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

AIDS. 2018 Nov 13;32(17):2517-2524. 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Absorptiometry, Photon
  • Adolescent
  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods
  • Bone Density
  • Bone Diseases, Metabolic / pathology*
  • Bone Diseases, Metabolic / prevention & control*
  • CD4 Lymphocyte Count
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Humans
  • Hypophosphatemia, Familial / complications*
  • Immune Reconstitution*
  • Male
  • Middle Aged
  • Pelvic Bones / pathology
  • Randomized Controlled Trials as Topic
  • Spine / pathology
  • Sustained Virologic Response*
  • Treatment Outcome
  • Viral Load
  • Young Adult


  • Anti-Retroviral Agents

Grant support