Osteoporosis

Major Finding: Regular use of PPIs posed fracture risks of 35%-45% when adjusted for age, calcium intake, and body mass index. The fully adjusted hazard ratio was 1.37.

Data Source: A prospective examination of the relationship between chronic PPI use and incident hip fracture among 79,899 postmenopausal women enrolled in the Nurses' Health Study.

Disclosures: Dr. Khalili reported having no conflicts of interest.

CHICAGO – Regular use of proton pump inhibitors is associated with an elevated risk of hip fractures, even after adjusting for important lifestyle risk factors, according to the findings of a prospective evaluation from the Nurses' Health Study.

The association was most striking for women with a history of smoking, observed Dr. Hamed Khalili of Massachusetts General Hospital, Boston.

The Food and Drug Association recently issued an advisory regarding a potential link between PPIs and fractures. While acid-suppressing medications have been hypothesized to increase the risk of osteoporotic fractures, studies examining this association have been inconsistent. These analyses have mostly been based on retrospective studies of small populations that have not controlled for important dietary and lifestyle confounders, and they have ascertained PPI use only at a single time point, Dr. Khalili said.

The current study aimed to be more definitive by prospectively examining the relationship between chronic PPI use and incident hip fracture among 79,899 postmenopausal women enrolled in the Nurses' Health Study, he said.

“We found that longer duration of use was associated with increased risk, and the strongest risk was confined to individuals with a history of smoking. … Our findings support the recent decision of the FDA to revise labeling of PPIs to incorporate concerns about a possible increase in the risk of fractures,” he said at the meeting.

In 1982, participants in the Nurses' Health Study were first asked to report all previous fractures and were queried biennially for new fractures. Among the nearly 80,000 subjects, with 565,786 person-years of follow-up, there were 893 incident hip fractures over 8 years. PPI use was reported by 7% of participants in 2000 and by 19% of participants in 2008.

Regular use of PPIs posed fracture risks of 35%-45% when adjusted for age, calcium intake, and body mass index. The fully adjusted hazard ratio was 1.37, Dr. Khalili reported.

Current smoking status stood out as a significant effect modifier. Women who were current or past smokers and who regularly took a PPI had a 51% increased risk for fracture. In contrast, women who never smoked had only a 6% increased risk, “almost equal to women who never used PPIs,” he noted.

Longer duration of use was significantly associated with greater risk. Compared with never-users, risk in the multivariate analysis was 36% after 2 years of use, 42% after 4 years and 54% when PPIs were used for 6 years or longer, he said.

The investigators adjusted for multiple other risk factors, including physical activity; alcohol intake; total daily calcium and vitamin D intake; history of osteoporosis; and use of hormone replacement therapy, bisphosphonates, and thiazides. “This did not materially alter this association,” he noted.

When PPIs were discontinued, the risks declined. Two or more years after discontinuation, the risk of hip fracture was just 9%-10%, he noted.

“The strengths of our study are that it offers detailed, prospectively collected and validated information on PPI use and other risk factors. We had a high response rate, and the participants are educated health professionals,” he said. “But the study lacks information about PPI use prior to 2000, and it lacks specific information about brand and dose of PPI. It's not clear whether this is generalizable to other populations.”

The study, however, is in line with other reports of an association, and adds weight to the recommendation that clinicians carefully monitor the necessity of postmenopausal women to continue taking PPIs over the long-term, especially those who smoke.

Response from the audience was robust, with one attendee noting, “This is truly excellent work,” and another calling the study “impressive.”

Major Finding: Regular use of PPIs posed fracture risks of 35%-45% when adjusted for age, calcium intake, and body mass index. The fully adjusted hazard ratio was 1.37.

Data Source: A prospective examination of the relationship between chronic PPI use and incident hip fracture among 79,899 postmenopausal women enrolled in the Nurses' Health Study.

Disclosures: Dr. Khalili reported having no conflicts of interest.

CHICAGO – Regular use of proton pump inhibitors is associated with an elevated risk of hip fractures, even after adjusting for important lifestyle risk factors, according to the findings of a prospective evaluation from the Nurses' Health Study.

The association was most striking for women with a history of smoking, observed Dr. Hamed Khalili of Massachusetts General Hospital, Boston.

The Food and Drug Association recently issued an advisory regarding a potential link between PPIs and fractures. While acid-suppressing medications have been hypothesized to increase the risk of osteoporotic fractures, studies examining this association have been inconsistent. These analyses have mostly been based on retrospective studies of small populations that have not controlled for important dietary and lifestyle confounders, and they have ascertained PPI use only at a single time point, Dr. Khalili said.

The current study aimed to be more definitive by prospectively examining the relationship between chronic PPI use and incident hip fracture among 79,899 postmenopausal women enrolled in the Nurses' Health Study, he said.

“We found that longer duration of use was associated with increased risk, and the strongest risk was confined to individuals with a history of smoking. … Our findings support the recent decision of the FDA to revise labeling of PPIs to incorporate concerns about a possible increase in the risk of fractures,” he said at the meeting.

In 1982, participants in the Nurses' Health Study were first asked to report all previous fractures and were queried biennially for new fractures. Among the nearly 80,000 subjects, with 565,786 person-years of follow-up, there were 893 incident hip fractures over 8 years. PPI use was reported by 7% of participants in 2000 and by 19% of participants in 2008.

Regular use of PPIs posed fracture risks of 35%-45% when adjusted for age, calcium intake, and body mass index. The fully adjusted hazard ratio was 1.37, Dr. Khalili reported.

Current smoking status stood out as a significant effect modifier. Women who were current or past smokers and who regularly took a PPI had a 51% increased risk for fracture. In contrast, women who never smoked had only a 6% increased risk, “almost equal to women who never used PPIs,” he noted.

Longer duration of use was significantly associated with greater risk. Compared with never-users, risk in the multivariate analysis was 36% after 2 years of use, 42% after 4 years and 54% when PPIs were used for 6 years or longer, he said.

The investigators adjusted for multiple other risk factors, including physical activity; alcohol intake; total daily calcium and vitamin D intake; history of osteoporosis; and use of hormone replacement therapy, bisphosphonates, and thiazides. “This did not materially alter this association,” he noted.

When PPIs were discontinued, the risks declined. Two or more years after discontinuation, the risk of hip fracture was just 9%-10%, he noted.

“The strengths of our study are that it offers detailed, prospectively collected and validated information on PPI use and other risk factors. We had a high response rate, and the participants are educated health professionals,” he said. “But the study lacks information about PPI use prior to 2000, and it lacks specific information about brand and dose of PPI. It's not clear whether this is generalizable to other populations.”

The study, however, is in line with other reports of an association, and adds weight to the recommendation that clinicians carefully monitor the necessity of postmenopausal women to continue taking PPIs over the long-term, especially those who smoke.

Response from the audience was robust, with one attendee noting, “This is truly excellent work,” and another calling the study “impressive.”

Major Finding: Regular use of PPIs posed fracture risks of 35%-45% when adjusted for age, calcium intake, and body mass index. The fully adjusted hazard ratio was 1.37.

Data Source: A prospective examination of the relationship between chronic PPI use and incident hip fracture among 79,899 postmenopausal women enrolled in the Nurses' Health Study.

Disclosures: Dr. Khalili reported having no conflicts of interest.

CHICAGO – Regular use of proton pump inhibitors is associated with an elevated risk of hip fractures, even after adjusting for important lifestyle risk factors, according to the findings of a prospective evaluation from the Nurses' Health Study.

The association was most striking for women with a history of smoking, observed Dr. Hamed Khalili of Massachusetts General Hospital, Boston.

The Food and Drug Association recently issued an advisory regarding a potential link between PPIs and fractures. While acid-suppressing medications have been hypothesized to increase the risk of osteoporotic fractures, studies examining this association have been inconsistent. These analyses have mostly been based on retrospective studies of small populations that have not controlled for important dietary and lifestyle confounders, and they have ascertained PPI use only at a single time point, Dr. Khalili said.

The current study aimed to be more definitive by prospectively examining the relationship between chronic PPI use and incident hip fracture among 79,899 postmenopausal women enrolled in the Nurses' Health Study, he said.

“We found that longer duration of use was associated with increased risk, and the strongest risk was confined to individuals with a history of smoking. … Our findings support the recent decision of the FDA to revise labeling of PPIs to incorporate concerns about a possible increase in the risk of fractures,” he said at the meeting.

In 1982, participants in the Nurses' Health Study were first asked to report all previous fractures and were queried biennially for new fractures. Among the nearly 80,000 subjects, with 565,786 person-years of follow-up, there were 893 incident hip fractures over 8 years. PPI use was reported by 7% of participants in 2000 and by 19% of participants in 2008.

Regular use of PPIs posed fracture risks of 35%-45% when adjusted for age, calcium intake, and body mass index. The fully adjusted hazard ratio was 1.37, Dr. Khalili reported.

Current smoking status stood out as a significant effect modifier. Women who were current or past smokers and who regularly took a PPI had a 51% increased risk for fracture. In contrast, women who never smoked had only a 6% increased risk, “almost equal to women who never used PPIs,” he noted.

Longer duration of use was significantly associated with greater risk. Compared with never-users, risk in the multivariate analysis was 36% after 2 years of use, 42% after 4 years and 54% when PPIs were used for 6 years or longer, he said.

The investigators adjusted for multiple other risk factors, including physical activity; alcohol intake; total daily calcium and vitamin D intake; history of osteoporosis; and use of hormone replacement therapy, bisphosphonates, and thiazides. “This did not materially alter this association,” he noted.

When PPIs were discontinued, the risks declined. Two or more years after discontinuation, the risk of hip fracture was just 9%-10%, he noted.

“The strengths of our study are that it offers detailed, prospectively collected and validated information on PPI use and other risk factors. We had a high response rate, and the participants are educated health professionals,” he said. “But the study lacks information about PPI use prior to 2000, and it lacks specific information about brand and dose of PPI. It's not clear whether this is generalizable to other populations.”

The study, however, is in line with other reports of an association, and adds weight to the recommendation that clinicians carefully monitor the necessity of postmenopausal women to continue taking PPIs over the long-term, especially those who smoke.

Response from the audience was robust, with one attendee noting, “This is truly excellent work,” and another calling the study “impressive.”

Major Finding: Physiologic doses of estrogen significantly increased bone mineral density z scores in the lumbar spine and hip in adolescent girls with anorexia nervosa.

Data Source: A prospective trial of 110 girls with anorexia nervosa randomized to receive estrogen replacement or placebo, and 40 healthy controls who were followed for 18 months.

Disclosures: Dr. Misra received support from Genentech.

BOSTON – Significant increases in bone mineral density at the spine and hip were seen in adolescent girls with anorexia nervosa treated with physiological doses of estrogen, as compared with placebo, according to Dr. Madhusmita Misra, who presented the findings at the meeting.

“We know that low bone mineral density is common in adolescent girls with anorexia nervosa. On dual-energy x-ray absorptiometry (DXA), about 50% have low z scores at one or more sites and they also have low bone accrual rates. This is a special concern during adolescence, when peak bone mass accrual normally occurs,” said Dr. Misra, a pediatrician at Harvard Medical School and Massachusetts General Hospital in Boston.

While previous studies have shown that giving oral estrogen combined with progesterone as birth control pills is not effective at increasing bone density in these girls, the effect of giving estrogen in a more natural or physiologic form to mimic puberty or as a transdermal patch had not been studied before.

In a prospective, randomized study, 110 girls with anorexia nervosa and 40 normal-weight girls of similar pubertal stage and bone age between the ages of 12 and 19 years were enrolled. The girls with anorexia nervosa were randomized to receive either placebo or estrogen, but which type of estrogen they received depended upon their bone maturity based on wrist and hand x-rays.

In order to avoid adversely affecting growth with estrogen, those with immature bone age (n = 14) received low-dose oral ethinyl estradiol in gradually increasing doses (3.75 mcg daily for 0-6 months, 7.5 mcg daily for 6-12 months, and 11.25 mcg daily for 12-18 months) while those with mature bone age (n = 96) received transdermal estradiol at full replacement doses (100 mcg 17-beta estradiol). All received calcium and vitamin D supplementation and were followed for 18 months (J. Bone Miner. Res. 2011 June 22 [doi.10.1002/jbmr.447]).

The results showed that after 18 months, spine and hip bone mineral density z scores increased significantly in girls with anorexia nervosa who received estrogen replacement, compared with those who received placebo, even after controlling for baseline age and weight.

Changes in lumbar bone mineral density were significantly lower at 6, 12, and 18 months in anorexic girls who did not receive estrogen, compared with either anorexic girls who received estrogen or healthy controls.

No significant differences were seen in these measures between anorexic girls who received estrogen and healthy controls. Similar trends were seen for hip bone mineral density, with significant differences at all time points between non–estrogen-treated anorexic girls and healthy controls; differences between treated and untreated anorexic girls were significant only at 18 months.

The two anorexic groups did not differ in body mass index, fat mass, or lean mass after estrogen treatment, indicating that estrogen replacement does not cause weight gain or changes in body composition.

“This is very encouraging and exciting data,” said Dr. Misra.

“I would strongly emphasize that the first step in treating anorexia nervosa has to be to encourage weight gain and menses resumption. As we know, there may be many girls who are recalcitrant about formal treatment, and the adolescent years are a difficult time to accrue bone mass. This is a strategy to optimize bone accrual in girls with anorexia nervosa, even if they are not recovering otherwise.”

She added that it was important to note that although estrogen replacement improves bone density, it often falls short of complete restoration of bone density to normal levels.

'This is a strategy to optimize bone accrual in girls with anorexia nervosa, even if they are not recovering.'

Source DR. MISRA

Major Finding: Physiologic doses of estrogen significantly increased bone mineral density z scores in the lumbar spine and hip in adolescent girls with anorexia nervosa.

Data Source: A prospective trial of 110 girls with anorexia nervosa randomized to receive estrogen replacement or placebo, and 40 healthy controls who were followed for 18 months.

Disclosures: Dr. Misra received support from Genentech.

BOSTON – Significant increases in bone mineral density at the spine and hip were seen in adolescent girls with anorexia nervosa treated with physiological doses of estrogen, as compared with placebo, according to Dr. Madhusmita Misra, who presented the findings at the meeting.

“We know that low bone mineral density is common in adolescent girls with anorexia nervosa. On dual-energy x-ray absorptiometry (DXA), about 50% have low z scores at one or more sites and they also have low bone accrual rates. This is a special concern during adolescence, when peak bone mass accrual normally occurs,” said Dr. Misra, a pediatrician at Harvard Medical School and Massachusetts General Hospital in Boston.

While previous studies have shown that giving oral estrogen combined with progesterone as birth control pills is not effective at increasing bone density in these girls, the effect of giving estrogen in a more natural or physiologic form to mimic puberty or as a transdermal patch had not been studied before.

In a prospective, randomized study, 110 girls with anorexia nervosa and 40 normal-weight girls of similar pubertal stage and bone age between the ages of 12 and 19 years were enrolled. The girls with anorexia nervosa were randomized to receive either placebo or estrogen, but which type of estrogen they received depended upon their bone maturity based on wrist and hand x-rays.

In order to avoid adversely affecting growth with estrogen, those with immature bone age (n = 14) received low-dose oral ethinyl estradiol in gradually increasing doses (3.75 mcg daily for 0-6 months, 7.5 mcg daily for 6-12 months, and 11.25 mcg daily for 12-18 months) while those with mature bone age (n = 96) received transdermal estradiol at full replacement doses (100 mcg 17-beta estradiol). All received calcium and vitamin D supplementation and were followed for 18 months (J. Bone Miner. Res. 2011 June 22 [doi.10.1002/jbmr.447]).

The results showed that after 18 months, spine and hip bone mineral density z scores increased significantly in girls with anorexia nervosa who received estrogen replacement, compared with those who received placebo, even after controlling for baseline age and weight.

Changes in lumbar bone mineral density were significantly lower at 6, 12, and 18 months in anorexic girls who did not receive estrogen, compared with either anorexic girls who received estrogen or healthy controls.

No significant differences were seen in these measures between anorexic girls who received estrogen and healthy controls. Similar trends were seen for hip bone mineral density, with significant differences at all time points between non–estrogen-treated anorexic girls and healthy controls; differences between treated and untreated anorexic girls were significant only at 18 months.

The two anorexic groups did not differ in body mass index, fat mass, or lean mass after estrogen treatment, indicating that estrogen replacement does not cause weight gain or changes in body composition.

“This is very encouraging and exciting data,” said Dr. Misra.

“I would strongly emphasize that the first step in treating anorexia nervosa has to be to encourage weight gain and menses resumption. As we know, there may be many girls who are recalcitrant about formal treatment, and the adolescent years are a difficult time to accrue bone mass. This is a strategy to optimize bone accrual in girls with anorexia nervosa, even if they are not recovering otherwise.”

She added that it was important to note that although estrogen replacement improves bone density, it often falls short of complete restoration of bone density to normal levels.

'This is a strategy to optimize bone accrual in girls with anorexia nervosa, even if they are not recovering.'

Source DR. MISRA

Major Finding: Physiologic doses of estrogen significantly increased bone mineral density z scores in the lumbar spine and hip in adolescent girls with anorexia nervosa.

Data Source: A prospective trial of 110 girls with anorexia nervosa randomized to receive estrogen replacement or placebo, and 40 healthy controls who were followed for 18 months.

Disclosures: Dr. Misra received support from Genentech.

BOSTON – Significant increases in bone mineral density at the spine and hip were seen in adolescent girls with anorexia nervosa treated with physiological doses of estrogen, as compared with placebo, according to Dr. Madhusmita Misra, who presented the findings at the meeting.

“We know that low bone mineral density is common in adolescent girls with anorexia nervosa. On dual-energy x-ray absorptiometry (DXA), about 50% have low z scores at one or more sites and they also have low bone accrual rates. This is a special concern during adolescence, when peak bone mass accrual normally occurs,” said Dr. Misra, a pediatrician at Harvard Medical School and Massachusetts General Hospital in Boston.

While previous studies have shown that giving oral estrogen combined with progesterone as birth control pills is not effective at increasing bone density in these girls, the effect of giving estrogen in a more natural or physiologic form to mimic puberty or as a transdermal patch had not been studied before.

In a prospective, randomized study, 110 girls with anorexia nervosa and 40 normal-weight girls of similar pubertal stage and bone age between the ages of 12 and 19 years were enrolled. The girls with anorexia nervosa were randomized to receive either placebo or estrogen, but which type of estrogen they received depended upon their bone maturity based on wrist and hand x-rays.

In order to avoid adversely affecting growth with estrogen, those with immature bone age (n = 14) received low-dose oral ethinyl estradiol in gradually increasing doses (3.75 mcg daily for 0-6 months, 7.5 mcg daily for 6-12 months, and 11.25 mcg daily for 12-18 months) while those with mature bone age (n = 96) received transdermal estradiol at full replacement doses (100 mcg 17-beta estradiol). All received calcium and vitamin D supplementation and were followed for 18 months (J. Bone Miner. Res. 2011 June 22 [doi.10.1002/jbmr.447]).

The results showed that after 18 months, spine and hip bone mineral density z scores increased significantly in girls with anorexia nervosa who received estrogen replacement, compared with those who received placebo, even after controlling for baseline age and weight.

Changes in lumbar bone mineral density were significantly lower at 6, 12, and 18 months in anorexic girls who did not receive estrogen, compared with either anorexic girls who received estrogen or healthy controls.

No significant differences were seen in these measures between anorexic girls who received estrogen and healthy controls. Similar trends were seen for hip bone mineral density, with significant differences at all time points between non–estrogen-treated anorexic girls and healthy controls; differences between treated and untreated anorexic girls were significant only at 18 months.

The two anorexic groups did not differ in body mass index, fat mass, or lean mass after estrogen treatment, indicating that estrogen replacement does not cause weight gain or changes in body composition.

“This is very encouraging and exciting data,” said Dr. Misra.

“I would strongly emphasize that the first step in treating anorexia nervosa has to be to encourage weight gain and menses resumption. As we know, there may be many girls who are recalcitrant about formal treatment, and the adolescent years are a difficult time to accrue bone mass. This is a strategy to optimize bone accrual in girls with anorexia nervosa, even if they are not recovering otherwise.”

She added that it was important to note that although estrogen replacement improves bone density, it often falls short of complete restoration of bone density to normal levels.

'This is a strategy to optimize bone accrual in girls with anorexia nervosa, even if they are not recovering.'

Source DR. MISRA

Without Congressional action, Medicare payments for dual-energy x-ray absorptiometry will be cut in about half at the beginning of 2012.

But a small, bipartisan group of lawmakers in the House and Senate is pushing to extend DXA payment rates, which were passed as part of the Affordable Care Act and are set to expire at the end of this year, through 2013. Under the ACA, Congress instructed officials at the Centers for Medicare and Medicaid Services to increase DXA payments to 70% of the rate paid by Medicare in 2006.

The Preservation of Access to Osteoporosis Testing for Medicare Beneficiaries Act of 2011 (H.R. 2020/S. 1096) was introduced at the end of May; it would keep the current DXA payment rate in place for 2 years.

Rep. Michael Burgess (R-Tex.), one of the bill’s sponsors, said that cutting DXA payments is shortsighted. "Osteoporosis and related bone diseases pose a public health issue of enormous proportions, affecting millions of Americans and costing billions of dollars," he said in a statement. "As a physician, I diagnosed and treated many patients during my 25 years of practicing medicine in Texas, and I saw firsthand the way osteoporosis affects patients and their families. The more we can do to promote and encourage education, awareness, and prevention, the better. Why Medicare will pay for a fracture, but not reimburse a reasonable amount for a scan that can prevent that fracture, is beyond me."

Medicare began cutting DXA payments in 2007, after Congress included bone densitometry among a group of high-cost imaging services that were slashed as part of the Deficit Reduction Act of 2005. Since then, physicians have been struggling to cover their costs as reimbursement steadily declined from around $148 per scan in 2006 to about $54 in 2010. Exacerbating the problem is that private insurers have largely followed Medicare’s lead, ratcheting down their reimbursements as well. The ACA brought DXA payments up to about $98.

Physicians’ organizations, including the American College of Rheumatology (ACR) and the American Association of Clinical Endocrinologists (AACE), are urging lawmakers to pass an extension of the current DXA payment rate

Dr. Timothy J. Laing, government affairs committee chair for the ACR and a rheumatologist at the University of Michigan, Ann Arbor, said that if the reimbursement for the test falls below current levels, it will become economically unsustainable for physicians to provide the test in their offices.

Patients still will be able to get a DXA scan in the hospital, but there are downsides to that limited access, Dr. Laing said. Patients are far more likely to get the test if it can be done at the time it’s recommended, he said, adding that providing DXA scans in the office also provides an opportunity for on-the-spot, in-depth counseling from a physician who is knowledgeable about both interpreting the test and treating osteoporosis.

Forcing patients to seek osteoporosis screening in the hospital also means higher Medicare copayments, and usually means longer waits to get the test, said Dr. R. Mack Harrell, secretary of the AACE and an endocrinologist in the South Florida area.

AACE officials are concerned that a drop in reimbursement for DXA will create access problems for Medicare patients, Dr. Harrell said. This is troubling, he said, because osteoporosis testing is a service that is touted by the CMS in its "Your Medicare Benefits" booklet as an important preventive service available under Medicare. "If Medicare is going to make this a priority item for retired people, they have to make it accessible," he said.

Already, many physicians have stopped offering DXA services because of fee cuts, Dr. Harrell said. The good news is that there are still a substantial number of office practices and outpatient centers that can afford to keep their DXA scanners operating at the current reimbursement levels. But Dr. Harrell cautioned that the current payment level is the break-even point for most physicians who are really "hanging on by their fingernails." If rates are cut again, it will become "fiscally impossible" to offer the service in the office, he said.

ACR’s Dr. Laing predicted that getting the legislation passed this year will be an uphill battle. The major issue is the cost of extending the current payment rate.

"Right now, Congress is deadlocked over the budget, so any bill that is introduced that adds costs to anything is going to be difficult." Conversely, Dr. Laing said he is encouraged because the bill has bipartisan support in both the House and Senate.

Without Congressional action, Medicare payments for dual-energy x-ray absorptiometry will be cut in about half at the beginning of 2012.

But a small, bipartisan group of lawmakers in the House and Senate is pushing to extend DXA payment rates, which were passed as part of the Affordable Care Act and are set to expire at the end of this year, through 2013. Under the ACA, Congress instructed officials at the Centers for Medicare and Medicaid Services to increase DXA payments to 70% of the rate paid by Medicare in 2006.

The Preservation of Access to Osteoporosis Testing for Medicare Beneficiaries Act of 2011 (H.R. 2020/S. 1096) was introduced at the end of May; it would keep the current DXA payment rate in place for 2 years.

Rep. Michael Burgess (R-Tex.), one of the bill’s sponsors, said that cutting DXA payments is shortsighted. "Osteoporosis and related bone diseases pose a public health issue of enormous proportions, affecting millions of Americans and costing billions of dollars," he said in a statement. "As a physician, I diagnosed and treated many patients during my 25 years of practicing medicine in Texas, and I saw firsthand the way osteoporosis affects patients and their families. The more we can do to promote and encourage education, awareness, and prevention, the better. Why Medicare will pay for a fracture, but not reimburse a reasonable amount for a scan that can prevent that fracture, is beyond me."

Medicare began cutting DXA payments in 2007, after Congress included bone densitometry among a group of high-cost imaging services that were slashed as part of the Deficit Reduction Act of 2005. Since then, physicians have been struggling to cover their costs as reimbursement steadily declined from around $148 per scan in 2006 to about $54 in 2010. Exacerbating the problem is that private insurers have largely followed Medicare’s lead, ratcheting down their reimbursements as well. The ACA brought DXA payments up to about $98.

Physicians’ organizations, including the American College of Rheumatology (ACR) and the American Association of Clinical Endocrinologists (AACE), are urging lawmakers to pass an extension of the current DXA payment rate

Dr. Timothy J. Laing, government affairs committee chair for the ACR and a rheumatologist at the University of Michigan, Ann Arbor, said that if the reimbursement for the test falls below current levels, it will become economically unsustainable for physicians to provide the test in their offices.

Patients still will be able to get a DXA scan in the hospital, but there are downsides to that limited access, Dr. Laing said. Patients are far more likely to get the test if it can be done at the time it’s recommended, he said, adding that providing DXA scans in the office also provides an opportunity for on-the-spot, in-depth counseling from a physician who is knowledgeable about both interpreting the test and treating osteoporosis.

Forcing patients to seek osteoporosis screening in the hospital also means higher Medicare copayments, and usually means longer waits to get the test, said Dr. R. Mack Harrell, secretary of the AACE and an endocrinologist in the South Florida area.

AACE officials are concerned that a drop in reimbursement for DXA will create access problems for Medicare patients, Dr. Harrell said. This is troubling, he said, because osteoporosis testing is a service that is touted by the CMS in its "Your Medicare Benefits" booklet as an important preventive service available under Medicare. "If Medicare is going to make this a priority item for retired people, they have to make it accessible," he said.

Already, many physicians have stopped offering DXA services because of fee cuts, Dr. Harrell said. The good news is that there are still a substantial number of office practices and outpatient centers that can afford to keep their DXA scanners operating at the current reimbursement levels. But Dr. Harrell cautioned that the current payment level is the break-even point for most physicians who are really "hanging on by their fingernails." If rates are cut again, it will become "fiscally impossible" to offer the service in the office, he said.

ACR’s Dr. Laing predicted that getting the legislation passed this year will be an uphill battle. The major issue is the cost of extending the current payment rate.

"Right now, Congress is deadlocked over the budget, so any bill that is introduced that adds costs to anything is going to be difficult." Conversely, Dr. Laing said he is encouraged because the bill has bipartisan support in both the House and Senate.

Without Congressional action, Medicare payments for dual-energy x-ray absorptiometry will be cut in about half at the beginning of 2012.

But a small, bipartisan group of lawmakers in the House and Senate is pushing to extend DXA payment rates, which were passed as part of the Affordable Care Act and are set to expire at the end of this year, through 2013. Under the ACA, Congress instructed officials at the Centers for Medicare and Medicaid Services to increase DXA payments to 70% of the rate paid by Medicare in 2006.

The Preservation of Access to Osteoporosis Testing for Medicare Beneficiaries Act of 2011 (H.R. 2020/S. 1096) was introduced at the end of May; it would keep the current DXA payment rate in place for 2 years.

Rep. Michael Burgess (R-Tex.), one of the bill’s sponsors, said that cutting DXA payments is shortsighted. "Osteoporosis and related bone diseases pose a public health issue of enormous proportions, affecting millions of Americans and costing billions of dollars," he said in a statement. "As a physician, I diagnosed and treated many patients during my 25 years of practicing medicine in Texas, and I saw firsthand the way osteoporosis affects patients and their families. The more we can do to promote and encourage education, awareness, and prevention, the better. Why Medicare will pay for a fracture, but not reimburse a reasonable amount for a scan that can prevent that fracture, is beyond me."

Medicare began cutting DXA payments in 2007, after Congress included bone densitometry among a group of high-cost imaging services that were slashed as part of the Deficit Reduction Act of 2005. Since then, physicians have been struggling to cover their costs as reimbursement steadily declined from around $148 per scan in 2006 to about $54 in 2010. Exacerbating the problem is that private insurers have largely followed Medicare’s lead, ratcheting down their reimbursements as well. The ACA brought DXA payments up to about $98.

Physicians’ organizations, including the American College of Rheumatology (ACR) and the American Association of Clinical Endocrinologists (AACE), are urging lawmakers to pass an extension of the current DXA payment rate

Dr. Timothy J. Laing, government affairs committee chair for the ACR and a rheumatologist at the University of Michigan, Ann Arbor, said that if the reimbursement for the test falls below current levels, it will become economically unsustainable for physicians to provide the test in their offices.

Patients still will be able to get a DXA scan in the hospital, but there are downsides to that limited access, Dr. Laing said. Patients are far more likely to get the test if it can be done at the time it’s recommended, he said, adding that providing DXA scans in the office also provides an opportunity for on-the-spot, in-depth counseling from a physician who is knowledgeable about both interpreting the test and treating osteoporosis.

Forcing patients to seek osteoporosis screening in the hospital also means higher Medicare copayments, and usually means longer waits to get the test, said Dr. R. Mack Harrell, secretary of the AACE and an endocrinologist in the South Florida area.

AACE officials are concerned that a drop in reimbursement for DXA will create access problems for Medicare patients, Dr. Harrell said. This is troubling, he said, because osteoporosis testing is a service that is touted by the CMS in its "Your Medicare Benefits" booklet as an important preventive service available under Medicare. "If Medicare is going to make this a priority item for retired people, they have to make it accessible," he said.

Already, many physicians have stopped offering DXA services because of fee cuts, Dr. Harrell said. The good news is that there are still a substantial number of office practices and outpatient centers that can afford to keep their DXA scanners operating at the current reimbursement levels. But Dr. Harrell cautioned that the current payment level is the break-even point for most physicians who are really "hanging on by their fingernails." If rates are cut again, it will become "fiscally impossible" to offer the service in the office, he said.

ACR’s Dr. Laing predicted that getting the legislation passed this year will be an uphill battle. The major issue is the cost of extending the current payment rate.

"Right now, Congress is deadlocked over the budget, so any bill that is introduced that adds costs to anything is going to be difficult." Conversely, Dr. Laing said he is encouraged because the bill has bipartisan support in both the House and Senate.

Major Finding: A 5-mg infusion of zoledronic acid given to 31 patients with knee OA and associated bone marrow lesions reduced pain by 15 points more on a visual analog scale than did placebo, and reduced maximal bone marrow lesion area by 170 mm

Data Source: A single-center, randomized study with 31 patients who received a zoledronic acid infusion and 28 patients who received a placebo infusion.

Disclosures: The study was funded by Novartis, which markets zoledronic acid. Dr. Jones said that he has received speaker fees, travel sponsorship, and research support from Novartis and several other drug companies. Dr. Conaghan said that they had no disclosures.

LONDON – A single 5-mg infusion of zoledronic acid, a bisphosphonate, in patients with knee osteoarthritis led to significant pain reduction and shrinkage of bone marrow lesions in a randomized, placebo-controlled study with 59 patients.

The zoledronic acid treatment led to an average 15-point drop in pain (on a visual analog scale of 0-100) beyond what occurred in the placebo group, and the active treatment was also linked with an average 170-mm

“This is the first intervention shown to work on BMLs” in patients with osteoarthritis (OA), said Dr. Jones, professor of rheumatology and epidemiology and head of the musculoskeletal unit at the Menzies Research Institute Tasmania, Hobart, Australia.

“This is exciting for treating existing OA. It is one of the first positive structure modification trials,” commented Dr. Philip Conaghan, professor and chairman of musculoskeletal medicine at the University of Leeds (England).

“Results from several studies have linked BMLs with pain and cartilage damage in OA patients. The larger the BML, the faster the cartilage loss and the worse the pain,” Dr. Jones said in an interview. Based on studies his group has done, about 20% of BMLs that are associated with knee OA spontaneously enlarge over the course of 3 years, another 20% shrink in size, and about 60% remain the same, he said. Their earlier research findings also showed that BMLs are independently linked with fast progression of OA and the need for knee replacement. “If you reduce BMLs, it should produce good outcomes in patients,” he said.

“The next step is to show that treatment with zoledronic acid not only reduces BML size but also slows cartilage loss. Sixty patients followed for 12 months were not enough to assess cartilage. We will need about 400 patients followed for 2 years,” Dr. Jones added.

Despite not yet having information on cartilage effects, he said that his results so far have convinced him that treatment with zoledronic acid is reasonable for patients with painful knee OA and BMLs.

“I use it off label. Patients need to know it's off label, and they [therefore] must be willing to pay for it, but I use it. It's been shown to work, and nothing else works. Zoledronic acid [Reclast] is available, we know about its safety, and it's been used for a long time to treat osteoporosis and cancers. If you have OA patients with BMLs, this is something to actively consider for them. Patients with OA have very limited treatment options. This can make a large difference in their pain, and it has long-lasting benefit so it can be given once a year,” Dr. Jones said.

The benefits of zoledronic acid that were seen in his study might be a class effect that may be replicated by treatment with another bisphosphonate, but zoledronic acid is more potent than oral bisphosphonates and hence the drug's beneficial effect on pain and BML shrinkage may exceed the effect that other bisphosphonates might have, he said.

The pain benefit appeared to start wearing off about a year after the zoledronic acid injection. Dr. Jones said that he has a small number of patients whom he has infused a second time, which produced a second round of pain reduction.

The 59 patients who were enrolled in the study had an average age of about 60 years, with an average knee pain score of about 52 on the visual analog scale; all patients had BMLs as seen on MRI scans of their affected knees. In all, 31 patients received a 5-mg infusion of zoledronic acid and 28 patients received a placebo infusion. All patients also continued their conventional pain medication regimens.

The Food and Drug Administration has approved zoledronic acid under a number of brand names to prevent or treat osteoporosis in postmenopausal women or patients who are at risk for osteoporosis because they are taking or have taken corticosteroid therapy; to manage Paget's disease; and to prevent chemotherapy-induced bone fractures or fractures in patients with multiple myeloma or cancer that has metastasized to the bones from other locations.

MRI knee scans from two patients taken before (left) and 6 months after treatment with zoledronic acid show shrinkage of bone marrow lesions.

Source Courtesy Dr. Graeme Jones

Major Finding: A 5-mg infusion of zoledronic acid given to 31 patients with knee OA and associated bone marrow lesions reduced pain by 15 points more on a visual analog scale than did placebo, and reduced maximal bone marrow lesion area by 170 mm

Data Source: A single-center, randomized study with 31 patients who received a zoledronic acid infusion and 28 patients who received a placebo infusion.

Disclosures: The study was funded by Novartis, which markets zoledronic acid. Dr. Jones said that he has received speaker fees, travel sponsorship, and research support from Novartis and several other drug companies. Dr. Conaghan said that they had no disclosures.

LONDON – A single 5-mg infusion of zoledronic acid, a bisphosphonate, in patients with knee osteoarthritis led to significant pain reduction and shrinkage of bone marrow lesions in a randomized, placebo-controlled study with 59 patients.

The zoledronic acid treatment led to an average 15-point drop in pain (on a visual analog scale of 0-100) beyond what occurred in the placebo group, and the active treatment was also linked with an average 170-mm

“This is the first intervention shown to work on BMLs” in patients with osteoarthritis (OA), said Dr. Jones, professor of rheumatology and epidemiology and head of the musculoskeletal unit at the Menzies Research Institute Tasmania, Hobart, Australia.

“This is exciting for treating existing OA. It is one of the first positive structure modification trials,” commented Dr. Philip Conaghan, professor and chairman of musculoskeletal medicine at the University of Leeds (England).

“Results from several studies have linked BMLs with pain and cartilage damage in OA patients. The larger the BML, the faster the cartilage loss and the worse the pain,” Dr. Jones said in an interview. Based on studies his group has done, about 20% of BMLs that are associated with knee OA spontaneously enlarge over the course of 3 years, another 20% shrink in size, and about 60% remain the same, he said. Their earlier research findings also showed that BMLs are independently linked with fast progression of OA and the need for knee replacement. “If you reduce BMLs, it should produce good outcomes in patients,” he said.

“The next step is to show that treatment with zoledronic acid not only reduces BML size but also slows cartilage loss. Sixty patients followed for 12 months were not enough to assess cartilage. We will need about 400 patients followed for 2 years,” Dr. Jones added.

Despite not yet having information on cartilage effects, he said that his results so far have convinced him that treatment with zoledronic acid is reasonable for patients with painful knee OA and BMLs.

“I use it off label. Patients need to know it's off label, and they [therefore] must be willing to pay for it, but I use it. It's been shown to work, and nothing else works. Zoledronic acid [Reclast] is available, we know about its safety, and it's been used for a long time to treat osteoporosis and cancers. If you have OA patients with BMLs, this is something to actively consider for them. Patients with OA have very limited treatment options. This can make a large difference in their pain, and it has long-lasting benefit so it can be given once a year,” Dr. Jones said.

The benefits of zoledronic acid that were seen in his study might be a class effect that may be replicated by treatment with another bisphosphonate, but zoledronic acid is more potent than oral bisphosphonates and hence the drug's beneficial effect on pain and BML shrinkage may exceed the effect that other bisphosphonates might have, he said.

The pain benefit appeared to start wearing off about a year after the zoledronic acid injection. Dr. Jones said that he has a small number of patients whom he has infused a second time, which produced a second round of pain reduction.

The 59 patients who were enrolled in the study had an average age of about 60 years, with an average knee pain score of about 52 on the visual analog scale; all patients had BMLs as seen on MRI scans of their affected knees. In all, 31 patients received a 5-mg infusion of zoledronic acid and 28 patients received a placebo infusion. All patients also continued their conventional pain medication regimens.

The Food and Drug Administration has approved zoledronic acid under a number of brand names to prevent or treat osteoporosis in postmenopausal women or patients who are at risk for osteoporosis because they are taking or have taken corticosteroid therapy; to manage Paget's disease; and to prevent chemotherapy-induced bone fractures or fractures in patients with multiple myeloma or cancer that has metastasized to the bones from other locations.

MRI knee scans from two patients taken before (left) and 6 months after treatment with zoledronic acid show shrinkage of bone marrow lesions.

Source Courtesy Dr. Graeme Jones

Major Finding: A 5-mg infusion of zoledronic acid given to 31 patients with knee OA and associated bone marrow lesions reduced pain by 15 points more on a visual analog scale than did placebo, and reduced maximal bone marrow lesion area by 170 mm

Data Source: A single-center, randomized study with 31 patients who received a zoledronic acid infusion and 28 patients who received a placebo infusion.

Disclosures: The study was funded by Novartis, which markets zoledronic acid. Dr. Jones said that he has received speaker fees, travel sponsorship, and research support from Novartis and several other drug companies. Dr. Conaghan said that they had no disclosures.

LONDON – A single 5-mg infusion of zoledronic acid, a bisphosphonate, in patients with knee osteoarthritis led to significant pain reduction and shrinkage of bone marrow lesions in a randomized, placebo-controlled study with 59 patients.

The zoledronic acid treatment led to an average 15-point drop in pain (on a visual analog scale of 0-100) beyond what occurred in the placebo group, and the active treatment was also linked with an average 170-mm

“This is the first intervention shown to work on BMLs” in patients with osteoarthritis (OA), said Dr. Jones, professor of rheumatology and epidemiology and head of the musculoskeletal unit at the Menzies Research Institute Tasmania, Hobart, Australia.

“This is exciting for treating existing OA. It is one of the first positive structure modification trials,” commented Dr. Philip Conaghan, professor and chairman of musculoskeletal medicine at the University of Leeds (England).

“Results from several studies have linked BMLs with pain and cartilage damage in OA patients. The larger the BML, the faster the cartilage loss and the worse the pain,” Dr. Jones said in an interview. Based on studies his group has done, about 20% of BMLs that are associated with knee OA spontaneously enlarge over the course of 3 years, another 20% shrink in size, and about 60% remain the same, he said. Their earlier research findings also showed that BMLs are independently linked with fast progression of OA and the need for knee replacement. “If you reduce BMLs, it should produce good outcomes in patients,” he said.

“The next step is to show that treatment with zoledronic acid not only reduces BML size but also slows cartilage loss. Sixty patients followed for 12 months were not enough to assess cartilage. We will need about 400 patients followed for 2 years,” Dr. Jones added.

Despite not yet having information on cartilage effects, he said that his results so far have convinced him that treatment with zoledronic acid is reasonable for patients with painful knee OA and BMLs.

“I use it off label. Patients need to know it's off label, and they [therefore] must be willing to pay for it, but I use it. It's been shown to work, and nothing else works. Zoledronic acid [Reclast] is available, we know about its safety, and it's been used for a long time to treat osteoporosis and cancers. If you have OA patients with BMLs, this is something to actively consider for them. Patients with OA have very limited treatment options. This can make a large difference in their pain, and it has long-lasting benefit so it can be given once a year,” Dr. Jones said.

The benefits of zoledronic acid that were seen in his study might be a class effect that may be replicated by treatment with another bisphosphonate, but zoledronic acid is more potent than oral bisphosphonates and hence the drug's beneficial effect on pain and BML shrinkage may exceed the effect that other bisphosphonates might have, he said.

The pain benefit appeared to start wearing off about a year after the zoledronic acid injection. Dr. Jones said that he has a small number of patients whom he has infused a second time, which produced a second round of pain reduction.

The 59 patients who were enrolled in the study had an average age of about 60 years, with an average knee pain score of about 52 on the visual analog scale; all patients had BMLs as seen on MRI scans of their affected knees. In all, 31 patients received a 5-mg infusion of zoledronic acid and 28 patients received a placebo infusion. All patients also continued their conventional pain medication regimens.

The Food and Drug Administration has approved zoledronic acid under a number of brand names to prevent or treat osteoporosis in postmenopausal women or patients who are at risk for osteoporosis because they are taking or have taken corticosteroid therapy; to manage Paget's disease; and to prevent chemotherapy-induced bone fractures or fractures in patients with multiple myeloma or cancer that has metastasized to the bones from other locations.

MRI knee scans from two patients taken before (left) and 6 months after treatment with zoledronic acid show shrinkage of bone marrow lesions.

Source Courtesy Dr. Graeme Jones

TAMPA – The treatment of osteoporosis is in flux because of a variety of forces, including a substantial increase in the number of aging patients deemed eligible for treatments, a leading geriatrician said. Just as baby boomers begin reaching senior status, a recently developed tool for assessing people's fracture risk is increasing the number of patients considered suitable for preventive therapy.

Meanwhile, those therapy options are multiplying, and emerging evidence suggests that one, bisphosphonates, is associated with an increased risk for atypical fractures, although the absolute risk appears to be low, Dr. Barbara Messinger-Rapport, said at the meeting.

The assessment tool making a difference is the Web-based Fracture Risk Assessment Tool (FRAX), released by the World Health Organization in 2008. FRAX guides clinicians to consider drug therapy for patients with T scores (deviations from healthy bone density) of −2.5 or lower at the femoral neck or spine, a T score between −1.0 and −2.5 as well as a 3% or higher calculated risk for hip fracture over 10 years, or a 20% or greater risk of major osteoporosis-related fracture.

Even if a person's T score never reaches −2.5, his or her hip fracture risk can climb to 3% or higher, said Dr. Messinger-Rapport, director of the Center for Geriatric Medicine at the Cleveland Clinic and medical director of the Fairfax Health Care Center Nursing Home, also in Cleveland. “This could widen the number of people who could be put on treatment.”

Bisphosphonates remain the most-common treatment strategy, but optimal duration of therapy, timing of drug holidays, and how age and gender play into risk for adverse events remains unclear, she said.

A newer option, the monoclonal antibody denosumab (Prolia, Amgen), significantly reduced vertebral fractures compared with a placebo in published studies. Administered as a subcutaneous injection every 6 months, denosumab also may be more convenient than agents requiring infusion, Dr. Messinger-Rapport said.

Higher cost is a consideration, however. Wholesale cost of denosumab is approximately $850/60-mg subcutaneous injection. In contrast, generic alendronate costs $100-$200/year; brand-name oral bisphosphonate costs up to $1,000/year; and zoledronic acid, delivered via intravenous infusion, is approximately $1,100/year, she said.

Denosumab's impact on clinical care is not yet known, Dr. Messinger-Rapport said. She suggested that clinicians consider this agent in high-risk elders, women or men with osteoporosis, men with prostate cancer with androgen deprivation, patients with metastatic prostate or breast cancer, and possibly patients with renal impairment (denosumab clearance is not renal). Also consider denosumab for patients who cannot tolerate a bisphosphonate either orally or by infusion, she added.

Researchers showed a 68% decrease in vertebral fractures, a 40% decline in hip fractures, and a 20% decrease in nonvertebral fractures with denosumab versus placebo in the FREEDOM study of osteoporotic women treated for 36 months (N. Engl. J. Med. 2009;361:756-65). A similar 62% decrease in vertebral fractures with denosumab, compared with placebo, was observed in a 24-month study of men with androgen deprivation for prostate cancer (N. Engl. J. Med. 2009;361:745-55).

Researchers also have examined reports of atypical femoral fractures associated with bisphosphonate use and found an association. For example, in a study published last year, 17 of 20 atypical femoral fractures occurred in patients taking oral bisphosphonates (N. Engl. J. Med. 2010;363:1848-9).

In a letter (N. Engl. J. Med. 2010; 362:1848-9), the researchers stated that although they found the association, “overall the anti-fracture effects of bisphosphonates far outweigh their potential risks.”

More recently, other investigators found an increased risk of subtrochanteric and femoral shaft fractures in women treated for 5 years or more with oral bisphosphonates (JAMA 2011;305:783-9). The authors stated that the absolute risk of the atypical fractures is low, however.

Dr. Messinger-Rapport listed the contraindications to bisphosphonates as a prior allergic reaction, vitamin D depletion (less than 30 ng/mL), hypocalcemia, dysphagia, esophageal disorders, and severe gastroesophageal reflux disorder.

A person attending the meeting asked if it is appropriate to continue bisphosphonate therapy after a patient's T score improves. “Yes, even if the T score only improves by a few percentage points,” Dr. Messinger-Rapport replied, because there is a disproportionate benefit in terms of fracture risk reduction.

Dr. Messinger-Rapport has disclosed that she is a member of the editorial board for the National Osteoporosis Foundation.

To watch an interview with Dr. Messinger-Rapport, scan this QR code with a smartphone.

TAMPA – The treatment of osteoporosis is in flux because of a variety of forces, including a substantial increase in the number of aging patients deemed eligible for treatments, a leading geriatrician said. Just as baby boomers begin reaching senior status, a recently developed tool for assessing people's fracture risk is increasing the number of patients considered suitable for preventive therapy.

Meanwhile, those therapy options are multiplying, and emerging evidence suggests that one, bisphosphonates, is associated with an increased risk for atypical fractures, although the absolute risk appears to be low, Dr. Barbara Messinger-Rapport, said at the meeting.

The assessment tool making a difference is the Web-based Fracture Risk Assessment Tool (FRAX), released by the World Health Organization in 2008. FRAX guides clinicians to consider drug therapy for patients with T scores (deviations from healthy bone density) of −2.5 or lower at the femoral neck or spine, a T score between −1.0 and −2.5 as well as a 3% or higher calculated risk for hip fracture over 10 years, or a 20% or greater risk of major osteoporosis-related fracture.

Even if a person's T score never reaches −2.5, his or her hip fracture risk can climb to 3% or higher, said Dr. Messinger-Rapport, director of the Center for Geriatric Medicine at the Cleveland Clinic and medical director of the Fairfax Health Care Center Nursing Home, also in Cleveland. “This could widen the number of people who could be put on treatment.”

Bisphosphonates remain the most-common treatment strategy, but optimal duration of therapy, timing of drug holidays, and how age and gender play into risk for adverse events remains unclear, she said.

A newer option, the monoclonal antibody denosumab (Prolia, Amgen), significantly reduced vertebral fractures compared with a placebo in published studies. Administered as a subcutaneous injection every 6 months, denosumab also may be more convenient than agents requiring infusion, Dr. Messinger-Rapport said.

Higher cost is a consideration, however. Wholesale cost of denosumab is approximately $850/60-mg subcutaneous injection. In contrast, generic alendronate costs $100-$200/year; brand-name oral bisphosphonate costs up to $1,000/year; and zoledronic acid, delivered via intravenous infusion, is approximately $1,100/year, she said.

Denosumab's impact on clinical care is not yet known, Dr. Messinger-Rapport said. She suggested that clinicians consider this agent in high-risk elders, women or men with osteoporosis, men with prostate cancer with androgen deprivation, patients with metastatic prostate or breast cancer, and possibly patients with renal impairment (denosumab clearance is not renal). Also consider denosumab for patients who cannot tolerate a bisphosphonate either orally or by infusion, she added.

Researchers showed a 68% decrease in vertebral fractures, a 40% decline in hip fractures, and a 20% decrease in nonvertebral fractures with denosumab versus placebo in the FREEDOM study of osteoporotic women treated for 36 months (N. Engl. J. Med. 2009;361:756-65). A similar 62% decrease in vertebral fractures with denosumab, compared with placebo, was observed in a 24-month study of men with androgen deprivation for prostate cancer (N. Engl. J. Med. 2009;361:745-55).

Researchers also have examined reports of atypical femoral fractures associated with bisphosphonate use and found an association. For example, in a study published last year, 17 of 20 atypical femoral fractures occurred in patients taking oral bisphosphonates (N. Engl. J. Med. 2010;363:1848-9).

In a letter (N. Engl. J. Med. 2010; 362:1848-9), the researchers stated that although they found the association, “overall the anti-fracture effects of bisphosphonates far outweigh their potential risks.”

More recently, other investigators found an increased risk of subtrochanteric and femoral shaft fractures in women treated for 5 years or more with oral bisphosphonates (JAMA 2011;305:783-9). The authors stated that the absolute risk of the atypical fractures is low, however.

Dr. Messinger-Rapport listed the contraindications to bisphosphonates as a prior allergic reaction, vitamin D depletion (less than 30 ng/mL), hypocalcemia, dysphagia, esophageal disorders, and severe gastroesophageal reflux disorder.

A person attending the meeting asked if it is appropriate to continue bisphosphonate therapy after a patient's T score improves. “Yes, even if the T score only improves by a few percentage points,” Dr. Messinger-Rapport replied, because there is a disproportionate benefit in terms of fracture risk reduction.

Dr. Messinger-Rapport has disclosed that she is a member of the editorial board for the National Osteoporosis Foundation.

To watch an interview with Dr. Messinger-Rapport, scan this QR code with a smartphone.

TAMPA – The treatment of osteoporosis is in flux because of a variety of forces, including a substantial increase in the number of aging patients deemed eligible for treatments, a leading geriatrician said. Just as baby boomers begin reaching senior status, a recently developed tool for assessing people's fracture risk is increasing the number of patients considered suitable for preventive therapy.

Meanwhile, those therapy options are multiplying, and emerging evidence suggests that one, bisphosphonates, is associated with an increased risk for atypical fractures, although the absolute risk appears to be low, Dr. Barbara Messinger-Rapport, said at the meeting.

The assessment tool making a difference is the Web-based Fracture Risk Assessment Tool (FRAX), released by the World Health Organization in 2008. FRAX guides clinicians to consider drug therapy for patients with T scores (deviations from healthy bone density) of −2.5 or lower at the femoral neck or spine, a T score between −1.0 and −2.5 as well as a 3% or higher calculated risk for hip fracture over 10 years, or a 20% or greater risk of major osteoporosis-related fracture.

Even if a person's T score never reaches −2.5, his or her hip fracture risk can climb to 3% or higher, said Dr. Messinger-Rapport, director of the Center for Geriatric Medicine at the Cleveland Clinic and medical director of the Fairfax Health Care Center Nursing Home, also in Cleveland. “This could widen the number of people who could be put on treatment.”

Bisphosphonates remain the most-common treatment strategy, but optimal duration of therapy, timing of drug holidays, and how age and gender play into risk for adverse events remains unclear, she said.

A newer option, the monoclonal antibody denosumab (Prolia, Amgen), significantly reduced vertebral fractures compared with a placebo in published studies. Administered as a subcutaneous injection every 6 months, denosumab also may be more convenient than agents requiring infusion, Dr. Messinger-Rapport said.

Higher cost is a consideration, however. Wholesale cost of denosumab is approximately $850/60-mg subcutaneous injection. In contrast, generic alendronate costs $100-$200/year; brand-name oral bisphosphonate costs up to $1,000/year; and zoledronic acid, delivered via intravenous infusion, is approximately $1,100/year, she said.

Denosumab's impact on clinical care is not yet known, Dr. Messinger-Rapport said. She suggested that clinicians consider this agent in high-risk elders, women or men with osteoporosis, men with prostate cancer with androgen deprivation, patients with metastatic prostate or breast cancer, and possibly patients with renal impairment (denosumab clearance is not renal). Also consider denosumab for patients who cannot tolerate a bisphosphonate either orally or by infusion, she added.

Researchers showed a 68% decrease in vertebral fractures, a 40% decline in hip fractures, and a 20% decrease in nonvertebral fractures with denosumab versus placebo in the FREEDOM study of osteoporotic women treated for 36 months (N. Engl. J. Med. 2009;361:756-65). A similar 62% decrease in vertebral fractures with denosumab, compared with placebo, was observed in a 24-month study of men with androgen deprivation for prostate cancer (N. Engl. J. Med. 2009;361:745-55).

Researchers also have examined reports of atypical femoral fractures associated with bisphosphonate use and found an association. For example, in a study published last year, 17 of 20 atypical femoral fractures occurred in patients taking oral bisphosphonates (N. Engl. J. Med. 2010;363:1848-9).

In a letter (N. Engl. J. Med. 2010; 362:1848-9), the researchers stated that although they found the association, “overall the anti-fracture effects of bisphosphonates far outweigh their potential risks.”

More recently, other investigators found an increased risk of subtrochanteric and femoral shaft fractures in women treated for 5 years or more with oral bisphosphonates (JAMA 2011;305:783-9). The authors stated that the absolute risk of the atypical fractures is low, however.

Dr. Messinger-Rapport listed the contraindications to bisphosphonates as a prior allergic reaction, vitamin D depletion (less than 30 ng/mL), hypocalcemia, dysphagia, esophageal disorders, and severe gastroesophageal reflux disorder.

A person attending the meeting asked if it is appropriate to continue bisphosphonate therapy after a patient's T score improves. “Yes, even if the T score only improves by a few percentage points,” Dr. Messinger-Rapport replied, because there is a disproportionate benefit in terms of fracture risk reduction.

Dr. Messinger-Rapport has disclosed that she is a member of the editorial board for the National Osteoporosis Foundation.

To watch an interview with Dr. Messinger-Rapport, scan this QR code with a smartphone.

DESTIN, FLA. – More is not necessarily better when it comes to vitamin D.

“The optimal intake and blood levels are probably much more moderate than many have led us to believe,” Dr. JoAnn E. Manson said at the meeting.

As a member of the 14-person Institute of Medicine Committee charged with developing a recently published report on dietary reference intakes of vitamin D and calcium, Dr. Manson assisted in a “rigorous comprehensive review” of more than 1,000 studies, and while many researchers and clinicians have argued that people need much higher levels than the 400-800 IU/day intake (depending on age) recommended by the IOM to promote optimal health, the available evidence simply has not borne that out, said Dr. Manson, professor of epidemiology at Harvard University and chief of the division of preventive medicine at Brigham and Women's Hospital, Boston.

Although some IOM report naysayers advocate for levels up to 6,000 IU/day – and the lay press is replete with stories touting vitamin D as a panacea, it is actually very difficult to find any solid data showing increased benefit with higher doses, she said.

In fact, the committee's findings indicate that adequate intake for infants through age 12 months is 400 IU/day, and that the Recommended Dietary Allowance for individuals aged 1-70 years should be at least 600 IU/day, and those over age 70 years it should be 800 IU/day. The upper intake levels are 1,000 and 1,500 IU/day for those ages 0-6 months and 6-12 months, respectively, 2,500 IU/day for those ages 1-3 years, 3,000 IU/day for those ages 4-8 years, and 4,000 IU/day for those over age 8 years, according to the IOM report (J. Clin. Endocrinol. Metab. 2011;96:53-8).

These minimum levels represent the intake needed to meet the vitamin D requirements of 97.5% of the population, and correspond to a serum 25-hydroxyvitamin D (25-OHD) level of 20 ng/mL, which the data indicate is the optimal level. At levels above the upper intake level, which correspond to a serum 25-OHD level of about 50 ng/mL, adverse effects have been reported, Dr. Manson said.

Emerging evidence suggests excess intake may be associated with increased all-cause mortality, cancer, cardiovascular disease, falls, and fractures, she noted.

National Health and Nutrition Examination Survey (NHANES) data from 2008, for example, showed that age-adjusted mortality was highest among those with serum 25-OHD levels below 19 ng/mL in African Americans and below 27.5 ng/mL in the entire cohort, and that mortality decreased with increasing levels – but only to a certain point. At levels in the 50 ng/mL range for African Americans, and above 85 ng/mL in the entire cohort, mortality increased steadily.

Data on the effects of vitamin D on skeletal health, which provided the strongest basis for the IOM committee's report as they were most plentiful and convincing in terms of showing cause and effect (although evidence regarding numerous other diseases such as cancer, diabetes, and more were also considered), also suggest that too much vitamin D can lead to adverse effects. Women's Health Initiative findings, for example, show that adjusted hip fracture rates are highest among those with serum 25-OHD levels of 19.04 ng/mL and those greater than 28.3 ng/mL, and lowest among those between these levels (Ann. Intern. Med. 2008;149:242-50), Dr. Manson said.

In older men in the Osteoporotic Fractures in Men (MrOS) study, the adjusted risk of hip fractures was shown to be highest in those with serum 25-OHD levels less than 19 ng/mL (odds ratio 2.36, compared with those with levels greater than 28 ng/mL), with risk declining steadily in those with levels up to 28 ng/mL (J. Bone Miner. Res. 2010;25:545-53).

Other findings indicate the skeletal benefits of vitamin D are dependent on adequate calcium intake, which the committee determined is 200 and 260 mg/day for those aged 0-6 and 6-12 months, respectively; 700 mg/day for those aged 1-3 years; 1,000 mg/day for those aged 4-8 years, 19-70 years, and for women aged 19-50 years who are pregnant or lactating; 1,200 mg/day for those aged 51 years and older; and 1,300 mg/day for those aged 9-18 years, and for women aged 14-18 years who are pregnant or lactating.

An Agency for Healthcare Research and Quality report in 2009, for example, showed that three randomized controlled trials indicated no significant effect of vitamin D alone on fracture risk, but that one randomized controlled trial showed a benefit in those who received 800 IU of vitamin D₃ plus 1,200 mg/day of calcium for 2 years (odds ratio of fractures 0.80), Dr. Manson said.

Dr. Manson has received funding from the National Institutes of Health to conduct a large-scale randomized trial of vitamin D and omega-3 fatty acids.

DESTIN, FLA. – More is not necessarily better when it comes to vitamin D.

“The optimal intake and blood levels are probably much more moderate than many have led us to believe,” Dr. JoAnn E. Manson said at the meeting.

As a member of the 14-person Institute of Medicine Committee charged with developing a recently published report on dietary reference intakes of vitamin D and calcium, Dr. Manson assisted in a “rigorous comprehensive review” of more than 1,000 studies, and while many researchers and clinicians have argued that people need much higher levels than the 400-800 IU/day intake (depending on age) recommended by the IOM to promote optimal health, the available evidence simply has not borne that out, said Dr. Manson, professor of epidemiology at Harvard University and chief of the division of preventive medicine at Brigham and Women's Hospital, Boston.

Although some IOM report naysayers advocate for levels up to 6,000 IU/day – and the lay press is replete with stories touting vitamin D as a panacea, it is actually very difficult to find any solid data showing increased benefit with higher doses, she said.

In fact, the committee's findings indicate that adequate intake for infants through age 12 months is 400 IU/day, and that the Recommended Dietary Allowance for individuals aged 1-70 years should be at least 600 IU/day, and those over age 70 years it should be 800 IU/day. The upper intake levels are 1,000 and 1,500 IU/day for those ages 0-6 months and 6-12 months, respectively, 2,500 IU/day for those ages 1-3 years, 3,000 IU/day for those ages 4-8 years, and 4,000 IU/day for those over age 8 years, according to the IOM report (J. Clin. Endocrinol. Metab. 2011;96:53-8).

These minimum levels represent the intake needed to meet the vitamin D requirements of 97.5% of the population, and correspond to a serum 25-hydroxyvitamin D (25-OHD) level of 20 ng/mL, which the data indicate is the optimal level. At levels above the upper intake level, which correspond to a serum 25-OHD level of about 50 ng/mL, adverse effects have been reported, Dr. Manson said.

Emerging evidence suggests excess intake may be associated with increased all-cause mortality, cancer, cardiovascular disease, falls, and fractures, she noted.

National Health and Nutrition Examination Survey (NHANES) data from 2008, for example, showed that age-adjusted mortality was highest among those with serum 25-OHD levels below 19 ng/mL in African Americans and below 27.5 ng/mL in the entire cohort, and that mortality decreased with increasing levels – but only to a certain point. At levels in the 50 ng/mL range for African Americans, and above 85 ng/mL in the entire cohort, mortality increased steadily.

Data on the effects of vitamin D on skeletal health, which provided the strongest basis for the IOM committee's report as they were most plentiful and convincing in terms of showing cause and effect (although evidence regarding numerous other diseases such as cancer, diabetes, and more were also considered), also suggest that too much vitamin D can lead to adverse effects. Women's Health Initiative findings, for example, show that adjusted hip fracture rates are highest among those with serum 25-OHD levels of 19.04 ng/mL and those greater than 28.3 ng/mL, and lowest among those between these levels (Ann. Intern. Med. 2008;149:242-50), Dr. Manson said.

In older men in the Osteoporotic Fractures in Men (MrOS) study, the adjusted risk of hip fractures was shown to be highest in those with serum 25-OHD levels less than 19 ng/mL (odds ratio 2.36, compared with those with levels greater than 28 ng/mL), with risk declining steadily in those with levels up to 28 ng/mL (J. Bone Miner. Res. 2010;25:545-53).

Other findings indicate the skeletal benefits of vitamin D are dependent on adequate calcium intake, which the committee determined is 200 and 260 mg/day for those aged 0-6 and 6-12 months, respectively; 700 mg/day for those aged 1-3 years; 1,000 mg/day for those aged 4-8 years, 19-70 years, and for women aged 19-50 years who are pregnant or lactating; 1,200 mg/day for those aged 51 years and older; and 1,300 mg/day for those aged 9-18 years, and for women aged 14-18 years who are pregnant or lactating.

An Agency for Healthcare Research and Quality report in 2009, for example, showed that three randomized controlled trials indicated no significant effect of vitamin D alone on fracture risk, but that one randomized controlled trial showed a benefit in those who received 800 IU of vitamin D₃ plus 1,200 mg/day of calcium for 2 years (odds ratio of fractures 0.80), Dr. Manson said.

Dr. Manson has received funding from the National Institutes of Health to conduct a large-scale randomized trial of vitamin D and omega-3 fatty acids.

DESTIN, FLA. – More is not necessarily better when it comes to vitamin D.

“The optimal intake and blood levels are probably much more moderate than many have led us to believe,” Dr. JoAnn E. Manson said at the meeting.

As a member of the 14-person Institute of Medicine Committee charged with developing a recently published report on dietary reference intakes of vitamin D and calcium, Dr. Manson assisted in a “rigorous comprehensive review” of more than 1,000 studies, and while many researchers and clinicians have argued that people need much higher levels than the 400-800 IU/day intake (depending on age) recommended by the IOM to promote optimal health, the available evidence simply has not borne that out, said Dr. Manson, professor of epidemiology at Harvard University and chief of the division of preventive medicine at Brigham and Women's Hospital, Boston.

Although some IOM report naysayers advocate for levels up to 6,000 IU/day – and the lay press is replete with stories touting vitamin D as a panacea, it is actually very difficult to find any solid data showing increased benefit with higher doses, she said.

In fact, the committee's findings indicate that adequate intake for infants through age 12 months is 400 IU/day, and that the Recommended Dietary Allowance for individuals aged 1-70 years should be at least 600 IU/day, and those over age 70 years it should be 800 IU/day. The upper intake levels are 1,000 and 1,500 IU/day for those ages 0-6 months and 6-12 months, respectively, 2,500 IU/day for those ages 1-3 years, 3,000 IU/day for those ages 4-8 years, and 4,000 IU/day for those over age 8 years, according to the IOM report (J. Clin. Endocrinol. Metab. 2011;96:53-8).

These minimum levels represent the intake needed to meet the vitamin D requirements of 97.5% of the population, and correspond to a serum 25-hydroxyvitamin D (25-OHD) level of 20 ng/mL, which the data indicate is the optimal level. At levels above the upper intake level, which correspond to a serum 25-OHD level of about 50 ng/mL, adverse effects have been reported, Dr. Manson said.

Emerging evidence suggests excess intake may be associated with increased all-cause mortality, cancer, cardiovascular disease, falls, and fractures, she noted.

National Health and Nutrition Examination Survey (NHANES) data from 2008, for example, showed that age-adjusted mortality was highest among those with serum 25-OHD levels below 19 ng/mL in African Americans and below 27.5 ng/mL in the entire cohort, and that mortality decreased with increasing levels – but only to a certain point. At levels in the 50 ng/mL range for African Americans, and above 85 ng/mL in the entire cohort, mortality increased steadily.

Data on the effects of vitamin D on skeletal health, which provided the strongest basis for the IOM committee's report as they were most plentiful and convincing in terms of showing cause and effect (although evidence regarding numerous other diseases such as cancer, diabetes, and more were also considered), also suggest that too much vitamin D can lead to adverse effects. Women's Health Initiative findings, for example, show that adjusted hip fracture rates are highest among those with serum 25-OHD levels of 19.04 ng/mL and those greater than 28.3 ng/mL, and lowest among those between these levels (Ann. Intern. Med. 2008;149:242-50), Dr. Manson said.

In older men in the Osteoporotic Fractures in Men (MrOS) study, the adjusted risk of hip fractures was shown to be highest in those with serum 25-OHD levels less than 19 ng/mL (odds ratio 2.36, compared with those with levels greater than 28 ng/mL), with risk declining steadily in those with levels up to 28 ng/mL (J. Bone Miner. Res. 2010;25:545-53).

Other findings indicate the skeletal benefits of vitamin D are dependent on adequate calcium intake, which the committee determined is 200 and 260 mg/day for those aged 0-6 and 6-12 months, respectively; 700 mg/day for those aged 1-3 years; 1,000 mg/day for those aged 4-8 years, 19-70 years, and for women aged 19-50 years who are pregnant or lactating; 1,200 mg/day for those aged 51 years and older; and 1,300 mg/day for those aged 9-18 years, and for women aged 14-18 years who are pregnant or lactating.

An Agency for Healthcare Research and Quality report in 2009, for example, showed that three randomized controlled trials indicated no significant effect of vitamin D alone on fracture risk, but that one randomized controlled trial showed a benefit in those who received 800 IU of vitamin D₃ plus 1,200 mg/day of calcium for 2 years (odds ratio of fractures 0.80), Dr. Manson said.

Dr. Manson has received funding from the National Institutes of Health to conduct a large-scale randomized trial of vitamin D and omega-3 fatty acids.

Major Finding: In older adults with diabetes, any given BMD T score or FRAX score carried a higher fracture risk than did the same score in those without diabetes. The risk of hip fracture in a woman with diabetes was equivalent to that of a nondiabetic woman with a T score of about 0.5 units lower.

Data Source: Analysis of data from three prospective observational studies involving more than 16,000 older subjects in whom fractures were tracked for about 10 years.

Disclosures: This study was funded by an investigator-initiated grant from Amgen to Dr. Schwartz. She and her associates also reported receiving support from Novartis, Merck, Pfizer, Nycomed, and Roche.

Two measures of fracture risk – bone mineral density T score and FRAX score – are clinically useful in patients with type 2 diabetes, even though they tend to underestimate the increased fracture risk in this patient population, according to the results of a large study.

But to be more accurate for older adults with diabetes, these treatment and diagnostic algorithms should undergo “refinements,” said Ann V. Schwartz, Ph.D., of the department of epidemiology and biostatistics, University of California, San Francisco, and her associates (JAMA 2011;305:2184-92).

Type 2 diabetes is known to be associated with a higher bone mineral density (BMD) but, paradoxically, also with a higher risk of fracture. There has been concern that established methods for predicting fractures “may not perform adequately in patients with type 2 diabetes,” the researchers said.

In what they described as the first study to prospectively examine the relationship between BMD and fractures in older adults with type 2 diabetes, Dr. Schwartz and her colleagues analyzed data from three large, prospective, observational studies that all used radiology reports and radiographs to confirm fracture diagnoses. The three studies also ascertained subjects' diabetes status.

The Study of Osteoporotic Fractures (SOF) involved 7,926 white women at four U.S. clinical centers who underwent femoral neck-hip BMD measurement and were followed for the occurrence of fractures from 1988 through 2008. The Osteoporotic Fractures in Men Study (MrOS) involved 5,994 men at six U.S. clinical centers who underwent hip BMD measurement and were followed from 2000 through 2009. And the Health, Aging, and Body Composition (Health ABC) study involved 1,523 women and 1,442 men in their 70s, approximately half of whom were white and half black, who underwent hip BMD measurement and were followed from 1997 through 2007.

The FRAX (Fracture Risk Algorithm) scores were calculated for subjects in the SOF and MrOS studies by the World Health Organization (WHO) Collaborating Center for Metabolic Bone Disease, but not for subjects in the Health ABC study.

Dr. Schwartz and her associates found that both low BMD T score and high FRAX score were predictive of hip and nonspinal fracture in patients with diabetes. “However, for a given T score and age, those adults with diabetes had a higher risk of fracture than those without diabetes,” they said.

For example, the risk of hip fracture in a woman with diabetes was equivalent to that of a nondiabetic woman with a T score of about 0.5 units lower.

The subjects with diabetes showed higher rates of fracture at any given FRAX score than did subjects who did not have diabetes, they noted.

“Interpretation of T score or FRAX score in an older patient with diabetes must take into account the higher fracture risk associated with diabetes. For example, … a T score in a woman with diabetes is associated with hip fracture risk equivalent to a woman without diabetes with a T score of approximately 0.5 units lower,” the investigators said.

“The FRAX score has been incorporated into U.S. guidelines for prevention and treatment of osteoporosis. The FRAX algorithm does not currently include type 2 diabetes as a risk factor for fracture, and our results indicate that use of the FRAX score in patients with diabetes will likely underestimate risk.

“An adjustment of this algorithm for type 2 diabetes seems justified, given the prevalence of diabetes among older adults,” Dr. Schwartz and her associates said.

The reason diabetes raises fracture risk even as it appears to protect against loss of BMD is not understood. “Bone strength may be compromised through changes that are not captured with dual-energy x-ray absorptiometry, such as higher levels of advanced glycation end products in bone collagen. More frequent falls in older adults with diabetes could also increase fracture risk for a given BMD,” they said.

This study was funded by an investigator-initiated grant from Amgen to Dr. Schwartz. She and her associates also reported receiving support from Novartis, Merck, Pfizer, Nycomed, and Roche.

Major Finding: In older adults with diabetes, any given BMD T score or FRAX score carried a higher fracture risk than did the same score in those without diabetes. The risk of hip fracture in a woman with diabetes was equivalent to that of a nondiabetic woman with a T score of about 0.5 units lower.

Data Source: Analysis of data from three prospective observational studies involving more than 16,000 older subjects in whom fractures were tracked for about 10 years.

Disclosures: This study was funded by an investigator-initiated grant from Amgen to Dr. Schwartz. She and her associates also reported receiving support from Novartis, Merck, Pfizer, Nycomed, and Roche.

Two measures of fracture risk – bone mineral density T score and FRAX score – are clinically useful in patients with type 2 diabetes, even though they tend to underestimate the increased fracture risk in this patient population, according to the results of a large study.

But to be more accurate for older adults with diabetes, these treatment and diagnostic algorithms should undergo “refinements,” said Ann V. Schwartz, Ph.D., of the department of epidemiology and biostatistics, University of California, San Francisco, and her associates (JAMA 2011;305:2184-92).

Type 2 diabetes is known to be associated with a higher bone mineral density (BMD) but, paradoxically, also with a higher risk of fracture. There has been concern that established methods for predicting fractures “may not perform adequately in patients with type 2 diabetes,” the researchers said.

In what they described as the first study to prospectively examine the relationship between BMD and fractures in older adults with type 2 diabetes, Dr. Schwartz and her colleagues analyzed data from three large, prospective, observational studies that all used radiology reports and radiographs to confirm fracture diagnoses. The three studies also ascertained subjects' diabetes status.

The Study of Osteoporotic Fractures (SOF) involved 7,926 white women at four U.S. clinical centers who underwent femoral neck-hip BMD measurement and were followed for the occurrence of fractures from 1988 through 2008. The Osteoporotic Fractures in Men Study (MrOS) involved 5,994 men at six U.S. clinical centers who underwent hip BMD measurement and were followed from 2000 through 2009. And the Health, Aging, and Body Composition (Health ABC) study involved 1,523 women and 1,442 men in their 70s, approximately half of whom were white and half black, who underwent hip BMD measurement and were followed from 1997 through 2007.

The FRAX (Fracture Risk Algorithm) scores were calculated for subjects in the SOF and MrOS studies by the World Health Organization (WHO) Collaborating Center for Metabolic Bone Disease, but not for subjects in the Health ABC study.

Dr. Schwartz and her associates found that both low BMD T score and high FRAX score were predictive of hip and nonspinal fracture in patients with diabetes. “However, for a given T score and age, those adults with diabetes had a higher risk of fracture than those without diabetes,” they said.

For example, the risk of hip fracture in a woman with diabetes was equivalent to that of a nondiabetic woman with a T score of about 0.5 units lower.

The subjects with diabetes showed higher rates of fracture at any given FRAX score than did subjects who did not have diabetes, they noted.

“Interpretation of T score or FRAX score in an older patient with diabetes must take into account the higher fracture risk associated with diabetes. For example, … a T score in a woman with diabetes is associated with hip fracture risk equivalent to a woman without diabetes with a T score of approximately 0.5 units lower,” the investigators said.

“The FRAX score has been incorporated into U.S. guidelines for prevention and treatment of osteoporosis. The FRAX algorithm does not currently include type 2 diabetes as a risk factor for fracture, and our results indicate that use of the FRAX score in patients with diabetes will likely underestimate risk.

“An adjustment of this algorithm for type 2 diabetes seems justified, given the prevalence of diabetes among older adults,” Dr. Schwartz and her associates said.

The reason diabetes raises fracture risk even as it appears to protect against loss of BMD is not understood. “Bone strength may be compromised through changes that are not captured with dual-energy x-ray absorptiometry, such as higher levels of advanced glycation end products in bone collagen. More frequent falls in older adults with diabetes could also increase fracture risk for a given BMD,” they said.

This study was funded by an investigator-initiated grant from Amgen to Dr. Schwartz. She and her associates also reported receiving support from Novartis, Merck, Pfizer, Nycomed, and Roche.

Major Finding: In older adults with diabetes, any given BMD T score or FRAX score carried a higher fracture risk than did the same score in those without diabetes. The risk of hip fracture in a woman with diabetes was equivalent to that of a nondiabetic woman with a T score of about 0.5 units lower.

Data Source: Analysis of data from three prospective observational studies involving more than 16,000 older subjects in whom fractures were tracked for about 10 years.

Disclosures: This study was funded by an investigator-initiated grant from Amgen to Dr. Schwartz. She and her associates also reported receiving support from Novartis, Merck, Pfizer, Nycomed, and Roche.

Two measures of fracture risk – bone mineral density T score and FRAX score – are clinically useful in patients with type 2 diabetes, even though they tend to underestimate the increased fracture risk in this patient population, according to the results of a large study.

But to be more accurate for older adults with diabetes, these treatment and diagnostic algorithms should undergo “refinements,” said Ann V. Schwartz, Ph.D., of the department of epidemiology and biostatistics, University of California, San Francisco, and her associates (JAMA 2011;305:2184-92).

Type 2 diabetes is known to be associated with a higher bone mineral density (BMD) but, paradoxically, also with a higher risk of fracture. There has been concern that established methods for predicting fractures “may not perform adequately in patients with type 2 diabetes,” the researchers said.

In what they described as the first study to prospectively examine the relationship between BMD and fractures in older adults with type 2 diabetes, Dr. Schwartz and her colleagues analyzed data from three large, prospective, observational studies that all used radiology reports and radiographs to confirm fracture diagnoses. The three studies also ascertained subjects' diabetes status.

The Study of Osteoporotic Fractures (SOF) involved 7,926 white women at four U.S. clinical centers who underwent femoral neck-hip BMD measurement and were followed for the occurrence of fractures from 1988 through 2008. The Osteoporotic Fractures in Men Study (MrOS) involved 5,994 men at six U.S. clinical centers who underwent hip BMD measurement and were followed from 2000 through 2009. And the Health, Aging, and Body Composition (Health ABC) study involved 1,523 women and 1,442 men in their 70s, approximately half of whom were white and half black, who underwent hip BMD measurement and were followed from 1997 through 2007.

The FRAX (Fracture Risk Algorithm) scores were calculated for subjects in the SOF and MrOS studies by the World Health Organization (WHO) Collaborating Center for Metabolic Bone Disease, but not for subjects in the Health ABC study.

Dr. Schwartz and her associates found that both low BMD T score and high FRAX score were predictive of hip and nonspinal fracture in patients with diabetes. “However, for a given T score and age, those adults with diabetes had a higher risk of fracture than those without diabetes,” they said.

For example, the risk of hip fracture in a woman with diabetes was equivalent to that of a nondiabetic woman with a T score of about 0.5 units lower.

The subjects with diabetes showed higher rates of fracture at any given FRAX score than did subjects who did not have diabetes, they noted.

“Interpretation of T score or FRAX score in an older patient with diabetes must take into account the higher fracture risk associated with diabetes. For example, … a T score in a woman with diabetes is associated with hip fracture risk equivalent to a woman without diabetes with a T score of approximately 0.5 units lower,” the investigators said.

“The FRAX score has been incorporated into U.S. guidelines for prevention and treatment of osteoporosis. The FRAX algorithm does not currently include type 2 diabetes as a risk factor for fracture, and our results indicate that use of the FRAX score in patients with diabetes will likely underestimate risk.

“An adjustment of this algorithm for type 2 diabetes seems justified, given the prevalence of diabetes among older adults,” Dr. Schwartz and her associates said.

The reason diabetes raises fracture risk even as it appears to protect against loss of BMD is not understood. “Bone strength may be compromised through changes that are not captured with dual-energy x-ray absorptiometry, such as higher levels of advanced glycation end products in bone collagen. More frequent falls in older adults with diabetes could also increase fracture risk for a given BMD,” they said.

This study was funded by an investigator-initiated grant from Amgen to Dr. Schwartz. She and her associates also reported receiving support from Novartis, Merck, Pfizer, Nycomed, and Roche.

TAMPA – The treatment of osteoporosis is in flux because of a variety of forces, including a substantial increase in the number of aging patients deemed eligible for treatments, a leading geriatrician said. Just as baby boomers begin reaching senior status, a recently developed tool for assessing people's fracture risk is increasing the number of patients considered suitable for preventive therapy.

Meanwhile, those therapy options are multiplying, and emerging evidence suggests that one, bisphosphonates, is associated with an increased risk for atypical fractures, although the absolute risk appears to be low, Dr. Barbara Messinger-Rapport, said at the meeting.

The assessment tool making a difference is the Web-based Fracture Risk Assessment Tool (FRAX), released by the World Health Organization in 2008. FRAX guides clinicians to consider drug therapy for patients with T scores (deviations from healthy bone density) of –2.5 or lower at the femoral neck or spine, a T score between –1.0 and –2.5 as well as a 3% or higher calculated risk for hip fracture over 10 years, or a 20% or greater risk of major osteoporosis-related fracture.

Even if a person's T score never reaches –2.5, his or her hip fracture risk can climb to 3% or higher, said Dr. Messinger-Rapport, director of the Center for Geriatric Medicine at the Cleveland Clinic and medical director of the Fairfax Health Care Center Nursing Home, also in Cleveland. “This could widen the number of people who could be put on treatment.”

Bisphosphonates remain the most-common treatment strategy, but optimal duration of therapy, timing of drug holidays, and how age and gender play into risk for adverse events remains unclear, she said.

A newer option, the monoclonal antibody denosumab (Prolia, Amgen), significantly reduced vertebral fractures compared with a placebo in published studies. Administered as a subcutaneous injection every 6 months, denosumab also may be more convenient than agents requiring infusion, Dr. Messinger-Rapport said.

Higher cost is a consideration, however. Wholesale cost of denosumab is approximately $850 per 60-mg subcutaneous injection. In contrast, generic alendronate costs $100–$200/year; brand-name oral bisphosphonate costs up to $1,000 a year; and zoledronic acid, delivered via intravenous infusion, is about $1,100 a year, she said.

Denosumab's impact on clinical care is not yet known, Dr. Messinger-Rapport said. She suggested that clinicians consider this agent in high-risk elders, women or men with osteoporosis, men with prostate cancer with androgen deprivation, patients with metastatic prostate or breast cancer, and possibly patients with renal impairment (denosumab clearance is not renal). Also consider denosumab for patients who cannot tolerate a bisphosphonate either orally or by infusion, she added.

Researchers showed a 68% decrease in vertebral fractures, a 40% decline in hip fractures, and a 20% decrease in nonvertebral fractures with denosumab versus placebo in the FREEDOM study of osteoporotic women treated for 36 months (N. Engl. J. Med. 2009;361:756–65). A similar 62% decrease in vertebral fractures with denosumab, compared with placebo, was observed in a 24-month study of men with androgen deprivation for prostate cancer (N. Engl. J. Med. 2009;361:745–55).

Researchers also have examined reports of atypical femoral fractures associated with bisphosphonate use and found an association. For example, in a study published last year, 17 of 20 atypical femoral fractures occurred in patients taking oral bisphosphonates (N. Engl. J. Med. 2010;363:1848–9). In a New England Journal letter (N. Engl. J. Med. 2010;362:1848–9), the researchers stated that although they found the association, “overall the anti-fracture effects of bisphosphonates far outweigh their potential risks.”

More recently, other investigators found an increased risk of subtrochanteric and femoral shaft fractures in women treated for 5 years or more with oral bisphosphonates (JAMA 2011;305:783-9). The authors stated that the absolute risk of the atypical fractures is low, however.

Dr. Messinger-Rapport listed contraindications to bisphosphonates as a prior allergic reaction, vitamin D depletion (less than 30 ng/mL), hypocalcemia, dysphagia, esophageal disorders, and severe gastroesophageal reflux disorder.

A person attending the meeting asked if it is appropriate to continue bisphosphonate therapy after a patient's T score improves. “Yes, even if the T score only improves by a few percentage points,” Dr. Messinger-Rapport replied, because there is a disproportionate benefit in terms of fracture risk reduction.

Dr. Messinger-Rapport is a member of the National Osteoporosis Foundation's editorial board.

To watch an interview with Dr. Messinger-Rapport, scan this QR code with a smartphone.

TAMPA – The treatment of osteoporosis is in flux because of a variety of forces, including a substantial increase in the number of aging patients deemed eligible for treatments, a leading geriatrician said. Just as baby boomers begin reaching senior status, a recently developed tool for assessing people's fracture risk is increasing the number of patients considered suitable for preventive therapy.

Meanwhile, those therapy options are multiplying, and emerging evidence suggests that one, bisphosphonates, is associated with an increased risk for atypical fractures, although the absolute risk appears to be low, Dr. Barbara Messinger-Rapport, said at the meeting.

The assessment tool making a difference is the Web-based Fracture Risk Assessment Tool (FRAX), released by the World Health Organization in 2008. FRAX guides clinicians to consider drug therapy for patients with T scores (deviations from healthy bone density) of –2.5 or lower at the femoral neck or spine, a T score between –1.0 and –2.5 as well as a 3% or higher calculated risk for hip fracture over 10 years, or a 20% or greater risk of major osteoporosis-related fracture.

Even if a person's T score never reaches –2.5, his or her hip fracture risk can climb to 3% or higher, said Dr. Messinger-Rapport, director of the Center for Geriatric Medicine at the Cleveland Clinic and medical director of the Fairfax Health Care Center Nursing Home, also in Cleveland. “This could widen the number of people who could be put on treatment.”

Bisphosphonates remain the most-common treatment strategy, but optimal duration of therapy, timing of drug holidays, and how age and gender play into risk for adverse events remains unclear, she said.

A newer option, the monoclonal antibody denosumab (Prolia, Amgen), significantly reduced vertebral fractures compared with a placebo in published studies. Administered as a subcutaneous injection every 6 months, denosumab also may be more convenient than agents requiring infusion, Dr. Messinger-Rapport said.

Higher cost is a consideration, however. Wholesale cost of denosumab is approximately $850 per 60-mg subcutaneous injection. In contrast, generic alendronate costs $100–$200/year; brand-name oral bisphosphonate costs up to $1,000 a year; and zoledronic acid, delivered via intravenous infusion, is about $1,100 a year, she said.

Denosumab's impact on clinical care is not yet known, Dr. Messinger-Rapport said. She suggested that clinicians consider this agent in high-risk elders, women or men with osteoporosis, men with prostate cancer with androgen deprivation, patients with metastatic prostate or breast cancer, and possibly patients with renal impairment (denosumab clearance is not renal). Also consider denosumab for patients who cannot tolerate a bisphosphonate either orally or by infusion, she added.

Researchers showed a 68% decrease in vertebral fractures, a 40% decline in hip fractures, and a 20% decrease in nonvertebral fractures with denosumab versus placebo in the FREEDOM study of osteoporotic women treated for 36 months (N. Engl. J. Med. 2009;361:756–65). A similar 62% decrease in vertebral fractures with denosumab, compared with placebo, was observed in a 24-month study of men with androgen deprivation for prostate cancer (N. Engl. J. Med. 2009;361:745–55).

Researchers also have examined reports of atypical femoral fractures associated with bisphosphonate use and found an association. For example, in a study published last year, 17 of 20 atypical femoral fractures occurred in patients taking oral bisphosphonates (N. Engl. J. Med. 2010;363:1848–9). In a New England Journal letter (N. Engl. J. Med. 2010;362:1848–9), the researchers stated that although they found the association, “overall the anti-fracture effects of bisphosphonates far outweigh their potential risks.”

More recently, other investigators found an increased risk of subtrochanteric and femoral shaft fractures in women treated for 5 years or more with oral bisphosphonates (JAMA 2011;305:783-9). The authors stated that the absolute risk of the atypical fractures is low, however.

Dr. Messinger-Rapport listed contraindications to bisphosphonates as a prior allergic reaction, vitamin D depletion (less than 30 ng/mL), hypocalcemia, dysphagia, esophageal disorders, and severe gastroesophageal reflux disorder.

A person attending the meeting asked if it is appropriate to continue bisphosphonate therapy after a patient's T score improves. “Yes, even if the T score only improves by a few percentage points,” Dr. Messinger-Rapport replied, because there is a disproportionate benefit in terms of fracture risk reduction.

Dr. Messinger-Rapport is a member of the National Osteoporosis Foundation's editorial board.

To watch an interview with Dr. Messinger-Rapport, scan this QR code with a smartphone.

TAMPA – The treatment of osteoporosis is in flux because of a variety of forces, including a substantial increase in the number of aging patients deemed eligible for treatments, a leading geriatrician said. Just as baby boomers begin reaching senior status, a recently developed tool for assessing people's fracture risk is increasing the number of patients considered suitable for preventive therapy.

Meanwhile, those therapy options are multiplying, and emerging evidence suggests that one, bisphosphonates, is associated with an increased risk for atypical fractures, although the absolute risk appears to be low, Dr. Barbara Messinger-Rapport, said at the meeting.

The assessment tool making a difference is the Web-based Fracture Risk Assessment Tool (FRAX), released by the World Health Organization in 2008. FRAX guides clinicians to consider drug therapy for patients with T scores (deviations from healthy bone density) of –2.5 or lower at the femoral neck or spine, a T score between –1.0 and –2.5 as well as a 3% or higher calculated risk for hip fracture over 10 years, or a 20% or greater risk of major osteoporosis-related fracture.

Even if a person's T score never reaches –2.5, his or her hip fracture risk can climb to 3% or higher, said Dr. Messinger-Rapport, director of the Center for Geriatric Medicine at the Cleveland Clinic and medical director of the Fairfax Health Care Center Nursing Home, also in Cleveland. “This could widen the number of people who could be put on treatment.”

Bisphosphonates remain the most-common treatment strategy, but optimal duration of therapy, timing of drug holidays, and how age and gender play into risk for adverse events remains unclear, she said.

A newer option, the monoclonal antibody denosumab (Prolia, Amgen), significantly reduced vertebral fractures compared with a placebo in published studies. Administered as a subcutaneous injection every 6 months, denosumab also may be more convenient than agents requiring infusion, Dr. Messinger-Rapport said.

Higher cost is a consideration, however. Wholesale cost of denosumab is approximately $850 per 60-mg subcutaneous injection. In contrast, generic alendronate costs $100–$200/year; brand-name oral bisphosphonate costs up to $1,000 a year; and zoledronic acid, delivered via intravenous infusion, is about $1,100 a year, she said.

Denosumab's impact on clinical care is not yet known, Dr. Messinger-Rapport said. She suggested that clinicians consider this agent in high-risk elders, women or men with osteoporosis, men with prostate cancer with androgen deprivation, patients with metastatic prostate or breast cancer, and possibly patients with renal impairment (denosumab clearance is not renal). Also consider denosumab for patients who cannot tolerate a bisphosphonate either orally or by infusion, she added.

Researchers showed a 68% decrease in vertebral fractures, a 40% decline in hip fractures, and a 20% decrease in nonvertebral fractures with denosumab versus placebo in the FREEDOM study of osteoporotic women treated for 36 months (N. Engl. J. Med. 2009;361:756–65). A similar 62% decrease in vertebral fractures with denosumab, compared with placebo, was observed in a 24-month study of men with androgen deprivation for prostate cancer (N. Engl. J. Med. 2009;361:745–55).

Researchers also have examined reports of atypical femoral fractures associated with bisphosphonate use and found an association. For example, in a study published last year, 17 of 20 atypical femoral fractures occurred in patients taking oral bisphosphonates (N. Engl. J. Med. 2010;363:1848–9). In a New England Journal letter (N. Engl. J. Med. 2010;362:1848–9), the researchers stated that although they found the association, “overall the anti-fracture effects of bisphosphonates far outweigh their potential risks.”

More recently, other investigators found an increased risk of subtrochanteric and femoral shaft fractures in women treated for 5 years or more with oral bisphosphonates (JAMA 2011;305:783-9). The authors stated that the absolute risk of the atypical fractures is low, however.

Dr. Messinger-Rapport listed contraindications to bisphosphonates as a prior allergic reaction, vitamin D depletion (less than 30 ng/mL), hypocalcemia, dysphagia, esophageal disorders, and severe gastroesophageal reflux disorder.

A person attending the meeting asked if it is appropriate to continue bisphosphonate therapy after a patient's T score improves. “Yes, even if the T score only improves by a few percentage points,” Dr. Messinger-Rapport replied, because there is a disproportionate benefit in terms of fracture risk reduction.

Dr. Messinger-Rapport is a member of the National Osteoporosis Foundation's editorial board.

To watch an interview with Dr. Messinger-Rapport, scan this QR code with a smartphone.

Two measures of fracture risk – bone mineral density T score and FRAX score – are clinically useful in patients with type 2 diabetes, even though they tend to underestimate the increased fracture risk in this patient population, according to the results of a large study reported in the June 1 issue of JAMA.

But to be more accurate for older adults with diabetes, these treatment and diagnostic algorithms should undergo "refinements," said Ann V. Schwartz, Ph.D., of the department of epidemiology and biostatistics, University of California, San Francisco, and her associates (JAMA 2011;305:2184-92).

Type 2 diabetes is known to be associated with a higher bone mineral density (BMD) but, paradoxically, also with a higher risk of fracture. There has been concern that established methods for predicting fractures "may not perform adequately in patients with type 2 diabetes," the researchers said.

In what they described as the first study to prospectively examine the relationship between BMD and fractures in older adults with type 2 diabetes, Dr. Schwartz and her colleagues analyzed data from three large, prospective, observational studies that all used radiology reports and radiographs to confirm fracture diagnoses. The three studies also ascertained subjects’ diabetes status.

The Study of Osteoporotic Fractures (SOF) involved 7,926 white women at four U.S. clinical centers who underwent femoral neck-hip BMD measurement and were followed for the occurrence of fractures from 1988 through 2008. The Osteoporotic Fractures in Men Study (MrOS) involved 5,994 men at six U.S. clinical centers who underwent hip BMD measurement and were followed from 2000 through 2009. And the Health, Aging, and Body Composition (Health ABC) study involved 1,523 women and 1,442 men in their 70s, approximately half of whom were white and half black, who underwent hip BMD measurement and were followed from 1997 through 2007.

The FRAX (Fracture Risk Algorithm) scores were calculated for subjects in the SOF and MrOS studies by the World Health Organization (WHO) Collaborating Center for Metabolic Bone Disease, but not for subjects in the Health ABC study.

Dr. Schwartz and her associates found that both low BMD T score and high FRAX score were predictive of hip and nonspinal fracture in patients with diabetes. "However, for a given T score and age, those adults with diabetes had a higher risk of fracture than those without diabetes," they said.

For example, the risk of hip fracture in a woman with diabetes was equivalent to that of a nondiabetic woman with a T score of about 0.5 units lower.

The subjects with diabetes showed higher rates of fracture at any given FRAX score than did subjects who didn’t have diabetes, they noted.

"Interpretation of T score or FRAX score in an older patient with diabetes must take into account the higher fracture risk associated with diabetes. For example, ... a T score in a woman with diabetes is associated with hip fracture risk equivalent to a woman without diabetes with a T score of approximately 0.5 units lower," the investigators said.

"The FRAX score has been incorporated into U.S. guidelines for prevention and treatment of osteoporosis. The FRAX algorithm does not currently include type 2 diabetes as a risk factor for fracture, and our results indicate that use of the FRAX score in patients with diabetes will likely underestimate risk.

"An adjustment of this algorithm for type 2 diabetes seems justified, given the prevalence of diabetes among older adults," Dr. Schwartz and her associates said.

The reason diabetes raises fracture risk even as it appears to protect against loss of BMD is not understood. "Bone strength may be compromised through changes that are not captured with dual-energy x-ray absorptiometry, such as higher levels of advanced glycation end products in bone collagen. More frequent falls in older adults with diabetes could also increase fracture risk for a given BMD," they said.

This study was funded by an investigator-initiated grant from Amgen to Dr. Schwartz. She and her associates also reported receiving support from Novartis, Merck, Pfizer, Nycomed, and Roche.

Two measures of fracture risk – bone mineral density T score and FRAX score – are clinically useful in patients with type 2 diabetes, even though they tend to underestimate the increased fracture risk in this patient population, according to the results of a large study reported in the June 1 issue of JAMA.

But to be more accurate for older adults with diabetes, these treatment and diagnostic algorithms should undergo "refinements," said Ann V. Schwartz, Ph.D., of the department of epidemiology and biostatistics, University of California, San Francisco, and her associates (JAMA 2011;305:2184-92).

Type 2 diabetes is known to be associated with a higher bone mineral density (BMD) but, paradoxically, also with a higher risk of fracture. There has been concern that established methods for predicting fractures "may not perform adequately in patients with type 2 diabetes," the researchers said.

In what they described as the first study to prospectively examine the relationship between BMD and fractures in older adults with type 2 diabetes, Dr. Schwartz and her colleagues analyzed data from three large, prospective, observational studies that all used radiology reports and radiographs to confirm fracture diagnoses. The three studies also ascertained subjects’ diabetes status.

The Study of Osteoporotic Fractures (SOF) involved 7,926 white women at four U.S. clinical centers who underwent femoral neck-hip BMD measurement and were followed for the occurrence of fractures from 1988 through 2008. The Osteoporotic Fractures in Men Study (MrOS) involved 5,994 men at six U.S. clinical centers who underwent hip BMD measurement and were followed from 2000 through 2009. And the Health, Aging, and Body Composition (Health ABC) study involved 1,523 women and 1,442 men in their 70s, approximately half of whom were white and half black, who underwent hip BMD measurement and were followed from 1997 through 2007.

The FRAX (Fracture Risk Algorithm) scores were calculated for subjects in the SOF and MrOS studies by the World Health Organization (WHO) Collaborating Center for Metabolic Bone Disease, but not for subjects in the Health ABC study.

Dr. Schwartz and her associates found that both low BMD T score and high FRAX score were predictive of hip and nonspinal fracture in patients with diabetes. "However, for a given T score and age, those adults with diabetes had a higher risk of fracture than those without diabetes," they said.

For example, the risk of hip fracture in a woman with diabetes was equivalent to that of a nondiabetic woman with a T score of about 0.5 units lower.

The subjects with diabetes showed higher rates of fracture at any given FRAX score than did subjects who didn’t have diabetes, they noted.

"Interpretation of T score or FRAX score in an older patient with diabetes must take into account the higher fracture risk associated with diabetes. For example, ... a T score in a woman with diabetes is associated with hip fracture risk equivalent to a woman without diabetes with a T score of approximately 0.5 units lower," the investigators said.

"The FRAX score has been incorporated into U.S. guidelines for prevention and treatment of osteoporosis. The FRAX algorithm does not currently include type 2 diabetes as a risk factor for fracture, and our results indicate that use of the FRAX score in patients with diabetes will likely underestimate risk.

"An adjustment of this algorithm for type 2 diabetes seems justified, given the prevalence of diabetes among older adults," Dr. Schwartz and her associates said.

The reason diabetes raises fracture risk even as it appears to protect against loss of BMD is not understood. "Bone strength may be compromised through changes that are not captured with dual-energy x-ray absorptiometry, such as higher levels of advanced glycation end products in bone collagen. More frequent falls in older adults with diabetes could also increase fracture risk for a given BMD," they said.

This study was funded by an investigator-initiated grant from Amgen to Dr. Schwartz. She and her associates also reported receiving support from Novartis, Merck, Pfizer, Nycomed, and Roche.

Two measures of fracture risk – bone mineral density T score and FRAX score – are clinically useful in patients with type 2 diabetes, even though they tend to underestimate the increased fracture risk in this patient population, according to the results of a large study reported in the June 1 issue of JAMA.

But to be more accurate for older adults with diabetes, these treatment and diagnostic algorithms should undergo "refinements," said Ann V. Schwartz, Ph.D., of the department of epidemiology and biostatistics, University of California, San Francisco, and her associates (JAMA 2011;305:2184-92).

Type 2 diabetes is known to be associated with a higher bone mineral density (BMD) but, paradoxically, also with a higher risk of fracture. There has been concern that established methods for predicting fractures "may not perform adequately in patients with type 2 diabetes," the researchers said.

In what they described as the first study to prospectively examine the relationship between BMD and fractures in older adults with type 2 diabetes, Dr. Schwartz and her colleagues analyzed data from three large, prospective, observational studies that all used radiology reports and radiographs to confirm fracture diagnoses. The three studies also ascertained subjects’ diabetes status.

The Study of Osteoporotic Fractures (SOF) involved 7,926 white women at four U.S. clinical centers who underwent femoral neck-hip BMD measurement and were followed for the occurrence of fractures from 1988 through 2008. The Osteoporotic Fractures in Men Study (MrOS) involved 5,994 men at six U.S. clinical centers who underwent hip BMD measurement and were followed from 2000 through 2009. And the Health, Aging, and Body Composition (Health ABC) study involved 1,523 women and 1,442 men in their 70s, approximately half of whom were white and half black, who underwent hip BMD measurement and were followed from 1997 through 2007.

The FRAX (Fracture Risk Algorithm) scores were calculated for subjects in the SOF and MrOS studies by the World Health Organization (WHO) Collaborating Center for Metabolic Bone Disease, but not for subjects in the Health ABC study.

Dr. Schwartz and her associates found that both low BMD T score and high FRAX score were predictive of hip and nonspinal fracture in patients with diabetes. "However, for a given T score and age, those adults with diabetes had a higher risk of fracture than those without diabetes," they said.

For example, the risk of hip fracture in a woman with diabetes was equivalent to that of a nondiabetic woman with a T score of about 0.5 units lower.

The subjects with diabetes showed higher rates of fracture at any given FRAX score than did subjects who didn’t have diabetes, they noted.

"Interpretation of T score or FRAX score in an older patient with diabetes must take into account the higher fracture risk associated with diabetes. For example, ... a T score in a woman with diabetes is associated with hip fracture risk equivalent to a woman without diabetes with a T score of approximately 0.5 units lower," the investigators said.

"The FRAX score has been incorporated into U.S. guidelines for prevention and treatment of osteoporosis. The FRAX algorithm does not currently include type 2 diabetes as a risk factor for fracture, and our results indicate that use of the FRAX score in patients with diabetes will likely underestimate risk.

"An adjustment of this algorithm for type 2 diabetes seems justified, given the prevalence of diabetes among older adults," Dr. Schwartz and her associates said.

The reason diabetes raises fracture risk even as it appears to protect against loss of BMD is not understood. "Bone strength may be compromised through changes that are not captured with dual-energy x-ray absorptiometry, such as higher levels of advanced glycation end products in bone collagen. More frequent falls in older adults with diabetes could also increase fracture risk for a given BMD," they said.

This study was funded by an investigator-initiated grant from Amgen to Dr. Schwartz. She and her associates also reported receiving support from Novartis, Merck, Pfizer, Nycomed, and Roche.

It may be appropriate to forgo dual-energy x-ray absorptiometry scanning and instead use body mass index to rule out osteoporosis in some obese patients, according to the findings of a large study presented by Dr. Thomas Nelson at the annual European Congress of Rheumatology. Our reporter, Heidi Splete, was able to sit down with Dr. Nelson  to talk about the study results.

Click here for the full story.

It may be appropriate to forgo dual-energy x-ray absorptiometry scanning and instead use body mass index to rule out osteoporosis in some obese patients, according to the findings of a large study presented by Dr. Thomas Nelson at the annual European Congress of Rheumatology. Our reporter, Heidi Splete, was able to sit down with Dr. Nelson  to talk about the study results.

Click here for the full story.

It may be appropriate to forgo dual-energy x-ray absorptiometry scanning and instead use body mass index to rule out osteoporosis in some obese patients, according to the findings of a large study presented by Dr. Thomas Nelson at the annual European Congress of Rheumatology. Our reporter, Heidi Splete, was able to sit down with Dr. Nelson  to talk about the study results.

Click here for the full story.