Reference Intervals for Bone Turnover Markers and Their Association With Incident Hip Fractures in Older Men: The Health In Men Study

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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.

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