Excess osteoclastic activity is believed to be responsible for the destruction in Charcot neuropathic joint disease. By intervening early in the destructive process, it may be possible to halt the progression toward the devastating bone and joint deformity responsible for morbidity in Charcot feet. This retrospective study evaluated the effects of the bisphosphonate pamidronate on associated signs of Charcot. The 13 study patients (14 infusions) administered pamidronate were compared with 10 control patients who were treated with traditional immobilization methods. Limb temperature and alkaline phosphatase levels were measured as markers of the Charcot process. After pamidronate infusion, limb temperature decreased a mean 2.8 degrees F by 48 hours and 7.4 degrees F by 2 weeks. The alkaline phosphatase levels also decreased an average 53% 2 weeks after infusion. The control group showed no reduction in limb temperature at 48 hours, and had an average limb temperature reduction of 2.3 degrees F at 2 to 3 weeks. This was significantly less than the temperature reduction in the treated group ( P = .008 at 48 hours and P = .001 at 2 weeks). Mean alkaline phosphatase levels declined only 9% in the control group, a significantly smaller decline than in the pamidronate-infusion group ( P = .001). These results suggest that pamidronate may be useful in halting the acute phase of Charcot neuroarthropathy.