A double-blind placebo-controlled study of intravenous clodronate for prevention of steroid-induced bone loss in inflammatory bowel disease

Abstract

Background & aims: Osteoporosis is common in patients with inflammatory bowel disease (IBD). Corticosteroids induce a rapid and important bone loss. Clinical trials have shown oral bisphosphonates to effectively prevent steroid-induced bone loss. However, patients with IBD have been excluded from most of these studies because of potential digestive adverse events. Clodronate is a non-amino-bisphosphonate available in intravenous form without expected digestive (as oral bisphosphonates) or proinflammatory (as amine bisphosphonates) side effects. Our aim was to assess the efficacy of intravenous clodronate in preventing steroid-induced bone loss.

Methods: A 12-month, double-blind, randomized, placebo-controlled trial was conducted in IBD patients beginning a steroid therapy. Sixty-seven patients (median disease duration, 38 mo; range, 1-240 mo) were randomized to receive one infusion per 3 months of either intravenous clodronate (900 mg, n = 33) or placebo. All the patients received calcium (1 g/day) and vitamin D (800 IU/day). The main outcome was the change in lumbar bone mineral density (BMD) between baseline and 1 year. Secondary outcomes included change in femoral neck BMD and adverse events.

Results: After 1 year, there was no change in BMD in the clodronate group, neither at the spine (-0.2%, not significant) nor at the femoral neck (2.3%, NS). In contrast, there was a significant decrease in lumbar spine (-2.0%, P = .0018) and femoral neck (-1.7%, P = .045) BMD in the placebo group. Tolerance to treatment was good.

Conclusions: Intravenous clodronate is effective in the prevention of bone loss induced by steroids in patients with IBD.