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Multicenter Study
. 2019 Sep;30(9):1755-1765.
doi: 10.1007/s00198-019-05043-1. Epub 2019 Jun 21.

Biochemical markers of bone turnover and risk of incident hip fracture in older women: the Cardiovascular Health Study

D Massera  1 , S Xu  2 , M D Walker  3 , R J Valderrábano  4 , K J Mukamal  5 , J H Ix  6 , D S Siscovick  7 , R P Tracy  8 , J A Robbins  9 , M L Biggs  10 , X Xue  2 , J R Kizer  11
Affiliations
Multicenter Study

Biochemical markers of bone turnover and risk of incident hip fracture in older women: the Cardiovascular Health Study

D Massera et al. Osteoporos Int. 2019 Sep.

Abstract

The relationships of osteocalcin (OC) and C-telopeptide of type I collagen (CTX) with long-term incidence of hip fracture were examined in 1680 post-menopausal women from a population-based study. CTX, but not OC, levels were associated with incident hip fracture in these participants, a relationship characterized by an inverted U-shape.

Introduction: We sought to investigate the relationships of OC, a marker of bone formation, and CTX, a marker of bone resorption, with long-term incidence of hip fracture in older women.

Methods: We included 1680 women from the population-based Cardiovascular Health Study (mean [SD] age 74.5 [5.0] years). The longitudinal association of both markers with incidence of hip fracture was examined using multivariable Cox models.

Results: During a median follow-up of 12.3 years, 288 incident hip fractures occurred. Linear spline analysis did not demonstrate an association between OC levels and incident hip fracture. By contrast, increasing levels of CTX up to the middle-upper range were associated with a significantly greater risk of hip fracture (HR = 1.52 per SD increment, 95% CI = 1.10-2.09), while further increases were associated with a marginally non-significant lower risk (HR = 0.80 per SD increment, 95% CI = 0.63-1.01), after full adjustment for potential confounders. In analyses of quartiles, CTX exhibited a similar inverted U-shaped relationship with incident fracture after adjustment, with a significant association observed only for the comparison of quartile 3 to quartile 1 (HR = 1.63, 95% CI = 1.10-2.43). In a subset with available measures, both OC and CTX were inversely associated with bone mineral density of the hip.

Conclusion: CTX, but not OC, levels were associated with incident hip fracture in post-menopausal women, a relationship characterized by an inverted U-shape. These findings highlight the complex relationship of bone turnover markers with hip fracture risk.

Keywords: Bone turnover markers; Hip fracture risk; Osteoporosis; Postmenopausal women.

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Figures

Figure 1.
Figure 1.
Penalized cubic splines plot for OC (A) and CTX (B) winsorized at the 99% percentile. Linear splines plot for OC (C) and CTX (D) winsorized at the 99% percentile. Models are adjusted for covariates in Model 4.
Figure 1.
Figure 1.
Penalized cubic splines plot for OC (A) and CTX (B) winsorized at the 99% percentile. Linear splines plot for OC (C) and CTX (D) winsorized at the 99% percentile. Models are adjusted for covariates in Model 4.
Figure 1.
Figure 1.
Penalized cubic splines plot for OC (A) and CTX (B) winsorized at the 99% percentile. Linear splines plot for OC (C) and CTX (D) winsorized at the 99% percentile. Models are adjusted for covariates in Model 4.
Figure 1.
Figure 1.
Penalized cubic splines plot for OC (A) and CTX (B) winsorized at the 99% percentile. Linear splines plot for OC (C) and CTX (D) winsorized at the 99% percentile. Models are adjusted for covariates in Model 4.
See this image and copyright information in PMC

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