Assessment of biochemical markers of bone metabolism in relation to the occurrence of fracture: a retrospective and prospective population-based study of women

Abstract

We have in a population-based setting evaluated biochemical markers of bone metabolism in 328 women, aged 40-80 years, and related it to contents of bone mineral measurements and the retrospective and prospective presence of fracture. The participants were recruited from the city population files. Serum samples for analysis of osteocalcin (Oc), procollagen I carboxy-terminal extension peptide (PICP), and carboxy-terminal telopeptide of type I collagen (ICTP) were taken, and forearm bone mineral content (BMC) was measured by single photon absorptiometry (SPA). Fracture history was recorded, and the information was verified and supplemented from both radiologic and orthopedic files. Five years later the registration of fractures was repeated. At the initial investigation, Oc was 23% lower in women who had sustained a fracture (n = 37) within 6 years before measurement (6.3 +/- 3.6 microgram/l vs 8.2 +/- 4.2 microgram/l (p = 0.006)), after adjusting for age and BMC difference. PICP and ICTP were not different from values in the women without fracture. However, in women aged 70-80 years with a fracture sustained during the previous 6 years, PICP was lower (128 +/- 32 microgram/l vs 144 +/- 34 microgram/l, p = 0.046). Oc and ICTP were significantly correlated to age and BMC (Oc-age r = 0.36, Oc-BMC r = -0.31, ICTP-age r = 0.44, ICTP-BMC r = -0.24). The correlations of PICP were weaker. Prospectively, logistic regression gave an odds ratio (OR) of 1.8 (p = 0.015) for a low PICP and fracture susceptibility, at a change of 1 SD, independent of age and BMC. In the age bracket 70-80, the odds ratio was 2.4 (p = 0.036). The odds ratio for ICTP, independent of age and BMC, was 1.9 (P = 0.043) for 1 SD decrease and subsequent fracture risk. We concluded that women who had sustained at least one recent fracture had an altered bone turnover with decreased bone formation but an unaltered resorption. Women with retrospectively registered fractures also sustained subsequent fractures. A decrease from the mean of the collagen markers PICP and ICTP was associated with an increased risk for future fracture. Utilizing these biochemical markers of bone metabolism in a female population, PICP and ICTP had a similar influence on the risk of future fracture as forearm BMC (OR = 1.6, p = 0.03).