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Reduced Bone Mineral Density in Human Immunodeficiency Virus-Infected Patients and Its Association with Increased Central Adiposity and Postload Hyperglycemia

Divisions of Endocrinology (T.K.), Infectious Diseases (P.K., J.T.), Department of Medicine (T.T.B., M.D.R.), General Clinical Research Center (R.K.), Georgetown University Medical Center, Washington, D.C. 20007; and Division of Endocrinology and Metabolism (T.T.B., M.D.R., A.S.D.), Johns Hopkins University, Baltimore, Maryland 21287

Address all correspondence and requests for reprints to: Todd T. Brown, M.D., Division of Endocrinology and Metabolism, Johns Hopkins University, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287. E-mail: tbrown27{at}jhmi.edu.

Reduced bone mineral density (BMD) and abnormalities in fat redistribution, glucose homeostasis, and lipid metabolism are prevalent among HIV-infected patients on highly active antiretroviral therapy (HAART). The relationship between the metabolic and skeletal complications of HIV is unclear. Fifty-one HIV patients on HAART (aged 30–54 yr, 86% male) and 21 HIV-negative control subjects (aged 31–51 yr, 82% male) were examined with oral glucose tolerance testing, a fasting lipid profile, and dual x-ray absorptiometry, and markers of bone formation (serum osteocalcin) and resorption (urinary deoxypyridinoline). HIV-infected subjects had a higher prevalence of either osteopenia or osteoporosis (World Health Organization criteria) at the spine, hip, or forearm, compared with HIV-negative controls (63% vs. 32%, P = 0.02) and evidence of increased bone resorption (urine deoxypyridinoline, 14.7 ± 6.5 vs. 10.9 ± 2.5 nmol/mmol creatinine, P = 0.012). Among the HIV-infected patients, those with reduced bone mineral density (n = 32) were similar to the group with normal BMD (n = 19) in the use of protease inhibitors, duration of HAART therapy, or other demographic variables. Plasma glucose 2 h after a glucose load (odds ratio 1.02 per 1 mg/dl increase, 95% confidence interval 1.01–1.05, P = 0.009) and central adiposity (trunk fat/total fat) (odds ratio 1.09 per 1% ratio increase, 95% confidence interval 1.00–1.18, P = 0.012) were associated with reduced BMD. These associations remained significant in a multivariate model including age and body mass index. Bone resorption was associated with female gender (P < 0.001) and non-high-density lipoprotein cholesterol (P = 0.034) in a multivariate linear regression model controlling for age, body mass index, protease inhibitor use, duration of HAART, and extremity fat. Reduced BMD is prevalent in HIV-infected patients on HAART and is related to central adiposity and postload hyperglycemia. Bone resorption is independently associated with female gender and dyslipidemia. HIV-infected patients with metabolic abnormalities may represent a population that would benefit from bone density screening.

This work was supported by Grant M01-RR13297 from the General Clinical Research Program of the National Center for Research Resources, National Institutes of Health.

This work was presented in part at the 9th Conference on Retroviruses and Opportunistic Infections, Seattle, Washington, 2002.

Abbreviations: AUC, Area under the curve; BMD, bone mineral density; BMI, body mass index; DXA, dual x-ray absorptiometry; HAART, highly active antiretroviral therapy; HDL, high-density lipoprotein; NNRTI, nonnucleoside reverse transcriptase inhibitor; OGTT, oral glucose tolerance test; PI, protease inhibitor.

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