Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort

Clin Infect Dis. 2017 May 15;64(10):1413-1421. doi: 10.1093/cid/cix167.


Background: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes.

Methods: EuroSIDA participants were followed to assess fractures and osteonecrosis. Poisson regression identified clinical, laboratory and demographic predictors of either bone outcome. Ever, current, and cumulative exposures to ARVs were assessed.

Results: During 86118 PYFU among 11820 included persons (median age 41y, 75% male, median baseline CD4 440/mm3, 70.4% virologically suppressed), there were 619 fractures (incidence/1000 PYFU 7.2; 95% CI 6.6-7.7) and 89 osteonecrosis (1.0; 0.8-1.3). Older age, white race, lower BMI, IV drug use, lower baseline CD4, HCV coinfection, prior osteonecrosis, prior fracture, cardiovascular disease, and recent non-AIDS cancer (last 12 months) were associated with fractures. After adjustment, persons who had ever used tenofovir disoproxil fumarate (TDF) (1.40; 1.15-1.70) or who were currently on TDF (1.25; 1.05-1.49) had higher incidence of fractures. There was no association between cumulative exposure to TDF and fractures (1.08/5 y exposure; 0.94-1.25). No other ARV was associated with fractures (all P > .1). Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no ARV was associated with osteonecrosis.

Conclusions: In human immunodeficiency virus (HIV) infection, host factors, HIV-specific variables, and comorbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.

Keywords: HIV.; avascular necrosis; bone; fractures; osteonecrosis.

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Bone Density / drug effects
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Coinfection / epidemiology
  • Data Collection
  • Europe / epidemiology
  • Female
  • Femoral Fractures / epidemiology
  • Femoral Fractures / etiology
  • Femoral Fractures / virology
  • Fractures, Bone / epidemiology
  • Fractures, Bone / ethnology
  • Fractures, Bone / etiology*
  • Fractures, Bone / virology
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology
  • HIV Infections / virology
  • Humans
  • Male
  • Middle Aged
  • Osteonecrosis / epidemiology
  • Osteonecrosis / etiology*
  • Osteonecrosis / virology
  • Regression Analysis
  • Risk Factors
  • Tenofovir / adverse effects
  • Tenofovir / therapeutic use


  • Anti-HIV Agents
  • Tenofovir