Background:We previously reported that the prevalence of sarcopenia was 28% in patients with rheumatoid arthritis (RA) in a cohort study 1. RA patients have a high risk of falls and fractures 2. However, the predictors of falls and fractures in RA patients are not known.Objectives:Whether evaluation of muscle mass and function at baseline could predict falls and fractures during four-year follow-up was investigated.Methods:The four-year follow-up data from a prospective, observational study (CHIKARA study: Correlation researcH of sarcopenIa, sKeletal muscle and disease Activity in Rheumatoid Arthritis) were used. Muscle mass was measured by a body impedance analyzer, and leg muscle mass was calculated. The leg muscle score (max: 100, min: 0) reflected the ratio of leg muscle mass to overall weight. Grip strength as an indicator of muscle function was evaluated using a digital, hand-held, isokinetic dynamometer. The correlations between muscle mass or function and falls or fractures were analyzed by survival rates and Cox hazard ratios. Leg muscle mass and grip strength were investigated by receiver operating characteristic (ROC) curve analysis for correlations with falls or fractures.Results:A total of 100 RA patients (female: 78%, mean age: 66.1 years) were enrolled; 35 patients had falls, and 19 patients had fractures during the four-year follow-up. The leg muscle score, grip strength, age, and fractures at baseline were significantly correlated with falls. The cut-off values of the leg muscle score and grip strength were calculated to be 84.5 points (sensitivity: 0.79, specificity: 0.43) and 15.9 kg (sensitivity: 0.56, specificity: 0.70), respectively, by ROC curve analysis. The patients were divided into four groups by their leg muscle scores and grip strength; the numbers of falls and fractures are shown in Table 1 for each group. The fall-free survival rate was significantly lower in the group with low leg muscle score and low grip strength (35.3%) than in the other groups (P=0.002) (Figure 1). The hazard ratio for the both low group was significantly increased, 3.6-fold (95%CI: 1.1-11.5), compared to that in the both high group.Table 1.Numbers of falls and fractures by category of leg muscle score and grip strengthLG + GS+(n=34)LG - GS+(n=12)LG + GS-(n=37)LG - GS-(n=17)P value*Falls, N6515110.010Fractures, N34660.072LG+: leg muscle score >84.5 points, GS+: grip strength >15.9kg, LG-: leg muscle score ≤84.5 points, GS+: grip strength ≤15.9kg*: compared in four groups by Kruskal-Walls test.Figure 1.Fall-free survival rate in the four groupsConclusion:RA patients with both low leg muscle score and low grip strength at baseline were at high risk for falls during the four-year follow-up period. Evaluation of muscle mass and function can predict falls in RA patients.References:[1]Tada, M., Yamada, Y., Mandai, K. & Hidaka, N. Matrix metalloprotease 3 is associated with sarcopenia in rheumatoid arthritis - results from the CHIKARA study. Int J Rheum Dis21, 1962-1969, doi:10.1111/1756-185X.13335 (2018).[2]van Staa, T. P., Geusens, P., Bijlsma, J. W., Leufkens, H. G. & Cooper, C. Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum54, 3104-3112, doi:10.1002/art.22117 (2006).Disclosure of Interests:None declared
Discovery of small molecules targeting the tandem tudor domain of the epigenetic factor UHRF1 using fragment-based ligand discovery
