Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study

Osteoporos Int. 2016 Jan;27(1):21-31. doi: 10.1007/s00198-015-3145-7. Epub 2015 May 20.

Abstract

We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis. Response was more likely with alendronate and ibandronate than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80 % of her medication.

Introduction: Biochemical response to bisphosphonate therapy can be assessed using either a decrease in bone turnover marker beyond the least significant change (LSC) or a reduction to within a reference interval (RI). We compared the performance of these target responses and determined whether response was related to the type of bisphosphonate, compliance and baseline bone turnover markers.

Methods: Biochemical responses to three oral bisphosphonates were assessed in an open, controlled trial comprising 172 postmenopausal osteoporotic women (age 53-84 years), randomised to alendronate, ibandronate or risedronate, plus calcium and vitamin D supplementation for 2 years. The LSC for each marker was derived within the study population, whereas RIs were obtained from a control group of healthy premenopausal women (age 35-40 years).

Results: Over 70 % of women achieved a target response for serum CTX and PINP, irrespective of the approach used. The percentage decrease at 12 weeks was greater for women with baseline PINP above the RI -63 % (difference 13 %, 95 % CI 0 to 27.1, P = 0.049) and good compliance -67 % (difference 15.9 %, 95 % CI 6.3 to 25.5, P = 0.001). Responders had a greater increase in spine bone density compared to nonresponders; for example 6.2 vs. 2.3 % (difference 3.9 %, 95 % CI 1.6 to 6.3, P = 0.0011) for PINP LSC. The magnitude of change in bone markers was greater with ibandronate and alendronate than risedronate.

Conclusions: Both approaches to response identified similar proportions of women as responders. Nonresponders had smaller increases in BMD, and we suggest that biochemical assessment of response is a useful tool for the management of women with postmenopausal osteoporosis.

Keywords: Bisphosphonate; Bone turnover markers; Postmenopausal osteoporosis; Variability.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Alendronate / administration & dosage
  • Alendronate / pharmacology
  • Alendronate / therapeutic use
  • Biomarkers / blood
  • Bone Density / drug effects
  • Bone Density / physiology
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / pharmacology
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Remodeling / drug effects*
  • Bone Remodeling / physiology
  • Diphosphonates / administration & dosage
  • Diphosphonates / pharmacology
  • Diphosphonates / therapeutic use*
  • Female
  • Humans
  • Ibandronic Acid
  • Lumbar Vertebrae / physiopathology
  • Middle Aged
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / physiopathology
  • Premenopause / blood
  • Reference Values
  • Risedronic Acid / administration & dosage
  • Risedronic Acid / pharmacology
  • Risedronic Acid / therapeutic use
  • Treatment Outcome

Substances

  • Biomarkers
  • Bone Density Conservation Agents
  • Diphosphonates
  • Risedronic Acid
  • Ibandronic Acid
  • Alendronate