title: Impact of switching from zidovudine to tenofovir disoproxil fumarate on bone mineral density and markers of bone metabolism in virologically suppressed HIV-1 infected patients; a substudy of the PREPARE study.
abstract: BACKGROUND
  In virologically suppressed, antiretroviral-treated patients, the effect of switching to tenofovir (TDF) on bone biomarkers compared to patients remaining on stable antiretroviral therapy is unknown.
  
  
  METHODS
  We examined bone biomarkers (osteocalcin [OC], procollagen type 1 amino-terminal propeptide, and C-terminal cross-linking telopeptide of type 1 collagen) and bone mineral density (BMD) over 48 weeks in virologically suppressed patients (HIV RNA < 50 copies/ml) randomized to switch to TDF/emtricitabine (FTC) or remain on first-line zidovudine (AZT)/lamivudine (3TC). PTH was also measured. Between-group differences in bone biomarkers and associations between change in bone biomarkers and BMD measures were assessed by Student's t tests, Pearson correlation, and multivariable linear regression, respectively. All data are expressed as mean (SD), unless otherwise specified.
  
  
  RESULTS
  Of 53 subjects (aged 46.0 y; 84.9% male; 75.5% Caucasian), 29 switched to TDF/FTC. There were reductions in total hip and lumbar spine BMD in those switching to TDF/FTC (total hip, TDF/FTC, -1.73 (2.76)% vs AZT/3TC, -0.39 (2.41)%; between-group P = .07; lumbar spine, TDF/FTC, -1.50 (3.49)% vs AZT/3TC, +0.25 (2.82)%; between-group P = .06), but they did not reach statistical significance. Greater declines in lumbar spine BMD correlated with greater increases in OC (r = -0.28; P = .05). The effect of TDF/FTC on bone biomarkers remained significant when adjusted for baseline biomarker levels, gender, and ethnicity. There was no difference in change in PTH levels over 48 weeks between treatment groups (between-group P = .23). All biomarkers increased significantly from weeks 0 to 48 in the switch group, with no significant change in those remaining on AZT/3TC (between-group, all biomarkers, P < .0001).
  
  
  CONCLUSIONS
  A switch to TDF/FTC compared to remaining on a stable regimen is associated with increases in bone turnover that correlate with reductions in BMD, suggesting that TDF exposure directly affects bone metabolism in vivo.
authors: HIV Molecular Research Group, School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland. Aoife.cotter@ucdconnect.ie
authors: Aoife G
authors: AG
authors: Cotter
authors: Saskia M E
authors: SM
authors: Vrouenraets
authors: Jennifer J
authors: JJ
authors: Brady
authors: Ferdinand W
authors: FW
authors: Wit
authors: Christoph A
authors: CA
authors: Fux
authors: Hansjakob
authors: H
authors: Furrer
authors: Kees
authors: K
authors: Brinkman
authors: Caroline A
authors: CA
authors: Sabin
authors: Peter
authors: P
authors: Reiss
authors: Patrick W G
authors: PW
authors: Mallon
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis / Q000097:blood*; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D015331:Cohort Studies; D015536:Down-Regulation / Q000187:drug effects; D057915:Drug Substitution; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010281:Parathyroid Hormone / Q000097:blood; D000068698:Tenofovir; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D015215:Zidovudine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D063065:Organophosphonates; D010281:Parathyroid Hormone; D014807:Vitamin D; D015215:Zidovudine; D000068698:Tenofovir; C104450:25-hydroxyvitamin D; D000225:Adenine