Bone Resorption and Osteoporotic Fractures in Elderly Men: The Dubbo Osteoporosis Epidemiology Study

Abstract

Among the potential risk factors for fragility fractures, bone turnover is considered an important determinant. In a case-cohort control study of 151 elderly men followed prospectively over 6.3 years, high bone resorption as assessed by S-ICTP was associated with increased risk of osteoporotic fracture, independent of BMD. Combining measurements of BMD and bone turnover may improve fracture prediction in elderly men. Approximately one-third of osteoporotic fractures occur in men. Among the potential risk factors for fragility fractures, bone turnover is considered an important determinant. The association between fracture risk and rates of bone turnover has not been well established in men. We examined this relationship in elderly community-dwelling men. This case-cohort control study included 50 men with incident low-trauma fractures (cases; age, 72.3 +/- 6.7 years) and 101 men without fracture (controls; age, 70.4 +/- 4.1 years), who have been prospectively followed in the Dubbo Osteoporosis Epidemiology Study for a median of 6.3 years (range, 2-13 years). BMD at the lumbar spine (LSBMD) and at the femoral neck (FNBMD) and markers of bone turnover were measured at baseline. Bone resorption was assessed by measuring nonfasting serum concentrations of the carboxyterminal cross-linked telopeptide of type I collagen (S-ICTP) and of a linear octapeptide derived from the carboxyterminal type I collagen telopeptide (S-CTX). Bone formation was assessed by measuring the serum levels of the aminoterminal propeptide of type I procollagen (S-PINP). Men with subsequent fractures had lower BMD at baseline, both at the femoral neck and the spine, lower dietary calcium intake, and higher S-ICTP levels than age-and weight-matched controls. Smoking habits, S-CTX, and S-PINP did not differ between groups. Based on univariate regression analyses, S-ICTP (relative risk [RR] for 1 SD change: 1.8; 95% CI, 1.4-2.3) and serum creatinine levels (RR, 1.4; 95% CI, 1.1-1.7) were associated with increased risk of fracture. In multivariate regression analyses, S-ICTP (RR, 1.4; 95% CI, 1.0-1.9) and FNBMD (RR, 1.8; 95% CI, 1.4-2.3) remained independent predictors of fracture risk. Men within the highest quartile of S-ICTP had a 2.8-fold (95% CI 1.4-5.4) increased risk of fracture compared with those in the lowest quartile. The incidence of osteoporotic fractures was 10 times higher in men with high S-ICTP and low FNBMD compared with men with low S-ICTP and high FNBMD. Of the fracture risk in the population, 20% was attributable to high S-ICTP and low FNBMD, and S-ICTP contributed 17% to this increased risk. High bone resorption is associated with an increased risk of osteoporotic fracture in elderly men, independent of BMD. Combining measurements of BMD and bone turnover, which correlated with fracture in this cohort, could improve fracture risk prediction in elderly men.