Osteoimmunology and Beyond

Abstract

ObjectiveOsteoimmunology investigates interactions between skeleton and immune system. In the light of recent discoveries in this field, a new reading register of osteoporosis is actually emerging, in which bone and immune cells are strictly interconnected. Osteoporosis could therefore be considered a chronic immune mediated disease which shares with other age related disorders a common inflammatory background. Here, we highlight these recent discoveries and the new landscape that is emerging.MethodExtensive literature search in PubMed central.ResultsWhile the inflammatory nature of osteoporosis has been clearly recognized, other interesting aspects of osteoimmunology are currently emerging. In addition, mounting evidence indicates that the immunoskeletal interface is involved in the regulation of important body functions beyond bone remodeling. Bone cells take part with cells of the immune system in various immunological functions, configuring a real expanded immune system, and are therefore variously involved not only as target but also as main actors in various pathological conditions affecting primarily the immune system, such as autoimmunity and immune deficiencies, as well as in aging, menopause and other diseases sharing an inflammatory background.ConclusionThe review highlights the complexity of interwoven pathways and shared mechanisms of the crosstalk between the immune and bone systems. More interestingly, the interdisciplinary field of osteoimmunology is now expanding beyond bone and immune cells, defining new homeostatic networks in which other organs and systems are functionally interconnected. Therefore, the correct skeletal integrity maintenance may be also relevant to other functions outside its involvement in bone mineral homeostasis, hemopoiesis and immunity.

Paradoxical side effects of bisphosphonates on the skeleton: What do we know and what can we do?

“…Teriparatide PTH is an endocrine regulator for calcium and phosphorus metabolism (Ginaldi & Martinis, 2016). Low doses of PTH stimulate bone formation through osteoblast activation by Wnt signaling (increase in β-catenin levels and LRP6 signaling in osteoblast, and decrease in sclerostin production) (Ginaldi & Martinis, 2016;Williams & O'Ryan, 2015).…”

The alarmin S100A9 hampers osteoclast differentiation from human circulating precursors by reducing the expression of RANK

“…A close relation between bone turnover and the immune system has been previously shown by Ginaldi et al (14). Various proinflammatory cytokines, such as TNF-a and IL-1b, have been associated with increased bone turnover by affecting osteoclast differentiation and function (4,(15)(16)(17).…”

Elucidating the Mechanism(s) Underlying Antipsychotic- and Antidepressant-Mediated Fractures

“…Shared mediators intervene in the regulation of the function of both bone and nervous system cells. The existence of these integrated systems partially explains, at the biological level, the interference between neuropsychiatric disorders and bone remodelling, as well as the osteoresorptive effect of some antipsychotic and antidepressant drugs 49,50 . Given the large patient population which is prescribed these medications and the enhanced risk for vulnerable populations such as children and the elderly, prescribing practices for off-label use as well as patient monitoring for metabolic and fracture risk should be carefully evaluated.…”