The Rising Era of “Immunoporosis”: Role of Immune System in the Pathophysiology of Osteoporosis

Abstract

Discoveries in the last few years have emphasized the existence of an enormous breadth of communication between bone and the immune system in maintaining skeletal homeostasis. Originally, the discovery of various factors was assigned to the immune system viz. interleukin (IL)-6, IL-10, IL-17, tumor necrosis factor (TNF)-α, receptor activator of nuclear factor kappa B ligand (RANKL), nuclear factor of activated T cells (NFATc1), etc., but now these factors have also been shown to have a significant impact on osteoblasts (OBs) and osteoclasts (OCs) biology. These discoveries led to an alteration in the approach for the treatment of several bone pathologies including osteoporosis. Osteoporosis is an inflammatory bone anomaly affecting more than 500 million people globally. In 2018, to highlight the importance of the immune system in the pathophysiology of osteoporosis, our group coined the term “immunoporosis”. In the present review, we exhaustively revisit the characteristics, mechanism of action, and function of both innate and adaptive immune cells with the goal of understanding the potential of immune cells in osteoporosis. We also highlight the Immunoporotic role of gut microbiota (GM) for the treatment and management of osteoporosis. Importantly, we further discuss whether an immune cell-based strategy to treat and manage osteoporosis is feasible and relevant in clinical settings.

Integrated Bioinformatic Analysis of the Shared Molecular Mechanisms Between Osteoporosis and Atherosclerosis

“…In adaptive immune system, T cells are major players of it and the results of our enrichment analysis were also involved in T H 1, T H 2, and T H 17 cell differentiation and inflammatory factor-related pathways. Previous studies have found that T H 1 and T H 2 cells inhibit osteoclastogenesis via secreting IFN-g and IL-4 cytokines and thus act as an osteoprotective role (41). Lower serum levels of IFN-g and IL-4 cytokines in postmenopausal osteoporotic patients further suggest its osteoprotective role (42).…”

Exercise and Exercise Mimetics for the Treatment of Musculoskeletal Disorders

“…In aging, changes in hormones and other circulating factors, together with inactivity, move the balance towards bone resorption, impairing bone structure, eventually resulting in osteoporosis and fractures [8]. Despite preclinical results attributed for long to endocrine mechanisms, in particular estrogen and vitamin D deficiency and reduced dietary intake that have a central role in postmenopausal osteoporosis, in the last years the active role played by the immune system has emerged [13]. In this context, several studies focused the attention on the interplay between osteoclasts and immune cells, able to trigger bone destruction in inflammatory diseases, demonstrating the influence of common molecules of both immune and bone systems, including cytokines, chemokines and signaling factors [14].…”

Immunoporosis: Role of immune system in the pathophysiology of different types of osteoporosis

“…The term “immunoporosis” was proposed and coined by Srivastava et al. (2018, 2022) to establish a novel field emphasizing the role of immune cells in the development of osteoporosis ( 8 , 9 ).…”

“…Recently, accumulating evidence demonstrated that both innate and adaptive immune cells contribute to the pathogenesis of osteoporosis by producing pro-inflammatory mediators (6,7). The term "immunoporosis" was proposed and coined by Srivastava et al (2018Srivastava et al ( , 2022 to establish a novel field emphasizing the role of immune cells in the development of osteoporosis (8,9). This review will present the relationship between immune cells and bone remodeling.…”

“…Classical theories hold that osteoporosis is essentially a bone remodeling disorder caused by estrogen deficiency/aging (primary osteoporosis) or secondary to diseases/drugs (secondary osteoporosis). However, with the in-depth understanding of the intricate nexus between both bone and the immune system in recent decades, the novel field of "Immunoporosis" was proposed by Srivastava et al (2018Srivastava et al ( , 2022, which delineated and characterized the growing importance of immune cells in osteoporosis. This review aimed to summarize the response of the immune system (immune cells and inflammatory factors) in different types of osteoporosis.…”