Women have enhanced bone loss associated with phosphaturia and CD4R cell restoration during initial antiretroviral therapy

Objective: We compared bone mineral density (BMD) changes and their correlates, between men and women participating in two randomized trials of initial [antiretroviral therapy (ART)] regimens, with or without tenofovir disoproxil fumarate (TDF). Methods: Covariates in linear regression models of 48-week hip and spine %BMD changes, by dual energy X-ray absorptiometry, included baseline and 48-week changes in plasma viral load, CD4 cells, plasma C-Terminal telopeptide, procollagen 1 N-Terminal propeptide and glomerular filtration rates, and the 48-week area under the curve of fractional excretion of phosphate. Results: Despite overall hip and spine BMDdeclines of 2.8 and 2.9%, respectively, plasma viral load suppression to less than 50 vs. at least 50 copies/mlwas associated 1.0% (P 0.02) and 0.8% (P 0.01) less BMD decline.Women had lower baseline spine (P 0.04; n 59 women, 418men) and hip BMD(P 0.01) in adjusted models,with 1.7% more hip decline on ART than men (P 0.001). Serum phosphate was positively associated with baseline spine BMD in women (P 0.03) but not men, and area under the curve of fractional excretion of phosphate was negatively associated with spine BMD changes, particularly in women randomized to TDF regimens (P 0.03 and 0.054 for interactions by sex, and randomization to TDF vs. non-TDF regimens, respectively; n 44 women, 326 men). Women also had 0.6%(P 0.004) more hip BMD decline than men associated with each 100 CD4 cells/ml increase on ART (P 0.02; n 49 women, 379 men). Conclusion: Women randomized to TDF-containing ART had accentuated spine loss associated with phosphaturia, and accentuated hip loss associated with CD4 restoration, regardless of TDF exposure. Viral load suppression reduced bone loss.