title: Bone turnover marker reference intervals in young females.
abstract: Background The use of bone turnover markers in clinical practice and research in younger people is limited by the lack of normative data and understanding of common causes of variation in bone turnover marker values in this demographic. To appropriately interpret bone turnover markers, robust reference intervals specific to age, development and sex are necessary. This study aimed to determine reference intervals of bone turnover markers in females aged 16-25 years participating in the Safe-D study. Methods Participants were recruited through social networking site Facebook and were asked to complete an extensive, online questionnaire and attend a site visit. Participants were tested for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and total procollagen type 1 N-propeptide using the Roche Elecsys automated analyser. Reference intervals were determined using the 2.5th to 97.5th percentiles of normalized bone turnover marker values. Results Of 406 participants, 149 were excluded due to medical conditions or medication use (except hormonal contraception) which may affect bone metabolism. In the remaining 257 participants, the reference interval was 230-1000 ng/L for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and 27-131  µg/L for procollagen type 1 N-propeptide. Both marker concentrations were inversely correlated with age and oral contraceptive pill use. Therefore, intervals specific to these variables were calculated. Conclusions We defined robust reference intervals for cross-linking telopeptide of type 1 collagen and procollagen type 1 N-propeptide in young females grouped by age and contraceptive pill use. We examined bone turnover markers' relationship with several lifestyle, clinical and demographic factors. Our normative intervals should aid interpretation of bone turnover markers in young females particularly in those aged 16 to 19 years where reference intervals are currently provisional.
authors: 1 Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.
authors: Emma T
authors: ET
authors: Callegari
authors: 2 Melbourne EpiCentre, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
authors: Alexandra
authors: A
authors: Gorelik
authors: 3 Murdoch Childrens Research Institute, Parkville, VIC, Australia.|4 Royal Women's Hospital, Parkville, VIC, Australia.|5 Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, VIC, Australia.
authors: Suzanne M
authors: SM
authors: Garland
authors: 6 The University of Melbourne, Parkville, VIC, Australia.|7 Melbourne Health Shared Pathology Service, Royal Melbourne Hospital, Parkville, VIC, Australia.
authors: Cherie Y
authors: CY
authors: Chiang
authors: 1 Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.|8 Bone and Mineral Medicine, Royal Melbourne Hospital, Parkville, VIC, Australia.
authors: John D
authors: JD
authors: Wark
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism*; D024043:Collagen Type II / Q000097:blood*; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D020407:Internet; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D012016:Reference Values; D012737:Sex Factors; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; C000590554:C-terminal cross-linking telopeptide of type II collagen, human; D024043:Collagen Type II; D003278:Contraceptives, Oral, Hormonal; D010446:Peptide Fragments; D011347:Procollagen; C042813:procollagen type I carboxy terminal peptide
keywords: Bone turnover markers; CTX; P1NP; Safe-D study; reference intervals; young females