Effects of tofacitinib in early arthritis-induced bone loss in an adjuvant-induced arthritis rat model

Vidal, Bruno; Cascão, Rita; Finnilä, Mikko A. J.; Lopes, Inês; Glória, Vânia G da; Saarakkala, Simo; Zioupos, Peter; Canhão, Helena; Fonseca, João Eurico

doi:10.1093/rheumatology/kex258

Cited by 28 publications

(23 citation statements)

References 31 publications

(16 reference statements)

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“…[ 20 ] JAK inhibition with tofacitinib suppressed the inflammatory response of rats with adjuvant-induced arthritis, illustrating decreased infiltration of synovial sub-lining and lining layers. [ 21 ] Another study showed that increased synovial lining hyperplasia in a rabbit model of chronic antigen induced arthritis was significantly inhibited by tofacitinib. [ 22 ] Changes in musculoskeletal images after treatment with tofacitinib were investigated using ultrasound.…”

Section: Discussionmentioning

confidence: 99%

The beneficial effect of baricitinib on ultrasound-detected synovial inflammation and bone damage in rheumatoid arthritis

Kim¹,

Jung²,

Kim³

et al. 2021

Medicine

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Section: Discussionmentioning

confidence: 99%

The beneficial effect of baricitinib on ultrasound-detected synovial inflammation and bone damage in rheumatoid arthritis

Kim¹,

Jung²,

Kim³

et al. 2021

Medicine

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“…The most modern and very promising antirheumatic drugs include the JAK inhibitors. Despite no studies having been published on BMD and JAK inhibition, baricitinib has been shown to suppress osteoclast development by inhibiting expression of RANKL on osteoblasts in vitro, while tofacitinib preserved cortical trabecular hardness in rats [106, 107]. The coming era will reveal whether these drugs will serve as potent osteoprotective agents.…”

Section: Disease-modifying Antirheumatic Drugs (Dmards)mentioning

confidence: 99%

Pharmacological Management of Osteoporosis in Rheumatoid Arthritis Patients: A Review of the Literature and Practical Guide

Raterman

Lems

2019

Drugs Aging

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Rheumatoid arthritis (RA) is a chronic disabling disease that is associated with increased localized and generalized osteoporosis (OP). Previous studies estimated that approximately one-third of the RA population experience bone loss. Moreover, RA patients suffer from a doubled fracture incidence depending on several clinical factors, such as disease severity, age, glucocorticoid (GC) use, and immobility. As OP fractures are related to impaired quality of life and increased mortality rates, OP has an enormous impact on global health status. Therefore, there is an urgent need for a holistic approach in daily clinical practice. In other words, both OP-and RA-related factors should be taken into account in treatment guidelines for OP in RA. First, to determine the actual fracture risk, dual-energy X-ray absorptiometry (DXA), including vertebral fracture assessment (VFA) and calculation of the 10-year fracture risk with FRAX ® , should be performed. In case of high fracture risk, calcium and vitamin D should be supplemented alongside anti-osteoporotic treatment. Importantly, RA treatment should be optimal, aiming at low disease activity or remission. Moreover, GC treatment should be at the lowest possible dose. In this way, good fracture risk management will lead to fracture risk reduction in RA patients. This review provides a practical guide for clinicians regarding pharmacological treatment options in RA patients with OP, taking into account both osteoporotic-related factors and factors related to RA.

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“…We selected adjuvant-induced arthritis (AIA) because it mimics the signs and symptoms of human RA, such as the histopathological changes of inflammation, vascular proliferation, and importantly, the progression to joint destruction [18]. The AIA model has been widely used in the development of antirheumatic drugs, including several non-steroid anti-inflammatories, methotrexate [19], and also biologic drugs, including tocilizumab [20] and Jak-inhibitors like tofacitinib [21].…”

Section: Introductionmentioning

confidence: 99%

Exercise Exacerbates the Transcriptional Profile of Hypoxia, Oxidative Stress and Inflammation in Rats with Adjuvant-Induced Arthritis

González-Chávez

Quiñonez-Flores

Espino-Solís

et al. 2019

Cells

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Physical exercise (PE) is recommended for Rheumatoid Arthritis (RA), but the molecular and biological mechanisms that impact the inflammatory process and joint destruction in RA remain unknown. The objective of this study was to evaluate the effect of PE on the histological and transcriptional changes in the joints of adjuvant-induced arthritis (AIA) rat model. AIA rats were subjected to PE on a treadmill for eight weeks. The joints were subjected to histological and microarray analysis. The differentially expressed genes (DEGs) by PE in the arthritic rats were obtained from the microarray. The bioinformatic analysis allowed the association of these genes in biological processes and signaling pathways. PE induced the differential expression of 719 genes. The DEGs were significantly associated with pathogenic mechanisms in RA, including HIF-1, VEGF, PI3-Akt, and Jak-STAT signaling pathways, as well as response to oxidative stress and inflammatory response. At a histological level, PE exacerbated joint inflammatory infiltrate and tissue destruction. The PE exacerbated the stressed joint environment aggravating the inflammatory process, the hypoxia, and the oxidative stress, conditions described as detrimental in the RA joints. Research on the effect of PE on the pathogenesis process of RA is still necessary for animal models and human.

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Effects of tofacitinib in early arthritis-induced bone loss in an adjuvant-induced arthritis rat model

Abstract: Possible reasons for these observations might be related to the mechanism of action of tofacitinib, which leads to direct interactions with bone metabolism, and/or to the kinetics of its bone effects, which might need longer exposure.

Cited by 28 publications

References 31 publications

The beneficial effect of baricitinib on ultrasound-detected synovial inflammation and bone damage in rheumatoid arthritis

The beneficial effect of baricitinib on ultrasound-detected synovial inflammation and bone damage in rheumatoid arthritis

Pharmacological Management of Osteoporosis in Rheumatoid Arthritis Patients: A Review of the Literature and Practical Guide

Exercise Exacerbates the Transcriptional Profile of Hypoxia, Oxidative Stress and Inflammation in Rats with Adjuvant-Induced Arthritis

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