title: Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: when is it reasonable to discontinue treatment?
abstract: BACKGROUND
  Data are needed to guide therapeutic decisions about stopping bisphosphonates after an initial treatment period.
  
  
  OBJECTIVE
  To define significant predictors of fracture and quantify fracture incidence in risk factor-defined subgroups of women who discontinue zoledronic acid (ZOL) after 3 years of treatment. To determine if continuing ZOL reduces fracture risk in subgroups.
  
  
  METHODS
  This study is based on data from the 3 year extension of HORIZON.
  
  
  METHODS
  Subjects were in the ZOL arm of the Multicenter HORIZON trial.
  
  
  METHODS
  One thousand two hundred thirty three women who previously received 3 ZOL treatments during the Core trial.
  
  
  METHODS
  Randomization to three additional annual ZOL (Z6, n = 616) or placebo infusions (Z3P3, n = 617).
  
  
  RESULTS
  The risk of morphometric vertebral fractures (MorphVertFx) and clinical nonvertebral fractures (NVF).
  
  
  RESULTS
  The incidence of MorphVertFx in Z3P3 was predicted by femoral neck (FN) t-score ≤-2.5 [OR 3.3 (1.4, 8.0), p = .008], total hip (TH) t-score ≤-2.5 [OR 4.0 (1.8, 9.0), p = .0007], and incident MorphVertFx during Core [OR 4.75 (1.4, 16.8), p < .015]. Incidence of NVF was predicted by TH t-score [for 1 decline, HR 1.7 (1.2, 2.6), p = .008], incident NVF during Core [HR 2.5 (1.2, 5.3), p = .014], and prevalent vertebral fracture [HR 3.0 (1.4, 6.3), p = .005]. For MorphVertFx, there were no significant treatment subgroup interactions; absolute fracture reductions with continued ZOL were greatest in high-risk subgroups. For NVF, there were no significant treatment reductions overall or in subgroups and no significant interactions.
  
  
  CONCLUSIONS
  After 3 years of ZOL, in women who have a TH t-score above -2.5, no recent incident fracture and no more than one risk factor (almost 55% of the population), risk for subsequent fracture (over three additional years) is low if treatment is discontinued (for MorphVertFx, average risk 3.2% and for NVF, average risk 5.8%). In these patients, discontinuation for up to 3 years is reasonable.
authors.affiliation: Helen Hayes Hospital (F.C.), West Haverstraw, New York 10993; Department of Medicine (F.C.), Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Epidemiology (J.A.C.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261; Academic Unit of Bone Metabolism (R.E.), University of Sheffield, Sheffield, United Kingdon, S5 7AU; Department of Experimental Medicine (S.B.); Leuven University Hospital, Leuven, B-3000 Belgium; Department of Epidemiology and Department of Biostatistics (L.P., S.R.C., D.M.B.), University of California San Francisco, San Francisco, California 94107; and Faculty of Medical and Health Sciences (I.R.R.), University of Auckland, Auckland, New Zealand, 1023.
authors.forename: Felicia
authors.initials: F
authors.lastname: Cosman
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Lisa
authors.initials: L
authors.lastname: Palermo
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Black
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology* / Q000517:prevention & control*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy; D017698:Postmenopause; D018570:Risk Assessment; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid