Bisphosphonates inhibit osteoclast activity, which is central to the development of bone damage in rheumatoid arthritis (RA). The aim of this study was to assess whether treatment with zoledronic acid, compared with placebo, could achieve a ≥50% reduction in the development of new erosions on magnetic resonance imaging (MRI) in patients with early RA.

In this proof‐of‐concept study, 39 patients with early RA and clinical synovitis of the hand/wrist were randomized to receive infusions with either zoledronic acid (5 mg) or placebo, administered at baseline and week 13. Patients in both groups received methotrexate (MTX) at a dosage of 7.5–20 mg/week. MRI and plain radiography were performed at baseline and week 26.

At week 26, the mean ± SD change in MRI hand and wrist erosions was 61% lower in the zoledronic acid group compared with the placebo group (0.9 ± 1.63 versus 2.3 ± 3.09; P = 0.176). The mean ± SD increase in the number of hand and wrist bones with erosions was 0.3 ± 0.75 for zoledronic acid compared with 1.4 ± 1.77 for placebo (P = 0.029). The proportion of patients in whom new MRI‐visualized bone edema developed was smaller in the zoledronic acid group compared with the placebo group (33% versus 58%; P = 0.121). The zoledronic acid group had a mean change in the number of radiographic erosions of 0.1 compared with 0.5 for the placebo group (P = 0.677). The safety profile of zoledronic acid was similar to that of placebo.

The results of this study suggest a structural benefit associated with zoledronic acid therapy in patients with RA, as demonstrated by consistent results in structural end points in favor of zoledronic acid plus MTX compared with MTX alone.