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Women have enhanced bone loss associated with phosphaturia and CD4+ cell restoration during initial antiretroviral therapy

Kalayjian, Robert C.a,b; Albert, Jeffrey M.c; Cremers, Serged; Gupta, Samir K.e; McComsey, Grace A.f; Klingman, Karin L.g; Fichtenbaum, Carl J.h; Brown, Todd T.i; Taiwo, Babafemi O.j for the ACTG A5224s, A5303 Teams

doi: 10.1097/QAD.0000000000001995

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 BMD declines of 2.8 and 2.9%, respectively, plasma viral load suppression to less than 50 vs. at least 50 copies/ml was 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, 418 men) 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/μl 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.

aDepartment of Medicine, MetroHealth Medical Center

bGeriatric Research Education and Clinical Center, Louis Stokes Cleveland Veterans Administration Medical Center

cDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio

dDepartment of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York

eDepartment of Medicine, Indiana University School of Medicine, Indianapolis, Indiana

fDepartment of Pediatrics and Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio

gHIV Research Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland

hDivision of Infectious Diseases, Department of Medicine, University of Cincinnati, Cincinnati, Ohio

iDivision of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University, Baltimore, Maryland

jDivision of Infectious Diseases, Northwestern University, Chicago, Illinois, USA.

Correspondence to Robert C. Kalayjian, MD, Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio, USA. Tel: +1 216 778 5295; fax +1 216 778 3019; e-mail:

Received 28 December, 2017

Accepted 27 March, 2018

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