Metabolic shifts in ratio of ucOcn to cOcn toward bone resorption contribute to age-dependent bone loss in male mice

The study of the senile osteoporosis in men still lags significantly behind that in women. The changes of protein molecule levels and their relationships with bone loss remain poorly understood. In the present study, we used C57BL/6J male mice at ages from 3 to 24 mo to delineate the mechanisms of aging effects on bone loss. We used the microcomputed tomography, mechanical testing, histomorphometry assays, and detection of serum levels of undercarboxylated osteocalcin (ucOcn) and carboxylated osteocalcin (cOcn) to assess bone mass changes and their relationships with the ratios of ucOcn-to-cOcn in mice from different age groups. The results showed that mouse trabecular bone mass reduced gradually with age, whereas cortical bone loss and mechanical property changes mostly occurred in advanced age. Our findings further demonstrated that the increase in osteoclast activity and the decrease in osteoblast function were significantly corelated with blood levels of ucOcn and cOcn, respectively. The dynamic metabolic changes of ucOcn to cOcn ratio were correlated with age-dependent bone loss in mice. In summary, metabolic shifts in the ratio of ucOcn to cOcn toward bone resorption from young adult to elderly mice contribute to the pathogenesis of age-related bone loss. Simultaneously monitoring blood ratios of ucOcn-to-cOcn may be useful to predict the status of bone mass in vivo.<b>NEW & NOTEWORTHY</b> To our knowledge, our finding in this study shows for the first time that metabolic shifts in ratio of ucOcn to cOcn toward bone resorption are markedly correlated with age-dependent bone loss in male mice. These findings for the effects of aging on bone loss will assist in studying the pathogenesis of human type II osteoporosis.