Strong prediction of fractures among older adults by the ratio of carboxylated to total serum osteocalcin.

We examined serum total osteocalcin (TOC), carboxylated osteocalcin (COC), and their ratio (COC/TOC) by one-step two-site immunofluorescent assays in 87% (n = 792) of all home-dwelling persons of 70 years or older living in a defined area in northern Finland. Other baseline subject-related risk factors of fractures were assessed by postal questionnaires, interviews, clinical examinations, and tests. During a 5-year follow-up period, all falls and fractures (n = 106) were recorded by regular phone calls and by examining all the medical records yearly. Serum TOC and COC concentrations increased with advancing age and were higher in women than in men, but corresponding differences were not found in the case of COC/TOC. The adjusted relative risk of fracture was elevated in association with low (< or =-1 SD from the mean) COC; hazard ratio (HR, 95% CI) 2.00 (1.20-3.36) and low COC/TOC; HR 5.32 (3.26-8.68), the relative risk being highest in the population older than 80 years; and HR 7.02 (2.42-20.39). The predictive value of low COC/TOC lasted 3 years. The multivariable-adjusted relative risk of hip fracture (n = 26) in regard to low COC/TOC ratio was 3.49 (1.12-10.86), as compared with the persons who did not suffer hip fractures. Our results suggest that serum COC concentrations and, more strongly, COC/TOC, predict the occurrence of fractures in older community-dwelling adults. The risk of fracture associated with low COC/TOC equals the hip fracture risk previously verified for concomitant high serum undercarboxylated OC concentrations and low bone mineral density.