Bone turnover markers and bone mineral density response with risedronate therapy: relationship with fracture risk and patient adherence

J Bone Miner Res. 2011 Jul;26(7):1662-9. doi: 10.1002/jbmr.342.


Surrogate markers of fracture risk--bone turnover markers (BTMs) and bone mineral density (BMD)--can be used to monitor treatment response. We assessed whether changes in these markers greater than the least significant change (LSC) were associated with fracture risk reduction and greater adherence. This secondary analysis of the Improving Measurements of Persistence on ACtonel Treatment (IMPACT) study--a multinational prospective, open-label, cluster-randomized study of postmenopausal women on oral risedronate 5 mg/d for 52 weeks-assessed adherence by electronic monitors. Urinary N-terminal cross-linked telopeptide of type 1 collagen (uNTX) and serum C-terminal cross-linked telopeptide of type 1 collagen (sCTX) levels were assessed at baseline and weeks 10 and 22, and BMD at baseline and week 52. Fractures were recorded as adverse events. In 2302 women, responses beyond LSC in BTMs (uNTX and sCTX) and BMD (spine only) were associated with a reduced risk of nonvertebral fractures (NVFs) and all fractures. NVF incidence was about 50% lower in patients with 30% or more of uNTX reduction at week 22 (1.6%) than in those with less than 30% reduction (3.2%, p = .015). NVFs also were reduced in patients with more than 3% spine BMD increase at 52 weeks than those with 3% or less. Responses greater than LSC in BTMs and BMD were associated with greater adherence, but there was no association between adherence and fracture outcomes at 52 weeks. Changes greater than the LSC in BTMs and BMD reflect better treatment adherence, were associated with fracture risk reduction, and identify differences in individual responsiveness to risedronate.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / metabolism*
  • Bone Density / physiology*
  • Bone Remodeling / physiology*
  • Etidronic Acid / administration & dosage
  • Etidronic Acid / analogs & derivatives*
  • Etidronic Acid / therapeutic use
  • Female
  • Fractures, Bone / chemically induced*
  • Fractures, Bone / epidemiology
  • Fractures, Bone / physiopathology
  • Humans
  • Incidence
  • Patient Compliance*
  • Risedronic Acid
  • Risk Factors


  • Biomarkers
  • Risedronic Acid
  • Etidronic Acid