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

Álvaro H Borges, Jennifer Hoy, Eric Florence, Dalibor Sedlacek, Hans-Jürgen Stellbrink, Vilma Uzdaviniene, Janez Tomazic, Panagiotis Gargalianos-Kakolyris, Patrick Schmid, Chloe Orkin, Court Pedersen, Clifford Leen, Christian Pradier, Fiona Mulcahy, Anna Lisa Ridolfo, Therese Staub, Fernando Maltez, Rainer Weber, Leo Flamholc, Galina KyselyovaJens D Lundgren, Amanda Mocroft, for EuroSIDA, Mauro Zaccarelli, Andrea Antinori, Rosa Antonietta Acinapura, Maria Maddalena Plazzi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1413-1421
Number of pages9
JournalClinical Infectious Diseases
Volume64
Issue number10
DOIs
Publication statusPublished - May 15 2017

    Fingerprint

Keywords

  • Adult
  • Anti-HIV Agents
  • Bone Density
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Coinfection
  • Data Collection
  • Europe
  • Female
  • Femoral Fractures
  • Fractures, Bone
  • HIV Infections
  • Humans
  • Male
  • Middle Aged
  • Osteonecrosis
  • Regression Analysis
  • Risk Factors
  • Tenofovir
  • Journal Article

Cite this

Borges, Á. H., Hoy, J., Florence, E., Sedlacek, D., Stellbrink, H-J., Uzdaviniene, V., Tomazic, J., Gargalianos-Kakolyris, P., Schmid, P., Orkin, C., Pedersen, C., Leen, C., Pradier, C., Mulcahy, F., Ridolfo, A. L., Staub, T., Maltez, F., Weber, R., Flamholc, L., ... Plazzi, M. M. (2017). Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort. Clinical Infectious Diseases, 64(10), 1413-1421. https://doi.org/10.1093/cid/cix167