Background Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that most typically occurs in middle-age women. Generalized osteoporosis is a common and important comorbidity in RA. The increased fracture risk in RA patients is independent of areal bone mineral density (aBMD) by dual energy x-ray absorptiometry (DXA).
Objectives The objectives of this study is to compare the effects of denosumab and alendronate on cortical and trabecular microarchitecture at the distal radius in RA patients with low BMD using high-resolution peripheral quantitative compute tomography (HR-pQCT).
Methods This was a 6 month open-label randomized controlled trial. Forty Chinese RA females were randomized into 2 groups, receiving either subcutaneous injection of denosumab 60mg every 6 months or oral alendronate 70mg weekly. All patients were given calcium supplement 1500mg daily and 1 tablet of multi-vitamin daily. Efficacy assessment, including bone geometry, volumetric BMD (vBMD) and cortical and trabecular microarchitecture, was performed by HR-pQCT at the distal radius at baseline, month 3 and month 6.
Results The study cohort involved 40 RA females with average age of 57.8 years and average disease duration of 12.4 years. At baseline, there was no significant difference in age, body weight, body height and aBMD at femoral neck, total hip and lumbar spine between the two groups.
At 6 months, there was significant increase in cortical area in both groups with no significant group-wise difference (denosumab vs. alendronate: 2.30% vs 2.83%, p>0.05). Trabecular area showed significant decrease in denosumab group (-0.54%, p<0.0001) but showed maintenance in alendronate group (-0.48%, p=0.071). Within each group, there was significant increase in integral and cortical vBMD and these increases were comparable between the two groups (integral vBMD: 2.3% vs. 2.2%, p>0.05; cortical vBMD: 0.61% vs. 0.98%, p>0.05). Changes of trabecular vBMD over time were not significant but appeared to be larger in denosumab group (3.37% vs. 1.51%, p>0.05). Trabecular microarchitecture did not change significantly over the study period. Cortical thickness increased (1.75%, p=0.04) and cortical porosity decreased (-10.5%, p=0.010) significantly in alendronate group but showed maintenance in denosumab group (1.44% and -6.71%, respectively, both p>0.05). There was no group-wise difference in change of cortical thickness and porosity.
Conclusions During a 6-months treatment, in female RA patients with low bone mass, both denosumab and alendronate have demonstrated significant and comparable effect on improving bone density and cortical bone macro- and microarchitecture. However, these two treatment appeared to have differing effects on bone compartments. Denosumab seems to produce larger increase in trabecular vBMD while alendronate larger improvement in cortical microarchitecture.
Cohen SB, et al. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum 2008;58:1299-309.
Disclosure of Interest None declared