Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs Do Not Arrest Bone Loss in Patients With Rheumatoid Arthritis: A Long-Term Multicenter Observational Study.

Abstract

Osteoporosis causes fractures that further increase the disease burden of rheumatoid arthritis (RA); however, osteoporosis treatment rates remain low. Although several studies have reported that biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) can prevent or improve osteoporosis in RA, our large-scale, real-world study showed that one-year b/tsDMARDs use did not arrest osteoporosis progression. This study aimed to examine longer-term changes in bone mineral density (BMD). BMD was observed for up to five years in patients receiving b/tsDMARDs for active RA. The primary endpoint was change in BMD (T score), and the secondary endpoint was change in T score-related factors. In total, 797 patients (antiosteoporosis-, n = 645; antiosteoporosis+, n = 152) were included, with a median 3.1-year follow-up (2,489 patient-years). Clinical Disease Activity Index (CDAI) improved in both groups (antiosteoporosis- 26.0 to 6.6; antiosteoporosis+ 24.4 to 6.8). T scores decreased significantly in the femoral neck and radius in the antiosteoporosis- group but not in the antiosteoporosis+ group (antiosteoporosis-: mean change -0.11 to -0.33, both P < 0.001; antiosteoporosis+ -0.01 to -0.10, P = 0.830 and 0.071, respectively). Overall, 460 patients (58%) experienced a decrease in T score. A high baseline T score correlated with a subsequent decrease, whereas longer osteoporosis treatment duration correlated with an increase. Unexpectedly, the duration of b/tsDMARD use and mean CDAI during observation were not associated with BMD maintenance. Even when RA activity was controlled with b/tsDMARDs, BMD still decreased. This study emphasizes the importance of considering osteoporosis as an independent aspect of RA, beyond inflammation control.