Calcified Tissue International

, Volume 94, Issue 5, pp 560–567 | Cite as

A Meta-Analysis of Reference Markers of Bone Turnover for Prediction of Fracture

  • Helena JohanssonEmail author
  • Anders Odén
  • John A. Kanis
  • Eugene V. McCloskey
  • Howard A. Morris
  • Cyrus Cooper
  • Samuel Vasikaran
  • IFCC-IOF Joint Working Group on Standardisation of Biochemical Markers of Bone Turnover
Original Research


The aim of this report was to summarize the clinical performance of two reference bone turnover markers (BTMs) in the prediction of fracture risk. We used an updated systematic review to examine the performance characteristics of serum procollagen type I N propeptide (s-PINP) and serum C-terminal cross-linking telopeptide of type I collagen (s-CTX) in fracture risk prediction in untreated individuals in prospective cohort studies. We excluded cross-sectional studies. Ten potentially eligible publications were identified and six included in the meta-analysis. There was a significant association between s-PINP and the risk of fracture. The hazard ratio per SD increase in s-PINP (gradient of risk [GR]) was 1.23 (95 % CI 1.09–1.39) for men and women combined unadjusted for bone mineral density. There was also a significant association between s-CTX and risk of fracture, GR = 1.18 (95 % CI 1.05–1.34) unadjusted for bone mineral density. For the outcome of hip fracture, the association between s-CTX and risk of fracture was slightly higher, 1.23 (95 % CI 1.04–1.47). Thus, there is a modest but significant association between BTMs and risk of future fractures.


Marker of bone turnover Fracture Serum procollagen type I N propeptide Serum carboxy-terminal cross-linking telopeptide of type I collagen Meta-analysis 



H. J. was supported by an ESCEO-AMGEN Osteoporosis Fellowship Award. Amgen had no input into the analysis plan or the writing of this report.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Helena Johansson
    • 1
    Email author
  • Anders Odén
    • 1
  • John A. Kanis
    • 1
  • Eugene V. McCloskey
    • 1
  • Howard A. Morris
    • 2
  • Cyrus Cooper
    • 3
    • 4
  • Samuel Vasikaran
    • 5
    • 6
  • IFCC-IOF Joint Working Group on Standardisation of Biochemical Markers of Bone Turnover
  1. 1.WHO Collaborating Centre for Metabolic Bone DiseasesUniversity of Sheffield Medical SchoolSheffieldUK
  2. 2.School of Pharmacy and Medical SciencesUniversity of South AustraliaAdelaideAustralia
  3. 3.The MRC Epidemiology Resource CentreSouthampton General Hospital, University of SouthamptonSouthamptonUK
  4. 4.NIHR Musculoskeletal Biomedical Research Unit, Institute of Musculoskeletal SciencesUniversity of OxfordOxfordUK
  5. 5.Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory MedicineRoyal Perth HospitalPerthAustralia
  6. 6.School of Pathology and Laboratory MedicineUniversity of Western AustraliaNedlandsAustralia

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