Osteoporosis International

, Volume 27, Issue 1, pp 21–31 | Cite as

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

  • K. E. NaylorEmail author
  • R. M. Jacques
  • M. Paggiosi
  • F. Gossiel
  • N. F. A. Peel
  • E. V. McCloskey
  • J. S. Walsh
  • R. Eastell
Original Article



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.


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.


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).


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.


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.


Bisphosphonate Bone turnover markers Postmenopausal osteoporosis Variability 



This study was funded by Warner Chilcott, the bone turnover marker measurements were funded by Immunodiagnostics Systems. Professor Richard Eastell (Academic Unit of Bone Metabolism, The University of Sheffield) is a National Institute for Health Research (NIHR) Senior Investigator. The authors approved the manuscript for publication and vouch for the completeness and accuracy of the data. The funder was involved in the design, but not in the conduct, analysis or reporting of the study.

We are grateful to the data safety monitoring board, the Clinical Trials Research Unit, School of Health and Related Research, for data management and statistical support and the staff of the Academic Unit of Bone Metabolism for conducting the study. We would also like to acknowledge the Lay Advisory Panel for Bone Research and the participants of the TRIO study. We acknowledge the support of the NIHR Clinical Research Facility. The views expressed in this publication are those of the author(s) and not necessarily those of the National Institute for Health Research.

Conflicts of interest

Dr Naylor, Dr Paggiosi, Dr Jacques and Miss Gossiel have no disclosures. Dr N Peel has received speaker’s honoraria and funding to attend educational events from Warner Chilcott, Lilly, Servier, Merck, Roche, GSK and Prostrakan and consultancy fees from Internis Pharma and Lilly. Dr Walsh has received speaker’s honoraria from Lilly and the donation of drug and placebo from Prostrakan. Professor McCloskey has received speaker’s honoraria and/or research funding and/or advisory board funding from Warner Chilcott, Merck, Amgen, GSK, Bayer, Consilient Healthcare, Hologic, Lilly, Novartis, Pfizer, Servier, Wyeth and Roche. Professor Eastell has received grant funding from Warner Chilcott and the National Institute for Health research (NIHR) and consultancy funding from Warner Chilcott, Roche, Immunodiagnostic Systems and Merck.


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2015

Authors and Affiliations

  • K. E. Naylor
    • 1
    Email author
  • R. M. Jacques
    • 2
  • M. Paggiosi
    • 1
  • F. Gossiel
    • 1
  • N. F. A. Peel
    • 3
  • E. V. McCloskey
    • 1
  • J. S. Walsh
    • 1
  • R. Eastell
    • 1
  1. 1.Academic Unit of Bone Metabolism, The Mellanby Centre for Bone ResearchUniversity of SheffieldSheffieldUK
  2. 2.School of Health and Related ResearchUniversity of SheffieldSheffieldUK
  3. 3.Metabolic Bone Centre, Sheffield Teaching Hospitals NHS Foundation TrustNorthern General HospitalSheffieldUK

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