title: Establishing a reference interval for bone turnover markers in 637 healthy, young, premenopausal women from the United Kingdom, France, Belgium, and the United States.
abstract: Robust reference intervals are needed for the interpretation of bone turnover markers in large phase III fracture trials. The objectives of the study were to (1) estimate reference intervals for serum bone alkaline phosphatase (bone ALP), serum procollagen type I N propeptide (PINP), serum beta cross-linked C-telopeptides of type I collagen (S-betaCTX), and urinary cross-linked N-telopeptides of type I collagen (U-NTX) in healthy young premenopausal women; (2) examine geographical differences on bone turnover markers; and (3) assess factors known to influence bone turnover and test whether these explain any regional differences. We studied 637 eligible women from four countries that participated in the Horizon-PFT study (United Kingdom, France, Belgium, United States). The women were 30-39 yr of age (mean, 34.6 yr), with regular cyclic menses. Subjects completed a medical and lifestyle questionnaire. Two-sided 95% reference intervals were estimated on transformed values and transformed back to the original scale using the proposed methodology of the International Federation of Clinical Chemistry. S-betaCTX was significantly higher in France relative to the United Kingdom (p = 0.01), and PINP was higher in France (p < 0.001) and Belgium (p = 0.02) relative to the United Kingdom and significantly higher in France relative to the United States (p < 0.01) by ANOVA. Overall, one could associate low bone turnover markers with nonsmoking, use of a contraceptive pill, exercise, being close to the time of ovulation, and having high 25-hydroxyvitamin D levels. Countries differed by these characteristics, and once allowed for in the statistical model, any country differences were attenuated or removed.
authors.affiliation: University of Sheffield, Sheffield, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Glover
authors.forename: Martin
authors.initials: M
authors.lastname: Gall
authors.forename: Oliver
authors.initials: O
authors.lastname: Schoenborn-Kellenberger
authors.forename: Michael
authors.initials: M
authors.lastname: Wagener
authors.forename: Patrick
authors.initials: P
authors.lastname: Garnero
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Black
authors.forename: Pierre D
authors.initials: PD
authors.lastname: Delmas
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
mesh_terms: D000328:Adult; D001530:Belgium; D015415:Biomarkers / Q000097:blood* / Q000652:urine*; D016723:Bone Remodeling / Q000502:physiology*; D001862:Bone Resorption / Q000097:blood / Q000652:urine; D003710:Demography; D005260:Female; D005602:France; D006262:Health; D006801:Humans; D015999:Multivariate Analysis; D010012:Osteogenesis / Q000502:physiology; D017697:Premenopause / Q000097:blood* / Q000652:urine*; D012016:Reference Values; D006113:United Kingdom; D014481:United States
chemical_list: D015415:Biomarkers