Impact of sustaining SDAI remission for preventing incident of bone fragility fracture in patient with rheumatoid arthritis

Abstract

It is well known that rheumatoid arthritis (RA) has a determinant risk for bone fragility, and patient with RA has a seriously high risk for bone fragility fracture (BFF). On the other hand, the BFF risks in the patient with RA owe disease activity. 3 We hypothesised that if disease activity is successfully controlled and achieved clinical remission, adverse effects on bone metabolism would be minimised, resulting in a lower incidence of BFF. We therefore statistically examined whether there was a difference in the incidence of BFF between patients with and without RA who achieved clinical remission. Patients who matched the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria under the T2T since August 2010, have been treating RA and were measured bone mineral density (BMD) with dualenergy Xray absorptiometry, were recruited. The initial target of therapy is the attainment of remission with a Simplified Disease Activity Index (SDAI) within 6 months of initiation. The primary outcome was incident BFF. Followup started at BMD measurement (baseline) and continued until the development of the first fracture or censoring at death, loss to followup or end of the study. KaplanMeier survival curves were determined for incident BFF incidence up to the last observation. Risks for the incidence of BFF were classified as RA specific and general candidate. In general candidate, comorbidities that might affect the incidence of BFF, such as lifestylerelated diseases, and increased ability to fall or a disorder were included. Candidate risk factors are shown in table 1. Each evidence was evaluated using Cox regression analysis to identify significantly higher risk factors within 5% in univariate models and to evaluate using multivariate model. In a preliminary study with our dataset, we examined the incidence of bone erosion score (BE) and BFF, and BE correlated with the incidence of BMD and prBFF, but not with the incidence of new BFF using linear and binary logistic regression analyses (online supplemental table 1). We compared the incidence of BFF between RA and nonRA groups, in setting as a control group consisting of patients without RA and matched for general candidate risk factors. Furtherly, mean 10year probability of major osteoporotic fracture (MOF) calculated with fracture assessment tool (FRAX) in the two groups was compared using MannWhitney U test. Patients in the RA group were classified according to the mean SDAI score ≤3.3 or >3.3 (RArem and RAnonrem). The incidence of BFF among the nonRA, the RArem and the RAnonrem groups were compared using KaplanMeier survival curve analysis. Factors with significantly higher risk ratios in the RA group were higher anticyclic citrullinated polypeptide antibodies (ACPA) titre, higher mean SDAI score, lower mean SDAI remission rate, presence of lifestylerelated diseases (LSD), presence of Fallability, glucocorticoid steroid (GCS) administration, lower Tscore and presence of prevalent fracture (prBFF). Among these, ACPA, mean SDAI remission rate and prBFF showed a significantly higher risk ratio in the multivariate model (figure 1A). The incidence rate of BFF was significantly lower in the RArem group than in the RAnonrem and the nonRA group, whereas no significant difference between the nonRA and the RAnonrem groups as well as HRs were shown (figure 1B,C). These trends were also shown when SDAI was replaced by the clinical disease activity index (CDAI) (online supplemental figure 1). The 10year MOF in both of the RA groups were significantly higher than in the nonRA group (figure 1D). These results suggest that disease activity control is the most important factor in the prevention of BFF. The incidence of fractures increases in patients with RA in whom SDAI or CDAI remission is difficult to achieve, or unless it is maintained above a certain level during SDAI or CDAI remission. Higher SDAI or CDAI remission rate is desirable to prevent BFF.