Reference intervals for bone turnover markers and their association with incident hip fractures in older men: the Health in Men study

J Clin Endocrinol Metab. 2015 Jan;100(1):90-9. doi: 10.1210/jc.2014-2646.

Abstract

Context: 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.

Participants and setting: We studied a population-based cohort of 4248 men aged 70 to 89 years, 4008 of whom had serum samples available for analysis.

Interventions: 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.

Main outcome measures: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Bone Remodeling*
  • Collagen Type I / blood*
  • Health Surveys
  • Hip Fractures / blood*
  • Hip Fractures / epidemiology
  • Humans
  • Incidence
  • Male
  • Osteocalcin / blood*
  • Peptide Fragments / blood*
  • Peptides / blood*
  • Procollagen / blood*
  • Reference Values
  • Risk Factors

Substances

  • Biomarkers
  • Collagen Type I
  • Peptide Fragments
  • Peptides
  • Procollagen
  • collagen type I trimeric cross-linked peptide
  • procollagen Type I N-terminal peptide
  • Osteocalcin