The effect of biologic agents on bone homeostasis in chronic inflammatory rheumatic diseases

Abstract

Osteoporosis (OP) and increased fracture risk are widely observed comorbidities in chronic inflammatory rheumatic diseases (CIRDs). Improved knowledge of the immune/inflammatory pathways, which characterise the pathophysiology of rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA), such as ankylosing spondylitis (AS) and psoriatic arthritis (PsA), have provided the link between inflammation and bone loss, via a complex network of bone cells, T and B cells, pro-inflammatory cytokines such as TNF-α, IL1, IL6, IL17, IL23, costimulator molecules, signalling pathways including both RANKL/RANK/OPG and Wnt signallings. The complex osteoimmunologic network in CIRDs suggested that the powerful anti-inflammatory activity of biologic drugs, beyond the control of the disease, was likely to reduce OP and fracture risk. In this respect, the available data deriving from clinical and experimental studies, conducted with TNF-α, IL6 and IL1 blockers, and B and T cell therapies, have demonstrated a beneficial effect on bone mineral density (BMD) and/or bone turnover markers (BTs). However, whether these drugs are able to positively influence also fracture risk has not yet been established, since the data available are sparse and inconclusive. Thus, systemic bone loss and increased fracture rates still remain relevant comorbidities that should be considered for screening and prevention, and proper treatment of patients with CIRDs despite the biologic therapy.