[New actors in bone remodelling: a role for the immune system].

Bone metabolism is mainly under estrogenic control. Estrogen induces the expression or activation of transcription factors, leading to phenotypic cellular changes that are critical for the balance between bone formation and resorption. The two activities are linked via the RANK ligand/osteoprotegerin pathway. Fine regulation of bone metabolism and the bone-specific response to estrogen deficiency implies the participation of immune cells, and especially T cells. Indeed, T cells are activated by estrogen deficiency and produce pro-inflammatory cytokines such as TNFalpha, which stimulates osteoclastogenesis both directly and indirectly through the RENKL pathway. Antigen hyperactivity mechanisms may potentiate T cell activation. Other cytokines such as IL-1 and IL-7 also participate in the cross-takl between immune cells and osteoclasts. TGFbeta and IFNgamma modulate these redundant and multiple pathways in a more complex fashion. B cells may also participate, especially after IL-7-induced activation. Although many of these findings remain to be validated in humans, they open up the possibility of new therapeutic approaches, especially given the growing evidence that post-menopausal osteoporosis is associated with a mild chronic inflammatory state.