Osteoimmunology in rheumatoid and psoriatic arthritis: potential effects of tofacitinib on bone involvement

• Published in: Clinical rheumatology Vol. 39; no. 3; pp. 727 - 736
• Main Authors: Orsolini, Giovanni, Bertoldi, Ilaria, Rossini, Maurizio
• Format: Journal Article
• Language: English
• Published: London Springer London 01-03-2020; Springer Nature B.V
• Subjects: Bone loss; Bone remodeling; Bone turnover; Clinical trials; Cytokines; Homeostasis; Immune system; Inflammation; Janus kinase; Medicine; Medicine & Public Health; Osteoblasts; Osteoclastogenesis; Osteoclasts; Psoriatic arthritis; Review Article; Rheumatoid arthritis; Rheumatology; Signal transduction; Skeleton; Transcription; Osteoimmunology; Tofacitinib; JAK-STAT; Rheumatoid arthritis; Psoriatic arthritis
• ISSN: 0770-3198; 1434-9949
• DOI: 10.1007/s10067-020-04930-x

Chronic inflammation, such as that present in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), leads to aberrations in bone remodeling, which is mediated by several signaling pathways, including the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. In this light, pro-inflammatory cytokines are now clearly implicated in these processes as they can perturb normal bone remodeling through their action on osteoclasts and osteoblasts at both intra- and extra-articular skeletal sites. As a selective inhibitor of JAK1 and JAK3, tofacitinib has the potential to play a role in the management of rheumatic diseases such as RA and PsA. Preclinical studies have demonstrated that tofacitinib can inhibit disturbed osteoclastogenesis in RA, which suggests that targeting the JAK-STAT pathway may help limit bone erosion. Evidence from clinical trials with tofacitinib in RA and PsA is encouraging, as tofacitinib treatment has been shown to decrease articular bone erosion. In this review, the authors summarize current knowledge on the relationship between the immune system and the skeleton before examining the involvement of JAK-STAT signaling in bone homeostasis as well as the available preclinical and clinical evidence on the benefits of tofacitinib on prevention of bone involvement in RA and PsA.
Key Points
•
Chronic inflammation in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) leads to disturbances in bone remodeling
• Bone remodeling is mediated by several signaling pathways, including the JAK-STAT pathway
• Tofacitinib, a selective inhibitor of JAK1 and JAK3, is active in RA and PsA and may help limit systemic bone loss through inhibiting disturbed osteoclastogenesis
• Clinical trials show that tofacitinib reduces articular bone erosion