Osteoporosis in the view of osteoimmunology: common feature underlined by different pathogenic mechanisms

Osteoporosis is a skeletal disorder characterized by low bone mineral density and microarchitectural changes with increased susceptibility to fractures, resulting in significant morbidity and mortality. Although it predominantly affects postmenopausal women, it is now well known that systemic bone loss is a common underlying feature of different metabolic, endocrine and inflammatory diseases. Investigations of osteoporosis as a complication of chronic inflammatory conditions revealed immune mechanisms behind the increased osteoclast bone resorption and impaired osteoblast bone formation. This concept was particularly emphasized after the research field of osteoimmunology emerged, focusing on the interaction between the immune system and bone. It is increasingly becoming evident that immune cells and mediators critically regulate osteoclast and osteoblast development, function and coupling activity. Among other mediators, receptor activator of nuclear factor-kB ligand (RANKL), receptor activator of nuclear factor-kB (RANK) and soluble decoy receptor osteoprotegerin (OPG) form a key functional link between the immune system and bone, regulating both osteoclast formation and activity as well as immune cell functions. Excessive production of inflammatory mediators exerts autocrine, paracrine and endocrine signaling effects on bone remodeling with the net increase in bone resorption locally, in diseases primarily affecting joints, bones or surrounding tissues, and systemically, causing osteoporosis in various chronic inflammatory diseases. This brief review particularly focuses on bone pathology in rheumatoid arthritis, as one of the most extensively studied conditions accompanied by local and systemic inflammation-induced bone loss