Osteoporosis

SAN ANTONIO — Arzoxifene, a once-promising selective estrogen-receptor modulator, experienced a fatal meltdown in a phase III trial involving nearly 10,000 women.

Arzoxifene was being developed for prevention of both fractures and breast cancer in postmenopausal women with osteoporosis or osteopenia.

But the 9,354-patient randomized, double-blind, placebo-controlled, multinational GENERATIONS trial has put an end to that, Dr. Trevor Powles said at the San Antonio Breast Cancer Symposium.

The breast cancer prevention portion of GENERATIONS went well: After 48 months of follow-up, arzoxifene reduced the incidence of invasive breast cancer by 56%, compared with placebo, and reduced estrogen-receptor–positive invasive breast cancer by 70% (see chart).

Arzoxifene also significantly reduced the incidence of vertebral fractures by 41% after 36 months of follow-up in GENERATIONS participants, who were aged 60-85 years at enrollment.

But there was a deal breaker: the selective estrogen-receptor modulator (SERM) produced no significant reduction in nonvertebral fractures.

“This is disappointing because as an antiosteoporosis drug we really need to have a SERM that would not only reduce vertebral fractures, but nonvertebral fractures as well,” explained Dr. Powles, a medical oncologist who is professor emeritus at the Institute of Cancer Research, London.

Moreover, arzoxifene was associated with increased rates of venous thromboembolism, endometrial polyps, leg cramps, hot flashes, and cholelithiasis, while offering no better protection against cardiovascular events than did placebo.

“The overall benefit/risk profile of arzoxifene does not represent a meaningful advancement in the treatment of osteoporosis, so further development of this drug will not take place. It's obviously disappointing, given that so much time and effort has been put into a major trial with good preclinical and early clinical data,” he said.

The investigators are still puzzling over how the earlier studies could have been so misleading.

Arzoxifene is a benzothiophene SERM, like raloxifene, which is approved in postmenopausal women for the treatment and prevention of osteoporosis as well as for invasive breast cancer risk reduction in such women who are at high risk for the cancer or who have osteoporosis.

In early clinical studies, arzoxifene had greater effects on bone mineral density and bone turnover markers than did raloxifene.

Moreover, in the GENERATIONS trial arzoxifene resulted in increased bone density at nonvertebral sites as well as in the spine.

GENERATIONS was funded by Eli Lilly & Co.

Dr. Powles disclosed that he has no relevant financial relationships.

It's disappointing, given the time and effort 'put into a major trial with good preclinical and early clinical data.'

Source DR. POWLES

Elsevier Global Medical News

SAN ANTONIO — Arzoxifene, a once-promising selective estrogen-receptor modulator, experienced a fatal meltdown in a phase III trial involving nearly 10,000 women.

Arzoxifene was being developed for prevention of both fractures and breast cancer in postmenopausal women with osteoporosis or osteopenia.

But the 9,354-patient randomized, double-blind, placebo-controlled, multinational GENERATIONS trial has put an end to that, Dr. Trevor Powles said at the San Antonio Breast Cancer Symposium.

The breast cancer prevention portion of GENERATIONS went well: After 48 months of follow-up, arzoxifene reduced the incidence of invasive breast cancer by 56%, compared with placebo, and reduced estrogen-receptor–positive invasive breast cancer by 70% (see chart).

Arzoxifene also significantly reduced the incidence of vertebral fractures by 41% after 36 months of follow-up in GENERATIONS participants, who were aged 60-85 years at enrollment.

But there was a deal breaker: the selective estrogen-receptor modulator (SERM) produced no significant reduction in nonvertebral fractures.

“This is disappointing because as an antiosteoporosis drug we really need to have a SERM that would not only reduce vertebral fractures, but nonvertebral fractures as well,” explained Dr. Powles, a medical oncologist who is professor emeritus at the Institute of Cancer Research, London.

Moreover, arzoxifene was associated with increased rates of venous thromboembolism, endometrial polyps, leg cramps, hot flashes, and cholelithiasis, while offering no better protection against cardiovascular events than did placebo.

“The overall benefit/risk profile of arzoxifene does not represent a meaningful advancement in the treatment of osteoporosis, so further development of this drug will not take place. It's obviously disappointing, given that so much time and effort has been put into a major trial with good preclinical and early clinical data,” he said.

The investigators are still puzzling over how the earlier studies could have been so misleading.

Arzoxifene is a benzothiophene SERM, like raloxifene, which is approved in postmenopausal women for the treatment and prevention of osteoporosis as well as for invasive breast cancer risk reduction in such women who are at high risk for the cancer or who have osteoporosis.

In early clinical studies, arzoxifene had greater effects on bone mineral density and bone turnover markers than did raloxifene.

Moreover, in the GENERATIONS trial arzoxifene resulted in increased bone density at nonvertebral sites as well as in the spine.

GENERATIONS was funded by Eli Lilly & Co.

Dr. Powles disclosed that he has no relevant financial relationships.

It's disappointing, given the time and effort 'put into a major trial with good preclinical and early clinical data.'

Source DR. POWLES

Elsevier Global Medical News

SAN ANTONIO — Arzoxifene, a once-promising selective estrogen-receptor modulator, experienced a fatal meltdown in a phase III trial involving nearly 10,000 women.

Arzoxifene was being developed for prevention of both fractures and breast cancer in postmenopausal women with osteoporosis or osteopenia.

But the 9,354-patient randomized, double-blind, placebo-controlled, multinational GENERATIONS trial has put an end to that, Dr. Trevor Powles said at the San Antonio Breast Cancer Symposium.

The breast cancer prevention portion of GENERATIONS went well: After 48 months of follow-up, arzoxifene reduced the incidence of invasive breast cancer by 56%, compared with placebo, and reduced estrogen-receptor–positive invasive breast cancer by 70% (see chart).

Arzoxifene also significantly reduced the incidence of vertebral fractures by 41% after 36 months of follow-up in GENERATIONS participants, who were aged 60-85 years at enrollment.

But there was a deal breaker: the selective estrogen-receptor modulator (SERM) produced no significant reduction in nonvertebral fractures.

“This is disappointing because as an antiosteoporosis drug we really need to have a SERM that would not only reduce vertebral fractures, but nonvertebral fractures as well,” explained Dr. Powles, a medical oncologist who is professor emeritus at the Institute of Cancer Research, London.

Moreover, arzoxifene was associated with increased rates of venous thromboembolism, endometrial polyps, leg cramps, hot flashes, and cholelithiasis, while offering no better protection against cardiovascular events than did placebo.

“The overall benefit/risk profile of arzoxifene does not represent a meaningful advancement in the treatment of osteoporosis, so further development of this drug will not take place. It's obviously disappointing, given that so much time and effort has been put into a major trial with good preclinical and early clinical data,” he said.

The investigators are still puzzling over how the earlier studies could have been so misleading.

Arzoxifene is a benzothiophene SERM, like raloxifene, which is approved in postmenopausal women for the treatment and prevention of osteoporosis as well as for invasive breast cancer risk reduction in such women who are at high risk for the cancer or who have osteoporosis.

In early clinical studies, arzoxifene had greater effects on bone mineral density and bone turnover markers than did raloxifene.

Moreover, in the GENERATIONS trial arzoxifene resulted in increased bone density at nonvertebral sites as well as in the spine.

GENERATIONS was funded by Eli Lilly & Co.

Dr. Powles disclosed that he has no relevant financial relationships.

It's disappointing, given the time and effort 'put into a major trial with good preclinical and early clinical data.'

Source DR. POWLES

Elsevier Global Medical News

WASHINGTON — Obese women are less likely to be screened for osteoporosis than are normal- or overweight women, according to a study of more than 140,000 patients in an integrated health care plan database.

Previous studies showed mixed results on the disparity in preventive health care for obese patients, compared with normal-weight patients, said Kristi Reynolds, Ph.D., and colleagues, of Kaiser Permanente, Pasadena, Calif.

“It is largely unknown whether obesity is associated with the quality of care for osteoporosis, which is both preventable and treatable but is often undiagnosed and untreated,” the researchers said. Physicians may be less inclined to screen obese women for osteoporosis because body weight is associated with higher bone density, they noted.

Data from 146,975 health care provider visits between July 1, 2007, and June 30, 2008, were reviewed.

Average age was 73 years; 35% were normal weight; 35% were overweight; and 19%, 7%, and 4% fell into obesity categories I, II, and III, respectively. Normal weight body mass index was defined as 18.5-24.9 kg/m

About 67% of the women had undergone bone mineral density testing within 4 years of the study, the criteria by which participants were considered “screened.” Only 52% of women with a BMI of 40 kg/m

After adjustment for age, race, and income, the odds ratio of osteoporosis screening for overweight women was 0.99, while the ratios for women in obese classes I, II, and III were 0.90, 0.77, and 0.60, respectively. The findings were presented in a poster at the the annual meeting of the Obesity Society.

The results suggest that many overweight and obese women aren't screened for osteoporosis, said the researchers, who reported having no conflicts of interest.

WASHINGTON — Obese women are less likely to be screened for osteoporosis than are normal- or overweight women, according to a study of more than 140,000 patients in an integrated health care plan database.

Previous studies showed mixed results on the disparity in preventive health care for obese patients, compared with normal-weight patients, said Kristi Reynolds, Ph.D., and colleagues, of Kaiser Permanente, Pasadena, Calif.

“It is largely unknown whether obesity is associated with the quality of care for osteoporosis, which is both preventable and treatable but is often undiagnosed and untreated,” the researchers said. Physicians may be less inclined to screen obese women for osteoporosis because body weight is associated with higher bone density, they noted.

Data from 146,975 health care provider visits between July 1, 2007, and June 30, 2008, were reviewed.

Average age was 73 years; 35% were normal weight; 35% were overweight; and 19%, 7%, and 4% fell into obesity categories I, II, and III, respectively. Normal weight body mass index was defined as 18.5-24.9 kg/m

About 67% of the women had undergone bone mineral density testing within 4 years of the study, the criteria by which participants were considered “screened.” Only 52% of women with a BMI of 40 kg/m

After adjustment for age, race, and income, the odds ratio of osteoporosis screening for overweight women was 0.99, while the ratios for women in obese classes I, II, and III were 0.90, 0.77, and 0.60, respectively. The findings were presented in a poster at the the annual meeting of the Obesity Society.

The results suggest that many overweight and obese women aren't screened for osteoporosis, said the researchers, who reported having no conflicts of interest.

WASHINGTON — Obese women are less likely to be screened for osteoporosis than are normal- or overweight women, according to a study of more than 140,000 patients in an integrated health care plan database.

Previous studies showed mixed results on the disparity in preventive health care for obese patients, compared with normal-weight patients, said Kristi Reynolds, Ph.D., and colleagues, of Kaiser Permanente, Pasadena, Calif.

“It is largely unknown whether obesity is associated with the quality of care for osteoporosis, which is both preventable and treatable but is often undiagnosed and untreated,” the researchers said. Physicians may be less inclined to screen obese women for osteoporosis because body weight is associated with higher bone density, they noted.

Data from 146,975 health care provider visits between July 1, 2007, and June 30, 2008, were reviewed.

Average age was 73 years; 35% were normal weight; 35% were overweight; and 19%, 7%, and 4% fell into obesity categories I, II, and III, respectively. Normal weight body mass index was defined as 18.5-24.9 kg/m

About 67% of the women had undergone bone mineral density testing within 4 years of the study, the criteria by which participants were considered “screened.” Only 52% of women with a BMI of 40 kg/m

After adjustment for age, race, and income, the odds ratio of osteoporosis screening for overweight women was 0.99, while the ratios for women in obese classes I, II, and III were 0.90, 0.77, and 0.60, respectively. The findings were presented in a poster at the the annual meeting of the Obesity Society.

The results suggest that many overweight and obese women aren't screened for osteoporosis, said the researchers, who reported having no conflicts of interest.

DENVER — Menopausal status appears to modify the relationship between inflammation and bone mineral density, on the basis of findings from the Framingham Osteoporosis Study.

Postmenopausal women on estrogen replacement therapy (ERT) with higher levels of C-reactive protein—a measure of systemic inflammation—had greater bone mineral density (BMD) at the femoral neck than did those in the same group with lower CRP levels, Dr. Robert R. McLean and his coinvestigators reported in a poster at the annual meeting of the American Society for Bone and Mineral Research. In contrast, in premenopausal women, increased CRP levels were associated with a decrease in BMD at the trochanter.

The Framingham Heart Study Offspring Cohort enrolled 5,124 children and spouses of the original Framingham cohort. From 1996 to 2001, BMD was measured in 3,035 offspring in the Framingham Osteoporosis Study. Fasting blood samples were collected from 2,095 of them during 1998-2001. C-reactive protein levels were measured after BMD in 72% of participants, with a median time between assessments of 1.4 years.

BMD was measured at the right femoral neck and trochanter, and at the lumbar spine. Other variables obtained at the time of BMD measurement included age, height, weight, physical activity, smoking status, and use of NSAIDs. In women, menopause status, current ERT use, and years since menopause were recorded. Separate analyses were performed for the 1,291 men, 229 premenopausal women, 497 postmenopausal women using ERT, and 888 postmenopausal women not using ERT. Analyses were adjusted for age, height, weight, physical activity, and smoking status, with additional adjustment for NSAID use.

Median CRP levels were higher for postmenopausal women (3.9 mg/L for those on ERT and 2.3 mg/L for those not on ERT) than for men (1.9 mg/L) or for premenopausal women (1.4 mg/L). In all, 74% of men, 62% of premenopausal women, 86% of postmenopausal women on ERT, and 77% of postmenopausal women not on ERT had CRP levels of at least 1 mg/L.

CRP level was not associated with BMD in men or in postmenopausal women using ERT. However, in those women, there was a significant association between years since menopause and BMD at all three sites. The researchers repeated the analysis for women fewer than 10 years past menopause and those at least 10 years past menopause. “The association of CRP with femoral neck BMD tended to be negative for those less than 10 years past menopause and positive for those at least 10 years past menopause, while there was no significant association at the trochanter or lumbar spine,” they wrote.

For postmenopausal women not using ERT, those with CRP levels of at least 1 mg/L had 2.5% greater BMD at the femoral neck, compared with the lower CRP level group, a significant difference. However, there were no significant associations at the trochanter or lumbar spine. “Contrary to our hypothesis, greater inflammation may be associated with higher BMD among postmenopausal women not using ERT,” wrote Dr. McLean, who is a researcher at the Institute for Aging Research, a research affiliate of Harvard Medical School, Boston.

In premenopausal women, CRP level was not associated with BMD at the femoral neck or the lumbar spine. However, each unit increase in CRP was associated with 0.005 g/cm

Preclinical studies have suggested that proinflammatory cytokines play a role in bone resorption, but the impact on BMD is not clear.

Dr. McLean reported that he has no relevant financial relationships.

DENVER — Menopausal status appears to modify the relationship between inflammation and bone mineral density, on the basis of findings from the Framingham Osteoporosis Study.

Postmenopausal women on estrogen replacement therapy (ERT) with higher levels of C-reactive protein—a measure of systemic inflammation—had greater bone mineral density (BMD) at the femoral neck than did those in the same group with lower CRP levels, Dr. Robert R. McLean and his coinvestigators reported in a poster at the annual meeting of the American Society for Bone and Mineral Research. In contrast, in premenopausal women, increased CRP levels were associated with a decrease in BMD at the trochanter.

The Framingham Heart Study Offspring Cohort enrolled 5,124 children and spouses of the original Framingham cohort. From 1996 to 2001, BMD was measured in 3,035 offspring in the Framingham Osteoporosis Study. Fasting blood samples were collected from 2,095 of them during 1998-2001. C-reactive protein levels were measured after BMD in 72% of participants, with a median time between assessments of 1.4 years.

BMD was measured at the right femoral neck and trochanter, and at the lumbar spine. Other variables obtained at the time of BMD measurement included age, height, weight, physical activity, smoking status, and use of NSAIDs. In women, menopause status, current ERT use, and years since menopause were recorded. Separate analyses were performed for the 1,291 men, 229 premenopausal women, 497 postmenopausal women using ERT, and 888 postmenopausal women not using ERT. Analyses were adjusted for age, height, weight, physical activity, and smoking status, with additional adjustment for NSAID use.

Median CRP levels were higher for postmenopausal women (3.9 mg/L for those on ERT and 2.3 mg/L for those not on ERT) than for men (1.9 mg/L) or for premenopausal women (1.4 mg/L). In all, 74% of men, 62% of premenopausal women, 86% of postmenopausal women on ERT, and 77% of postmenopausal women not on ERT had CRP levels of at least 1 mg/L.

CRP level was not associated with BMD in men or in postmenopausal women using ERT. However, in those women, there was a significant association between years since menopause and BMD at all three sites. The researchers repeated the analysis for women fewer than 10 years past menopause and those at least 10 years past menopause. “The association of CRP with femoral neck BMD tended to be negative for those less than 10 years past menopause and positive for those at least 10 years past menopause, while there was no significant association at the trochanter or lumbar spine,” they wrote.

For postmenopausal women not using ERT, those with CRP levels of at least 1 mg/L had 2.5% greater BMD at the femoral neck, compared with the lower CRP level group, a significant difference. However, there were no significant associations at the trochanter or lumbar spine. “Contrary to our hypothesis, greater inflammation may be associated with higher BMD among postmenopausal women not using ERT,” wrote Dr. McLean, who is a researcher at the Institute for Aging Research, a research affiliate of Harvard Medical School, Boston.

In premenopausal women, CRP level was not associated with BMD at the femoral neck or the lumbar spine. However, each unit increase in CRP was associated with 0.005 g/cm

Preclinical studies have suggested that proinflammatory cytokines play a role in bone resorption, but the impact on BMD is not clear.

Dr. McLean reported that he has no relevant financial relationships.

DENVER — Menopausal status appears to modify the relationship between inflammation and bone mineral density, on the basis of findings from the Framingham Osteoporosis Study.

Postmenopausal women on estrogen replacement therapy (ERT) with higher levels of C-reactive protein—a measure of systemic inflammation—had greater bone mineral density (BMD) at the femoral neck than did those in the same group with lower CRP levels, Dr. Robert R. McLean and his coinvestigators reported in a poster at the annual meeting of the American Society for Bone and Mineral Research. In contrast, in premenopausal women, increased CRP levels were associated with a decrease in BMD at the trochanter.

The Framingham Heart Study Offspring Cohort enrolled 5,124 children and spouses of the original Framingham cohort. From 1996 to 2001, BMD was measured in 3,035 offspring in the Framingham Osteoporosis Study. Fasting blood samples were collected from 2,095 of them during 1998-2001. C-reactive protein levels were measured after BMD in 72% of participants, with a median time between assessments of 1.4 years.

BMD was measured at the right femoral neck and trochanter, and at the lumbar spine. Other variables obtained at the time of BMD measurement included age, height, weight, physical activity, smoking status, and use of NSAIDs. In women, menopause status, current ERT use, and years since menopause were recorded. Separate analyses were performed for the 1,291 men, 229 premenopausal women, 497 postmenopausal women using ERT, and 888 postmenopausal women not using ERT. Analyses were adjusted for age, height, weight, physical activity, and smoking status, with additional adjustment for NSAID use.

Median CRP levels were higher for postmenopausal women (3.9 mg/L for those on ERT and 2.3 mg/L for those not on ERT) than for men (1.9 mg/L) or for premenopausal women (1.4 mg/L). In all, 74% of men, 62% of premenopausal women, 86% of postmenopausal women on ERT, and 77% of postmenopausal women not on ERT had CRP levels of at least 1 mg/L.

CRP level was not associated with BMD in men or in postmenopausal women using ERT. However, in those women, there was a significant association between years since menopause and BMD at all three sites. The researchers repeated the analysis for women fewer than 10 years past menopause and those at least 10 years past menopause. “The association of CRP with femoral neck BMD tended to be negative for those less than 10 years past menopause and positive for those at least 10 years past menopause, while there was no significant association at the trochanter or lumbar spine,” they wrote.

For postmenopausal women not using ERT, those with CRP levels of at least 1 mg/L had 2.5% greater BMD at the femoral neck, compared with the lower CRP level group, a significant difference. However, there were no significant associations at the trochanter or lumbar spine. “Contrary to our hypothesis, greater inflammation may be associated with higher BMD among postmenopausal women not using ERT,” wrote Dr. McLean, who is a researcher at the Institute for Aging Research, a research affiliate of Harvard Medical School, Boston.

In premenopausal women, CRP level was not associated with BMD at the femoral neck or the lumbar spine. However, each unit increase in CRP was associated with 0.005 g/cm

Preclinical studies have suggested that proinflammatory cytokines play a role in bone resorption, but the impact on BMD is not clear.

Dr. McLean reported that he has no relevant financial relationships.

The risk for hip fracture rises steeply after patients have a major cardiovascular event, most likely because of genetic factors common to both vascular and bone disorders, a Swedish study has shown.

In a population-based study of nearly 32,000 twins in Sweden, the rate of hip fracture rose “considerably” in both men and women following any of several cardiovascular disease (CVD) diagnoses. Most of that increase appeared to be explained “by genes or by early environmental sharing” rather than individual lifestyle habits or other individual-specific environmental factors, said Dr. Ulf Sennerby of Uppsala (Sweden) University and associates.

“We advocate that individuals with a recent diagnosis of CVD should have their future fracture risk evaluated with clinical risk factors and bone scans,” such as the recently established 10-year probability using the FRAX (the World Health Organization's fracture risk assessment tool) algorithm, they noted.

The researchers used data from an extensive twin registry to examine the relation between CVD events and hip fracture. It included twin pairs who were born between 1914 and 1944 and were subsequently followed from the age of 50 years. It identified 31,936 pairs in which one twin developed CVD or hip fracture by Dec. 31, 2005.

The crude absolute rate of hip fractures in the cohort was 12.6 per 1,000 person-years after a diagnosis of heart failure, 12.6 per 1,000 person-years after a stroke, 6.6 per 1,000 person-years after a diagnosis of peripheral atherosclerosis, and 5.2 per 1,000 person-years after a diagnosis of ischemic heart disease, compared with 1.2 per 1,000 person-years for those without a CVD diagnosis.

All CVD diagnoses were associated with a higher risk of hip fracture independent of other CVD diagnoses and other comorbidities, the investigators said (JAMA 2009;302:1666-73).

The association was stronger in women than in men, but it was significant in both sexes.

Co-twins of subjects who had CVD also were at increased risk of sustaining hip fracture during follow-up, even if they had not had a cardiovascular event. For example, co-twins of subjects who had heart failure were at fourfold higher risk of fracturing a hip, compared with co-twins of subjects with no CVD.

The risk of hip fracture was higher in identical twins who had such “pseudoexposure” and lower in fraternal twins, indicating that an as-yet unidentified genetic factor predisposes people to both vascular and bone disorders, Dr. Sennerby and his associates said.

A subgroup of 24,598 subjects participated in telephone interviews to assess anthropomorphic, lifestyle, and medical factors. The inclusion of these factors into the data analysis did not materially change the results.

It is possible that “specific genes involved in cellular mechanisms shared by the vasculature and bone” may eventually explain this association between CVD and hip fracture, the authors wrote. “Matrix proteins supporting bone, vessel walls, and the myocardium [may] be of special relevance.

Dr. Sennerby reported no financial conflicts of interest.

The risk for hip fracture rises steeply after patients have a major cardiovascular event, most likely because of genetic factors common to both vascular and bone disorders, a Swedish study has shown.

In a population-based study of nearly 32,000 twins in Sweden, the rate of hip fracture rose “considerably” in both men and women following any of several cardiovascular disease (CVD) diagnoses. Most of that increase appeared to be explained “by genes or by early environmental sharing” rather than individual lifestyle habits or other individual-specific environmental factors, said Dr. Ulf Sennerby of Uppsala (Sweden) University and associates.

“We advocate that individuals with a recent diagnosis of CVD should have their future fracture risk evaluated with clinical risk factors and bone scans,” such as the recently established 10-year probability using the FRAX (the World Health Organization's fracture risk assessment tool) algorithm, they noted.

The researchers used data from an extensive twin registry to examine the relation between CVD events and hip fracture. It included twin pairs who were born between 1914 and 1944 and were subsequently followed from the age of 50 years. It identified 31,936 pairs in which one twin developed CVD or hip fracture by Dec. 31, 2005.

The crude absolute rate of hip fractures in the cohort was 12.6 per 1,000 person-years after a diagnosis of heart failure, 12.6 per 1,000 person-years after a stroke, 6.6 per 1,000 person-years after a diagnosis of peripheral atherosclerosis, and 5.2 per 1,000 person-years after a diagnosis of ischemic heart disease, compared with 1.2 per 1,000 person-years for those without a CVD diagnosis.

All CVD diagnoses were associated with a higher risk of hip fracture independent of other CVD diagnoses and other comorbidities, the investigators said (JAMA 2009;302:1666-73).

The association was stronger in women than in men, but it was significant in both sexes.

Co-twins of subjects who had CVD also were at increased risk of sustaining hip fracture during follow-up, even if they had not had a cardiovascular event. For example, co-twins of subjects who had heart failure were at fourfold higher risk of fracturing a hip, compared with co-twins of subjects with no CVD.

The risk of hip fracture was higher in identical twins who had such “pseudoexposure” and lower in fraternal twins, indicating that an as-yet unidentified genetic factor predisposes people to both vascular and bone disorders, Dr. Sennerby and his associates said.

A subgroup of 24,598 subjects participated in telephone interviews to assess anthropomorphic, lifestyle, and medical factors. The inclusion of these factors into the data analysis did not materially change the results.

It is possible that “specific genes involved in cellular mechanisms shared by the vasculature and bone” may eventually explain this association between CVD and hip fracture, the authors wrote. “Matrix proteins supporting bone, vessel walls, and the myocardium [may] be of special relevance.

Dr. Sennerby reported no financial conflicts of interest.

The risk for hip fracture rises steeply after patients have a major cardiovascular event, most likely because of genetic factors common to both vascular and bone disorders, a Swedish study has shown.

In a population-based study of nearly 32,000 twins in Sweden, the rate of hip fracture rose “considerably” in both men and women following any of several cardiovascular disease (CVD) diagnoses. Most of that increase appeared to be explained “by genes or by early environmental sharing” rather than individual lifestyle habits or other individual-specific environmental factors, said Dr. Ulf Sennerby of Uppsala (Sweden) University and associates.

“We advocate that individuals with a recent diagnosis of CVD should have their future fracture risk evaluated with clinical risk factors and bone scans,” such as the recently established 10-year probability using the FRAX (the World Health Organization's fracture risk assessment tool) algorithm, they noted.

The researchers used data from an extensive twin registry to examine the relation between CVD events and hip fracture. It included twin pairs who were born between 1914 and 1944 and were subsequently followed from the age of 50 years. It identified 31,936 pairs in which one twin developed CVD or hip fracture by Dec. 31, 2005.

The crude absolute rate of hip fractures in the cohort was 12.6 per 1,000 person-years after a diagnosis of heart failure, 12.6 per 1,000 person-years after a stroke, 6.6 per 1,000 person-years after a diagnosis of peripheral atherosclerosis, and 5.2 per 1,000 person-years after a diagnosis of ischemic heart disease, compared with 1.2 per 1,000 person-years for those without a CVD diagnosis.

All CVD diagnoses were associated with a higher risk of hip fracture independent of other CVD diagnoses and other comorbidities, the investigators said (JAMA 2009;302:1666-73).

The association was stronger in women than in men, but it was significant in both sexes.

Co-twins of subjects who had CVD also were at increased risk of sustaining hip fracture during follow-up, even if they had not had a cardiovascular event. For example, co-twins of subjects who had heart failure were at fourfold higher risk of fracturing a hip, compared with co-twins of subjects with no CVD.

The risk of hip fracture was higher in identical twins who had such “pseudoexposure” and lower in fraternal twins, indicating that an as-yet unidentified genetic factor predisposes people to both vascular and bone disorders, Dr. Sennerby and his associates said.

A subgroup of 24,598 subjects participated in telephone interviews to assess anthropomorphic, lifestyle, and medical factors. The inclusion of these factors into the data analysis did not materially change the results.

It is possible that “specific genes involved in cellular mechanisms shared by the vasculature and bone” may eventually explain this association between CVD and hip fracture, the authors wrote. “Matrix proteins supporting bone, vessel walls, and the myocardium [may] be of special relevance.

Dr. Sennerby reported no financial conflicts of interest.

BANGKOK, THAILAND — Long-term antiepileptic drug therapy is associated with worsening bone health in premenopausal women.

Dr. Rungsan Chaisewikul of Siriraj Hospital, Bangkok, included 50 women with epilepsy and 51 matched controls in his study, presented during the meeting's poster session. All the women were premenopausal, with a mean age of 33 years. Patients had been receiving antiepileptic drugs (AEDs) for at least 3 years. Most (62%) were taking more than one drug, and most (84%) were taking an enzyme-inducing AED. All participants had bone mineral density (BMD) measured at the lumbar spine, left femur, and left radius.

Compared with controls, patients had significantly lower T-scores at the femoral neck (0.30 vs. −0.08). BMD at the lumbar spine was lower, but not significantly lower, in patients than in controls, as was BMD at the radius.

With measurements at the femoral neck and lumbar spine significantly more patients than controls were rated as having osteopenia and osteoporosis. More patients than controls also were rated as osteopenic or osteoporotic when considering the radius measurement, although the difference was not statistically significant.

BANGKOK, THAILAND — Long-term antiepileptic drug therapy is associated with worsening bone health in premenopausal women.

Dr. Rungsan Chaisewikul of Siriraj Hospital, Bangkok, included 50 women with epilepsy and 51 matched controls in his study, presented during the meeting's poster session. All the women were premenopausal, with a mean age of 33 years. Patients had been receiving antiepileptic drugs (AEDs) for at least 3 years. Most (62%) were taking more than one drug, and most (84%) were taking an enzyme-inducing AED. All participants had bone mineral density (BMD) measured at the lumbar spine, left femur, and left radius.

Compared with controls, patients had significantly lower T-scores at the femoral neck (0.30 vs. −0.08). BMD at the lumbar spine was lower, but not significantly lower, in patients than in controls, as was BMD at the radius.

With measurements at the femoral neck and lumbar spine significantly more patients than controls were rated as having osteopenia and osteoporosis. More patients than controls also were rated as osteopenic or osteoporotic when considering the radius measurement, although the difference was not statistically significant.

BANGKOK, THAILAND — Long-term antiepileptic drug therapy is associated with worsening bone health in premenopausal women.

Dr. Rungsan Chaisewikul of Siriraj Hospital, Bangkok, included 50 women with epilepsy and 51 matched controls in his study, presented during the meeting's poster session. All the women were premenopausal, with a mean age of 33 years. Patients had been receiving antiepileptic drugs (AEDs) for at least 3 years. Most (62%) were taking more than one drug, and most (84%) were taking an enzyme-inducing AED. All participants had bone mineral density (BMD) measured at the lumbar spine, left femur, and left radius.

Compared with controls, patients had significantly lower T-scores at the femoral neck (0.30 vs. −0.08). BMD at the lumbar spine was lower, but not significantly lower, in patients than in controls, as was BMD at the radius.

With measurements at the femoral neck and lumbar spine significantly more patients than controls were rated as having osteopenia and osteoporosis. More patients than controls also were rated as osteopenic or osteoporotic when considering the radius measurement, although the difference was not statistically significant.

BERLIN — Denosumab was superior to zoledronic acid in the treatment of bone metastases in advanced breast cancer, but not so in the treatment of multiple myeloma or select solid tumors, according to data from two phase III trials.

The trials—Denosumab 136 and Denosumab 244—were presented at the joint congress of the European Cancer Organization and the European Society for Medical Oncology.

Dr. Alison Stopeck, who led the Denosumab 136 study in breast cancer, told reporters at an Amgen-sponsored press briefing that denosumab is clearly a first-line therapy.

In the Denosumab 136 trial, denosumab was superior to zoledronic acid in delaying the time to a first on-study skeletal-related event (SRE), defined as fracture, spinal cord compression, or radiation or surgery to bone. In all, 2,046 advanced breast cancer patients with bone metastases were studied. The median time to first SRE was not reached for denosumab, and was 26.5 months for zoledronic acid, said Dr. Stopeck, director of the clinical breast cancer program at the University of Arizona, Tucson.

Denosumab also significantly delayed the time to first and subsequent SREs, with 474 events reported in the denosumab arm and 608 in the zoledronic acid arm.

Renal failure occurred significantly more often in patients treated with zoledronic acid than denosumab (25 vs. 2 patients), as did acute renal failure (7 vs. 1 patient).

In the Denosumab 244 trial, the median time to first on-study SRE was 20.6 months for denosumab and 16.3 months for zoledronic acid among 1,776 advanced cancer patients with multiple myeloma or solid tumors, excluding breast and prostate cancer, a nonsignificant difference, reported lead author Dr. David Henry.

There were 392 first and subsequent SREs with denosumab vs. 436 such events with zoledronic acid, but again the difference was not significant, said Dr. Henry, a hematologist/oncologist at the Pennsylvania Hospital in Philadelphia.

Renal failure occurred in 25 of the 878 patients in the zoledronic acid group and in 20 of the 878 patients in the denosumab group. Acute renal failure was seen in 16 vs. 11 patients, respectively.

The Food and Drug Administration is expected to announce an approval decision on denosumab for the treatment of osteoporosis soon.

Both trials were supported by Amgen. Dr. Stopeck disclosed financial relationships with Novartis and Amgen. Dr. Henry disclosed relationships with Amgen, Ortho-Biotech Products LP, and Watson Pharmaceuticals Inc.

Compared with zoledronic acid, denosumab delayed time to first on-study SRE, but not significantly.

Source DR. HENRY

BERLIN — Denosumab was superior to zoledronic acid in the treatment of bone metastases in advanced breast cancer, but not so in the treatment of multiple myeloma or select solid tumors, according to data from two phase III trials.

The trials—Denosumab 136 and Denosumab 244—were presented at the joint congress of the European Cancer Organization and the European Society for Medical Oncology.

Dr. Alison Stopeck, who led the Denosumab 136 study in breast cancer, told reporters at an Amgen-sponsored press briefing that denosumab is clearly a first-line therapy.

In the Denosumab 136 trial, denosumab was superior to zoledronic acid in delaying the time to a first on-study skeletal-related event (SRE), defined as fracture, spinal cord compression, or radiation or surgery to bone. In all, 2,046 advanced breast cancer patients with bone metastases were studied. The median time to first SRE was not reached for denosumab, and was 26.5 months for zoledronic acid, said Dr. Stopeck, director of the clinical breast cancer program at the University of Arizona, Tucson.

Denosumab also significantly delayed the time to first and subsequent SREs, with 474 events reported in the denosumab arm and 608 in the zoledronic acid arm.

Renal failure occurred significantly more often in patients treated with zoledronic acid than denosumab (25 vs. 2 patients), as did acute renal failure (7 vs. 1 patient).

In the Denosumab 244 trial, the median time to first on-study SRE was 20.6 months for denosumab and 16.3 months for zoledronic acid among 1,776 advanced cancer patients with multiple myeloma or solid tumors, excluding breast and prostate cancer, a nonsignificant difference, reported lead author Dr. David Henry.

There were 392 first and subsequent SREs with denosumab vs. 436 such events with zoledronic acid, but again the difference was not significant, said Dr. Henry, a hematologist/oncologist at the Pennsylvania Hospital in Philadelphia.

Renal failure occurred in 25 of the 878 patients in the zoledronic acid group and in 20 of the 878 patients in the denosumab group. Acute renal failure was seen in 16 vs. 11 patients, respectively.

The Food and Drug Administration is expected to announce an approval decision on denosumab for the treatment of osteoporosis soon.

Both trials were supported by Amgen. Dr. Stopeck disclosed financial relationships with Novartis and Amgen. Dr. Henry disclosed relationships with Amgen, Ortho-Biotech Products LP, and Watson Pharmaceuticals Inc.

Compared with zoledronic acid, denosumab delayed time to first on-study SRE, but not significantly.

Source DR. HENRY

BERLIN — Denosumab was superior to zoledronic acid in the treatment of bone metastases in advanced breast cancer, but not so in the treatment of multiple myeloma or select solid tumors, according to data from two phase III trials.

The trials—Denosumab 136 and Denosumab 244—were presented at the joint congress of the European Cancer Organization and the European Society for Medical Oncology.

Dr. Alison Stopeck, who led the Denosumab 136 study in breast cancer, told reporters at an Amgen-sponsored press briefing that denosumab is clearly a first-line therapy.

In the Denosumab 136 trial, denosumab was superior to zoledronic acid in delaying the time to a first on-study skeletal-related event (SRE), defined as fracture, spinal cord compression, or radiation or surgery to bone. In all, 2,046 advanced breast cancer patients with bone metastases were studied. The median time to first SRE was not reached for denosumab, and was 26.5 months for zoledronic acid, said Dr. Stopeck, director of the clinical breast cancer program at the University of Arizona, Tucson.

Denosumab also significantly delayed the time to first and subsequent SREs, with 474 events reported in the denosumab arm and 608 in the zoledronic acid arm.

Renal failure occurred significantly more often in patients treated with zoledronic acid than denosumab (25 vs. 2 patients), as did acute renal failure (7 vs. 1 patient).

In the Denosumab 244 trial, the median time to first on-study SRE was 20.6 months for denosumab and 16.3 months for zoledronic acid among 1,776 advanced cancer patients with multiple myeloma or solid tumors, excluding breast and prostate cancer, a nonsignificant difference, reported lead author Dr. David Henry.

There were 392 first and subsequent SREs with denosumab vs. 436 such events with zoledronic acid, but again the difference was not significant, said Dr. Henry, a hematologist/oncologist at the Pennsylvania Hospital in Philadelphia.

Renal failure occurred in 25 of the 878 patients in the zoledronic acid group and in 20 of the 878 patients in the denosumab group. Acute renal failure was seen in 16 vs. 11 patients, respectively.

The Food and Drug Administration is expected to announce an approval decision on denosumab for the treatment of osteoporosis soon.

Both trials were supported by Amgen. Dr. Stopeck disclosed financial relationships with Novartis and Amgen. Dr. Henry disclosed relationships with Amgen, Ortho-Biotech Products LP, and Watson Pharmaceuticals Inc.

Compared with zoledronic acid, denosumab delayed time to first on-study SRE, but not significantly.

Source DR. HENRY

SAN DIEGO — The combination of breastfeeding and delaying pregnancy until the majority of bone mass has been acquired appears to have a protective effect on bones, according to study involving more than 600 women.

“Several studies have shown that people who have had many pregnancies have less bone loss than women with no pregnancies,” lead author Dr. Peter F. Schnatz said in an interview.

“Our study is the first to our knowledge looking at the effect of pregnancy during the time of peak bone mineral acquisition and its eventual and ultimate effect on the development of postmenopausal osteoporosis,” he said at a poster session at the annual meeting of the North American Menopause Society.

Dr. Schnatz, of the department of obstetrics and gynecology at Reading (Pa.) Hospital and Medical Center, and his associates analyzed data from 619 women aged older than 49 years who presented for bone density scanning in the Hartford, Conn., area. They assessed risk factors for osteoporosis, including a previous atraumatic fracture of the hip or spine, pregnancy information, and dual-energy x-ray absorptiometry results. Mean age of the study participants was 62 years; 50% were either current or past smokers.

Women who had breastfed had a significantly lower prevalence of osteoporosis (8%) than did those who did not breastfeed (19%), a finding that surprised the researchers. “It would seem that breastfeeding, which requires acquisition of calcium from the mother to nourish the baby, would cause bone loss,” Dr. Schnatz said. “We wonder if there may be a rebound anabolic phenomenon, hence resulting in overall benefit.”

Among those who had breastfed, women aged younger than 27 years at the first pregnancy had a significantly higher prevalence of osteoporosis than did those who were 27 and older at first pregnancy (11% vs. 5%, respectively).

Of those who were at least 27 years old at first pregnancy, there was a significantly increased prevalence of osteoporosis in those who did not breastfeed, compared with those who did (25% vs. 5%, respectively).

Women who were at least 27 years old at their first pregnancy and who breastfed had a statistically lower prevalence of osteoporosis, compared with their counterparts who had their first pregnancy younger than age 27 and no history of breastfeeding (5% vs. 16%, respectively).

Among women who did not breastfeed, there was little difference in the risk of postmenopausal osteoporosis if the first pregnancy occurred at or after age 22 or 27 years, Dr. Schnatz wrote.

“Women should be encouraged to wait until the postadolescent years for childbearing and should be encouraged to breastfeed,” he concluded.

The study was supported by a grant from the Alliance for Better Bone Health. Dr. Schnatz and his associates had no other financial conflicts to disclose.

SAN DIEGO — The combination of breastfeeding and delaying pregnancy until the majority of bone mass has been acquired appears to have a protective effect on bones, according to study involving more than 600 women.

“Several studies have shown that people who have had many pregnancies have less bone loss than women with no pregnancies,” lead author Dr. Peter F. Schnatz said in an interview.

“Our study is the first to our knowledge looking at the effect of pregnancy during the time of peak bone mineral acquisition and its eventual and ultimate effect on the development of postmenopausal osteoporosis,” he said at a poster session at the annual meeting of the North American Menopause Society.

Dr. Schnatz, of the department of obstetrics and gynecology at Reading (Pa.) Hospital and Medical Center, and his associates analyzed data from 619 women aged older than 49 years who presented for bone density scanning in the Hartford, Conn., area. They assessed risk factors for osteoporosis, including a previous atraumatic fracture of the hip or spine, pregnancy information, and dual-energy x-ray absorptiometry results. Mean age of the study participants was 62 years; 50% were either current or past smokers.

Women who had breastfed had a significantly lower prevalence of osteoporosis (8%) than did those who did not breastfeed (19%), a finding that surprised the researchers. “It would seem that breastfeeding, which requires acquisition of calcium from the mother to nourish the baby, would cause bone loss,” Dr. Schnatz said. “We wonder if there may be a rebound anabolic phenomenon, hence resulting in overall benefit.”

Among those who had breastfed, women aged younger than 27 years at the first pregnancy had a significantly higher prevalence of osteoporosis than did those who were 27 and older at first pregnancy (11% vs. 5%, respectively).

Of those who were at least 27 years old at first pregnancy, there was a significantly increased prevalence of osteoporosis in those who did not breastfeed, compared with those who did (25% vs. 5%, respectively).

Women who were at least 27 years old at their first pregnancy and who breastfed had a statistically lower prevalence of osteoporosis, compared with their counterparts who had their first pregnancy younger than age 27 and no history of breastfeeding (5% vs. 16%, respectively).

Among women who did not breastfeed, there was little difference in the risk of postmenopausal osteoporosis if the first pregnancy occurred at or after age 22 or 27 years, Dr. Schnatz wrote.

“Women should be encouraged to wait until the postadolescent years for childbearing and should be encouraged to breastfeed,” he concluded.

The study was supported by a grant from the Alliance for Better Bone Health. Dr. Schnatz and his associates had no other financial conflicts to disclose.

SAN DIEGO — The combination of breastfeeding and delaying pregnancy until the majority of bone mass has been acquired appears to have a protective effect on bones, according to study involving more than 600 women.

“Several studies have shown that people who have had many pregnancies have less bone loss than women with no pregnancies,” lead author Dr. Peter F. Schnatz said in an interview.

“Our study is the first to our knowledge looking at the effect of pregnancy during the time of peak bone mineral acquisition and its eventual and ultimate effect on the development of postmenopausal osteoporosis,” he said at a poster session at the annual meeting of the North American Menopause Society.

Dr. Schnatz, of the department of obstetrics and gynecology at Reading (Pa.) Hospital and Medical Center, and his associates analyzed data from 619 women aged older than 49 years who presented for bone density scanning in the Hartford, Conn., area. They assessed risk factors for osteoporosis, including a previous atraumatic fracture of the hip or spine, pregnancy information, and dual-energy x-ray absorptiometry results. Mean age of the study participants was 62 years; 50% were either current or past smokers.

Women who had breastfed had a significantly lower prevalence of osteoporosis (8%) than did those who did not breastfeed (19%), a finding that surprised the researchers. “It would seem that breastfeeding, which requires acquisition of calcium from the mother to nourish the baby, would cause bone loss,” Dr. Schnatz said. “We wonder if there may be a rebound anabolic phenomenon, hence resulting in overall benefit.”

Among those who had breastfed, women aged younger than 27 years at the first pregnancy had a significantly higher prevalence of osteoporosis than did those who were 27 and older at first pregnancy (11% vs. 5%, respectively).

Of those who were at least 27 years old at first pregnancy, there was a significantly increased prevalence of osteoporosis in those who did not breastfeed, compared with those who did (25% vs. 5%, respectively).

Women who were at least 27 years old at their first pregnancy and who breastfed had a statistically lower prevalence of osteoporosis, compared with their counterparts who had their first pregnancy younger than age 27 and no history of breastfeeding (5% vs. 16%, respectively).

Among women who did not breastfeed, there was little difference in the risk of postmenopausal osteoporosis if the first pregnancy occurred at or after age 22 or 27 years, Dr. Schnatz wrote.

“Women should be encouraged to wait until the postadolescent years for childbearing and should be encouraged to breastfeed,” he concluded.

The study was supported by a grant from the Alliance for Better Bone Health. Dr. Schnatz and his associates had no other financial conflicts to disclose.

DENVER — The FRAX 10-year fracture risk tool was fairly accurate in predicting the observed number of hip fractures that occurred among more than 5,000 participants of the Framingham Heart Study, according to data presented as a poster at the annual meeting of the American Society for Bone and Mineral Research.

The 10-year observed incidence of hip fracture for women was 117 cases, which did not differ significantly from the FRAX predicted number of 113. For men, the observed incidence was 29 cases, not significantly different from the FRAX prediction of 38, reported Elizabeth J. Samelson, Ph.D., of the Institute for Aging Research in Boston, and her coinvestigators.

FRAX, developed by the World Health Organization, is an online tool to calculate the 10-year probability of hip fracture and major osteoporotic fracture in women and men aged 40–90 years, on the basis of bone mineral density (BMD), gender, age, smoking status, glucocorticoid use, height and weight, diagnosis of rheumatoid arthritis or secondary osteoporosis, history of fracture, and parental history of fracture.

This study included 5,204 Framingham cohort members (2,917 women and 2,287 men) who had a baseline examination between 1987 and 2001 and were followed for hip fracture over 10 years. All were white.

At baseline, patients were assessed for age, body mass index, current smoking status, alcohol consumption, glucocorticoid use, diagnosis of rheumatoid arthritis, prior fragility fracture, parental history of fracture, and T score. Original cohort members (1,456) for whom no parental hip fracture history was available were classified as having no such history. Femoral neck BMD was available for 4,224 participants.

The researchers used FRAX version 3.0 to calculate the 10-year probability of hip fracture and compared the expected number with that observed in the cohort.

Among women aged 40–75 years, the incidence was 52 cases, compared with 57 expected by FRAX; among men aged 40–75 years, the incidence was 12 cases, compared with 23 expected by FRAX.

The observed probability of hip fracture in the oldest adults (aged 76–90 years) exceeded the number predicted by FRAX, while the opposite was true for those aged 40–75. Among women aged 76–90 years, the incidence was 65 cases, compared with 55 expected by FRAX; among men aged 76–90 years, the incidence was 17 cases, compared with 14 expected by FRAX.

The study was supported by the National Institutes of Health. The researchers said they had no relevant financial relationships.

A video about the use of the FRAX tool is at www.youtube.com/clinicalendonews

DENVER — The FRAX 10-year fracture risk tool was fairly accurate in predicting the observed number of hip fractures that occurred among more than 5,000 participants of the Framingham Heart Study, according to data presented as a poster at the annual meeting of the American Society for Bone and Mineral Research.

The 10-year observed incidence of hip fracture for women was 117 cases, which did not differ significantly from the FRAX predicted number of 113. For men, the observed incidence was 29 cases, not significantly different from the FRAX prediction of 38, reported Elizabeth J. Samelson, Ph.D., of the Institute for Aging Research in Boston, and her coinvestigators.

FRAX, developed by the World Health Organization, is an online tool to calculate the 10-year probability of hip fracture and major osteoporotic fracture in women and men aged 40–90 years, on the basis of bone mineral density (BMD), gender, age, smoking status, glucocorticoid use, height and weight, diagnosis of rheumatoid arthritis or secondary osteoporosis, history of fracture, and parental history of fracture.

This study included 5,204 Framingham cohort members (2,917 women and 2,287 men) who had a baseline examination between 1987 and 2001 and were followed for hip fracture over 10 years. All were white.

At baseline, patients were assessed for age, body mass index, current smoking status, alcohol consumption, glucocorticoid use, diagnosis of rheumatoid arthritis, prior fragility fracture, parental history of fracture, and T score. Original cohort members (1,456) for whom no parental hip fracture history was available were classified as having no such history. Femoral neck BMD was available for 4,224 participants.

The researchers used FRAX version 3.0 to calculate the 10-year probability of hip fracture and compared the expected number with that observed in the cohort.

Among women aged 40–75 years, the incidence was 52 cases, compared with 57 expected by FRAX; among men aged 40–75 years, the incidence was 12 cases, compared with 23 expected by FRAX.

The observed probability of hip fracture in the oldest adults (aged 76–90 years) exceeded the number predicted by FRAX, while the opposite was true for those aged 40–75. Among women aged 76–90 years, the incidence was 65 cases, compared with 55 expected by FRAX; among men aged 76–90 years, the incidence was 17 cases, compared with 14 expected by FRAX.

The study was supported by the National Institutes of Health. The researchers said they had no relevant financial relationships.

A video about the use of the FRAX tool is at www.youtube.com/clinicalendonews

DENVER — The FRAX 10-year fracture risk tool was fairly accurate in predicting the observed number of hip fractures that occurred among more than 5,000 participants of the Framingham Heart Study, according to data presented as a poster at the annual meeting of the American Society for Bone and Mineral Research.

The 10-year observed incidence of hip fracture for women was 117 cases, which did not differ significantly from the FRAX predicted number of 113. For men, the observed incidence was 29 cases, not significantly different from the FRAX prediction of 38, reported Elizabeth J. Samelson, Ph.D., of the Institute for Aging Research in Boston, and her coinvestigators.

FRAX, developed by the World Health Organization, is an online tool to calculate the 10-year probability of hip fracture and major osteoporotic fracture in women and men aged 40–90 years, on the basis of bone mineral density (BMD), gender, age, smoking status, glucocorticoid use, height and weight, diagnosis of rheumatoid arthritis or secondary osteoporosis, history of fracture, and parental history of fracture.

This study included 5,204 Framingham cohort members (2,917 women and 2,287 men) who had a baseline examination between 1987 and 2001 and were followed for hip fracture over 10 years. All were white.

At baseline, patients were assessed for age, body mass index, current smoking status, alcohol consumption, glucocorticoid use, diagnosis of rheumatoid arthritis, prior fragility fracture, parental history of fracture, and T score. Original cohort members (1,456) for whom no parental hip fracture history was available were classified as having no such history. Femoral neck BMD was available for 4,224 participants.

The researchers used FRAX version 3.0 to calculate the 10-year probability of hip fracture and compared the expected number with that observed in the cohort.

Among women aged 40–75 years, the incidence was 52 cases, compared with 57 expected by FRAX; among men aged 40–75 years, the incidence was 12 cases, compared with 23 expected by FRAX.

The observed probability of hip fracture in the oldest adults (aged 76–90 years) exceeded the number predicted by FRAX, while the opposite was true for those aged 40–75. Among women aged 76–90 years, the incidence was 65 cases, compared with 55 expected by FRAX; among men aged 76–90 years, the incidence was 17 cases, compared with 14 expected by FRAX.

The study was supported by the National Institutes of Health. The researchers said they had no relevant financial relationships.

A video about the use of the FRAX tool is at www.youtube.com/clinicalendonews

DENVER — Patients with rheumatic diseases who were on long-term glucocorticoid therapy were almost twice as likely to have low bone mass as were those with who were not on glucocorticoids, results of a study of more than 200,000 patients have shown.

The findings were presented as a poster at the annual meeting of the American Society for Bone and Mineral Research by Dr. Viviana A. Reidel and her coinvestigators.

The researchers used UnitedHealth Group Inc.'s proprietary normative health information database of medical claims—both private and Medicare/Medicaid. In 2007, the database included information on 23.6 million people.

Dr. Reidel and her colleagues identified those who had had at least two visits resulting in an ICD-9-CM code for a rheumatic disease and an ICD-9-CM code for either osteoporosis or osteopenia occurring after the first prescription of a glucocorticoid.

Long-term glucocorticoid use was defined as one or more monthly prescriptions for at least 6 months. High-dose glucocorticoids were defined as a prednisone dosage of at least 7.5 mg/day, or the equivalent; low-dose use was a prednisone dosage of less than 7.5 mg/day, or the equivalent. The nonglucocorticoid group included patients with rheumatic diseases who were prescribed any other therapy or no therapy.

In all, 201,121 patients with rheumatic diseases were identified. The most common disease was rheumatoid arthritis (57%), followed by systemic lupus erythematosus, spondyloarthropathies, polymyalgia rheumatica, vasculitis, and enteropathic arthritis. Among those with long-term glucocorticoid use, 44% of women and 11% of men had low bone mineral density. Among those non–long-term users, 31% of women and 4% of men had low BMD.

Patients with rheumatic diseases who were on long-term glucocorticoids had a relative risk of 1.7 of having low bone mass, compared with those who were not on glucocorticoids. “However, our analysis suggests that the effect of long-term higher-dose glucocorticoid treatment on increasing risk of glucocorticoid-induced low bone mass compared to long-term lower-dose glucocorticoid treatment is weak,” wrote Dr. Reidel, medical director at i3 Research, a clinical research company. There was a slight but significantly increased risk of low bone mass in patients who were treated long term with high-dose glucocorticoids, compared with those treated long term with low doses.

The researchers also found that only 0.2% of patients with long-term glucocorticoid use had at least one dual-energy x-ray absorptiometry scan, compared with 8% of those with no known glucocorticoid exposure.

There are plans to look at any associations between long-term glucocorticoid use and BMD by rheumatic disease, Dr. Reidel said in an interview.

A whole-body dual-energy x-ray absorptiometry scan can provide information on total and regional BMD (left) and body composition (fat, muscle mass).

Source ©Elsevier

DENVER — Patients with rheumatic diseases who were on long-term glucocorticoid therapy were almost twice as likely to have low bone mass as were those with who were not on glucocorticoids, results of a study of more than 200,000 patients have shown.

The findings were presented as a poster at the annual meeting of the American Society for Bone and Mineral Research by Dr. Viviana A. Reidel and her coinvestigators.

The researchers used UnitedHealth Group Inc.'s proprietary normative health information database of medical claims—both private and Medicare/Medicaid. In 2007, the database included information on 23.6 million people.

Dr. Reidel and her colleagues identified those who had had at least two visits resulting in an ICD-9-CM code for a rheumatic disease and an ICD-9-CM code for either osteoporosis or osteopenia occurring after the first prescription of a glucocorticoid.

Long-term glucocorticoid use was defined as one or more monthly prescriptions for at least 6 months. High-dose glucocorticoids were defined as a prednisone dosage of at least 7.5 mg/day, or the equivalent; low-dose use was a prednisone dosage of less than 7.5 mg/day, or the equivalent. The nonglucocorticoid group included patients with rheumatic diseases who were prescribed any other therapy or no therapy.

In all, 201,121 patients with rheumatic diseases were identified. The most common disease was rheumatoid arthritis (57%), followed by systemic lupus erythematosus, spondyloarthropathies, polymyalgia rheumatica, vasculitis, and enteropathic arthritis. Among those with long-term glucocorticoid use, 44% of women and 11% of men had low bone mineral density. Among those non–long-term users, 31% of women and 4% of men had low BMD.

Patients with rheumatic diseases who were on long-term glucocorticoids had a relative risk of 1.7 of having low bone mass, compared with those who were not on glucocorticoids. “However, our analysis suggests that the effect of long-term higher-dose glucocorticoid treatment on increasing risk of glucocorticoid-induced low bone mass compared to long-term lower-dose glucocorticoid treatment is weak,” wrote Dr. Reidel, medical director at i3 Research, a clinical research company. There was a slight but significantly increased risk of low bone mass in patients who were treated long term with high-dose glucocorticoids, compared with those treated long term with low doses.

The researchers also found that only 0.2% of patients with long-term glucocorticoid use had at least one dual-energy x-ray absorptiometry scan, compared with 8% of those with no known glucocorticoid exposure.

There are plans to look at any associations between long-term glucocorticoid use and BMD by rheumatic disease, Dr. Reidel said in an interview.

A whole-body dual-energy x-ray absorptiometry scan can provide information on total and regional BMD (left) and body composition (fat, muscle mass).

Source ©Elsevier

DENVER — Patients with rheumatic diseases who were on long-term glucocorticoid therapy were almost twice as likely to have low bone mass as were those with who were not on glucocorticoids, results of a study of more than 200,000 patients have shown.

The findings were presented as a poster at the annual meeting of the American Society for Bone and Mineral Research by Dr. Viviana A. Reidel and her coinvestigators.

The researchers used UnitedHealth Group Inc.'s proprietary normative health information database of medical claims—both private and Medicare/Medicaid. In 2007, the database included information on 23.6 million people.

Dr. Reidel and her colleagues identified those who had had at least two visits resulting in an ICD-9-CM code for a rheumatic disease and an ICD-9-CM code for either osteoporosis or osteopenia occurring after the first prescription of a glucocorticoid.

Long-term glucocorticoid use was defined as one or more monthly prescriptions for at least 6 months. High-dose glucocorticoids were defined as a prednisone dosage of at least 7.5 mg/day, or the equivalent; low-dose use was a prednisone dosage of less than 7.5 mg/day, or the equivalent. The nonglucocorticoid group included patients with rheumatic diseases who were prescribed any other therapy or no therapy.

In all, 201,121 patients with rheumatic diseases were identified. The most common disease was rheumatoid arthritis (57%), followed by systemic lupus erythematosus, spondyloarthropathies, polymyalgia rheumatica, vasculitis, and enteropathic arthritis. Among those with long-term glucocorticoid use, 44% of women and 11% of men had low bone mineral density. Among those non–long-term users, 31% of women and 4% of men had low BMD.

Patients with rheumatic diseases who were on long-term glucocorticoids had a relative risk of 1.7 of having low bone mass, compared with those who were not on glucocorticoids. “However, our analysis suggests that the effect of long-term higher-dose glucocorticoid treatment on increasing risk of glucocorticoid-induced low bone mass compared to long-term lower-dose glucocorticoid treatment is weak,” wrote Dr. Reidel, medical director at i3 Research, a clinical research company. There was a slight but significantly increased risk of low bone mass in patients who were treated long term with high-dose glucocorticoids, compared with those treated long term with low doses.

The researchers also found that only 0.2% of patients with long-term glucocorticoid use had at least one dual-energy x-ray absorptiometry scan, compared with 8% of those with no known glucocorticoid exposure.

There are plans to look at any associations between long-term glucocorticoid use and BMD by rheumatic disease, Dr. Reidel said in an interview.

A whole-body dual-energy x-ray absorptiometry scan can provide information on total and regional BMD (left) and body composition (fat, muscle mass).

Source ©Elsevier

Rosiglitazone use was associated with an increased prevalence of vertebral fractures among men in a small cross-sectional study.

Most previous studies on the effect of thiazolidinediones on bone have been done in postmenopausal women, who are already at risk for osteoporosis. The present study provides evidence that osteoporotic fractures may be a general complication of this treatment, said Dr. Tatiana Mancini of San Marino (Italy) Hospital, and her associates.

On the basis of their findings, the investigators advocated that health care providers use spine x-ray in combination with dual-energy x-ray absorptiometry (DXA) to assess bone status in diabetic patients treated with these agents (Bone 2009;25:784–8). Of 43 men with type 2 dia-betes (mean age 69 years), 22 men used metformin alone and 21 used metformin plus rosiglitazone; 22 nondiabetic men from an outpatient bone clinic served as controls. Bone mineral density (BMD) was assessed by DXA, and quantitative morphometric analysis was used to identify radiological vertebral fractures.

Vertebral fractures were found in 46.5% of the men with diabetes with a significantly higher prevalence in patients treated with rosiglitazone plus metformin (66.7%) versus metformin alone (27.3%) or versus controls (22.7%).

Compared with diabetic men who received only metformin, those who received both drugs were significantly younger and had greater body mass index. Multivariate analysis corrected for these and other factors but still demonstrated a significant 6.5-fold increased risk associated with rosiglitazone.

Rosiglitazone use was associated with an increased prevalence of vertebral fractures among men in a small cross-sectional study.

Most previous studies on the effect of thiazolidinediones on bone have been done in postmenopausal women, who are already at risk for osteoporosis. The present study provides evidence that osteoporotic fractures may be a general complication of this treatment, said Dr. Tatiana Mancini of San Marino (Italy) Hospital, and her associates.

On the basis of their findings, the investigators advocated that health care providers use spine x-ray in combination with dual-energy x-ray absorptiometry (DXA) to assess bone status in diabetic patients treated with these agents (Bone 2009;25:784–8). Of 43 men with type 2 dia-betes (mean age 69 years), 22 men used metformin alone and 21 used metformin plus rosiglitazone; 22 nondiabetic men from an outpatient bone clinic served as controls. Bone mineral density (BMD) was assessed by DXA, and quantitative morphometric analysis was used to identify radiological vertebral fractures.

Vertebral fractures were found in 46.5% of the men with diabetes with a significantly higher prevalence in patients treated with rosiglitazone plus metformin (66.7%) versus metformin alone (27.3%) or versus controls (22.7%).

Compared with diabetic men who received only metformin, those who received both drugs were significantly younger and had greater body mass index. Multivariate analysis corrected for these and other factors but still demonstrated a significant 6.5-fold increased risk associated with rosiglitazone.

Rosiglitazone use was associated with an increased prevalence of vertebral fractures among men in a small cross-sectional study.

Most previous studies on the effect of thiazolidinediones on bone have been done in postmenopausal women, who are already at risk for osteoporosis. The present study provides evidence that osteoporotic fractures may be a general complication of this treatment, said Dr. Tatiana Mancini of San Marino (Italy) Hospital, and her associates.

On the basis of their findings, the investigators advocated that health care providers use spine x-ray in combination with dual-energy x-ray absorptiometry (DXA) to assess bone status in diabetic patients treated with these agents (Bone 2009;25:784–8). Of 43 men with type 2 dia-betes (mean age 69 years), 22 men used metformin alone and 21 used metformin plus rosiglitazone; 22 nondiabetic men from an outpatient bone clinic served as controls. Bone mineral density (BMD) was assessed by DXA, and quantitative morphometric analysis was used to identify radiological vertebral fractures.

Vertebral fractures were found in 46.5% of the men with diabetes with a significantly higher prevalence in patients treated with rosiglitazone plus metformin (66.7%) versus metformin alone (27.3%) or versus controls (22.7%).

Compared with diabetic men who received only metformin, those who received both drugs were significantly younger and had greater body mass index. Multivariate analysis corrected for these and other factors but still demonstrated a significant 6.5-fold increased risk associated with rosiglitazone.