title: Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Academic Unit of Bone Metabolism, The Mellanby Centre for Bone Research, University of Sheffield, Herries Road, Sheffield, South Yorkshire, S5 7AU, UK. k.e.naylor@sheffield.ac.uk.
authors.forename: K E
authors.initials: KE
authors.lastname: Naylor
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Jacques
authors.affiliation: Academic Unit of Bone Metabolism, The Mellanby Centre for Bone Research, University of Sheffield, Herries Road, Sheffield, South Yorkshire, S5 7AU, UK.
authors.forename: M
authors.initials: M
authors.lastname: Paggiosi
authors.affiliation: Academic Unit of Bone Metabolism, The Mellanby Centre for Bone Research, University of Sheffield, Herries Road, Sheffield, South Yorkshire, S5 7AU, UK.
authors.forename: F
authors.initials: F
authors.lastname: Gossiel
authors.affiliation: Metabolic Bone Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital, Sheffield, UK.
authors.forename: N F A
authors.initials: NF
authors.lastname: Peel
authors.affiliation: Academic Unit of Bone Metabolism, The Mellanby Centre for Bone Research, University of Sheffield, Herries Road, Sheffield, South Yorkshire, S5 7AU, UK.
authors.forename: E V
authors.initials: EV
authors.lastname: McCloskey
authors.affiliation: Academic Unit of Bone Metabolism, The Mellanby Centre for Bone Research, University of Sheffield, Herries Road, Sheffield, South Yorkshire, S5 7AU, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Walsh
authors.affiliation: Academic Unit of Bone Metabolism, The Mellanby Centre for Bone Research, University of Sheffield, Herries Road, Sheffield, South Yorkshire, S5 7AU, UK.
authors.forename: R
authors.initials: R
authors.lastname: Eastell
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077557:Ibandronic Acid; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology; D017697:Premenopause / Q000097:blood; D012016:Reference Values; D000068296:Risedronic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000068296:Risedronic Acid; D000077557:Ibandronic Acid; D019386:Alendronate
keywords: Bisphosphonate; Bone turnover markers; Postmenopausal osteoporosis; Variability