Osteoporosis in Rheumatoid Arthritis: Dangerous Liaisons

Abstract

Osteoporosis has been classically considered a comorbidity of rheumatoid arthritis (RA). However, recent advances in the pathogenesis of osteoporosis in RA have shown a close interplay between cells of the immune system and those involved in bone remodeling, introducing new actors into the classic route in which osteoclast activation is related to the RANK/RANKL/OPG pathway. In fact, the inflammatory state in early stages of RA, mediated by interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-α has the ability to activate and differentiate osteoclasts not only through their relationship with RANKL, but also through the Wnt/DKK1/sclerostin pathway, leading to bone loss. The role of synovial fibroblasts and activated T lymphocytes in the expression of the RANKL system and its connection to bone destruction is also depicted. In addition, autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are other pathogenic mechanisms for the development of bone erosions and systemic osteoporosis in RA, even before the onset of arthritis. The aim of this review is to unravel the relationship between different factors involved in the development of osteoporosis in RA patients, both the classic factors and the most novel, based on the relationship of autoantibodies with bone remodeling. Furthermore, we propose that bone mineral density measured by different techniques may be helpful as a biomarker of severity in early arthritis patients.

Influence of glucocorticoid treatment on trabecular bone score and bone remodeling regulators in early rheumatoid arthritis

“…Generalized osteoporosis is more frequent in RA patients than in general population, and it is associated to an increased fracture risk. The physiopathology of osteoporosis in RA is very complex; particularly, systemic inflammation and glucocorticoid (GC) treatment are two major determinants of generalized bone loss; inflammatory cytokines, such as TNFα, IL6, and IL1 are associated to enhanced osteoclast activity, mainly mediated by receptor activator of nuclear factor kappa-Β ligand (RANKL), while GC-induced bone loss is related to both inhibition of bone formation mediated by the inhibitory effects on Wnt signaling and to an increase of bone resorption associated to the dysregulation of RANKL/osteoprotegerin (OPG) system [ 2 ].…”

Galectin-1: a Potential Biomarker Differentiating Between Early Rheumatoid Arthritis and Spondyloarthritis

“…It is considered a complex disease in which the interaction between genetic, environmental and stochastic factors leads to breakdown of self-recognition resulting in chronic in ltration of the synovial membrane by a wide variety of immune cells. These in ltrating cells cause chronic production of proin ammatory cytokines (tumour necrosis factor [TNF]-α, interleukin [IL]-1β and IL-6) and metalloproteinases that, in absence of treatment, leads to joint destruction due to cartilage degradation and bone erosion (1,2) . Spondyloarthritis (SpA), with an estimated prevalence between 0.4 and 1.9%, is the second most frequent group of IMIDs causing arthritis (3,4).…”

Structural and Functional Changes of Hands and Legs in Early Rheumatoid Arthritis

“…In ERA subjects, arm and leg bone mass changes were not associated with smoking, RF positivity and OPG. Smoking is a risk factor for bone-structure changes [ 34 ], but we assumed that, in ERA, the changes were not so evident yet, due to the short duration of RA disease.…”