High level of serum undercarboxylated osteocalcin in patients with incident fractures during bisphosphonate treatment.

To evaluate the possible interaction of metabolic effects in the mevalonate pathway between amino-bisphosphonates (amino-BP) and vitamin K, the serum level of undercarboxylated osteocalcin (ucOC) was measured in amino-BP users in relationship to incident fracture occurrence. Osteoporotic patients (mean age, 70.7 +/- 9.1 years; n = 231) treated with alendronate or risedronate were followed for 3.4 +/- 2.1 years, and observations regarding the presence or absence of incident fractures in their vertebrae were made based on vertebral X-ray films every year. During the observation period, new fractures were found in a total of 71 patients (incident vertebral fracture, n = 61; the remaining 10 patients had long bone fractures). The baseline data of the patients with incident fractures indicated that incident fractures are more likely to occur in older patients who have a higher number of prevalent vertebral fractures and lower baseline lumbar bone mineral density (LBMD) as compared to patients without incident fractures. There was no significant difference in the changes of LBMD and urinary excretion of NTX after treatment. On the other hand, the serum level of ucOC in patients with incident fractures and with amino-BP treatment was significantly higher (2.75 +/- 0.19 ng/ml) than that in patients without incident fractures and with amino-BP treatment (2.28 +/- 0.13 ng/ml) (P = 0.038). These results indicate that older age, a greater number of prevalent fractures and higher ucOC levels, and lower LBMD are risks for incident fractures despite use of amino-BP. The time-dependent incident fracture rate was higher in accordance with an increase in the number of risk items (P < 0.001 in log-rank and Wilcoxon tests). In conclusion, measurement of undercarboxylated osteocalcin may be useful for assessing fracture risk in patients receiving amino-BP treatment.