The immune system has been recognized as one of the most important regulators of bone turnover and its de-regulation is implicated in several bone diseases as post-menopausal osteoporosis and inflammatory bone loss. The study of the relationship between immune system and bone metabolism is generally indicated under the term osteoimmunology, the vast majority of these studies have been performed in animal models, however several data have been confirmed also in humans. Post-menopausal osteoporosis (PMO) is the most frequent metabolic skeletal disease, it is characterized by reduced bone mineral density and micro architectural deterioration of bone with increased fracture risk. In PMO the uncoupling between osteoblast (OB)-mediated bone formation and osteoclast (OC)-mediated bone resorption results in bone loss. Estrogen deficiency is the main driver of post-menopausal bone loss: during estrogen depletion OCs formation and activity are increased, this increase is partially mediated trough the effect of estrogen deficiency on immune system. Estrogen deficiency influences immune response, in particular T cells, become more active and able to produce inflammatory and pro-osteoclastogenic cytokines as TNFα and RANKL. Despite of some inverse reports, the main body of literature firmly supports the essential role of activated T cells in regulating bone loss induced by estrogen deficiency, both in animal models and in humans. We recently demonstrated that immune system, and in particular T cells mediate the effect of PTH on bone turnover, in particular we demonstrated that during treatment with teriparatide for PMO T cells mediates osteoblastogenesis trough the production of Wnt10b, whereas primary hyperparathyroidism do not increase this molecule. Moreover we demonstrated that, both in mice and humans, continuous infusion of PTH and primary hyperparathyroidism increases the differentiation of T helper (TH) cells in TH17. These cells are responsible for increased OCs formation and activity both in inflammatory diseases and in PMO. In conclusion The interactions between immune system and bone are complex and play significant role in both health and disease, nevertheless not all the pathways discovered in animal models have been fully demonstrated in humans, and several challenging questions remains unsolved.
20 - 23 May 2017
European Society of Endocrinology