Background/Purpose:
The role of glucocorticoids (GCs) in the treatment of rheumatoid arthritis (RA) is widely debated. GCs stimulate bone resorption and impair bone formation. Inflammatory cytokines also stimulate bone resorption, and patients with RA have a high risk of osteoporosis (OP) and fragility fractures. However, in patients with both RA and OP, impairment of bone formation by GCs may be counter-balanced by reduced systemic inflammation and increased physical activity.
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. Prednisolone or prednisone was the intervention. BMD was measured by dual-energy absorptiometry at baseline and at least once thereafter. Two authors independently reviewed references, extracted data and assessed risk of bias. We used Cochrane’s risk of bias tool and assessed overall quality of evidence using the GRADE methodology. Primary outcomes were mean change in BMD over time. 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. Overall quality was rated high for BMD and disease activity outcomes and low for radiographic progression. Standard mean difference (SMD) in change in BMD from 0 to 24 months was -0.02 (95%CI -0.16, 0.12) at the lumbar spine and -0.11 (95% CI -0.25, 0.02) at the hip (Figures 1 and 2). Concomitant treatment of RA differed between studies, as did osteoporosis prophylaxis. However, sensitivity analyses excluding studies where anti-OP therapy was used yielded no difference in the estimate in the lumbar spine, but a small, not clinically relevant difference in the hip.

Conclusion:
In this group of RCT studies we found no difference in change in BMD in patients with RA who received GCs compared to placebo. The interpretation of this is difficult as it challenges the well-established fact that GCs negatively impact BMD through low calcium uptake and altered sex hormones. However, our findings suggest that in a population where BMD is affected by systemic inflammation, the dampening of the inflammation as well as increased physical activity may outweigh the inherent negative effects on bone when GCs are administered. 

Figure 1: Meta-analysis of change in BMD at the lumbar spine

Figure 2: Meta-analysis of change in BMD at the hip