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

D. Massera, S. Xu, M. D. Walker, R. J. Valderrábano, K. J. Mukamal, J. H. Ix, D. S. Siscovick, R. P. Tracy, J. A. Robbins, M. L. Biggs, X. Xue, Jorge Kizer

Research output: Contribution to journalArticle

Abstract

Summary: 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.

Original languageEnglish (US)
JournalOsteoporosis International
DOIs
StatePublished - Jan 1 2019

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Bone Remodeling
Hip Fractures
Women's Health
Biomarkers
Osteocalcin
Incidence
Bone Resorption
Collagen Type I
Proportional Hazards Models
Osteogenesis
Bone Density
Population
Hip
Health

Keywords

  • Bone turnover markers
  • Hip fracture risk
  • Osteoporosis
  • Postmenopausal women

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Biochemical markers of bone turnover and risk of incident hip fracture in older women : the Cardiovascular Health Study. / Massera, D.; Xu, S.; Walker, M. D.; Valderrábano, R. J.; Mukamal, K. J.; Ix, J. H.; Siscovick, D. S.; Tracy, R. P.; Robbins, J. A.; Biggs, M. L.; Xue, X.; Kizer, Jorge.

In: Osteoporosis International, 01.01.2019.

Research output: Contribution to journalArticle

Massera, D, Xu, S, Walker, MD, Valderrábano, RJ, Mukamal, KJ, Ix, JH, Siscovick, DS, Tracy, RP, Robbins, JA, Biggs, ML, Xue, X & Kizer, J 2019, 'Biochemical markers of bone turnover and risk of incident hip fracture in older women: the Cardiovascular Health Study', Osteoporosis International. https://doi.org/10.1007/s00198-019-05043-1
Massera, D. ; Xu, S. ; Walker, M. D. ; Valderrábano, R. J. ; Mukamal, K. J. ; Ix, J. H. ; Siscovick, D. S. ; Tracy, R. P. ; Robbins, J. A. ; Biggs, M. L. ; Xue, X. ; Kizer, Jorge. / Biochemical markers of bone turnover and risk of incident hip fracture in older women : the Cardiovascular Health Study. In: Osteoporosis International. 2019.
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abstract = "Summary: 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.",
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AU - Xu, S.

AU - Walker, M. D.

AU - Valderrábano, R. J.

AU - Mukamal, K. J.

AU - Ix, J. H.

AU - Siscovick, D. S.

AU - Tracy, R. P.

AU - Robbins, J. A.

AU - Biggs, M. L.

AU - Xue, X.

AU - Kizer, Jorge

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N2 - Summary: 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.

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