Background:Rheumatoid arthritis (RA) is associated with poor bone mineral density (BMD). We designed the current study owing to the lack of long-term prospective studies regarding whether a high disease activity leads to increased bone loss.Methods:We have continually enrolled patients with RA. According to the average disease activity score in 28 joints based on the erythrocyte sedimentation rate (DAS28-ESR) during follow-up, the patients were classified into remission, low disease activity, and moderate or high disease activity groups. Patients were examined with dual-energy X-ray absorptiometry at baseline and after 3 years of follow-up. BMD changes were compared among the groups.Results:We have studied 477 patients. Overall BMD was significantly reduced from baseline to the 3-year follow-up (p < 0.05). After stratifying according to the time-averaged DAS28-ESR levels and use of anti-osteoporosis treatment (AOT), the BMD values of the femur and spine significantly increased in patients in the remission group with AOT. The BMD changes of different DAS28-ESR patients were further compared using the generalized estimation equation model. For the patients on AOT, the negative change in femoral BMD values of the moderate or high activity group was significant when compared with the remission group with positive BMD changes (regression coefficient, –0.038; 95% confidence interval, –0.055 to –0.021).Conclusion:For RA patients, if remission is achieved, AOT can better improve BMD, especially in the femur. In addition, moderate or high disease activity will lead to significant bone loss; therefore, disease activity must be actively controlled.