Prevention of bone mineral density loss in patients with rheumatoid arthritis treated with anti-TNFα therapy

Abstract

This review focuses on recent advances in the effect of anti-TNFα therapy on bone metabolism and bone mineral density (BMD) in rheumatoid arthritis (RA). RA is a chronic disease characterized by infl ammation of the synovial joint, cartilage degradation, and subsequent bone destruction. Bone damage is often manifested as erosions, localized juxta-articular bone loss, or generalized bone loss. Thus, blockade of TNFa not only serves to block infl ammation, but also halts the erosive nature of RA and generalized/localized juxta-articular bone loss. Here, we review recent fi ndings showing that anti-TNFa therapy is also effective on halting systemic bone loss. In vitro, TNFa reduces osteoblast activity and increases osteoclast activity through RANKL-RANK pathway. In arthritis animal models, an imbalance between bone formation and resorption is observed. In humans, this coupling of destruction is restored by anti-TNFα therapy early on, but only for a few months. Thus, anti-TNFα prevents the BMD loss in RA patients. In summary, TNFa blockade is not only able to prevent joint destruction, but it is also able to prevent bone loss in RA patients. Future studies are needed to address if TNFa blockers have an effect on bone fractures.

Could Biomarkers of Bone, Cartilage or Synovium Turnover Be Used for Relapse Prediction in Rheumatoid Arthritis Patients?

“…This suggests a strong effect of anti-TNF on local subchondral bone related to joint inflammation. Since TNF blockers already showed a reduction of the bone biomarker unbalance, TNF blockers also demonstrated a positive effect on bone mineral density in RA patients with or without a clinical response as observed at the joint level [ 61 ]. Serum RANKL was decreased during anti-TNF therapy [ 62 ].…”

TNFα rs1800629 Polymorphism and Response to Anti-TNFα Treatment in Behçet Syndrome: Data from an Italian Cohort Study

“…In the present investigation, the distribution of rs1800629 genotypes showed a higher percentage of non-responder patients carrying the A allele (GA genotype) in agreement with previous data about the SNP role in influencing drug response. These studies reported that patients with inflammatory diseases having the AA genotype may be less likely to achieve improvements in clinical manifestations compared with patients carrying the GG genotype when treated with anti- TNFα drugs [ 4 , 20 , 24 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ].…”

“…In this study, we also performed an explorative analysis on the distribution of non-responder patients when our cohort was stratified for anti- TNFα drugs, and we found a lower response in the case of Infliximab, also depending on the higher number of patients treated with this drug. The role of genetic factors for the lack of therapeutic response to anti- TNFα agents was previously suggested in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), juvenile idiopathic arthritis (JIA), and Sjögren’s syndrome, as well as in inflammatory bowel disease, in particular Crohn’s disease (CD), but also in Wegener’s granulomatosis and sarcoidosis [ 4 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ].…”

Ultrasound-driven BaTiO 3 nanorobots patching immunologic barrier to cure chronic rheumatoid arthritis

“…TNF-α is a key inflammatory factor in RA [32]. Antagonists targeting TNF-α have been developed clinically and have achieved good curative effects in the treatment of RA [32]. It is demonstrated that the US applied on empty gel slightly alleviates the inflammation, but it shows no significant effect, while Gel+NR+US significantly reduces TNF-α and brings nearly back to the healthy level (Figs.…”

“…In RA, inflammatory factors are mainly secreted by M1 macrophages and pro-inflammatory FLS. TNF-α is a key inflammatory factor in RA [32]. Antagonists targeting TNF-α have been developed clinically and have achieved good curative effects in the treatment of RA [32].…”