Background The role of glucocorticoids (GCs) in the treatment of rheumatoid arthritis (RA) is widely debated. GCs stimulate bone resorption and impair bone formation (1). Inflammatory cytokines also stimulate bone resorption, and patients with RA have a high risk of osteoporosis (OP) and fragility fractures (2). However, in patients with RA, impairment of bone formation by GCs may be counter-balanced by reduced systemic inflammation and increased physical activity.
Objectives This systematic review aims to assess the effect of oral prednisolone and prednisone on bone mineral density (BMD) in patients with RA analyzed in randomized, controlled trials (RCT).
Methods We performed a systematic literature search and identified double-blinded RCTs comparing prednisolone or prednisone with placebo and measuring BMD dual-energy absorptiometry at baseline and at least once thereafter. Two authors independently reviewed references, extracted data and assessed risk of bias. We assessed quality of evidence using the GRADE methodology. Primary outcomes were mean change in BMD at the hip and lumbar spine. Secondary endpoints included RA disease activity and radiographic progression.
Results We identified 7 studies. Studies were comparable regarding study population and intervention. Risk of bias was considered low for BMD outcomes. Data completeness was low in some studies. We found no statistically significant difference in change in BMD from 0 to 24 months neither at the lumbar spine (Standard Mean Difference (SMD) 0.02 (95% CI -0.16, 0.12)) nor at the hip (SMD -0.11 (95% CI -0.25, 0.02)). Disease activity was significantly lower in the GC groups (mean difference in DAS28 -0.32 (95% CI -0.52, -0.11). Concomitant treatment of RA differed between studies, as did OP prophylaxis. However, sensitivity analyses excluding a study with different distribution of OP prophylaxis between groups receiving GCs or placebo did not alter the estimates. Quality of evidence was rated moderate for BMD outcomes.
Conclusions In this group of double-blinded RCT studies we found no difference in change in BMD in patients with RA who received GCs compared to those who received placebo. The interpretation of this is difficult as it challenges the well-established fact that GCs negatively impact BMD. However, our findings suggest that in a population with early RA, followed for two years, the dampening of inflammation as well as increased physical activity may outweigh the inherent effects of GCs. This concurs with our finding of lower disease activity in the groups receiving GCs.
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Disclosure of Interest A.-B. Blavnsfeldt: None declared, M. Thomsen: None declared, S. Tarp: None declared, B. Langdahl Grant/research support from: Novo Nordisk, Eli Lilly and Orkla Health, Speakers bureau: Merck, Amgen, Eli Lilly and UCB, E. Hauge Grant/research support from: AbbVie and Roche, Consultant for: MSD and AbbVie, A. de Thurah: None declared