Postmenopausal osteoporosis is a heterogeneous disorder begins after natural or surgical menopause and leads to fracture within 15～20 years from cessation of the ovarian function.Estrogen depletion during menopause results in significant loss of calcium in the urine consistent with an imbalance remodeling sequence.The discovery of estrogen receptor in osteoblasts,their stromal precursors and osteoclasts suggests that a direct effect on bone or bone marrow cells may be involved.It can block osteoclasteogenesis.Estrogen can also have indirect effect on bone by modulating the production of one or more of cytokines.these cytokines have complex and overlapping effects on bone formation and resorption such as IL 1,TNF,M CSF,IL 6, IL 11 and TGF β.Several lines of evidence derived from in vivo animal models and human studies support a critical role for cytokine in regulation of postmenopausal bone loss.In postmenopausal women circulating monocytic production of IL 1 and TNF is elevated in comparison with premenopausal women.IL 1 and TNF markedly stimulate osteoclast formation by both stimulation of osteoclast and precursor proliferation.They also can increase the secretion of M CSF and IL 6,which can induce proliferation and differentiation of hemopoetic osteoclast precursors.
Estrogen has been shown to decrease the steadystate expression of IL 1 and TNF mRNA in monocytes and then it can reduce the bone resorption.TGF b is a potent osteoblast mitogen.It can reduce the life span of osteoclasts through promoting apoptosis.Estrogen can increase the steady state level of TGF b mRNA and release of TGF b protein.So estrogen has a positive effect on bone formation. Cytokine inhibitors such as IL 1ra(IL 1 receptor antagonist) and TNFbp(TNF binding protein) have been isolated and sequenced.Rats treated with recombinant TNFbp and IL 1ra immediately after ovariectomey showed no bone loss,phenomenon identical to what is observed after ovariectomy in rats administered estrogen.The cytokine inhibitors may be used in the treatment of postmenopausal osteoporosis in future.