Osteoarthritis

BOSTON — An increased risk for osteoporosis or osteopenia is among the age-related complications faced by patients surviving long term with HIV disease.

Cross-sectional studies have shown that patients with HIV have a greater prevalence of reduced bone mineral density, compared with healthy controls, but longitudinal data that would demonstrate the significance of this increased risk are lacking, said Dr. William G. Powderly of University College Dublin.

To meet this need for data, the Centers for Disease Control and Prevention is prospectively following a cohort of more than 500 HIV-infected patients in the Study to Understand the Natural History of HIV and AIDS (SUN), Dr. Powderly said at the 15th Conference on Retroviruses and Opportunistic Infections.

On enrollment in SUN, patients had baseline bone densitometry and body composition measurements, clinical data, and fasting laboratory data collected, and were matched for age, race, sex, and body mass index with controls from the National Health and Nutrition Examination Study III.

Among the SUN patients (mean age 41 years), 52% had osteopenia and 10% had frank osteoporosis, Dr. Powderly said.

A total of 78% were men, 25% were black, and almost 80% were receiving antiretroviral therapy.

Analysis revealed that factors associated with an increased risk of low bone mineral density included age over 45 years (odds ratio 2.35) and CD4 count below 300 cells/mm3 (OR 2.10), Dr. Powderly said.

Duration of HIV infection longer than 98 months also was associated with an increased risk (OR 1.56).

Determining whether bone mineral loss will continue over time and translate into increased risk for fractures is a “critically important” area of HIV research, Dr. Powderly said at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the CDC.

Further information also is needed on HIV-associated risk factors. Aside from risk factors also present in the general population such as smoking, alcohol use, low body mass index, and lack of physical activity, the aging HIV patient also might have renal dysfunction and inadequate nutrition, which can further contribute to bone loss. HIV disease itself might alter the processes involved in bone mineralization and turnover, according to Dr. Powderly. In a study he and his colleagues performed, human osteoblast and mesenchymal stem cell lines were treated in vitro with several HIV proteins, including HIV p55-gag and HIV gp120.

Exposure to these proteins reduced calcium deposition, alkaline phosphatase activity, and mRNA levels of osteogenic transcription factors in osteoblasts, and the ability of stem cells to develop into osteoblasts was modulated (AIDS Res. Hum. Retroviruses 2007;23:1521-30).

There is also some evidence implicating potent antiretroviral medications in bone loss. In a meta-analysis of 20 studies that included 884 patients, 67% had reduced bone mineral density and 15% had osteoporosis. Those receiving antiretroviral therapy had a 2.5-fold increased risk of having reduced bone mineral density, compared with those who were treatment naive (AIDS 2006;20:2165-74).

The dynamic process of bone mineralization is another factor. “We reach the peak of bone mineralization at around 30 years, and then both men and women lose bone at a rate of approximately 0.5%-1% per year,” according to Dr. Powderly.

Because women have lower peak bone mass than do men, they have higher rates of osteoporosis as they age. Until the relative contributions to bone loss of the various factors can be more fully clarified, the routine care of older patients with HIV should include baseline and routine monitoring of markers of bone turnover, according to Dr. Powderly.

BOSTON — An increased risk for osteoporosis or osteopenia is among the age-related complications faced by patients surviving long term with HIV disease.

Cross-sectional studies have shown that patients with HIV have a greater prevalence of reduced bone mineral density, compared with healthy controls, but longitudinal data that would demonstrate the significance of this increased risk are lacking, said Dr. William G. Powderly of University College Dublin.

To meet this need for data, the Centers for Disease Control and Prevention is prospectively following a cohort of more than 500 HIV-infected patients in the Study to Understand the Natural History of HIV and AIDS (SUN), Dr. Powderly said at the 15th Conference on Retroviruses and Opportunistic Infections.

On enrollment in SUN, patients had baseline bone densitometry and body composition measurements, clinical data, and fasting laboratory data collected, and were matched for age, race, sex, and body mass index with controls from the National Health and Nutrition Examination Study III.

Among the SUN patients (mean age 41 years), 52% had osteopenia and 10% had frank osteoporosis, Dr. Powderly said.

A total of 78% were men, 25% were black, and almost 80% were receiving antiretroviral therapy.

Analysis revealed that factors associated with an increased risk of low bone mineral density included age over 45 years (odds ratio 2.35) and CD4 count below 300 cells/mm3 (OR 2.10), Dr. Powderly said.

Duration of HIV infection longer than 98 months also was associated with an increased risk (OR 1.56).

Determining whether bone mineral loss will continue over time and translate into increased risk for fractures is a “critically important” area of HIV research, Dr. Powderly said at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the CDC.

Further information also is needed on HIV-associated risk factors. Aside from risk factors also present in the general population such as smoking, alcohol use, low body mass index, and lack of physical activity, the aging HIV patient also might have renal dysfunction and inadequate nutrition, which can further contribute to bone loss. HIV disease itself might alter the processes involved in bone mineralization and turnover, according to Dr. Powderly. In a study he and his colleagues performed, human osteoblast and mesenchymal stem cell lines were treated in vitro with several HIV proteins, including HIV p55-gag and HIV gp120.

Exposure to these proteins reduced calcium deposition, alkaline phosphatase activity, and mRNA levels of osteogenic transcription factors in osteoblasts, and the ability of stem cells to develop into osteoblasts was modulated (AIDS Res. Hum. Retroviruses 2007;23:1521-30).

There is also some evidence implicating potent antiretroviral medications in bone loss. In a meta-analysis of 20 studies that included 884 patients, 67% had reduced bone mineral density and 15% had osteoporosis. Those receiving antiretroviral therapy had a 2.5-fold increased risk of having reduced bone mineral density, compared with those who were treatment naive (AIDS 2006;20:2165-74).

The dynamic process of bone mineralization is another factor. “We reach the peak of bone mineralization at around 30 years, and then both men and women lose bone at a rate of approximately 0.5%-1% per year,” according to Dr. Powderly.

Because women have lower peak bone mass than do men, they have higher rates of osteoporosis as they age. Until the relative contributions to bone loss of the various factors can be more fully clarified, the routine care of older patients with HIV should include baseline and routine monitoring of markers of bone turnover, according to Dr. Powderly.

BOSTON — An increased risk for osteoporosis or osteopenia is among the age-related complications faced by patients surviving long term with HIV disease.

Cross-sectional studies have shown that patients with HIV have a greater prevalence of reduced bone mineral density, compared with healthy controls, but longitudinal data that would demonstrate the significance of this increased risk are lacking, said Dr. William G. Powderly of University College Dublin.

To meet this need for data, the Centers for Disease Control and Prevention is prospectively following a cohort of more than 500 HIV-infected patients in the Study to Understand the Natural History of HIV and AIDS (SUN), Dr. Powderly said at the 15th Conference on Retroviruses and Opportunistic Infections.

On enrollment in SUN, patients had baseline bone densitometry and body composition measurements, clinical data, and fasting laboratory data collected, and were matched for age, race, sex, and body mass index with controls from the National Health and Nutrition Examination Study III.

Among the SUN patients (mean age 41 years), 52% had osteopenia and 10% had frank osteoporosis, Dr. Powderly said.

A total of 78% were men, 25% were black, and almost 80% were receiving antiretroviral therapy.

Analysis revealed that factors associated with an increased risk of low bone mineral density included age over 45 years (odds ratio 2.35) and CD4 count below 300 cells/mm3 (OR 2.10), Dr. Powderly said.

Duration of HIV infection longer than 98 months also was associated with an increased risk (OR 1.56).

Determining whether bone mineral loss will continue over time and translate into increased risk for fractures is a “critically important” area of HIV research, Dr. Powderly said at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the CDC.

Further information also is needed on HIV-associated risk factors. Aside from risk factors also present in the general population such as smoking, alcohol use, low body mass index, and lack of physical activity, the aging HIV patient also might have renal dysfunction and inadequate nutrition, which can further contribute to bone loss. HIV disease itself might alter the processes involved in bone mineralization and turnover, according to Dr. Powderly. In a study he and his colleagues performed, human osteoblast and mesenchymal stem cell lines were treated in vitro with several HIV proteins, including HIV p55-gag and HIV gp120.

Exposure to these proteins reduced calcium deposition, alkaline phosphatase activity, and mRNA levels of osteogenic transcription factors in osteoblasts, and the ability of stem cells to develop into osteoblasts was modulated (AIDS Res. Hum. Retroviruses 2007;23:1521-30).

There is also some evidence implicating potent antiretroviral medications in bone loss. In a meta-analysis of 20 studies that included 884 patients, 67% had reduced bone mineral density and 15% had osteoporosis. Those receiving antiretroviral therapy had a 2.5-fold increased risk of having reduced bone mineral density, compared with those who were treatment naive (AIDS 2006;20:2165-74).

The dynamic process of bone mineralization is another factor. “We reach the peak of bone mineralization at around 30 years, and then both men and women lose bone at a rate of approximately 0.5%-1% per year,” according to Dr. Powderly.

Because women have lower peak bone mass than do men, they have higher rates of osteoporosis as they age. Until the relative contributions to bone loss of the various factors can be more fully clarified, the routine care of older patients with HIV should include baseline and routine monitoring of markers of bone turnover, according to Dr. Powderly.

Calcium supplementation significantly increased the risk of a myocardial infarction among healthy, postmenopausal women, compared with those taking placebo, in a secondary analysis of an osteoporosis study.

“I would not recommend calcium supplementation based on this finding,” Dr. Rita F. Redberg, who was not involved in the study, said in an interview.

The HDL:LDL cholesterol ratios improved among the 732 women who took daily calcium supplementation, compared with the 739 participants who took placebo. This suggests that a different mechanism spurred the increase in myocardial infarction.

“This is an interesting point. It shows that just improving cholesterol does not reduce the risk of a heart attack,” said Dr. Redberg, a Robert Wood Johnson Foundation health policy fellow and director of women's cardiovascular services at the University of California, San Francisco. “It was the same finding with estrogen: It lowered LDL, increased HDL, but did not reduce the number of heart attacks in studies.”

The current findings contrast with previous suggestions of cardiovascular benefit from calcium supplementation. One study found that calcium increases the HDL:LDL cholesterol ratio by almost 20% (Am. J. Med. 2002;112:343-7).

Moreoover, there was a one-third decrease in deaths from cardiovascular events observed among women who had the greatest intake of calcium from either diet or supplements in the Iowa Women's Health Study (Am. J. Epidemiol. 1999;149:151-61).

Following completion of a 5-year osteoporosis study (Am. J. Med. 2006;1119:777-85), Dr. Mark J. Bolland and his associates at the University of Auckland (New Zealand) reassessed their data to compare cardiovascular events. Women were randomized to 1 g/day of elemental calcium (Citracal) or placebo. All of the 1,471 participants were postmenopausal for at least 5 years and older than age 55 years at baseline, and 10% of those were older than age 80 at baseline.

Death, sudden death, myocardial infarction, angina, other chest pain, stroke, and transient ischemic attacks events were recorded every 6 months. In all, 336 women stopped taking the calcium and 296 stopped taking the placebo before the study end.

A total of 21 of the 732 women in the calcium group experienced 24 myocardial infarctions, a statistically significant difference compared with 10 of the 739 in the placebo group who had 10 such events. A composite end point of sudden death, myocardial infarction, angina, or chest pain was also higher in the calcium group (155 events among 87 women) compared with the placebo group (135 events among 93 women).

No significant differences were found in angina, chest pain, transient ischemic attack, stroke, or sudden death events between groups. There were 34 deaths in the calcium group and 29 in the placebo, a nonsignificant difference.

Dr. Redberg was not surprised by the elevated MI risk. She said research by Dr. Linda Demer, vice chair of medicine at the University of California, Los Angeles, has indicated increased cardiovascular risk associated with calcium.

“It's called the calcium paradox. Women lose calcium from their bones as they get older and it ends up in their arteries and the lining of their vessel walls, leading to accelerated atherosclerosis,” Dr. Redberg said.

“This study is a confirmation of that hypothesis, that calcium can end up in the walls of your arteries.” Dr. Redberg is also a professor of medicine at the University of California, San Francisco.

There is a known paradox: The calcium women lose from their bones ends up in their arteries. DR. REDBERG

Calcium supplementation significantly increased the risk of a myocardial infarction among healthy, postmenopausal women, compared with those taking placebo, in a secondary analysis of an osteoporosis study.

“I would not recommend calcium supplementation based on this finding,” Dr. Rita F. Redberg, who was not involved in the study, said in an interview.

The HDL:LDL cholesterol ratios improved among the 732 women who took daily calcium supplementation, compared with the 739 participants who took placebo. This suggests that a different mechanism spurred the increase in myocardial infarction.

“This is an interesting point. It shows that just improving cholesterol does not reduce the risk of a heart attack,” said Dr. Redberg, a Robert Wood Johnson Foundation health policy fellow and director of women's cardiovascular services at the University of California, San Francisco. “It was the same finding with estrogen: It lowered LDL, increased HDL, but did not reduce the number of heart attacks in studies.”

The current findings contrast with previous suggestions of cardiovascular benefit from calcium supplementation. One study found that calcium increases the HDL:LDL cholesterol ratio by almost 20% (Am. J. Med. 2002;112:343-7).

Moreoover, there was a one-third decrease in deaths from cardiovascular events observed among women who had the greatest intake of calcium from either diet or supplements in the Iowa Women's Health Study (Am. J. Epidemiol. 1999;149:151-61).

Following completion of a 5-year osteoporosis study (Am. J. Med. 2006;1119:777-85), Dr. Mark J. Bolland and his associates at the University of Auckland (New Zealand) reassessed their data to compare cardiovascular events. Women were randomized to 1 g/day of elemental calcium (Citracal) or placebo. All of the 1,471 participants were postmenopausal for at least 5 years and older than age 55 years at baseline, and 10% of those were older than age 80 at baseline.

Death, sudden death, myocardial infarction, angina, other chest pain, stroke, and transient ischemic attacks events were recorded every 6 months. In all, 336 women stopped taking the calcium and 296 stopped taking the placebo before the study end.

A total of 21 of the 732 women in the calcium group experienced 24 myocardial infarctions, a statistically significant difference compared with 10 of the 739 in the placebo group who had 10 such events. A composite end point of sudden death, myocardial infarction, angina, or chest pain was also higher in the calcium group (155 events among 87 women) compared with the placebo group (135 events among 93 women).

No significant differences were found in angina, chest pain, transient ischemic attack, stroke, or sudden death events between groups. There were 34 deaths in the calcium group and 29 in the placebo, a nonsignificant difference.

Dr. Redberg was not surprised by the elevated MI risk. She said research by Dr. Linda Demer, vice chair of medicine at the University of California, Los Angeles, has indicated increased cardiovascular risk associated with calcium.

“It's called the calcium paradox. Women lose calcium from their bones as they get older and it ends up in their arteries and the lining of their vessel walls, leading to accelerated atherosclerosis,” Dr. Redberg said.

“This study is a confirmation of that hypothesis, that calcium can end up in the walls of your arteries.” Dr. Redberg is also a professor of medicine at the University of California, San Francisco.

There is a known paradox: The calcium women lose from their bones ends up in their arteries. DR. REDBERG

Calcium supplementation significantly increased the risk of a myocardial infarction among healthy, postmenopausal women, compared with those taking placebo, in a secondary analysis of an osteoporosis study.

“I would not recommend calcium supplementation based on this finding,” Dr. Rita F. Redberg, who was not involved in the study, said in an interview.

The HDL:LDL cholesterol ratios improved among the 732 women who took daily calcium supplementation, compared with the 739 participants who took placebo. This suggests that a different mechanism spurred the increase in myocardial infarction.

“This is an interesting point. It shows that just improving cholesterol does not reduce the risk of a heart attack,” said Dr. Redberg, a Robert Wood Johnson Foundation health policy fellow and director of women's cardiovascular services at the University of California, San Francisco. “It was the same finding with estrogen: It lowered LDL, increased HDL, but did not reduce the number of heart attacks in studies.”

The current findings contrast with previous suggestions of cardiovascular benefit from calcium supplementation. One study found that calcium increases the HDL:LDL cholesterol ratio by almost 20% (Am. J. Med. 2002;112:343-7).

Moreoover, there was a one-third decrease in deaths from cardiovascular events observed among women who had the greatest intake of calcium from either diet or supplements in the Iowa Women's Health Study (Am. J. Epidemiol. 1999;149:151-61).

Following completion of a 5-year osteoporosis study (Am. J. Med. 2006;1119:777-85), Dr. Mark J. Bolland and his associates at the University of Auckland (New Zealand) reassessed their data to compare cardiovascular events. Women were randomized to 1 g/day of elemental calcium (Citracal) or placebo. All of the 1,471 participants were postmenopausal for at least 5 years and older than age 55 years at baseline, and 10% of those were older than age 80 at baseline.

Death, sudden death, myocardial infarction, angina, other chest pain, stroke, and transient ischemic attacks events were recorded every 6 months. In all, 336 women stopped taking the calcium and 296 stopped taking the placebo before the study end.

A total of 21 of the 732 women in the calcium group experienced 24 myocardial infarctions, a statistically significant difference compared with 10 of the 739 in the placebo group who had 10 such events. A composite end point of sudden death, myocardial infarction, angina, or chest pain was also higher in the calcium group (155 events among 87 women) compared with the placebo group (135 events among 93 women).

No significant differences were found in angina, chest pain, transient ischemic attack, stroke, or sudden death events between groups. There were 34 deaths in the calcium group and 29 in the placebo, a nonsignificant difference.

Dr. Redberg was not surprised by the elevated MI risk. She said research by Dr. Linda Demer, vice chair of medicine at the University of California, Los Angeles, has indicated increased cardiovascular risk associated with calcium.

“It's called the calcium paradox. Women lose calcium from their bones as they get older and it ends up in their arteries and the lining of their vessel walls, leading to accelerated atherosclerosis,” Dr. Redberg said.

“This study is a confirmation of that hypothesis, that calcium can end up in the walls of your arteries.” Dr. Redberg is also a professor of medicine at the University of California, San Francisco.

There is a known paradox: The calcium women lose from their bones ends up in their arteries. DR. REDBERG

Variants in the LRP5 gene are associated with both bone mineral density and fracture risk, researchers in the Genetic Markers for Osteoporosis (GENOMOS) consortium reported.

Two LRP5 variants were found to have “modest” effects that were very consistent across different populations and independent of subject sex or age.

Based on these findings, carriers of these polymorphisms may have a fracture risk that is 15%-20% higher than that for noncarriers, wrote Joyce van Meurs, Ph.D., of Erasmus Medical Center, Rotterdam (the Netherlands), and her associates.

The study involved 37,534 subjects who underwent genotyping and assessment of bone mineral density. A total of 8,932 subjects had fractures, including 2,146 vertebral fractures (JAMA 2008;299:1277-90).

Members of the GENOMOS consortium—18 research teams in Europe and North America—performed prospective genotyping for several polymorphisms of the LRP5 gene that are thought to be related to osteoporosis. “Some scattered studies have tested this association, but results have not been conclusive due to limited sample size,” the researchers wrote.

“The current collaborative study has the potential to answer this question more definitively because of its large sample size and therefore large power to observe the expected modest associations,” Dr. van Meurs and her associates explained.

“Although any single marker explains only a small portion of the phenotype risk, identification of several such osteoporosis risk variants may eventually help in improving clinical prediction,” they wrote.

“Single genetic risk variants may also offer useful insights about mechanisms and pathways that may be useful in drug development.” The investigators cautioned that their results may not apply to Asian or African populations, since the study subjects were predominantly whites of European descent.

Variants in the LRP5 gene are associated with both bone mineral density and fracture risk, researchers in the Genetic Markers for Osteoporosis (GENOMOS) consortium reported.

Two LRP5 variants were found to have “modest” effects that were very consistent across different populations and independent of subject sex or age.

Based on these findings, carriers of these polymorphisms may have a fracture risk that is 15%-20% higher than that for noncarriers, wrote Joyce van Meurs, Ph.D., of Erasmus Medical Center, Rotterdam (the Netherlands), and her associates.

The study involved 37,534 subjects who underwent genotyping and assessment of bone mineral density. A total of 8,932 subjects had fractures, including 2,146 vertebral fractures (JAMA 2008;299:1277-90).

Members of the GENOMOS consortium—18 research teams in Europe and North America—performed prospective genotyping for several polymorphisms of the LRP5 gene that are thought to be related to osteoporosis. “Some scattered studies have tested this association, but results have not been conclusive due to limited sample size,” the researchers wrote.

“The current collaborative study has the potential to answer this question more definitively because of its large sample size and therefore large power to observe the expected modest associations,” Dr. van Meurs and her associates explained.

“Although any single marker explains only a small portion of the phenotype risk, identification of several such osteoporosis risk variants may eventually help in improving clinical prediction,” they wrote.

“Single genetic risk variants may also offer useful insights about mechanisms and pathways that may be useful in drug development.” The investigators cautioned that their results may not apply to Asian or African populations, since the study subjects were predominantly whites of European descent.

Variants in the LRP5 gene are associated with both bone mineral density and fracture risk, researchers in the Genetic Markers for Osteoporosis (GENOMOS) consortium reported.

Two LRP5 variants were found to have “modest” effects that were very consistent across different populations and independent of subject sex or age.

Based on these findings, carriers of these polymorphisms may have a fracture risk that is 15%-20% higher than that for noncarriers, wrote Joyce van Meurs, Ph.D., of Erasmus Medical Center, Rotterdam (the Netherlands), and her associates.

The study involved 37,534 subjects who underwent genotyping and assessment of bone mineral density. A total of 8,932 subjects had fractures, including 2,146 vertebral fractures (JAMA 2008;299:1277-90).

Members of the GENOMOS consortium—18 research teams in Europe and North America—performed prospective genotyping for several polymorphisms of the LRP5 gene that are thought to be related to osteoporosis. “Some scattered studies have tested this association, but results have not been conclusive due to limited sample size,” the researchers wrote.

“The current collaborative study has the potential to answer this question more definitively because of its large sample size and therefore large power to observe the expected modest associations,” Dr. van Meurs and her associates explained.

“Although any single marker explains only a small portion of the phenotype risk, identification of several such osteoporosis risk variants may eventually help in improving clinical prediction,” they wrote.

“Single genetic risk variants may also offer useful insights about mechanisms and pathways that may be useful in drug development.” The investigators cautioned that their results may not apply to Asian or African populations, since the study subjects were predominantly whites of European descent.

VANCOUVER, B.C. – Measuring a patient's height during routine primary care visits may be one of the simplest and least expensive ways to predict osteoporosis risk and to guide screening, according to a study at Virginia Commonwealth University, Richmond.

Height loss of 1.5 inches (about 4 cm) or more over 3 years was associated with almost a doubling of osteoporosis risk in patients aged 50 years or older in the study of 1,039 primary care patients, reported Dr. Emmeline Gasink at the annual meeting of the North American Primary Care Research Group.

Mean height loss in the study population was 0.596 inches, said Dr. Gasink, currently a resident in the family medicine program at Riverside Healthcare System in Carrollton, Va.

Among the 16% of patients who had a height loss of at least 1.5 inches, 3% had a diagnosis of osteoporosis (odds ratio, 1.8) of developing the disease.

Some patients (13%) had significant height loss but were not diagnosed with osteoporosis. Another 8% did not have significant height loss but had osteoporosis, perhaps representing osteoporosis in a nonvertebral site, said Dr. Gasink in an interview at the meeting.

Nonetheless, a height loss of 1.5 inches or greater over 3 years provided a positive predictive value of 21% for osteoporosis, she said.

The study population was 71% female, so the risk may be slightly less for males. Also, people with low bone density tend to lose height more rapidly than do those with greater bone density.

Still, the overall conclusion of the study, together with findings from five longitudinal trials reviewed by Dr. Gasink, suggest a “strong relationship” between height loss and a new vertebral fracture, lending strength to her findings.

“Height measurement should definitely be a part of a yearly physical for patients 50 and older, as recommended by the U.S. Preventive Health Task Force,” noted Dr. Gasink after the meeting. “As a family physician who follows these people over a period of years, [I suggest that] it would be an easy piece of data to help determine early risk factors for osteoporosis.”

VANCOUVER, B.C. – Measuring a patient's height during routine primary care visits may be one of the simplest and least expensive ways to predict osteoporosis risk and to guide screening, according to a study at Virginia Commonwealth University, Richmond.

Height loss of 1.5 inches (about 4 cm) or more over 3 years was associated with almost a doubling of osteoporosis risk in patients aged 50 years or older in the study of 1,039 primary care patients, reported Dr. Emmeline Gasink at the annual meeting of the North American Primary Care Research Group.

Mean height loss in the study population was 0.596 inches, said Dr. Gasink, currently a resident in the family medicine program at Riverside Healthcare System in Carrollton, Va.

Among the 16% of patients who had a height loss of at least 1.5 inches, 3% had a diagnosis of osteoporosis (odds ratio, 1.8) of developing the disease.

Some patients (13%) had significant height loss but were not diagnosed with osteoporosis. Another 8% did not have significant height loss but had osteoporosis, perhaps representing osteoporosis in a nonvertebral site, said Dr. Gasink in an interview at the meeting.

Nonetheless, a height loss of 1.5 inches or greater over 3 years provided a positive predictive value of 21% for osteoporosis, she said.

The study population was 71% female, so the risk may be slightly less for males. Also, people with low bone density tend to lose height more rapidly than do those with greater bone density.

Still, the overall conclusion of the study, together with findings from five longitudinal trials reviewed by Dr. Gasink, suggest a “strong relationship” between height loss and a new vertebral fracture, lending strength to her findings.

“Height measurement should definitely be a part of a yearly physical for patients 50 and older, as recommended by the U.S. Preventive Health Task Force,” noted Dr. Gasink after the meeting. “As a family physician who follows these people over a period of years, [I suggest that] it would be an easy piece of data to help determine early risk factors for osteoporosis.”

VANCOUVER, B.C. – Measuring a patient's height during routine primary care visits may be one of the simplest and least expensive ways to predict osteoporosis risk and to guide screening, according to a study at Virginia Commonwealth University, Richmond.

Height loss of 1.5 inches (about 4 cm) or more over 3 years was associated with almost a doubling of osteoporosis risk in patients aged 50 years or older in the study of 1,039 primary care patients, reported Dr. Emmeline Gasink at the annual meeting of the North American Primary Care Research Group.

Mean height loss in the study population was 0.596 inches, said Dr. Gasink, currently a resident in the family medicine program at Riverside Healthcare System in Carrollton, Va.

Among the 16% of patients who had a height loss of at least 1.5 inches, 3% had a diagnosis of osteoporosis (odds ratio, 1.8) of developing the disease.

Some patients (13%) had significant height loss but were not diagnosed with osteoporosis. Another 8% did not have significant height loss but had osteoporosis, perhaps representing osteoporosis in a nonvertebral site, said Dr. Gasink in an interview at the meeting.

Nonetheless, a height loss of 1.5 inches or greater over 3 years provided a positive predictive value of 21% for osteoporosis, she said.

The study population was 71% female, so the risk may be slightly less for males. Also, people with low bone density tend to lose height more rapidly than do those with greater bone density.

Still, the overall conclusion of the study, together with findings from five longitudinal trials reviewed by Dr. Gasink, suggest a “strong relationship” between height loss and a new vertebral fracture, lending strength to her findings.

“Height measurement should definitely be a part of a yearly physical for patients 50 and older, as recommended by the U.S. Preventive Health Task Force,” noted Dr. Gasink after the meeting. “As a family physician who follows these people over a period of years, [I suggest that] it would be an easy piece of data to help determine early risk factors for osteoporosis.”

SAN DIEGO – Osteoporosis management is about to undergo some changes, including a new international focus on assessing fracture risk in clinical practice and an emphasis on vitamin D, Dr. Stuart L. Silverman predicted at the Perspectives in Women's Health conference, sponsored by FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS.

“We're changing the whole way we approach osteoporosis in 2008,” said Dr. Silverman, with the International Working Group on Fracture Risk Assessment for the World Health Organization.

New guidelines will encourage the calculation of fracture risk based not only on their bone mineral density and T score, but also on age, body mass index, family history, and other factors, he explained.

This composite fracture score, expected to be incorporated into software linked with dual-energy x-ray absorptiometry (DXA) equipment by late 2008, will provide a much more comprehensive and easy-to-understand risk profile, he said.

“You will get a printout that says your patient has, [for example], a 10-year risk of hip fracture of 3%,” said Dr. Silverman, of the division of rheumatology at Cedars-Sinai Medical Center in Los Angeles.

The calculated 10-year risk for clinical fracture of the shoulder, forearm, or vertebra will be included in a separate score.

Factors in the 10-year predictions of fracture risk include:

▸ Age, which can change the 10-year risk for a woman with a T score of −2.5 at the femoral neck from 2% at age 50 to 12.5% at age 80.

▸ History of prior fragility fracture, which increases fracture risk fivefold.

▸ Low body weight/BMI.

▸ History of a hip fracture in the patient's mother or father.

▸ Lifetime history of ever using corticosteroids at a dose of 5 mg/day or greater for 3 months or longer.

▸ Current smoking.

▸ Consumption of more than two alcoholic drinks per day.

▸ Secondary osteoporosis caused by a disease process or a drug.

“Your goal is not to reduce risk of osteoporosis, but to reduce the risk of fracture,” Dr. Silverman said.

One way that risk can be reduced is through vitamin D supplementation recommendations, which are also likely to change soon, according to Dr. Silverman.

“Recently we've all come to appreciate that we really need much more vitamin D,” he said. “We're pushing for 800 to 1,000 IU day, and I will tell you that a lot of us in the field … are actually taking more than that,” he added.

New studies show vitamin D is useful not only for bones, but for balance and for reducing overall cancer risk, he noted.

RHEUMATOLOGY NEWS, like FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS, is published by the International Medical News Group, a division of Elsevier.

SAN DIEGO – Osteoporosis management is about to undergo some changes, including a new international focus on assessing fracture risk in clinical practice and an emphasis on vitamin D, Dr. Stuart L. Silverman predicted at the Perspectives in Women's Health conference, sponsored by FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS.

“We're changing the whole way we approach osteoporosis in 2008,” said Dr. Silverman, with the International Working Group on Fracture Risk Assessment for the World Health Organization.

New guidelines will encourage the calculation of fracture risk based not only on their bone mineral density and T score, but also on age, body mass index, family history, and other factors, he explained.

This composite fracture score, expected to be incorporated into software linked with dual-energy x-ray absorptiometry (DXA) equipment by late 2008, will provide a much more comprehensive and easy-to-understand risk profile, he said.

“You will get a printout that says your patient has, [for example], a 10-year risk of hip fracture of 3%,” said Dr. Silverman, of the division of rheumatology at Cedars-Sinai Medical Center in Los Angeles.

The calculated 10-year risk for clinical fracture of the shoulder, forearm, or vertebra will be included in a separate score.

Factors in the 10-year predictions of fracture risk include:

▸ Age, which can change the 10-year risk for a woman with a T score of −2.5 at the femoral neck from 2% at age 50 to 12.5% at age 80.

▸ History of prior fragility fracture, which increases fracture risk fivefold.

▸ Low body weight/BMI.

▸ History of a hip fracture in the patient's mother or father.

▸ Lifetime history of ever using corticosteroids at a dose of 5 mg/day or greater for 3 months or longer.

▸ Current smoking.

▸ Consumption of more than two alcoholic drinks per day.

▸ Secondary osteoporosis caused by a disease process or a drug.

“Your goal is not to reduce risk of osteoporosis, but to reduce the risk of fracture,” Dr. Silverman said.

One way that risk can be reduced is through vitamin D supplementation recommendations, which are also likely to change soon, according to Dr. Silverman.

“Recently we've all come to appreciate that we really need much more vitamin D,” he said. “We're pushing for 800 to 1,000 IU day, and I will tell you that a lot of us in the field … are actually taking more than that,” he added.

New studies show vitamin D is useful not only for bones, but for balance and for reducing overall cancer risk, he noted.

RHEUMATOLOGY NEWS, like FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS, is published by the International Medical News Group, a division of Elsevier.

SAN DIEGO – Osteoporosis management is about to undergo some changes, including a new international focus on assessing fracture risk in clinical practice and an emphasis on vitamin D, Dr. Stuart L. Silverman predicted at the Perspectives in Women's Health conference, sponsored by FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS.

“We're changing the whole way we approach osteoporosis in 2008,” said Dr. Silverman, with the International Working Group on Fracture Risk Assessment for the World Health Organization.

New guidelines will encourage the calculation of fracture risk based not only on their bone mineral density and T score, but also on age, body mass index, family history, and other factors, he explained.

This composite fracture score, expected to be incorporated into software linked with dual-energy x-ray absorptiometry (DXA) equipment by late 2008, will provide a much more comprehensive and easy-to-understand risk profile, he said.

“You will get a printout that says your patient has, [for example], a 10-year risk of hip fracture of 3%,” said Dr. Silverman, of the division of rheumatology at Cedars-Sinai Medical Center in Los Angeles.

The calculated 10-year risk for clinical fracture of the shoulder, forearm, or vertebra will be included in a separate score.

Factors in the 10-year predictions of fracture risk include:

▸ Age, which can change the 10-year risk for a woman with a T score of −2.5 at the femoral neck from 2% at age 50 to 12.5% at age 80.

▸ History of prior fragility fracture, which increases fracture risk fivefold.

▸ Low body weight/BMI.

▸ History of a hip fracture in the patient's mother or father.

▸ Lifetime history of ever using corticosteroids at a dose of 5 mg/day or greater for 3 months or longer.

▸ Current smoking.

▸ Consumption of more than two alcoholic drinks per day.

▸ Secondary osteoporosis caused by a disease process or a drug.

“Your goal is not to reduce risk of osteoporosis, but to reduce the risk of fracture,” Dr. Silverman said.

One way that risk can be reduced is through vitamin D supplementation recommendations, which are also likely to change soon, according to Dr. Silverman.

“Recently we've all come to appreciate that we really need much more vitamin D,” he said. “We're pushing for 800 to 1,000 IU day, and I will tell you that a lot of us in the field … are actually taking more than that,” he added.

New studies show vitamin D is useful not only for bones, but for balance and for reducing overall cancer risk, he noted.

RHEUMATOLOGY NEWS, like FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS, is published by the International Medical News Group, a division of Elsevier.

Trends in drug prescribing for osteoporosis following a hip fracture have changed dramatically over the last decade: The proportion of patients treated post fracture has increased, but fewer than one-third are ever prescribed drugs at all, according to a population-based study of nearly 16,000 fracture patients.

In an interview, lead author Suzanne M. Cadarette, Ph.D., said, “Many patients, following hip fracture, still do not receive adequate pharmacotherapy. While there have been some successful quality improvement interventions to address this gap in care, health systems must sit up and recognize that there is a problem.”

A total of 15,685 hip fracture patients, all enrollees from the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE), met inclusion criteria. (PACE is a state-run program that provides unrestricted drug coverage for patients aged 65 or older whose income is too high for Medicaid, but below $20,000. Dr. Cadarette conceded that the relatively low income status of this cohort, and the fact that the majority was white, means that “extrapolating the exact level of care to the rest of the U.S. population may be difficult, but I expect that the general trend of undertreatment holds nationwide.”) Although Dr. Cadarette did not confirm the presence of osteoporosis in this cohort, she pointed to a recent Canadian trial that found that 21% of hip fracture patients aged 50 years or older had normal bone mass, but 45% had osteoporosis and were thus clear candidates for pharmacotherapy (Arch. Intern. Med. 2007;167:2110-5). “Our population was much older than the [randomized clinical trial] referenced here, and thus I expect that fewer hip fracture patients in our study would have normal bones and rather the majority had osteoporosis.”

In 1995, 7% of patients received pharmacotherapy to treat osteoporosis within 6 months of fracture; this figure increased to 31% in 2002, and then remained stable through 2004, the study's cutoff date.

The study also found that the type of therapy patients receive varies according to what sort of physician treats them. The specialty of the prescribing physician was identified in 94% (3,038) of the total 3,231 treated cases. Rheumatologists and endocrinologists prescribed bisphosphonates in 59.5% of cases, calcitonin in 32.5%, hormone therapy in 3.5%, raloxifene in 3%, and teriparatide or a combination of drugs very rarely, in 1% or fewer of cases. Obstetricians and gynecologists most often prescribed hormone therapy, in 63.3% of patients, followed by bisphosphonates in 22.4%, calcitonin in 8.2%, raloxifene in 4%, and teriparatide or combination therapy hardly ever. Geriatricians prescribed calcitonin about half the time and for about the other half prescribed bisphosphonates.

Dr. Cadarette, of the Brigham and Women's Hospital, Boston, urged caution in interpreting this seemingly alarming finding. “Patients seeing specialists may have other chronic health conditions contraindicating bisphosphonate therapy, or may be more frail, making the complex bisphosphonate dosing difficult.” She also said her findings did not reflect the time periods in which the different therapies were prescribed. For example, fracture patients seen by obstetricians and gynecologists were largely treated in 1995, before the 2002 Women's Health Initiative results showed the potential harm associated with hormone therapy.

Also significant was the finding that, over time, family physicians and general practitioners have become the prescribing physicians in a greater proportion of these cases. In 1995, general practitioners were the prescribers in about 71% of treated fracture patients, and in 2004, they were responsible for 80% of these cases. Rheumatologists and endocrinologists, on the other hand, dropped from being the treating physician in 15% of cases in 1995 to only 3.5% in 2004. A similar decline was seen among obstetrics/gynecology physicians and orthopedic surgeons.

Responding to this finding, Dr. Steven Petak, chancellor of the American College of Endocrinology, said in an interview, “There are a limited number of endocrinologists and rheumatologists in proportion to the number of patients with or at risk for osteoporosis.”

Poorly responsive patients who have bone mineral density loss on DXA, continued fractures, intolerance of oral therapies, or secondary osteoporosis should have consultations with specialist, he said.

Dr. Cadarette reported no disclosures for herself or any of her fellow researchers in relation to this study.

Trends in drug prescribing for osteoporosis following a hip fracture have changed dramatically over the last decade: The proportion of patients treated post fracture has increased, but fewer than one-third are ever prescribed drugs at all, according to a population-based study of nearly 16,000 fracture patients.

In an interview, lead author Suzanne M. Cadarette, Ph.D., said, “Many patients, following hip fracture, still do not receive adequate pharmacotherapy. While there have been some successful quality improvement interventions to address this gap in care, health systems must sit up and recognize that there is a problem.”

A total of 15,685 hip fracture patients, all enrollees from the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE), met inclusion criteria. (PACE is a state-run program that provides unrestricted drug coverage for patients aged 65 or older whose income is too high for Medicaid, but below $20,000. Dr. Cadarette conceded that the relatively low income status of this cohort, and the fact that the majority was white, means that “extrapolating the exact level of care to the rest of the U.S. population may be difficult, but I expect that the general trend of undertreatment holds nationwide.”) Although Dr. Cadarette did not confirm the presence of osteoporosis in this cohort, she pointed to a recent Canadian trial that found that 21% of hip fracture patients aged 50 years or older had normal bone mass, but 45% had osteoporosis and were thus clear candidates for pharmacotherapy (Arch. Intern. Med. 2007;167:2110-5). “Our population was much older than the [randomized clinical trial] referenced here, and thus I expect that fewer hip fracture patients in our study would have normal bones and rather the majority had osteoporosis.”

In 1995, 7% of patients received pharmacotherapy to treat osteoporosis within 6 months of fracture; this figure increased to 31% in 2002, and then remained stable through 2004, the study's cutoff date.

The study also found that the type of therapy patients receive varies according to what sort of physician treats them. The specialty of the prescribing physician was identified in 94% (3,038) of the total 3,231 treated cases. Rheumatologists and endocrinologists prescribed bisphosphonates in 59.5% of cases, calcitonin in 32.5%, hormone therapy in 3.5%, raloxifene in 3%, and teriparatide or a combination of drugs very rarely, in 1% or fewer of cases. Obstetricians and gynecologists most often prescribed hormone therapy, in 63.3% of patients, followed by bisphosphonates in 22.4%, calcitonin in 8.2%, raloxifene in 4%, and teriparatide or combination therapy hardly ever. Geriatricians prescribed calcitonin about half the time and for about the other half prescribed bisphosphonates.

Dr. Cadarette, of the Brigham and Women's Hospital, Boston, urged caution in interpreting this seemingly alarming finding. “Patients seeing specialists may have other chronic health conditions contraindicating bisphosphonate therapy, or may be more frail, making the complex bisphosphonate dosing difficult.” She also said her findings did not reflect the time periods in which the different therapies were prescribed. For example, fracture patients seen by obstetricians and gynecologists were largely treated in 1995, before the 2002 Women's Health Initiative results showed the potential harm associated with hormone therapy.

Also significant was the finding that, over time, family physicians and general practitioners have become the prescribing physicians in a greater proportion of these cases. In 1995, general practitioners were the prescribers in about 71% of treated fracture patients, and in 2004, they were responsible for 80% of these cases. Rheumatologists and endocrinologists, on the other hand, dropped from being the treating physician in 15% of cases in 1995 to only 3.5% in 2004. A similar decline was seen among obstetrics/gynecology physicians and orthopedic surgeons.

Responding to this finding, Dr. Steven Petak, chancellor of the American College of Endocrinology, said in an interview, “There are a limited number of endocrinologists and rheumatologists in proportion to the number of patients with or at risk for osteoporosis.”

Poorly responsive patients who have bone mineral density loss on DXA, continued fractures, intolerance of oral therapies, or secondary osteoporosis should have consultations with specialist, he said.

Dr. Cadarette reported no disclosures for herself or any of her fellow researchers in relation to this study.

Trends in drug prescribing for osteoporosis following a hip fracture have changed dramatically over the last decade: The proportion of patients treated post fracture has increased, but fewer than one-third are ever prescribed drugs at all, according to a population-based study of nearly 16,000 fracture patients.

In an interview, lead author Suzanne M. Cadarette, Ph.D., said, “Many patients, following hip fracture, still do not receive adequate pharmacotherapy. While there have been some successful quality improvement interventions to address this gap in care, health systems must sit up and recognize that there is a problem.”

A total of 15,685 hip fracture patients, all enrollees from the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE), met inclusion criteria. (PACE is a state-run program that provides unrestricted drug coverage for patients aged 65 or older whose income is too high for Medicaid, but below $20,000. Dr. Cadarette conceded that the relatively low income status of this cohort, and the fact that the majority was white, means that “extrapolating the exact level of care to the rest of the U.S. population may be difficult, but I expect that the general trend of undertreatment holds nationwide.”) Although Dr. Cadarette did not confirm the presence of osteoporosis in this cohort, she pointed to a recent Canadian trial that found that 21% of hip fracture patients aged 50 years or older had normal bone mass, but 45% had osteoporosis and were thus clear candidates for pharmacotherapy (Arch. Intern. Med. 2007;167:2110-5). “Our population was much older than the [randomized clinical trial] referenced here, and thus I expect that fewer hip fracture patients in our study would have normal bones and rather the majority had osteoporosis.”

In 1995, 7% of patients received pharmacotherapy to treat osteoporosis within 6 months of fracture; this figure increased to 31% in 2002, and then remained stable through 2004, the study's cutoff date.

The study also found that the type of therapy patients receive varies according to what sort of physician treats them. The specialty of the prescribing physician was identified in 94% (3,038) of the total 3,231 treated cases. Rheumatologists and endocrinologists prescribed bisphosphonates in 59.5% of cases, calcitonin in 32.5%, hormone therapy in 3.5%, raloxifene in 3%, and teriparatide or a combination of drugs very rarely, in 1% or fewer of cases. Obstetricians and gynecologists most often prescribed hormone therapy, in 63.3% of patients, followed by bisphosphonates in 22.4%, calcitonin in 8.2%, raloxifene in 4%, and teriparatide or combination therapy hardly ever. Geriatricians prescribed calcitonin about half the time and for about the other half prescribed bisphosphonates.

Dr. Cadarette, of the Brigham and Women's Hospital, Boston, urged caution in interpreting this seemingly alarming finding. “Patients seeing specialists may have other chronic health conditions contraindicating bisphosphonate therapy, or may be more frail, making the complex bisphosphonate dosing difficult.” She also said her findings did not reflect the time periods in which the different therapies were prescribed. For example, fracture patients seen by obstetricians and gynecologists were largely treated in 1995, before the 2002 Women's Health Initiative results showed the potential harm associated with hormone therapy.

Also significant was the finding that, over time, family physicians and general practitioners have become the prescribing physicians in a greater proportion of these cases. In 1995, general practitioners were the prescribers in about 71% of treated fracture patients, and in 2004, they were responsible for 80% of these cases. Rheumatologists and endocrinologists, on the other hand, dropped from being the treating physician in 15% of cases in 1995 to only 3.5% in 2004. A similar decline was seen among obstetrics/gynecology physicians and orthopedic surgeons.

Responding to this finding, Dr. Steven Petak, chancellor of the American College of Endocrinology, said in an interview, “There are a limited number of endocrinologists and rheumatologists in proportion to the number of patients with or at risk for osteoporosis.”

Poorly responsive patients who have bone mineral density loss on DXA, continued fractures, intolerance of oral therapies, or secondary osteoporosis should have consultations with specialist, he said.

Dr. Cadarette reported no disclosures for herself or any of her fellow researchers in relation to this study.

The anabolic agent teriparatide outperformed alendronate in patients with glucocorticoid-induced osteoporosis who were at high risk for fractures in a large, randomized, controlled trial.

Study participants taking teriparatide were significantly less likely to sustain new vertebral fractures and showed greater increases in bone mineral density (BMD) at the spine and hip, the investigators wrote in the the New England Journal of Medicine.

International guidelines recommend bisphosphonates like alendronate for patients who either already have or are at risk for glucocorticoid-induced osteoporosis, they noted. But recombinant teriparatide—human parathyroid hormone (1–34)—is thought to stimulate bone formation, increase bone mass, and reduce the risk of vertebral and nonvertebral fractures.

“Teriparatide may be a rational treatment for glucocorticoid-induced osteoporosis because it directly stimulates osteoblastogenesis and inhibits osteoblast apoptosis, thereby counteracting two key mechanisms through which glucocorticoid therapy promotes bone loss,” reported Dr. Kenneth G. Saag of the University of Alabama at Birmingham, and his associates.

They are conducting what they called the first randomized, controlled clinical trial comparing teriparatide with a bisphosphonate in this patient population. Dr. Saag reported their results for the first 18 months of a planned 36. The trial is supported by Eli Lilly & Co., which markets teriparatide as Forteo in the United States.

Study participants in 12 countries in North America, South America, and Europe were randomly assigned to either injectable teriparatide plus an oral placebo or oral alendronate plus an injectable placebo every day. All also received daily calcium and vitamin D supplements.

The subjects were 345 women and 83 men aged 22–89 years who had established osteoporosis because of long-term glucocorticoid therapy for a variety of disorders.

After 18 months, BMD at the lumbar spine increased to a significantly greater degree in subjects taking teriparatide (7.2%) than in patients taking alendronate (3.4%). The same was true for total hip bone mineral density (3.8% and 2.4%, respectively).

Markers of bone formation increased almost 70% and those of bone resorption increased about 45% at 6 months in subjects taking teriparatide, while these markers decreased in subjects taking alendronate.

New vertebral fractures developed in 10 subjects taking alendronate, compared with only 1 taking teriparatide, a significant difference. The number of subjects who developed new nonvertebral fractures did not differ significantly between the two groups (N. Engl. J. Med. 2007;357:2028–39).

“Safety profiles in the two study groups were similar, with no significant differences in the overall incidence of adverse events, the incidence of serious adverse events, or the incidence of events either leading to withdrawal from the study or considered to be possibly related to the study drug,” they added.

However 70 subjects in the alendronate group and 64 in the teriparatide group dropped out of the study. Thirteen (6.1%) of the 214 patients in the alendronate group and 25 (11.7%) of the 214 in the teriparatide group discontinued because of an adverse event.

In an editorial accompanying this report, Dr. Philip N. Sambrook, of the University of Sidney (Australia), noted this “moderately high” dropout rate of 30% may indicate that adherence to either treatment may be limited, particularly because this patient group is “often already unwell.

“The persistence of [adverse] effects in the ongoing 18-month extension of the study will be of interest,” he noted (N. Engl. J. Med. 2007;357:2084–6).

Nevertheless, “for patients with low bone mineral density who are receiving long-term low-dose glucocorticoid therapy, the study by Saag et al. suggests that teriparatide should be considered as a potential first-line therapy,” he said.

'Teriparatide may be a rational treatment for glucocorticoid-induced osteoporosis.' DR. SAAG

The anabolic agent teriparatide outperformed alendronate in patients with glucocorticoid-induced osteoporosis who were at high risk for fractures in a large, randomized, controlled trial.

Study participants taking teriparatide were significantly less likely to sustain new vertebral fractures and showed greater increases in bone mineral density (BMD) at the spine and hip, the investigators wrote in the the New England Journal of Medicine.

International guidelines recommend bisphosphonates like alendronate for patients who either already have or are at risk for glucocorticoid-induced osteoporosis, they noted. But recombinant teriparatide—human parathyroid hormone (1–34)—is thought to stimulate bone formation, increase bone mass, and reduce the risk of vertebral and nonvertebral fractures.

“Teriparatide may be a rational treatment for glucocorticoid-induced osteoporosis because it directly stimulates osteoblastogenesis and inhibits osteoblast apoptosis, thereby counteracting two key mechanisms through which glucocorticoid therapy promotes bone loss,” reported Dr. Kenneth G. Saag of the University of Alabama at Birmingham, and his associates.

They are conducting what they called the first randomized, controlled clinical trial comparing teriparatide with a bisphosphonate in this patient population. Dr. Saag reported their results for the first 18 months of a planned 36. The trial is supported by Eli Lilly & Co., which markets teriparatide as Forteo in the United States.

Study participants in 12 countries in North America, South America, and Europe were randomly assigned to either injectable teriparatide plus an oral placebo or oral alendronate plus an injectable placebo every day. All also received daily calcium and vitamin D supplements.

The subjects were 345 women and 83 men aged 22–89 years who had established osteoporosis because of long-term glucocorticoid therapy for a variety of disorders.

After 18 months, BMD at the lumbar spine increased to a significantly greater degree in subjects taking teriparatide (7.2%) than in patients taking alendronate (3.4%). The same was true for total hip bone mineral density (3.8% and 2.4%, respectively).

Markers of bone formation increased almost 70% and those of bone resorption increased about 45% at 6 months in subjects taking teriparatide, while these markers decreased in subjects taking alendronate.

New vertebral fractures developed in 10 subjects taking alendronate, compared with only 1 taking teriparatide, a significant difference. The number of subjects who developed new nonvertebral fractures did not differ significantly between the two groups (N. Engl. J. Med. 2007;357:2028–39).

“Safety profiles in the two study groups were similar, with no significant differences in the overall incidence of adverse events, the incidence of serious adverse events, or the incidence of events either leading to withdrawal from the study or considered to be possibly related to the study drug,” they added.

However 70 subjects in the alendronate group and 64 in the teriparatide group dropped out of the study. Thirteen (6.1%) of the 214 patients in the alendronate group and 25 (11.7%) of the 214 in the teriparatide group discontinued because of an adverse event.

In an editorial accompanying this report, Dr. Philip N. Sambrook, of the University of Sidney (Australia), noted this “moderately high” dropout rate of 30% may indicate that adherence to either treatment may be limited, particularly because this patient group is “often already unwell.

“The persistence of [adverse] effects in the ongoing 18-month extension of the study will be of interest,” he noted (N. Engl. J. Med. 2007;357:2084–6).

Nevertheless, “for patients with low bone mineral density who are receiving long-term low-dose glucocorticoid therapy, the study by Saag et al. suggests that teriparatide should be considered as a potential first-line therapy,” he said.

'Teriparatide may be a rational treatment for glucocorticoid-induced osteoporosis.' DR. SAAG

The anabolic agent teriparatide outperformed alendronate in patients with glucocorticoid-induced osteoporosis who were at high risk for fractures in a large, randomized, controlled trial.

Study participants taking teriparatide were significantly less likely to sustain new vertebral fractures and showed greater increases in bone mineral density (BMD) at the spine and hip, the investigators wrote in the the New England Journal of Medicine.

International guidelines recommend bisphosphonates like alendronate for patients who either already have or are at risk for glucocorticoid-induced osteoporosis, they noted. But recombinant teriparatide—human parathyroid hormone (1–34)—is thought to stimulate bone formation, increase bone mass, and reduce the risk of vertebral and nonvertebral fractures.

“Teriparatide may be a rational treatment for glucocorticoid-induced osteoporosis because it directly stimulates osteoblastogenesis and inhibits osteoblast apoptosis, thereby counteracting two key mechanisms through which glucocorticoid therapy promotes bone loss,” reported Dr. Kenneth G. Saag of the University of Alabama at Birmingham, and his associates.

They are conducting what they called the first randomized, controlled clinical trial comparing teriparatide with a bisphosphonate in this patient population. Dr. Saag reported their results for the first 18 months of a planned 36. The trial is supported by Eli Lilly & Co., which markets teriparatide as Forteo in the United States.

Study participants in 12 countries in North America, South America, and Europe were randomly assigned to either injectable teriparatide plus an oral placebo or oral alendronate plus an injectable placebo every day. All also received daily calcium and vitamin D supplements.

The subjects were 345 women and 83 men aged 22–89 years who had established osteoporosis because of long-term glucocorticoid therapy for a variety of disorders.

After 18 months, BMD at the lumbar spine increased to a significantly greater degree in subjects taking teriparatide (7.2%) than in patients taking alendronate (3.4%). The same was true for total hip bone mineral density (3.8% and 2.4%, respectively).

Markers of bone formation increased almost 70% and those of bone resorption increased about 45% at 6 months in subjects taking teriparatide, while these markers decreased in subjects taking alendronate.

New vertebral fractures developed in 10 subjects taking alendronate, compared with only 1 taking teriparatide, a significant difference. The number of subjects who developed new nonvertebral fractures did not differ significantly between the two groups (N. Engl. J. Med. 2007;357:2028–39).

“Safety profiles in the two study groups were similar, with no significant differences in the overall incidence of adverse events, the incidence of serious adverse events, or the incidence of events either leading to withdrawal from the study or considered to be possibly related to the study drug,” they added.

However 70 subjects in the alendronate group and 64 in the teriparatide group dropped out of the study. Thirteen (6.1%) of the 214 patients in the alendronate group and 25 (11.7%) of the 214 in the teriparatide group discontinued because of an adverse event.

In an editorial accompanying this report, Dr. Philip N. Sambrook, of the University of Sidney (Australia), noted this “moderately high” dropout rate of 30% may indicate that adherence to either treatment may be limited, particularly because this patient group is “often already unwell.

“The persistence of [adverse] effects in the ongoing 18-month extension of the study will be of interest,” he noted (N. Engl. J. Med. 2007;357:2084–6).

Nevertheless, “for patients with low bone mineral density who are receiving long-term low-dose glucocorticoid therapy, the study by Saag et al. suggests that teriparatide should be considered as a potential first-line therapy,” he said.

'Teriparatide may be a rational treatment for glucocorticoid-induced osteoporosis.' DR. SAAG

HONOLULU — Though vegans do not eat dairy, they have surprisingly good bone health, according to results from a study presented at the annual meeting of the American Society for Bone and Mineral Research.

Heather J. Hinkley, Ph.D., of the British College of Osteopathic Medicine, in London, recruited 60 white females. Age ranged from 20 to 44 years, and all had been vegan for a minimum of 5 years. Exclusion criteria included use of hormone therapy, use of corticosteroids or thyroxine for more than 6 months, onset of menopause before age 45, lactation in the previous year, presence of rheumatoid arthritis, or previous osteoporosis-related fracture.

Broadband ultrasound attenuation of the calcaneum was examined for all women to assess bone mineral density. The results were compared with ultrasound attenuation data on 110 age-matched white female omnivores.

Though the vegan women had a slightly lower mean ultrasound attenuation, the difference was not significant. Weight also was not significantly different in vegan women, and no significant difference in body mass index was seen. There was no link between the duration of the vegan diet and ultrasound attenuation results.

The researchers observed that 66% of the vegans took calcium supplements, which may have benefited their bone density.

In addition, a lack of dietary animal protein in the vegan's diet may actually benefit the acid/base balance, resulting in less movement of bone mineral and decreasing calcium excretion, preserving bone health and integrity, they suggested.

HONOLULU — Though vegans do not eat dairy, they have surprisingly good bone health, according to results from a study presented at the annual meeting of the American Society for Bone and Mineral Research.

Heather J. Hinkley, Ph.D., of the British College of Osteopathic Medicine, in London, recruited 60 white females. Age ranged from 20 to 44 years, and all had been vegan for a minimum of 5 years. Exclusion criteria included use of hormone therapy, use of corticosteroids or thyroxine for more than 6 months, onset of menopause before age 45, lactation in the previous year, presence of rheumatoid arthritis, or previous osteoporosis-related fracture.

Broadband ultrasound attenuation of the calcaneum was examined for all women to assess bone mineral density. The results were compared with ultrasound attenuation data on 110 age-matched white female omnivores.

Though the vegan women had a slightly lower mean ultrasound attenuation, the difference was not significant. Weight also was not significantly different in vegan women, and no significant difference in body mass index was seen. There was no link between the duration of the vegan diet and ultrasound attenuation results.

The researchers observed that 66% of the vegans took calcium supplements, which may have benefited their bone density.

In addition, a lack of dietary animal protein in the vegan's diet may actually benefit the acid/base balance, resulting in less movement of bone mineral and decreasing calcium excretion, preserving bone health and integrity, they suggested.

HONOLULU — Though vegans do not eat dairy, they have surprisingly good bone health, according to results from a study presented at the annual meeting of the American Society for Bone and Mineral Research.

Heather J. Hinkley, Ph.D., of the British College of Osteopathic Medicine, in London, recruited 60 white females. Age ranged from 20 to 44 years, and all had been vegan for a minimum of 5 years. Exclusion criteria included use of hormone therapy, use of corticosteroids or thyroxine for more than 6 months, onset of menopause before age 45, lactation in the previous year, presence of rheumatoid arthritis, or previous osteoporosis-related fracture.

Broadband ultrasound attenuation of the calcaneum was examined for all women to assess bone mineral density. The results were compared with ultrasound attenuation data on 110 age-matched white female omnivores.

Though the vegan women had a slightly lower mean ultrasound attenuation, the difference was not significant. Weight also was not significantly different in vegan women, and no significant difference in body mass index was seen. There was no link between the duration of the vegan diet and ultrasound attenuation results.

The researchers observed that 66% of the vegans took calcium supplements, which may have benefited their bone density.

In addition, a lack of dietary animal protein in the vegan's diet may actually benefit the acid/base balance, resulting in less movement of bone mineral and decreasing calcium excretion, preserving bone health and integrity, they suggested.

HONOLULU — Men diagnosed with osteopenia through dual-energy x-ray absorptiometry are unlikely to have a change in diagnosis at a 3-year follow-up DXA, according to a study presented at the annual meeting of the American Society for Bone and Mineral Research.

“The interval for a follow-up bone density should be lengthened, or perhaps the repeat DXA should not be done unless there is an additional risk factor noted,” wrote Dr. Robert A. Adler of the endocrinology section of McGuire Veterans Affairs Medical Center and Virginia Commonwealth University, Richmond, and colleagues.

The researchers followed 78 men with osteopenia (T score of lumbar spine, femoral neck, total hip, total forearm or distal 1/3 forearm between -1 and -2.4) from a baseline DXA test through follow-up DXA testing an average of 998 days later.

The mean age and weight of the patients at baseline were 70.7 years and 76.4 kg, respectively.

All of the men had been referred for an initial DXA test after a screening program using the Osteoporosis Self-Assessment Tool had found them to be at increased risk for osteoporosis.

Mean percent changes in bone mineral density (BMD) from baseline to follow-up were 1.8% for lumbar spine, -0.4% for femoral neck, -0.7 for total hip, -1.1 for 1/3 radius, and -1.6 for total forearm.

“The BMD changes were minimal, approximately plus or minus 2%,” the researchers noted, and affected diagnosis very rarely: Only one patient started therapy for osteoporosis after the follow-up DXA test because of a significant change in BMD.

Although it was recommended upon diagnosis with osteopenia that the patients take calcium and vitamin D supplements, only about one-fourth to one-third actually received the supplementation after the baseline DXA.

“After the second DXA, an additional 17 men were prescribed supplements,” the researchers pointed out.

Although these results suggest that a second DXA test may encourage clinicians to prescribe such preventive measures as calcium and vitamin D supplements for their patients, “there should be cheaper ways to improve clinician behavior,” the researchers suggested.

Dr. Adler stated that he had no conflicts of interest.

HONOLULU — Men diagnosed with osteopenia through dual-energy x-ray absorptiometry are unlikely to have a change in diagnosis at a 3-year follow-up DXA, according to a study presented at the annual meeting of the American Society for Bone and Mineral Research.

“The interval for a follow-up bone density should be lengthened, or perhaps the repeat DXA should not be done unless there is an additional risk factor noted,” wrote Dr. Robert A. Adler of the endocrinology section of McGuire Veterans Affairs Medical Center and Virginia Commonwealth University, Richmond, and colleagues.

The researchers followed 78 men with osteopenia (T score of lumbar spine, femoral neck, total hip, total forearm or distal 1/3 forearm between -1 and -2.4) from a baseline DXA test through follow-up DXA testing an average of 998 days later.

The mean age and weight of the patients at baseline were 70.7 years and 76.4 kg, respectively.

All of the men had been referred for an initial DXA test after a screening program using the Osteoporosis Self-Assessment Tool had found them to be at increased risk for osteoporosis.

Mean percent changes in bone mineral density (BMD) from baseline to follow-up were 1.8% for lumbar spine, -0.4% for femoral neck, -0.7 for total hip, -1.1 for 1/3 radius, and -1.6 for total forearm.

“The BMD changes were minimal, approximately plus or minus 2%,” the researchers noted, and affected diagnosis very rarely: Only one patient started therapy for osteoporosis after the follow-up DXA test because of a significant change in BMD.

Although it was recommended upon diagnosis with osteopenia that the patients take calcium and vitamin D supplements, only about one-fourth to one-third actually received the supplementation after the baseline DXA.

“After the second DXA, an additional 17 men were prescribed supplements,” the researchers pointed out.

Although these results suggest that a second DXA test may encourage clinicians to prescribe such preventive measures as calcium and vitamin D supplements for their patients, “there should be cheaper ways to improve clinician behavior,” the researchers suggested.

Dr. Adler stated that he had no conflicts of interest.

HONOLULU — Men diagnosed with osteopenia through dual-energy x-ray absorptiometry are unlikely to have a change in diagnosis at a 3-year follow-up DXA, according to a study presented at the annual meeting of the American Society for Bone and Mineral Research.

“The interval for a follow-up bone density should be lengthened, or perhaps the repeat DXA should not be done unless there is an additional risk factor noted,” wrote Dr. Robert A. Adler of the endocrinology section of McGuire Veterans Affairs Medical Center and Virginia Commonwealth University, Richmond, and colleagues.

The researchers followed 78 men with osteopenia (T score of lumbar spine, femoral neck, total hip, total forearm or distal 1/3 forearm between -1 and -2.4) from a baseline DXA test through follow-up DXA testing an average of 998 days later.

The mean age and weight of the patients at baseline were 70.7 years and 76.4 kg, respectively.

All of the men had been referred for an initial DXA test after a screening program using the Osteoporosis Self-Assessment Tool had found them to be at increased risk for osteoporosis.

Mean percent changes in bone mineral density (BMD) from baseline to follow-up were 1.8% for lumbar spine, -0.4% for femoral neck, -0.7 for total hip, -1.1 for 1/3 radius, and -1.6 for total forearm.

“The BMD changes were minimal, approximately plus or minus 2%,” the researchers noted, and affected diagnosis very rarely: Only one patient started therapy for osteoporosis after the follow-up DXA test because of a significant change in BMD.

Although it was recommended upon diagnosis with osteopenia that the patients take calcium and vitamin D supplements, only about one-fourth to one-third actually received the supplementation after the baseline DXA.

“After the second DXA, an additional 17 men were prescribed supplements,” the researchers pointed out.

Although these results suggest that a second DXA test may encourage clinicians to prescribe such preventive measures as calcium and vitamin D supplements for their patients, “there should be cheaper ways to improve clinician behavior,” the researchers suggested.

Dr. Adler stated that he had no conflicts of interest.

Bazedoxifene, a novel selective estrogen-receptor modulator, is as safe as placebo in terms effects on the endometrium and will be a new therapy for preventing and treating postmenopausal osteoporosis, according to data presented at the annual meeting of the North American Menopause Society.

Dr. David F. Archer, professor of obstetrics and gynecology at Eastern Virginia Medical School, Norfolk, and a consultant for Wyeth Pharmaceuticals (the study's sponsor), presented data on endometrial safety in a subset of women in a large phase III trial comparing the efficacy of bazedoxifene, raloxifene, and placebo in reducing the relative risk of new vertebral fractures.

The results of that trial found bazedoxifene at 20 mg or 40 mg per day significantly reduced new vertebral fractures, versus placebo. Similar results were obtained with raloxifene 60 mg per day.

However, in the subanalysis raloxifene was linked to more endometrial hyperplasia, Dr. Archer said.

“Importantly, bazedoxifene exerted its beneficial effect on bone without increasing endometrial thickness or causing endometrial bleeding,” Dr. Archer added in an interview.

The endometrial safety substudy focused on 643 women who had transvaginal ultrasonography at baseline and at month 24. Endometrial biopsies also were performed at these two time points.

Endometrial thickness between baseline and 24 months increased by 0.1 mm with both doses of bazedoxifene and placebo, compared with an increase of 0.3 mm with raloxifene, Dr. Archer said.

About five women in each of the four treatment arms had 4 mm or more growth in endometrial thickness, but when they were biopsied, no evidence of hyperplasia was detected.

“We are not sure what the exact cause of this increase in endometrial thickness is, but it does not appear to be mycotic,” he commented.

Food and Drug Administration approval of bazedoxifene is pending, and Wyeth, the drug's developer, expects the FDA to approve it for the treatment of postmenopausal osteoporosis by the end of 2007, Dr. Archer said.

Bazedoxifene, a novel selective estrogen-receptor modulator, is as safe as placebo in terms effects on the endometrium and will be a new therapy for preventing and treating postmenopausal osteoporosis, according to data presented at the annual meeting of the North American Menopause Society.

Dr. David F. Archer, professor of obstetrics and gynecology at Eastern Virginia Medical School, Norfolk, and a consultant for Wyeth Pharmaceuticals (the study's sponsor), presented data on endometrial safety in a subset of women in a large phase III trial comparing the efficacy of bazedoxifene, raloxifene, and placebo in reducing the relative risk of new vertebral fractures.

The results of that trial found bazedoxifene at 20 mg or 40 mg per day significantly reduced new vertebral fractures, versus placebo. Similar results were obtained with raloxifene 60 mg per day.

However, in the subanalysis raloxifene was linked to more endometrial hyperplasia, Dr. Archer said.

“Importantly, bazedoxifene exerted its beneficial effect on bone without increasing endometrial thickness or causing endometrial bleeding,” Dr. Archer added in an interview.

The endometrial safety substudy focused on 643 women who had transvaginal ultrasonography at baseline and at month 24. Endometrial biopsies also were performed at these two time points.

Endometrial thickness between baseline and 24 months increased by 0.1 mm with both doses of bazedoxifene and placebo, compared with an increase of 0.3 mm with raloxifene, Dr. Archer said.

About five women in each of the four treatment arms had 4 mm or more growth in endometrial thickness, but when they were biopsied, no evidence of hyperplasia was detected.

“We are not sure what the exact cause of this increase in endometrial thickness is, but it does not appear to be mycotic,” he commented.

Food and Drug Administration approval of bazedoxifene is pending, and Wyeth, the drug's developer, expects the FDA to approve it for the treatment of postmenopausal osteoporosis by the end of 2007, Dr. Archer said.

Bazedoxifene, a novel selective estrogen-receptor modulator, is as safe as placebo in terms effects on the endometrium and will be a new therapy for preventing and treating postmenopausal osteoporosis, according to data presented at the annual meeting of the North American Menopause Society.

Dr. David F. Archer, professor of obstetrics and gynecology at Eastern Virginia Medical School, Norfolk, and a consultant for Wyeth Pharmaceuticals (the study's sponsor), presented data on endometrial safety in a subset of women in a large phase III trial comparing the efficacy of bazedoxifene, raloxifene, and placebo in reducing the relative risk of new vertebral fractures.

The results of that trial found bazedoxifene at 20 mg or 40 mg per day significantly reduced new vertebral fractures, versus placebo. Similar results were obtained with raloxifene 60 mg per day.

However, in the subanalysis raloxifene was linked to more endometrial hyperplasia, Dr. Archer said.

“Importantly, bazedoxifene exerted its beneficial effect on bone without increasing endometrial thickness or causing endometrial bleeding,” Dr. Archer added in an interview.

The endometrial safety substudy focused on 643 women who had transvaginal ultrasonography at baseline and at month 24. Endometrial biopsies also were performed at these two time points.

Endometrial thickness between baseline and 24 months increased by 0.1 mm with both doses of bazedoxifene and placebo, compared with an increase of 0.3 mm with raloxifene, Dr. Archer said.

About five women in each of the four treatment arms had 4 mm or more growth in endometrial thickness, but when they were biopsied, no evidence of hyperplasia was detected.

“We are not sure what the exact cause of this increase in endometrial thickness is, but it does not appear to be mycotic,” he commented.

Food and Drug Administration approval of bazedoxifene is pending, and Wyeth, the drug's developer, expects the FDA to approve it for the treatment of postmenopausal osteoporosis by the end of 2007, Dr. Archer said.