title: Effects of intravenous zoledronate on bone turnover and bone density persist for at least five years in HIV-infected men.
abstract: BACKGROUND
  In HIV-infected men, the antiresorptive effects of zoledronate persist for at least 2 yr after the second annual dose.
  
  
  OBJECTIVE
  Our objective was to determine the duration of action of zoledronate in men.
  
  
  METHODS
  This was 4-yr extension of a 2-yr, double-blind, randomized, placebo-controlled trial at an academic research center.
  
  
  METHODS
  Participants included 43 HIV-infected men with bone mineral density (BMD) T score below -0.5, 35 of whom entered the extension study.
  
  
  METHODS
  Intervention was annual administration of 4 mg iv zoledronate or placebo at baseline and 1 yr and no intervention subsequently.
  
  
  METHODS
  We evaluated changes in the bone turnover markers, serum osteocalcin and serum C-telopeptide (CTx), and changes in BMD at the lumbar spine, total hip, and total body.
  
  
  RESULTS
  There was no time × treatment interaction between 1 and 5 yr after the second zoledronate dose for osteocalcin or CTx (P > 0.4) or any BMD site (P > 0.7). Between 1 and 5 yr after the second dose, on average, osteocalcin was 41% lower (95% confidence interval = 19-62%; P < 0.001), CTx 52% lower (33-71%; P < 0.001), lumbar spine BMD 3.7% greater (0.3-7.0%; P = 0.03), total hip BMD 2.3% greater (0.3-4.3%; P = 0.02), and total body BMD 2.5% greater (0.8-4.1%; P = 0.004) in the zoledronate group than the placebo group. Five years after the second dose, the between-groups differences were 38% (13-62%) for osteocalcin, 49% (20-77%) for CTx, 3.5% (0.7-6.7%) for lumbar spine BMD, 3.4% (1.4-5.4%) for total hip BMD, and 1.6% (0.2-3.1%) for total body BMD.
  
  
  CONCLUSIONS
  The effects of two annual 4-mg doses of zoledronate in men persist for at least 5 yr after the second dose. Larger trials assessing the antifracture efficacy of less frequent dosing of zoledronate are justified.
authors.affiliation: Bone and Joint Research Group, Department of Medicine, University of Auckland, Private Bag 92 019, Auckland, New Zealand. m.bolland@auckland.ac.nz
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Bolland
authors.forename: Andrew
authors.initials: A
authors.lastname: Grey
authors.forename: Anne M
authors.initials: AM
authors.lastname: Horne
authors.forename: Simon E
authors.initials: SE
authors.lastname: Briggs
authors.forename: Mark G
authors.initials: MG
authors.lastname: Thomas
authors.forename: Rod B
authors.initials: RB
authors.lastname: Ellis-Pegler
authors.forename: Greg D
authors.initials: GD
authors.lastname: Gamble
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D016723:Bone Remodeling / Q000187:drug effects*; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007275:Injections, Intravenous; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010455:Peptides / Q000097:blood; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D000077211:Zoledronic Acid