BACKGROUND: Several epidemiological studies have shown an association between bone mineral density (BMD) and risk of breast cancer in postmenopausal women, but it remains unknown whether bone turnover is associated with increased risk of cancer. The aim of this study was to investigate if markers of bone formation and resorption are associated with increased risk of cancer.

MATERIAL AND METHODS: The study population included 5855 postmenopausal Danish women enrolled in the Prospective Epidemiologic Risk Factor (PERF) study. Cancer diagnosis was obtained from the Danish Cancer Registry. Baseline spine, femur, and whole-body BMD were evaluated by DXA-scanners. Baseline bone turnover (CTX-1 and osteocalcin) were measured in serum. Multivariate Cox analysis was performed with 3, 6 and 12 years of follow-up. All continuous variables were transformed into z-score for the cox analyses.

RESULTS: 252 developed cancer after 3 years, 462 developed cancer after 6 years, and 881 developed cancer with 12 years of follow-up. CTX-1, osteocalcin and spine BMD were all predictors of cancer at all time points (3 years of follow-up: Spine BMD, HR = 1.20, p = 0.003; CTX-1, HR = 0.82, p = 0.005; osteocalcin, HR = 0.75, p \u003c 0.001). After adjusting for cancer risk factors and other bone measures CTX-1 and osteocalcin remained independent predictors of cancer (3 years of follow-up: CTX-1, HR = 0.82, p = 0.02; osteocalcin, HR = 0.75, p = 0.002).

CONCLUSIONS: We found that levels of the bone turnover markers CTX-1 and osteocalcin were inversely associated with risk of cancer independent of BMD and other known cancer risk factors in postmenopausal women.

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