Pathogenesis of bone loss due to estrogen deficiency : Relationship between increased B-lymphopoiesis and bone resorption.

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Estrogen deficiency caused by ovariectomy (OVX) results in a marked bone loss due to stimulated osteoclastic bone resorption. Recent studies indicated the possible involvement of bone-resorbing cytokines such as interleukin (lL) -1, IL-6 and tumor necrosis factor alpha in bone loss due to estrogen deficiency.In this study, we found that OVX selectively stimulated B-lymphopoiesis which resulted in a marked accumulation of pre-B cells in mouse bone marrow. Like estrogen deficiency, androgen deficiency also stimulated B-lymphopoiesis in mouse bone marrow prior to bone loss. To examine the possible relationship between stimulated B-lymphopoiesis and bone loss, female mice were treated with IL-7, which stimulates B-lymphopoiesis in bone marrow. The increased B-lymphopoiesis induced by IL-7 resulted in a marked bone loss by stimulating bone resorption in mice with intact ovarian function. The extent of bone loss was similar to that in OVX mice, measured by bone mineral density (BMD) and muCT analysis. A higher bone mass was detected in IL-7 receptor-knockout mice in which B-lymphopoiesis was markedly reduced. The results obtained in this stuby show that the perturbation of B-lymphopoiesis in bone marrow is closely linked to the change in bone mass. Increased B-lymphopoiesis due to sex steroid deficiency may be involved in the mechanism of stimulated bone resorption.