelines. Osteoporosis is defined as bone mineral density at the femoral neck or the lumbar spine, or both, with a T score less than -2.5.
For postmenopausal women with osteoporosis, you should use a bisphosphonate as first-line treatment to reduce the risk for future fractures. This is given a strong recommendation based on a high certainty of evidence. Bisphosphonates vs. placebo over 3 years leads to one fewer hip fracture per 150 patients treated and one fewer vertebral fracture per 50 people treated.
All the other recommendations in the guidelines are considered “conditional recommendations” that are correct for most people. But whether they make sense for an individual patient depends upon other details, as well as their values and preferences. For instance, treatment of osteoporosis in men is given a conditional recommendation, not because the evidence suggests that it’s not as effective, but because there is not as much evidence. Initial treatment for a man with osteoporosis is with bisphosphonates. Men do get osteoporosis and account for about 30% of hip fractures. This is not a surprise to anyone who takes care of older adults.
For postmenopausal women or men who you would want to treat but who can’t tolerate a bisphosphonate, then the recommendation is to use a RANK ligand inhibitor. Denosumab can be used as second-line treatment to reduce the risk for fractures. Remember, bisphosphonates and denosumab are antiresorptive drugs, meaning they slow the progression of osteoporosis. The anabolic drugs, on the other hand, such as the sclerostin inhibitor romosozumab and recombinant human parathyroid hormone (PTH) teriparatide, increase bone density. The anabolic agents should be used only in women with primary osteoporosis who are at very high risk for fractures, and use of these agents always needs to be followed by an antiresorptive agent, because otherwise there’s a risk for rebound osteoporosis and an increased risk for vertebral fractures.
Now, how about osteopenia? The guidelines recommend that for women over 65 with osteopenia, use an individualized approach influenced by the level of risk for fracture, including increased age, low body weight, current smoking, hip fracture in a parent, fall risk, and a personal history of fracture. The guidelines note that increasing the duration of bisphosphonate therapy beyond 3-5 years does reduce the risk for new vertebral fractures, but it doesn’t reduce the risk for other fractures and it increases the risk for osteonecrosis of the jaw and atypical hip fractures. Therefore, the guidelines say that we should use bisphosphonates only for 3-5 years unless someone is at extremely high risk. It’s also important to note that there’s a fivefold higher risk for atypical femoral fractures among Asian women.
Don’t forget about adequate vitamin D and calcium. And most importantly, don’t forget about exercise, particularly exercise aimed at improving balance and quadriceps strength, which helps prevent falls.
Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He disclosed ties with AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck, Sanofi, Sanofi Pasteur, and Teva.
A version of this article originally appeared on Medscape.com.
Bone-bashing effects of air pollution becoming clearer
We have long recognized that our environment has a significant impact on our general health. Air pollution is known to contribute to respiratory conditions, poor cardiovascular outcomes, and certain kinds of cancer.
It’s increasingly important to identify factors that might contribute to suboptimal bone density and associated fracture risk in the population as a whole, and particularly in older adults. Aging is associated with a higher risk for osteoporosis and fractures, with their attendant morbidity, but individuals differ in their extent of bone loss and risk for fractures.
Known factors affecting bone health include genetics, age, sex, nutrition, physical activity, and hormonal factors. Certain medications, diseases, and lifestyle choices – such as smoking and alcohol intake – can also have deleterious effects on bone.
More recently, researchers have started examining the impact of air pollution on bone health.
As we know, the degree of pollution varies greatly from one region to another and can potentially significantly affect life in many parts of the world. In fact, the World Health Organization indicates that 99% of the world’s population breathes air exceeding the WHO guideline limits for pollutants.
Air pollutants include particulate matter (PM) as well as gases, such as nitric oxide, nitrogen dioxide, ammonia, carbon monoxide, sulfur dioxide, ozone, and certain volatile organic compounds. Particulate pollutants include a variety of substances produced from mostly human activities (such as vehicle emissions, biofuel combustion, mining, agriculture, and manufacturing, and also forest fires). They are classified not by their composition, but by their size (for example, PM1.0, PM2.5, and PM10 indicate PM with a diameter < 1.0, 2.5, and 10 microns, respectively). The finer the particle, the more likely it is to cross into the systemic circulation from the respiratory tract, with the potential to induce oxidative, inflammatory, and other changes in the body.
Many studies report that air pollution is a risk factor for osteoporosis. Some have found associations of lower bone density, osteoporosis, and fracture risk with higher concentrations of PM1.0, PM2.5, or PM10, even after controlling for other factors that could affect bone health. Some researchers have reported that although they didn’t find a significant association between PM and bone health, they did find an association between distance from the freeway and bone health – thus, exposure to polycyclic aromatic hydrocarbons and black carbon from vehicle emissions needs to be studied as a contributor to fracture risk.
Importantly, a prospective, observational study from the Women’s Health Initiative (which included more than 9,000 ethnically diverse women from three sites in the United States) reported a significant negative impact of PM10, nitric oxide, nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years on bone density at multiple sites, and particularly at the lumbar spine, in both cross-sectional and longitudinal analyses after controlling for demographic and socioeconomic factors. This study reported that nitrogen dioxide exposure may be a key determinant of bone density at the lumbar spine and in the whole body. Similarly, other studies have reported associations between atmospheric nitrogen dioxide or sulfur dioxide and risk for osteoporotic fractures.
Why the impact on bones?
The potential negative impact of pollution on bone has been attributed to many factors. PM induces systemic inflammation and an increase in cytokines that stimulate bone cells (osteoclasts) that cause bone loss. Other pollutants (gases and metal compounds) can cause oxidative damage to bone cells, whereas others act as endocrine disrupters and affect the functioning of these cells.
Pollution might also affect the synthesis and metabolism of vitamin D, which is necessary for absorption of calcium from the gut. High rates of pollution can reduce the amount of ultraviolet radiation reaching the earth which is important because certain wavelengths of ultraviolet radiation are necessary for vitamin D synthesis in our skin. Reduced vitamin D synthesis in skin can lead to poorly mineralized bone unless there is sufficient intake of vitamin D in diet or as supplements. Also, the conversion of vitamin D to its active form happens in the kidneys, and PM can be harmful to renal function. PM is also believed to cause increased breakdown of vitamin D into its inactive form.
Conversely, some studies have reported no association between pollution and bone density or osteoporosis risk, and two meta-analyses indicated that the association between the two is inconsistent. Some factors explaining variances in results include the number of individuals included in the study (larger studies are generally considered to be more reproducible), the fact that most studies are cross-sectional and not prospective, many do not control for other factors that might be deleterious to bone, and prediction models for the extent of PM or other exposure may not be completely accurate.
However, another recent meta-analysis reported an increased risk for lower total-body bone density and hip fracture after exposure to air pollution, particularly PM2.5 and nitrogen dioxide, but not to PM10, nitric oxide, or ozone. More studies are needed to confirm, or refute, the association between air pollution and impaired bone health. But accumulating evidence suggests that air pollution very likely has a deleterious effect on bone.
When feasible, it’s important to avoid living or working in areas with poor air quality and high pollution rates. However, this isn’t always possible based on one’s occupation, geography, circumstances, or economic status. Therefore, attention to a cleaner environment is critical at both the individual and the macro level.
As an example of the latter, the city of London extended its ultralow emission zone (ULEZ) farther out of the city in October 2021, and a further expansion is planned to include all of the city’s boroughs in August 2023.
We can do our bit by driving less and walking, biking, or using public transportation more often. We can also turn off the car engine when it’s not running, maintain our vehicles, switch to electric or hand-powered yard equipment, and not burn household garbage and limit backyard fires. We can also switch from gas to solar energy or wind, use efficient appliances and heating, and avoid unnecessary energy use. And we can choose sustainable products when possible.
For optimal bone health, we should remind patients to eat a healthy diet with the requisite amount of protein, calcium, and vitamin D. Vitamin D and calcium supplementation may be necessary for people whose intake of dairy and dairy products is low. Other important strategies to optimize bone health include engaging in healthy physical activity; avoiding smoking or excessive alcohol intake; and treating underlying gastrointestinal, endocrine, or other conditions that can reduce bone density.
Madhusmita Misra, MD, MPH, is the chief of the division of pediatric endocrinology, Mass General for Children; the associate director of the Harvard Catalyst Translation and Clinical Research Center; and the director of the Pediatric Endocrine-Sports Endocrine-Neuroendocrine Lab, Mass General Hospital, Boston.
A version of this article first appeared on Medscape.com.
We have long recognized that our environment has a significant impact on our general health. Air pollution is known to contribute to respiratory conditions, poor cardiovascular outcomes, and certain kinds of cancer.
It’s increasingly important to identify factors that might contribute to suboptimal bone density and associated fracture risk in the population as a whole, and particularly in older adults. Aging is associated with a higher risk for osteoporosis and fractures, with their attendant morbidity, but individuals differ in their extent of bone loss and risk for fractures.
Known factors affecting bone health include genetics, age, sex, nutrition, physical activity, and hormonal factors. Certain medications, diseases, and lifestyle choices – such as smoking and alcohol intake – can also have deleterious effects on bone.
More recently, researchers have started examining the impact of air pollution on bone health.
As we know, the degree of pollution varies greatly from one region to another and can potentially significantly affect life in many parts of the world. In fact, the World Health Organization indicates that 99% of the world’s population breathes air exceeding the WHO guideline limits for pollutants.
Air pollutants include particulate matter (PM) as well as gases, such as nitric oxide, nitrogen dioxide, ammonia, carbon monoxide, sulfur dioxide, ozone, and certain volatile organic compounds. Particulate pollutants include a variety of substances produced from mostly human activities (such as vehicle emissions, biofuel combustion, mining, agriculture, and manufacturing, and also forest fires). They are classified not by their composition, but by their size (for example, PM1.0, PM2.5, and PM10 indicate PM with a diameter < 1.0, 2.5, and 10 microns, respectively). The finer the particle, the more likely it is to cross into the systemic circulation from the respiratory tract, with the potential to induce oxidative, inflammatory, and other changes in the body.
Many studies report that air pollution is a risk factor for osteoporosis. Some have found associations of lower bone density, osteoporosis, and fracture risk with higher concentrations of PM1.0, PM2.5, or PM10, even after controlling for other factors that could affect bone health. Some researchers have reported that although they didn’t find a significant association between PM and bone health, they did find an association between distance from the freeway and bone health – thus, exposure to polycyclic aromatic hydrocarbons and black carbon from vehicle emissions needs to be studied as a contributor to fracture risk.
Importantly, a prospective, observational study from the Women’s Health Initiative (which included more than 9,000 ethnically diverse women from three sites in the United States) reported a significant negative impact of PM10, nitric oxide, nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years on bone density at multiple sites, and particularly at the lumbar spine, in both cross-sectional and longitudinal analyses after controlling for demographic and socioeconomic factors. This study reported that nitrogen dioxide exposure may be a key determinant of bone density at the lumbar spine and in the whole body. Similarly, other studies have reported associations between atmospheric nitrogen dioxide or sulfur dioxide and risk for osteoporotic fractures.
Why the impact on bones?
The potential negative impact of pollution on bone has been attributed to many factors. PM induces systemic inflammation and an increase in cytokines that stimulate bone cells (osteoclasts) that cause bone loss. Other pollutants (gases and metal compounds) can cause oxidative damage to bone cells, whereas others act as endocrine disrupters and affect the functioning of these cells.
Pollution might also affect the synthesis and metabolism of vitamin D, which is necessary for absorption of calcium from the gut. High rates of pollution can reduce the amount of ultraviolet radiation reaching the earth which is important because certain wavelengths of ultraviolet radiation are necessary for vitamin D synthesis in our skin. Reduced vitamin D synthesis in skin can lead to poorly mineralized bone unless there is sufficient intake of vitamin D in diet or as supplements. Also, the conversion of vitamin D to its active form happens in the kidneys, and PM can be harmful to renal function. PM is also believed to cause increased breakdown of vitamin D into its inactive form.
Conversely, some studies have reported no association between pollution and bone density or osteoporosis risk, and two meta-analyses indicated that the association between the two is inconsistent. Some factors explaining variances in results include the number of individuals included in the study (larger studies are generally considered to be more reproducible), the fact that most studies are cross-sectional and not prospective, many do not control for other factors that might be deleterious to bone, and prediction models for the extent of PM or other exposure may not be completely accurate.
However, another recent meta-analysis reported an increased risk for lower total-body bone density and hip fracture after exposure to air pollution, particularly PM2.5 and nitrogen dioxide, but not to PM10, nitric oxide, or ozone. More studies are needed to confirm, or refute, the association between air pollution and impaired bone health. But accumulating evidence suggests that air pollution very likely has a deleterious effect on bone.
When feasible, it’s important to avoid living or working in areas with poor air quality and high pollution rates. However, this isn’t always possible based on one’s occupation, geography, circumstances, or economic status. Therefore, attention to a cleaner environment is critical at both the individual and the macro level.
As an example of the latter, the city of London extended its ultralow emission zone (ULEZ) farther out of the city in October 2021, and a further expansion is planned to include all of the city’s boroughs in August 2023.
We can do our bit by driving less and walking, biking, or using public transportation more often. We can also turn off the car engine when it’s not running, maintain our vehicles, switch to electric or hand-powered yard equipment, and not burn household garbage and limit backyard fires. We can also switch from gas to solar energy or wind, use efficient appliances and heating, and avoid unnecessary energy use. And we can choose sustainable products when possible.
For optimal bone health, we should remind patients to eat a healthy diet with the requisite amount of protein, calcium, and vitamin D. Vitamin D and calcium supplementation may be necessary for people whose intake of dairy and dairy products is low. Other important strategies to optimize bone health include engaging in healthy physical activity; avoiding smoking or excessive alcohol intake; and treating underlying gastrointestinal, endocrine, or other conditions that can reduce bone density.
Madhusmita Misra, MD, MPH, is the chief of the division of pediatric endocrinology, Mass General for Children; the associate director of the Harvard Catalyst Translation and Clinical Research Center; and the director of the Pediatric Endocrine-Sports Endocrine-Neuroendocrine Lab, Mass General Hospital, Boston.
A version of this article first appeared on Medscape.com.
We have long recognized that our environment has a significant impact on our general health. Air pollution is known to contribute to respiratory conditions, poor cardiovascular outcomes, and certain kinds of cancer.
It’s increasingly important to identify factors that might contribute to suboptimal bone density and associated fracture risk in the population as a whole, and particularly in older adults. Aging is associated with a higher risk for osteoporosis and fractures, with their attendant morbidity, but individuals differ in their extent of bone loss and risk for fractures.
Known factors affecting bone health include genetics, age, sex, nutrition, physical activity, and hormonal factors. Certain medications, diseases, and lifestyle choices – such as smoking and alcohol intake – can also have deleterious effects on bone.
More recently, researchers have started examining the impact of air pollution on bone health.
As we know, the degree of pollution varies greatly from one region to another and can potentially significantly affect life in many parts of the world. In fact, the World Health Organization indicates that 99% of the world’s population breathes air exceeding the WHO guideline limits for pollutants.
Air pollutants include particulate matter (PM) as well as gases, such as nitric oxide, nitrogen dioxide, ammonia, carbon monoxide, sulfur dioxide, ozone, and certain volatile organic compounds. Particulate pollutants include a variety of substances produced from mostly human activities (such as vehicle emissions, biofuel combustion, mining, agriculture, and manufacturing, and also forest fires). They are classified not by their composition, but by their size (for example, PM1.0, PM2.5, and PM10 indicate PM with a diameter < 1.0, 2.5, and 10 microns, respectively). The finer the particle, the more likely it is to cross into the systemic circulation from the respiratory tract, with the potential to induce oxidative, inflammatory, and other changes in the body.
Many studies report that air pollution is a risk factor for osteoporosis. Some have found associations of lower bone density, osteoporosis, and fracture risk with higher concentrations of PM1.0, PM2.5, or PM10, even after controlling for other factors that could affect bone health. Some researchers have reported that although they didn’t find a significant association between PM and bone health, they did find an association between distance from the freeway and bone health – thus, exposure to polycyclic aromatic hydrocarbons and black carbon from vehicle emissions needs to be studied as a contributor to fracture risk.
Importantly, a prospective, observational study from the Women’s Health Initiative (which included more than 9,000 ethnically diverse women from three sites in the United States) reported a significant negative impact of PM10, nitric oxide, nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years on bone density at multiple sites, and particularly at the lumbar spine, in both cross-sectional and longitudinal analyses after controlling for demographic and socioeconomic factors. This study reported that nitrogen dioxide exposure may be a key determinant of bone density at the lumbar spine and in the whole body. Similarly, other studies have reported associations between atmospheric nitrogen dioxide or sulfur dioxide and risk for osteoporotic fractures.
Why the impact on bones?
The potential negative impact of pollution on bone has been attributed to many factors. PM induces systemic inflammation and an increase in cytokines that stimulate bone cells (osteoclasts) that cause bone loss. Other pollutants (gases and metal compounds) can cause oxidative damage to bone cells, whereas others act as endocrine disrupters and affect the functioning of these cells.
Pollution might also affect the synthesis and metabolism of vitamin D, which is necessary for absorption of calcium from the gut. High rates of pollution can reduce the amount of ultraviolet radiation reaching the earth which is important because certain wavelengths of ultraviolet radiation are necessary for vitamin D synthesis in our skin. Reduced vitamin D synthesis in skin can lead to poorly mineralized bone unless there is sufficient intake of vitamin D in diet or as supplements. Also, the conversion of vitamin D to its active form happens in the kidneys, and PM can be harmful to renal function. PM is also believed to cause increased breakdown of vitamin D into its inactive form.
Conversely, some studies have reported no association between pollution and bone density or osteoporosis risk, and two meta-analyses indicated that the association between the two is inconsistent. Some factors explaining variances in results include the number of individuals included in the study (larger studies are generally considered to be more reproducible), the fact that most studies are cross-sectional and not prospective, many do not control for other factors that might be deleterious to bone, and prediction models for the extent of PM or other exposure may not be completely accurate.
However, another recent meta-analysis reported an increased risk for lower total-body bone density and hip fracture after exposure to air pollution, particularly PM2.5 and nitrogen dioxide, but not to PM10, nitric oxide, or ozone. More studies are needed to confirm, or refute, the association between air pollution and impaired bone health. But accumulating evidence suggests that air pollution very likely has a deleterious effect on bone.
When feasible, it’s important to avoid living or working in areas with poor air quality and high pollution rates. However, this isn’t always possible based on one’s occupation, geography, circumstances, or economic status. Therefore, attention to a cleaner environment is critical at both the individual and the macro level.
As an example of the latter, the city of London extended its ultralow emission zone (ULEZ) farther out of the city in October 2021, and a further expansion is planned to include all of the city’s boroughs in August 2023.
We can do our bit by driving less and walking, biking, or using public transportation more often. We can also turn off the car engine when it’s not running, maintain our vehicles, switch to electric or hand-powered yard equipment, and not burn household garbage and limit backyard fires. We can also switch from gas to solar energy or wind, use efficient appliances and heating, and avoid unnecessary energy use. And we can choose sustainable products when possible.
For optimal bone health, we should remind patients to eat a healthy diet with the requisite amount of protein, calcium, and vitamin D. Vitamin D and calcium supplementation may be necessary for people whose intake of dairy and dairy products is low. Other important strategies to optimize bone health include engaging in healthy physical activity; avoiding smoking or excessive alcohol intake; and treating underlying gastrointestinal, endocrine, or other conditions that can reduce bone density.
Madhusmita Misra, MD, MPH, is the chief of the division of pediatric endocrinology, Mass General for Children; the associate director of the Harvard Catalyst Translation and Clinical Research Center; and the director of the Pediatric Endocrine-Sports Endocrine-Neuroendocrine Lab, Mass General Hospital, Boston.
A version of this article first appeared on Medscape.com.
Osteoporosis drugs may extend life after fracture
Long-term osteoporosis medications are associated with a reduced mortality risk following a fracture, new data suggest.
The findings, from nearly 50,000 individuals in a nationwide Taiwanese database from 2009 until 2018, suggest that alendronate/risedronate, denosumab, and zoledronic acid all result in a significantly lower mortality risk post fracture of 17%-22%, compared with raloxifene and bazedoxifene.
“Treatment for osteoporosis has the potential to minimize mortality risk in people of all ages and sexes for any type of fracture. The longer-acting treatments could lower mortality risk,” wrote Chih-Hsing Wu, MD, of the Institute of Gerontology at National Cheng Kung University, Tainan, Taiwan, and colleagues.
The findings have been published online in the Journal of Clinical Endocrinology and Metabolism.
Robert A. Adler, MD, who is chief of endocrinology at the Central Virginia Veterans Affairs Health Care System, Richmond, told this news organization that he hopes these new findings from a “really good database ... may be helpful in talking to a patient about the pros and cons of taking these drugs.”
“Patients have been made very fearful of the unusual side effects, particularly of the antiresorptive drugs,” which he notes include the rare adverse effects of jaw necrosis and atypical femoral fracture, which occur in about 1 per 10,000 patient-years.
“And because of that we have a hard time convincing people to want to take the drug in the first place or to stay on the drug once they start,” said Dr. Adler, who stressed that his viewpoints are his own and not representative of the VA.
“These data should help reinforce the advice already given in professional guidelines that their benefit outweighs any risks,” he stresses.
Dr. Adler also pointed out that both bisphosphonates included in the study, alendronate and zoledronic acid, are now available as generics and therefore inexpensive, but the latter can be subject to facility fees depending on where the infusion is delivered.
He added that hip fracture, in particular, triples the overall 1-year mortality risk in women aged 75-84 years and quadruples the risk in men. The study’s findings suggest that bisphosphonates, in particular, have pleiotropic effects beyond the bone; however, the underlying mechanisms are hard to determine.
“We don’t know all the reasons why people die after a fracture. These are older people who often have multiple medical problems, so it’s hard to dissect that out,” he said.
But whatever the mechanism for the salutary effect of the drugs, Dr. Adler said: “This is one other factor that might change people’s minds. You’re less likely to die. Well, that’s pretty good.”
‘Denosumab is a more potent antiresorptive than bisphosphonates’
Dr. Wu and colleagues analyzed data for individuals from Taiwan’s National Health Insurance Research Database. Between 2009 and 2017, 219,461 individuals had been newly diagnosed with an osteoporotic fracture. Of those, 46,729 were aged 40 and older and had been prescribed at least one anti-osteoporosis medication.
Participants were a mean age of 74.5 years, were 80% women, and 32% died during a mean follow-up of 4.7 years. The most commonly used anti-osteoporosis medications were the bisphosphonates alendronate or risedronate, followed by denosumab and the selective estrogen-receptor modulators (SERMs) daily oral raloxifene or bazedoxifene.
Patients treated with SERMs were used as the reference group because those drugs have been shown to have a neutral effect on mortality.
After adjustments, all but one of the medications had significantly lower mortality risks during follow-up, compared with raloxifene and bazedoxifene.
Compared with SERMs, at all fracture sites, the hazard ratios for mortality were 0.83 for alendronate/risedronate, 0.86 for denosumab, and 0.78 for zoledronic acid. Only ibandronate did not show the same protective effect.
Similar results were found for hip and vertebral fractures analyzed individually.
Women had a lower mortality risk than men.
Dr. Adler wrote an accompanying editorial for the article by Dr. Wu and colleagues.
Regarding the finding of benefit for denosumab, Dr. Adler notes: “I don’t know of another study that found denosumab leads to lower mortality. On the other hand, denosumab is a more potent antiresorptive than bisphosphonates.”
The study was funded by research grants from the Ministry of Science and Technology, Taiwan, partially supported by a research grant from the Taiwanese Osteoporosis Association and grants from National Cheng Kung University Hospital, Taiwan. Dr. Wu has reported receiving honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. Dr. Adler has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Long-term osteoporosis medications are associated with a reduced mortality risk following a fracture, new data suggest.
The findings, from nearly 50,000 individuals in a nationwide Taiwanese database from 2009 until 2018, suggest that alendronate/risedronate, denosumab, and zoledronic acid all result in a significantly lower mortality risk post fracture of 17%-22%, compared with raloxifene and bazedoxifene.
“Treatment for osteoporosis has the potential to minimize mortality risk in people of all ages and sexes for any type of fracture. The longer-acting treatments could lower mortality risk,” wrote Chih-Hsing Wu, MD, of the Institute of Gerontology at National Cheng Kung University, Tainan, Taiwan, and colleagues.
The findings have been published online in the Journal of Clinical Endocrinology and Metabolism.
Robert A. Adler, MD, who is chief of endocrinology at the Central Virginia Veterans Affairs Health Care System, Richmond, told this news organization that he hopes these new findings from a “really good database ... may be helpful in talking to a patient about the pros and cons of taking these drugs.”
“Patients have been made very fearful of the unusual side effects, particularly of the antiresorptive drugs,” which he notes include the rare adverse effects of jaw necrosis and atypical femoral fracture, which occur in about 1 per 10,000 patient-years.
“And because of that we have a hard time convincing people to want to take the drug in the first place or to stay on the drug once they start,” said Dr. Adler, who stressed that his viewpoints are his own and not representative of the VA.
“These data should help reinforce the advice already given in professional guidelines that their benefit outweighs any risks,” he stresses.
Dr. Adler also pointed out that both bisphosphonates included in the study, alendronate and zoledronic acid, are now available as generics and therefore inexpensive, but the latter can be subject to facility fees depending on where the infusion is delivered.
He added that hip fracture, in particular, triples the overall 1-year mortality risk in women aged 75-84 years and quadruples the risk in men. The study’s findings suggest that bisphosphonates, in particular, have pleiotropic effects beyond the bone; however, the underlying mechanisms are hard to determine.
“We don’t know all the reasons why people die after a fracture. These are older people who often have multiple medical problems, so it’s hard to dissect that out,” he said.
But whatever the mechanism for the salutary effect of the drugs, Dr. Adler said: “This is one other factor that might change people’s minds. You’re less likely to die. Well, that’s pretty good.”
‘Denosumab is a more potent antiresorptive than bisphosphonates’
Dr. Wu and colleagues analyzed data for individuals from Taiwan’s National Health Insurance Research Database. Between 2009 and 2017, 219,461 individuals had been newly diagnosed with an osteoporotic fracture. Of those, 46,729 were aged 40 and older and had been prescribed at least one anti-osteoporosis medication.
Participants were a mean age of 74.5 years, were 80% women, and 32% died during a mean follow-up of 4.7 years. The most commonly used anti-osteoporosis medications were the bisphosphonates alendronate or risedronate, followed by denosumab and the selective estrogen-receptor modulators (SERMs) daily oral raloxifene or bazedoxifene.
Patients treated with SERMs were used as the reference group because those drugs have been shown to have a neutral effect on mortality.
After adjustments, all but one of the medications had significantly lower mortality risks during follow-up, compared with raloxifene and bazedoxifene.
Compared with SERMs, at all fracture sites, the hazard ratios for mortality were 0.83 for alendronate/risedronate, 0.86 for denosumab, and 0.78 for zoledronic acid. Only ibandronate did not show the same protective effect.
Similar results were found for hip and vertebral fractures analyzed individually.
Women had a lower mortality risk than men.
Dr. Adler wrote an accompanying editorial for the article by Dr. Wu and colleagues.
Regarding the finding of benefit for denosumab, Dr. Adler notes: “I don’t know of another study that found denosumab leads to lower mortality. On the other hand, denosumab is a more potent antiresorptive than bisphosphonates.”
The study was funded by research grants from the Ministry of Science and Technology, Taiwan, partially supported by a research grant from the Taiwanese Osteoporosis Association and grants from National Cheng Kung University Hospital, Taiwan. Dr. Wu has reported receiving honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. Dr. Adler has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Long-term osteoporosis medications are associated with a reduced mortality risk following a fracture, new data suggest.
The findings, from nearly 50,000 individuals in a nationwide Taiwanese database from 2009 until 2018, suggest that alendronate/risedronate, denosumab, and zoledronic acid all result in a significantly lower mortality risk post fracture of 17%-22%, compared with raloxifene and bazedoxifene.
“Treatment for osteoporosis has the potential to minimize mortality risk in people of all ages and sexes for any type of fracture. The longer-acting treatments could lower mortality risk,” wrote Chih-Hsing Wu, MD, of the Institute of Gerontology at National Cheng Kung University, Tainan, Taiwan, and colleagues.
The findings have been published online in the Journal of Clinical Endocrinology and Metabolism.
Robert A. Adler, MD, who is chief of endocrinology at the Central Virginia Veterans Affairs Health Care System, Richmond, told this news organization that he hopes these new findings from a “really good database ... may be helpful in talking to a patient about the pros and cons of taking these drugs.”
“Patients have been made very fearful of the unusual side effects, particularly of the antiresorptive drugs,” which he notes include the rare adverse effects of jaw necrosis and atypical femoral fracture, which occur in about 1 per 10,000 patient-years.
“And because of that we have a hard time convincing people to want to take the drug in the first place or to stay on the drug once they start,” said Dr. Adler, who stressed that his viewpoints are his own and not representative of the VA.
“These data should help reinforce the advice already given in professional guidelines that their benefit outweighs any risks,” he stresses.
Dr. Adler also pointed out that both bisphosphonates included in the study, alendronate and zoledronic acid, are now available as generics and therefore inexpensive, but the latter can be subject to facility fees depending on where the infusion is delivered.
He added that hip fracture, in particular, triples the overall 1-year mortality risk in women aged 75-84 years and quadruples the risk in men. The study’s findings suggest that bisphosphonates, in particular, have pleiotropic effects beyond the bone; however, the underlying mechanisms are hard to determine.
“We don’t know all the reasons why people die after a fracture. These are older people who often have multiple medical problems, so it’s hard to dissect that out,” he said.
But whatever the mechanism for the salutary effect of the drugs, Dr. Adler said: “This is one other factor that might change people’s minds. You’re less likely to die. Well, that’s pretty good.”
‘Denosumab is a more potent antiresorptive than bisphosphonates’
Dr. Wu and colleagues analyzed data for individuals from Taiwan’s National Health Insurance Research Database. Between 2009 and 2017, 219,461 individuals had been newly diagnosed with an osteoporotic fracture. Of those, 46,729 were aged 40 and older and had been prescribed at least one anti-osteoporosis medication.
Participants were a mean age of 74.5 years, were 80% women, and 32% died during a mean follow-up of 4.7 years. The most commonly used anti-osteoporosis medications were the bisphosphonates alendronate or risedronate, followed by denosumab and the selective estrogen-receptor modulators (SERMs) daily oral raloxifene or bazedoxifene.
Patients treated with SERMs were used as the reference group because those drugs have been shown to have a neutral effect on mortality.
After adjustments, all but one of the medications had significantly lower mortality risks during follow-up, compared with raloxifene and bazedoxifene.
Compared with SERMs, at all fracture sites, the hazard ratios for mortality were 0.83 for alendronate/risedronate, 0.86 for denosumab, and 0.78 for zoledronic acid. Only ibandronate did not show the same protective effect.
Similar results were found for hip and vertebral fractures analyzed individually.
Women had a lower mortality risk than men.
Dr. Adler wrote an accompanying editorial for the article by Dr. Wu and colleagues.
Regarding the finding of benefit for denosumab, Dr. Adler notes: “I don’t know of another study that found denosumab leads to lower mortality. On the other hand, denosumab is a more potent antiresorptive than bisphosphonates.”
The study was funded by research grants from the Ministry of Science and Technology, Taiwan, partially supported by a research grant from the Taiwanese Osteoporosis Association and grants from National Cheng Kung University Hospital, Taiwan. Dr. Wu has reported receiving honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. Dr. Adler has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Holy smoke: Air pollution link to bone damage confirmed
Air pollution appears to contribute independently to bone damage in postmenopausal women, new data suggest.
The findings come from a new analysis of data from the Women’s Health Initiative (WHI) and location-specific air particulate information from the U.S. Environmental Protection Agency.
“Our findings confirm that poor air quality may be a risk factor for bone loss, independent of socioeconomic or demographic factors, and expands previous findings to postmenopausal women. Indeed, to our knowledge, this is the first study of the impact of criteria air pollutants on bone health in postmenopausal women,” Diddier Prada, MD, PhD, Columbia University, New York, and colleagues wrote.
The results are also the first to show that “nitrogen oxides contribute the most to bone damage and that the lumbar spine is one of the most susceptible sites,” they added.
Public health policies should aim to reduce air pollution in general, they wrote, and reducing nitrogen oxides, in particular, will reduce bone damage in postmenopausal women, prevent bone fractures, and reduce the health cost burden associated with osteoporosis in this population.
The findings were recently published in eClinicalMedicine.
Asked to comment, Giovanni Adami, MD, PhD, said in an interview that the study “adds to the body of literature on air pollution and bone health. The study confirms and provides further evidence linking air pollution exposure and osteoporosis.”
Dr. Adami, of the University of Verona (Italy), who also studies this topic, said that these new findings align with those from his group and others.
“The scientific literature in the field is clearly pointing toward a negative effect of chronic pollution exposure on bone health.”
He pointed to one study from his group that found chronic exposure to ultrafine particulate matter is associated with low BMD, and consequently, bone fragility, and another study that showed acute exposure to high levels of pollutants could actually cause fractures.
As for what might be done clinically, Dr. Adami said: “It is difficult to extrapolate direct and immediate recommendations for patients.
“However, it might be acceptable to say that patients at risk of osteoporosis, such as older women or those with prior bone fractures, should avoid chronic exposure to air pollution, perhaps using masks when walking in traffic or using air filters for indoor ventilation.”
Dr. Adami also said that this evidence so far might spur the future inclusion of chronic exposure to air pollution in fracture risk assessment tools, although this isn’t likely to come about in the near future.
Particulates linked to whole-body, hip, lumbar, and femoral neck BMD
The prospective observational study included 9,041 WHI participants seen over 32,663 visits who were an average of 63 years old at baseline. More than 70% were White, and just under half were college graduates.
With geocoded address data used to estimate particulate matter concentrations, mean levels of particulate matter of 10 mcm or less, nitrogen oxide nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years were all negatively associated with whole-body, total hip, femoral neck, and lumbar spine BMD.
In the multivariate analysis, the highest correlations were found between nitrogen oxide and nitrogen dioxide. For example, lumbar spine BMD decreased by 0.026 g/cm2 per year per 10% increase in 3-year mean nitrogen dioxide concentration.
“Our findings show that both particulate matter and gases may adversely impact BMD and that nitrogen oxides may play a critical role in bone damage and osteoporosis risk,” Dr. Prada and colleagues wrote.
Dr. Adami added: “We need more data to understand the precise magnitude of effect of air pollution on fractures, which might depend on levels of exposure but also on genetics and lifestyle.”
The study was funded by the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Adami reported receiving fees from Amgen, Eli Lilly, UCB, Fresenius Kabi, Galapagos, and Theramex.
A version of this article originally appeared on Medscape.com.
Air pollution appears to contribute independently to bone damage in postmenopausal women, new data suggest.
The findings come from a new analysis of data from the Women’s Health Initiative (WHI) and location-specific air particulate information from the U.S. Environmental Protection Agency.
“Our findings confirm that poor air quality may be a risk factor for bone loss, independent of socioeconomic or demographic factors, and expands previous findings to postmenopausal women. Indeed, to our knowledge, this is the first study of the impact of criteria air pollutants on bone health in postmenopausal women,” Diddier Prada, MD, PhD, Columbia University, New York, and colleagues wrote.
The results are also the first to show that “nitrogen oxides contribute the most to bone damage and that the lumbar spine is one of the most susceptible sites,” they added.
Public health policies should aim to reduce air pollution in general, they wrote, and reducing nitrogen oxides, in particular, will reduce bone damage in postmenopausal women, prevent bone fractures, and reduce the health cost burden associated with osteoporosis in this population.
The findings were recently published in eClinicalMedicine.
Asked to comment, Giovanni Adami, MD, PhD, said in an interview that the study “adds to the body of literature on air pollution and bone health. The study confirms and provides further evidence linking air pollution exposure and osteoporosis.”
Dr. Adami, of the University of Verona (Italy), who also studies this topic, said that these new findings align with those from his group and others.
“The scientific literature in the field is clearly pointing toward a negative effect of chronic pollution exposure on bone health.”
He pointed to one study from his group that found chronic exposure to ultrafine particulate matter is associated with low BMD, and consequently, bone fragility, and another study that showed acute exposure to high levels of pollutants could actually cause fractures.
As for what might be done clinically, Dr. Adami said: “It is difficult to extrapolate direct and immediate recommendations for patients.
“However, it might be acceptable to say that patients at risk of osteoporosis, such as older women or those with prior bone fractures, should avoid chronic exposure to air pollution, perhaps using masks when walking in traffic or using air filters for indoor ventilation.”
Dr. Adami also said that this evidence so far might spur the future inclusion of chronic exposure to air pollution in fracture risk assessment tools, although this isn’t likely to come about in the near future.
Particulates linked to whole-body, hip, lumbar, and femoral neck BMD
The prospective observational study included 9,041 WHI participants seen over 32,663 visits who were an average of 63 years old at baseline. More than 70% were White, and just under half were college graduates.
With geocoded address data used to estimate particulate matter concentrations, mean levels of particulate matter of 10 mcm or less, nitrogen oxide nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years were all negatively associated with whole-body, total hip, femoral neck, and lumbar spine BMD.
In the multivariate analysis, the highest correlations were found between nitrogen oxide and nitrogen dioxide. For example, lumbar spine BMD decreased by 0.026 g/cm2 per year per 10% increase in 3-year mean nitrogen dioxide concentration.
“Our findings show that both particulate matter and gases may adversely impact BMD and that nitrogen oxides may play a critical role in bone damage and osteoporosis risk,” Dr. Prada and colleagues wrote.
Dr. Adami added: “We need more data to understand the precise magnitude of effect of air pollution on fractures, which might depend on levels of exposure but also on genetics and lifestyle.”
The study was funded by the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Adami reported receiving fees from Amgen, Eli Lilly, UCB, Fresenius Kabi, Galapagos, and Theramex.
A version of this article originally appeared on Medscape.com.
Air pollution appears to contribute independently to bone damage in postmenopausal women, new data suggest.
The findings come from a new analysis of data from the Women’s Health Initiative (WHI) and location-specific air particulate information from the U.S. Environmental Protection Agency.
“Our findings confirm that poor air quality may be a risk factor for bone loss, independent of socioeconomic or demographic factors, and expands previous findings to postmenopausal women. Indeed, to our knowledge, this is the first study of the impact of criteria air pollutants on bone health in postmenopausal women,” Diddier Prada, MD, PhD, Columbia University, New York, and colleagues wrote.
The results are also the first to show that “nitrogen oxides contribute the most to bone damage and that the lumbar spine is one of the most susceptible sites,” they added.
Public health policies should aim to reduce air pollution in general, they wrote, and reducing nitrogen oxides, in particular, will reduce bone damage in postmenopausal women, prevent bone fractures, and reduce the health cost burden associated with osteoporosis in this population.
The findings were recently published in eClinicalMedicine.
Asked to comment, Giovanni Adami, MD, PhD, said in an interview that the study “adds to the body of literature on air pollution and bone health. The study confirms and provides further evidence linking air pollution exposure and osteoporosis.”
Dr. Adami, of the University of Verona (Italy), who also studies this topic, said that these new findings align with those from his group and others.
“The scientific literature in the field is clearly pointing toward a negative effect of chronic pollution exposure on bone health.”
He pointed to one study from his group that found chronic exposure to ultrafine particulate matter is associated with low BMD, and consequently, bone fragility, and another study that showed acute exposure to high levels of pollutants could actually cause fractures.
As for what might be done clinically, Dr. Adami said: “It is difficult to extrapolate direct and immediate recommendations for patients.
“However, it might be acceptable to say that patients at risk of osteoporosis, such as older women or those with prior bone fractures, should avoid chronic exposure to air pollution, perhaps using masks when walking in traffic or using air filters for indoor ventilation.”
Dr. Adami also said that this evidence so far might spur the future inclusion of chronic exposure to air pollution in fracture risk assessment tools, although this isn’t likely to come about in the near future.
Particulates linked to whole-body, hip, lumbar, and femoral neck BMD
The prospective observational study included 9,041 WHI participants seen over 32,663 visits who were an average of 63 years old at baseline. More than 70% were White, and just under half were college graduates.
With geocoded address data used to estimate particulate matter concentrations, mean levels of particulate matter of 10 mcm or less, nitrogen oxide nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years were all negatively associated with whole-body, total hip, femoral neck, and lumbar spine BMD.
In the multivariate analysis, the highest correlations were found between nitrogen oxide and nitrogen dioxide. For example, lumbar spine BMD decreased by 0.026 g/cm2 per year per 10% increase in 3-year mean nitrogen dioxide concentration.
“Our findings show that both particulate matter and gases may adversely impact BMD and that nitrogen oxides may play a critical role in bone damage and osteoporosis risk,” Dr. Prada and colleagues wrote.
Dr. Adami added: “We need more data to understand the precise magnitude of effect of air pollution on fractures, which might depend on levels of exposure but also on genetics and lifestyle.”
The study was funded by the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Adami reported receiving fees from Amgen, Eli Lilly, UCB, Fresenius Kabi, Galapagos, and Theramex.
A version of this article originally appeared on Medscape.com.
FROM ECLINICALMEDICINE