Changes in bone mineral density and fractures during 2 years of low-dose glucocorticoid treatment for rheumatoid arthritis: a systematic literature review and individual participant data meta-analysis

Objective: To evaluate the effects of 2 years of low-dose glucocorticoid (GC) treatment on bone mineral density and fracture risk in patients with rheumatoid arthritis (RA). Methods: We performed a protocolised (dx.doi.org/10.17504/protocols.io.6qpvr3ombvmk/v1) systematic literature review and individual participant data meta-analysis of randomised trials in early and established RA, which compared GCs at ≤7.5 mg prednisone equivalent/day with placebo or standard of care. All patients could receive background treatment with disease-modifying antirheumatic drugs. Changes in lumbar spine and femoral bone density and participants with ≥1 clinical fracture over 2 years in intention-to-treat analyses were coprimary endpoints. Main analyses were based on one-stage models; I² was estimated from two-stage models. Missing data were handled using multiple imputation. Several sensitivity analyses assessed the robustness of our results. Results: Out of 2336 articles, five out of six identified trials provided individual participant data (1112 participants). Greater bone loss was observed at the lumbar spine in the GC compared with the control group (−0.021 g/cm²; 95% CI −0.037 to −0.005; p=0.034; I²=31%) but not at the femur (0.004 g/cm²; 95% CI −0.008 to 0.016; p=0.47; I²=0%). Subgroup analyses did not reveal groups particularly susceptible to GC-induced bone loss at the lumbar spine. 35 participants experienced ≥1 fracture; fracture risk was comparable in both groups. Sensitivity analyses yielded consistent results. Conclusion: Low-dose GCs, used for 2 years to treat RA, lead to bone loss at the lumbar spine but not at the femur.