Purpose:
RA is associated with increased fracture risk due to systemic bone loss. While new DMARD therapy over the past 30 years has improved disease control, its impact on BMD remains controversial. This meta-analysis investigates the effects of csDMARDs, bDMARDs, and tsDMARDs on BMD in RA patients, accounting for disease activity and glucocorticoid exposure.
Methodology:
MEDLINE, EMBASE, Cochrane, and Scopus were searched for studies published after 1980 that assessed longitudinal changes in BMD at the femoral neck and lumbar spine in RA patients on modern pharmacotherapy therapy. The analysis stratified data based on DMARD class, baseline disease activity score, glucocorticoid use, and anti-osteoporotic therapy. Random-effect modelling was employed to estimate pooled BMD changes and multivariable analysis to control for confounding effects of steroids and anti-osteoporotic therapy.
Results:
Among 46 studies (n = 11,578), the pooled BMD change was +0.18% (95% CI: -2.33% to 2.68%) at the lumbar spine and -0.46% (95% CI: -1.17% to 0.25%) at the femoral neck. No significant difference was observed between csDMARDs and b/tsDMARDs in preserving BMD. Higher baseline DAS correlated with greater BMD loss (p = 0.009), whereas ΔDAS had no effect. GCS use >5 mg/day negatively influenced LSBMD (p = 0.006) but had no impact on FNBMD. The presence of anti-osteoporotic therapy was associated with improved BMD.
Conclusion:
Short-term improvements in disease activity did not lead to improvements in BMD; however, long-term low disease activity did, emphasising the importance of long-term disease control in maintaining bone health in RA patients. Modern pharmacotherapy appears to stabilise BMD in RA patients, with neither csDMARD or later therapy proving superior. Strategies to improve bone health in RA patients should continue to emphasise long-term disease control, GCS minimisation, and use of anti-osteoporotic therapies, while further research evaluates the role of specific DMARD.