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Low bone mineral density (BMD) is an emerging metabolic condition in HIV-infected patients; however, data on progression of this disease are scarce.We studied 671 patients with at least one dual-energy X-ray absorptiometry scan (391 of them ≥2 scans) to determine the prevalence and progression of BMD and establish related factors. Linear regression and logistic polytomic regression were used for the cross-sectional study and mixed effects and generalized estimating equations were used for the longitudinal study.Osteopenia and osteoporosis were diagnosed in 47.5 and 23%, respectively. Progression to bone demineralization was observed in 28% of the patients over a median of 2.5 years (12.5% progressed to osteopenia and 15.6% to osteoporosis). In the 105 patients with at least 5 years of follow-up, progression was 47% (18% to osteopenia; 29% to osteoporosis). Factors associated with bone loss and progression were age [odds ratio (OR) 1.07; 95% confidence interval (CI) 1.05–1.08; P < 0.0001], male sex (OR 2.23; 95% CI 1.77–2.8; P < 0.0001), low body mass index (OR 1.14; 95% CI 1.11–1.17; P < 0.0001), time on protease inhibitor (OR 1.18; 95% CI 1.12–1.24; P < 0.0001), time on tenofovir (OR 1.08; 95% CI 1.03–1.14; P < 0.0019), and current use of protease inhibitors (OR 1.64; 95% CI 1.35–2.04; P < 0.0001).Our results show a high prevalence of and considerable progression to osteopenia/osteoporosis in our cohort. Our findings support the importance of applying adequate strategies to prevent bone demineralization and of close monitoring of BMD in HIV-infected patients, specifically in at-risk patients who are taking antiretrovirals that affect bone mineralization.