Tenofovir Has Minimal Effect on Biomarkers of Bone Health in Youth with HIV Receiving Initial Antiretroviral Therapy

AIDS Res Hum Retroviruses. 2019 Aug;35(8):746-754. doi: 10.1089/AID.2018.0270. Epub 2019 Jun 27.


Both HIV infection and tenofovir disoproxil fumarate (TDF) treatment adversely impact bone metabolism and may lead to osteopenia, which has critical implications for youth with HIV (YWH). This study evaluates changes in the biomarkers of bone metabolism and inflammation among YWH receiving initial treatment with TDF- and non-TDF-containing antiretroviral therapies (ARTs). YWH [n = 23, median age 21 years (range 18-24), 87% male, 61% African American] were assessed for inflammatory and bone metabolism biomarkers at enrollment, after 48 weeks of TDF-containing ART, and 96 weeks of ART without TDF with continued viral suppression. Spearman's rank correlation evaluated biomarker associations. Bone alkaline phosphatase, parathyroid hormone, and osteopontin increased after TDF treatment. All fell after TDF was discontinued. Levels of RANKL and osteoprotegerin did not change throughout the study. There was little correlation between biomarkers of bone metabolism and either macrophage or lymphocyte activation at any time point. Our results establish baseline associations between bone metabolism and immune biomarkers for this population, and find that before CD4 T cell decline chronic inflammation does not perturb biomarkers of bone metabolism among YWH. The adverse effects of TDF on bone health may be marginal for YWH at the early stages of disease.

Keywords: biomarker; bone metabolism; lymphocyte activation; macrophage activation; tenofovir disoproxil fumarate (TDF); youth with HIV (YWH).

Publication types

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

MeSH terms

  • Adolescent
  • Alkaline Phosphatase / analysis
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Biomarkers / analysis
  • Bone Density / drug effects*
  • Bone Diseases, Metabolic / chemically induced*
  • Bone and Bones / metabolism
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Lymphocyte Activation / drug effects
  • Macrophage Activation / drug effects
  • Macrophages / immunology
  • Male
  • Osteopontin / analysis
  • Osteoprotegerin / analysis
  • Parathyroid Hormone / analysis
  • RANK Ligand / analysis
  • Tenofovir / adverse effects*
  • Tenofovir / therapeutic use
  • Young Adult


  • Anti-HIV Agents
  • Biomarkers
  • Osteoprotegerin
  • Parathyroid Hormone
  • RANK Ligand
  • TNFSF11 protein, human
  • Osteopontin
  • Tenofovir
  • Alkaline Phosphatase