Effects of targeted therapies on the bone in arthritides.
Inflammatory arthritides, such as rheumatoid arthritis (RA) and spondyloarthritides (SpA) have been associated with both localized bone resorption and/or formation, and generalized osteoporosis. Systemic inflammation may be the major driver for bone loss in arthritis. In RA and peripheral SpA the RANK-RANKL-OPG network is involved in bone resorption, while in axial SpA the Wnt-β-catenin axis and its inhibitors (DKK-1, sclerostin) are the most relevant. Targeted therapies including biologics and small molecule tyrosine kinase inhibitors may interfere with inflammatory bone metabolism. Most of these compounds are able to slow down radiographic progression and osteoporosis in arthritides. In very early cases of non-radiological SpA, there may be a window of opportunity allowing to prevent syndesmophyte formation. The inability of targeted therapies to increase the production of DKK-1 and sclerostin may explain the lack of efficacy of TNF inhibitors to halt syndesmophyte formation in SpA. Further clinical trials are needed to better understand the bone effects of targeted therapies.
University of Debrecen Faculty of Medicine, Department of Rheumatology, Hungary; Department of Rheumatology, School of Medicine, St. Vincent's Hospital, Dublin, Ireland.
Ágnes
Á
Szentpétery
University of Debrecen Faculty of Medicine, Department of Rheumatology, Hungary.
Ágnes
Á
Horváth
University of Debrecen Faculty of Medicine, Department of Rheumatology, Hungary.
Katalin
K
Gulyás
University of Debrecen Faculty of Medicine, Department of Rheumatology, Hungary.
Zsófia
Z
Pethö
University of Debrecen Faculty of Medicine, Department of Laboratory Medicine, Debrecen, Hungary.
Harjit Pal
HP
Bhattoa
University of Debrecen Faculty of Medicine, Department of Rheumatology, Hungary.
Sándor
S
Szántó
University of Debrecen Faculty of Medicine, Department of Rheumatology, Hungary.
Gabriella
G
Szücs
Department of Rheumatology, School of Medicine, St. Vincent's Hospital, Dublin, Ireland.
Oliver
O
FitzGerald
Department of Internal Medicine III and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Germany.
Georg
G
Schett
University of Debrecen Faculty of Medicine, Department of Rheumatology, Hungary. Electronic address: szekanecz.zoltan@med.unideb.hu.
Zoltán
Z
Szekanecz
D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D025241:Spondylarthritis / Q000188:drug therapy*
Biologics; Bone loss; DKK-1; Erosion; JAK inhibitors; Osteoporosis; Osteoprotegerin; RANKL; Rheumatoid arthritis; Sclerostin; Spondyloarthritis; Syndesmophyte