title: Reference intervals for bone turnover markers and their association with incident hip fractures in older men: the Health in Men study.
abstract: BACKGROUND
  Reference intervals for bone turnover markers (BTMs) and relationships between BTM and fracture risk in older men are not well characterized.
  
  
  OBJECTIVE
  The purpose of this article was to determine the reference intervals for serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), N-terminal propeptide of type I collagen (PINP), and collagen type I C-terminal cross-linked telopeptide (CTX-I) in healthy older men and to explore factors associated with BTMs, including hip fracture risk.
  
  
  METHODS
  We studied a population-based cohort of 4248 men aged 70 to 89 years, 4008 of whom had serum samples available for analysis.
  
  
  METHODS
  Morning blood samples were collected at the study visit. Comorbid conditions were assessed by questionnaire. The reference sample comprised fasting men (n = 298, median age 75.3 years [interquartile range 73.9-78.1 years) reporting excellent or very good health, without a history of diabetes, cardiovascular disease, cancer, depression, or dementia.
  
  
  METHODS
  Serum tOC, PINP, and CTX-I were estimated by automated electrochemiluminescence immunoassays, ucOC was estimated using hydroxyapatite binding, and incident hip fractures were captured from hospital admission data.
  
  
  RESULTS
  Reference intervals for tOC, ucOC, PINP, and CTX-I were 10.2 to 41.0, 5.2 to 21.9, 18 to 129 μg/L, and 117 to 740 ng/L, respectively. tOC, ucOC and CTX-I were associated with hip fracture incidence, but after adjustment for other risk factors only tOC remained significantly associated.
  
  
  CONCLUSIONS
  Reference intervals for BTMs in older men have been defined. tOC may be more informative for hip fracture risk in older men than CTX-I and PINP. Further studies are needed to clarify the utility of BTM reference intervals in the management of aging men at risk of osteoporosis.
authors.affiliation: School of Pathology and Laboratory Medicine (S.A.P.C., J.P.B., S.D.V.) and School of Medicine and Pharmacology (S.A.P.C., L.M., L.F., B.B.Y.), University of Western Australia, Crawley, Western Australia 6009, Australia; Biochemistry Department (S.A.P.C., E.B., J.P.B., S.D.V.), PathWest Laboratory Medicine, Nedlands, 6009 Western Australia, Australia; Department of Medicine (P.R.E.), Monash University, Clayton, Victoria 3146, Australia; Queensland Research Centre for Peripheral Vascular Disease (J.G.), School of Medicine and Dentistry, James Cook University, Townsville 4811, Queensland; Department of Vascular and Endovascular Surgery (J.G.), The Townsville Hospital, Townsville, Queensland 4810, Australia; and Department of Endocrinology and Diabetes (B.B.Y.), Fremantle Hospital, Fremantle 6160, Western Australia, Australia.
authors.forename: S A Paul
authors.initials: SA
authors.lastname: Chubb
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Byrnes
authors.forename: Laurens
authors.initials: L
authors.lastname: Manning
authors.forename: John P
authors.initials: JP
authors.lastname: Beilby
authors.forename: Peter R
authors.initials: PR
authors.lastname: Ebeling
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Vasikaran
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
authors.forename: Leon
authors.initials: L
authors.lastname: Flicker
authors.forename: Bu B
authors.initials: BB
authors.lastname: Yeap
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling; D024042:Collagen Type I / Q000097:blood*; D006306:Health Surveys; D006620:Hip Fractures / Q000097:blood* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D015675:Osteocalcin / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D010455:Peptides / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D012016:Reference Values; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin