High-bone-turnover osteoporosis and aortic calcification in Opg knockout mice

Bone turnover is regulated by local concentrations of cytokines such as osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL). To explore the in vivo biological function of Opg and the mechanism of osteoporosis due to deficiency of Opg, Opg knockout mice have been generated through homologous recombination. Opg(-/-) mice exhibit a sharply decrease in bone density and strength as expected. The number of osteoclasts in Qpg(-/-) mice significantly increases. Morphologically, osteoclasts appear more cuboidal in shape in Opg(-/-) mice than those of wt mice, suggesting that active osteoclastogenesis occurs in the absence of Qpg. In consistent with this finding, an increase of osteoblast activity was also observed with accelerated mineral accumulation rate by histomorphometric measurement and elevated serum alkaline phosphatase activity (ALP) in Opg(-/-) mice. Interestingly, more than 50% of 2-month-old Opg(-/-) mice manifest medial calcification of aorta with comparable serum concentrations of calcium and phosphor-us to wt mice. In conclusion, Opg(-/-) mice have a high-bone-turnover type osteoporosis. The aortic calcification in Opg(-/-) mice is not due to abnormality of calcium and phosphorus metabolism. The mechanism underlying aortic calcification in Opg(-/-) mice needs to be further investigated.