A majority of the men in their sixth decade of life had low bone mineral density, with lower levels among HIV-infected men than uninfected men with similar risk behaviors. After adjustment for other risk factors, the effect of HIV infection was statistically significant but modest. HIV infection also increased fracture risk by approximately one-third, but this finding was not significant. It is not clear whether an effect of HIV infection on BMD might become more pronounced as men reach even older ages, or whether the increased risk of fracture due to HIV would be significant with longer follow-up or a larger sample size.
Neither any antiretroviral therapy nor protease inhibitor therapy were associated with BMD among HIV-infected men. Other factors independently associated with BMD (older age, non-black race, lower body weight and low testosterone) are generally well-known risk factors for osteopenia. The prevalence of osteopenia and osteoporosis in this cohort was slightly higher among HIV-infected than uninfected men (55 versus 51%), but similar to national estimates among white men aged 50 years and older [31
]. However, the proportion of men with osteoporosis was substantially higher in this study (14%; 95% confidence interval 0.11−0.17) than in the general population. Previous studies among mostly younger male and female patients with HIV disease have estimated the prevalence of low BMD at 39 to 76% (33 to 65% with osteopenia and 6 to 16% with osteoporosis), [16
] consistent with our findings among older HIV-infected and uninfected men.
Previous studies of BMD in HIV-infected cohorts have included primarily subjects with lean or normal body mass [15
]. In this study, among the 52% of HIV-infected and 70% of HIV-uninfected men who were overweight or obese, HIV infection was not associated with BMD. This suggests that increased BMI, previously associated with slower HIV disease progression [33
], may also lessen the effect of HIV infection on BMD. As the association between HIV infection and BMD was much stronger in lean/normal weight than overweight/obese men, it further suggests that this association is not confounded by low body weight among the HIV-infected men.
Our findings also highlight the important problem of obesity among HIV-infected and drug-using men. Although HIV infection pre-HAART was characterized by wasting, advances in treatment may now be contributing to increasing obesity among HIV-infected persons in this country. Excess weight may be desirable for some HIV-infected men, suggesting a healthy immune system. Obesity may also mask opiate or cocaine addiction, which are frequently associated with weight loss. Among obese HIV-infected and drug-using men, weight loss may not be a priority for patients or their health care providers.
The independent association between HIV infection and BMD suggests that HIV may exert a direct effect on bone metabolism. Hormones, cytokines and body composition contribute to low BMD in HIV-infected women and men [15
] Hypogonadally-mediated alterations of bone metabolism may lead to increased bone resorption, while pro-inflammatory cytokines (e.g. interleukin-1, interleukin-6, tumor necrosis factor) act to increase bone resorption and decrease bone formation. We did not assess biochemical markers of bone turnover or cytokines to explain mechanistically how HIV infection might adversely affect BMD. Previous smaller cross-sectional studies have noted an association between increased visceral adiposity and reduced bone density, independent of BMI [15
], but prospective studies are needed to better describe the relationship between HIV-associated changes in body composition and BMD.
An independent association of current methadone therapy with reduced BMD of the lumbar spine in men has not previously been reported. Opiate use has been associated with central hypogonadism, leading to low BMD through reduced levels of circulating luteinizing hormone, estrogen and testosterone [11
]. However, studies demonstrating this association have been small and not controlled for confounding variables, such as body weight and comorbid illness. Further research is needed to determine whether HIV-infected men on methadone are at particular risk for osteopenia or osteoporosis.
The advantages of this study include the large and ethnically diverse cohort, enrollment of aging men, an HIV-negative comparison group with similar risk behaviors to those of HIV-infected men and follow-up for incident fractures. Smaller studies enrolling primarily younger men also demonstrate low BMD, but have not recruited simultaneous controls with similar drug-use behaviors. Our study, because it included both HIV-infected and HIV-uninfected men with similar risk behaviors, permitted identification of HIV infection as a risk factor for low BMD after controlling for lifestyle variables.
The study limitations include a cross-sectional design, which precludes the assessment of causal relationships between BMD, HIV infection and opiate use. The absence of biochemical or cytokine levels also precludes conclusions about the mechanism underlying observed associations. Abdominal visceral fat was not measured to determine its relationship to BMD. Finally, although HIV infection was associated with a 38% increase in fracture rate after adjustment for low BMD, this finding was not statistically significant. Further study is necessary to determine whether HIV infection affects fracture rates after adjustment for low BMD.
In conclusion, among aging HIV-infected men, low BMD was common and HIV infection was significantly associated with modestly lower BMD after adjusting for body weight. Non-black HIV-infected men with lower BMI may be at particular risk for osteopenia or osteoporosis. Among older men with or at risk for HIV infection, decreased BMD is associated with increased fracture risk.