Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial

Aims/hypothesis. The management of charcot neuroarthropathy. a severe disab ling condition in diabetic patients with peripheral neuropathy, is currentl y inadequate with no specific pharmacological treatment available. We under took a double-blind randomised controlled trial to study the effect of pami dronate, a bisphosphonate, in the management of acute diabetic Charcot neur oarthropathy. Methods. Altogether 39 diabetic patients with active Charcot neuroarthropat hy from four centres in England were randomised in a double-blind placebo-c ontrolled trial. Patients received a single infusion of 90 mg of pamidronat e or placebo (saline). Foot temperatures, symptoms and markers of bone turn over (bone specific alkaline phosphatase and deoxypyridinoline crosslinks) were measured over the 12 months., in 10 visits. All patients also had stan dard treatment of the Charcot foot. Results. Mean age of the study group (59% Type II (non-insulin-dependent) d iabetes mellitus) was 56.3 +/- 10.2 years. The mean temperature difference between active and control groups was 3.6 +/- 1.7 degreesC and 3.3 +/- 1.4 degreesC. respectively. There was a fall in temperature of the affected foo t in both groups after 2 weeks with a further reduction in temperature in t he active group at 4 weeks (active and placebo vs baseline, p = 0.001; p = 0.01, respectively), but no difference was seen between groups. An improvem ent in symptoms was seen in the active group compared with the placebo grou p (p < 0.001). Reduction in bone turnover (means +/- SEM) was greater in th e active than in the control group. Urinary deoxypyridinoline in the pamidr onate treated group fell to 4.4 +/- 0.4 nmol/mmol creatinine at 4 weeks com pared with 7.1 +/- 1.0 in the placebo group (p = 0.01) and bone-specific al kaline phosphatase fell to 14.1 +/- 1.2 u/1 compared with 18.6 +/- 1.6 u/1 after 4 weeks, respectively (p = 0.03). Conclusion/interpretation. The bisphosphonate, pamidronate, given as a sing le dose leads to a reduction in bone turnover, symptoms and disease activit y in diabetic patients with active Charcot neuroarthropathy.