title: Relationship between pretreatment rate of bone loss and bone density response to once-yearly ZOL: HORIZON-PFT extension study.
abstract: Several studies have shown that high bone turnover is associated with greater rates of bone loss and greater bone mineral density (BMD) response to antiresorptive therapy in postmenopausal osteoporosis. However, it is not known whether greater rates of bone loss before therapy are associated with greater BMD response to antiresorptive therapy. In the HORIZON-PFT study and its extension, one group of women who were randomized to receive placebo for 3 years (years 1, 2, and 3) were then switched to zoledronic acid (ZOL) 5 mg annually for up to three injections (years 4, 5, and 6, P3Z3 arm) (n = 1223). We measured total hip BMD at baseline, 1, 2, and 3 years on placebo and at 4.5 and 6 years on ZOL. The procollagen type I N-terminal propeptide (PINP) was measured at 3, 4.5, and 6 years. By design, not all subjects were followed for as long as 6 years, so this analysis focused on the results at 4.5 years. Those with the largest loss in total hip BMD on placebo in years 0 to 3 had the largest gain during ZOL (years 3 to 4.5): (r = -0.39, p < 0.0001). The change in total hip BMD in years 0 to 3 on placebo was related to the serum PINP at the end of the 3-year period (r = -0.24, p < 0.0001). The change in total hip BMD on ZOL from year 3 to 4.5 was related to the serum PINP at the end of the 3-year period (r = 0.26, p < 0.0001). We conclude that BMD response to ZOL is greater in postmenopausal women who had larger loss before treatment. This association may result from higher bone turnover being associated with both greater bone loss on placebo and greater BMD response to ZOL.
authors.affiliation: Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Felicia
authors.initials: F
authors.lastname: Cosman
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.forename: Lisa
authors.initials: L
authors.lastname: Palermo
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Black
mesh_terms: D000368:Aged; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D010919:Placebos; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D010919:Placebos; D000077211:Zoledronic Acid
keywords: BONE MINERAL DENSITY; PINP; TREATMENT RESPONSE; ZOL