title: Effects of intravenous zoledronate on bone turnover and BMD persist for at least 24 months.
abstract: The duration of the antiresorptive effects of the intravenous bisphosphonate, zoledronate, is not known. Recently, we reported that two annual 4-mg doses of zoledronate suppressed bone turnover and increased BMD in HIV-infected men over 24 mo. We set out to determine the persistence of these effects after two doses of zoledronate. Thirty-three HIV-infected men who completed a randomized trial of 4 mg annual zoledronate (n = 17) or placebo (n = 16) were studied for a further 12 mo, during which time no skeletal therapy was administered. Participants received calcium (400 mg/d) and vitamin D supplements (50,000 IU/mo) for the first 24 mo of the study only. Biochemical markers of bone turnover and BMD were measured every 6 mo. Bone turnover markers were stably suppressed at 24 and 36 mo (12 and 24 mo after the second annual dose of zoledronate, respectively). There were no significant within-group changes in urine N-telopeptide, serum C-telopeptide, and osteocalcin between 24 and 36 mo (p > 0.07), and at each time point, each of the turnover markers was significantly lower in the zoledronate group. There were also no significant between-group differences in the changes in BMD at each site between 24 and 36 mo (p > 0.5), and at each time point, BMD at each site was significantly higher in the zoledronate group. These results suggest that the antiresorptive effects of zoledronate last >12 mo and raise the possibility that zoledronate could be administered less frequently than annually. Randomized trials that address this issue should be performed.
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand. m.bolland@auckland.ac.nz
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Bolland
authors.forename: Andrew B
authors.initials: AB
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: Karen E
authors.initials: KE
authors.lastname: Callon
authors.forename: Greg D
authors.initials: GD
authors.lastname: Gamble
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
mesh_terms: D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000503:physiopathology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013997:Time Factors; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D010919:Placebos; D000077211:Zoledronic Acid