HIV Patients Have Higher Osteoporosis Risk

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/mm

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.

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. 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,” he said. “But we have no data on peak bone mineralization in HIV patients. It's quite possible that the high rates of osteoporosis and osteopenia we are seeing in these patients is not a result of accelerated bone mineral loss but because for some reason they never reached the same peak mineralization as healthy individuals,” Dr. Powderly said.

“Sorting out risk factors, the HIV effects, and the treatment effects in such a multifactorial situation is not going to be easy,” he noted.

Until the relative contributions to bone loss of the various factors can be clarified, the routine care of older patients with HIV should include monitoring of markers of bone turnover, he said.

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/mm

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.

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. 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,” he said. “But we have no data on peak bone mineralization in HIV patients. It's quite possible that the high rates of osteoporosis and osteopenia we are seeing in these patients is not a result of accelerated bone mineral loss but because for some reason they never reached the same peak mineralization as healthy individuals,” Dr. Powderly said.

“Sorting out risk factors, the HIV effects, and the treatment effects in such a multifactorial situation is not going to be easy,” he noted.

Until the relative contributions to bone loss of the various factors can be clarified, the routine care of older patients with HIV should include monitoring of markers of bone turnover, he said.

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/mm

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.

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. 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,” he said. “But we have no data on peak bone mineralization in HIV patients. It's quite possible that the high rates of osteoporosis and osteopenia we are seeing in these patients is not a result of accelerated bone mineral loss but because for some reason they never reached the same peak mineralization as healthy individuals,” Dr. Powderly said.

“Sorting out risk factors, the HIV effects, and the treatment effects in such a multifactorial situation is not going to be easy,” he noted.

Until the relative contributions to bone loss of the various factors can be clarified, the routine care of older patients with HIV should include monitoring of markers of bone turnover, he said.