University of Debrecen Faculty of Medicine, Department of Rheumatology, Hungary; Department of Rheumatology, School of Medicine, St. Vincent's Hospital, Dublin, Ireland.
University of Debrecen Faculty of Medicine, Department of Rheumatology, Hungary.
Autoimmun Rev. 2017 Mar;16(3):313-320. doi: 10.1016/j.autrev.2017.01.014. Epub 2017 Jan 31.
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.
炎症性关节炎，如类风湿关节炎（RA）和脊柱关节炎（SpA），与局部骨吸收和/或形成以及全身性骨质疏松症有关。全身炎症可能是关节炎导致骨质流失的主要驱动因素。在 RA 和外周型 SpA 中，RANK-RANKL-OPG 网络参与骨吸收，而在中轴型 SpA 中，Wnt-β-catenin 轴及其抑制剂（DKK-1、骨硬化蛋白）最为相关。包括生物制剂和小分子酪氨酸激酶抑制剂在内的靶向治疗可能会干扰炎症性骨代谢。这些化合物大多数能够减缓关节炎的放射学进展和骨质疏松症。在非放射学 SpA 的早期病例中，可能存在一个机会窗口，可以防止连接骨形成。靶向治疗不能增加 DKK-1 和骨硬化蛋白的产生，这可能解释了 TNF 抑制剂在 SpA 中阻止连接骨形成的疗效缺乏。需要进一步的临床试验来更好地了解靶向治疗的骨骼作用。
