Potential Mechanisms of Their Deleterious Effects on Bone

Glucocorticoid-induced bone disease is characterized by de-creased bone formation and in situ death of isolated seg-ments of bone (osteonecrosis) suggesting that glucocorticoid excess, the third most common cause of osteoporosis, may affect the birth or death rate of bone cells, thus reducing their numbers. To test this hypothesis, we administered prednisolone to 7-mo-old mice for 27 d and found decreased bone density, serum osteocalcin, and cancellous bone area along with trabecular narrowing. These changes were ac-companied by diminished bone formation and turnover, as determined by histomorphometric analysis of tetracycline-labeled vertebrae, and impaired osteoblastogenesis and os-teoclastogenesis, as determined by ex vivo bone marrow cell cultures. In addition, the mice exhibited a threefold increase in osteoblast apoptosis in vertebrae and showed apoptosis in 28 % of the osteocytes in metaphyseal cortical bone. As in mice, an increase in osteoblast and osteocyte apoptosis was documented in patients with glucocorticoid-induced os-teoporosis. Decreased production of osteoclasts explains the reduction in bone turnover, whereas decreased production and apoptosis of osteoblasts would account for the decline in bone formation and trabecular width. Furthermore, accu-mulation of apoptotic osteocytes may contribute to osteone-crosis. These findings provide evidence that glucocorticoid-induced bone disease arises from changes in the numbers of bone cells.