Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone.

TLDR

Glucocorticoid excess, the third most common cause of osteoporosis, leads to bone disease marked by reduced bone formation and osteonecrosis, implying that glucocorticoids alter bone cell birth and death rates. The authors treated 7‑month‑old mice with prednisolone for 27 days, measuring bone density, serum osteocalcin, and cancellous bone area, all of which decreased and showed trabecular narrowing. The treatment caused diminished bone formation and turnover, impaired osteoblastogenesis and osteoclastogenesis, a threefold rise in osteoblast apoptosis, 28 % osteocyte apoptosis, and similar apoptosis in patients, demonstrating that glucocorticoid‑induced bone disease stems from loss of bone cells and increased apoptosis, potentially contributing to osteonecrosis.

Abstract

Glucocorticoid-induced bone disease is characterized by decreased bone formation and in situ death of isolated segments 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 accompanied by diminished bone formation and turnover, as determined by histomorphometric analysis of tetracycline-labeled vertebrae, and impaired osteoblastogenesis and osteoclastogenesis, 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 osteoporosis. 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, accumulation of apoptotic osteocytes may contribute to osteonecrosis. These findings provide evidence that glucocorticoid-induced bone disease arises from changes in the numbers of bone cells.