Treatment of severe, recalcitrant reflex sympathetic dystrophy: assessment of efficacy and safety of the second generation bisphosphonate pamidronate.

The objective of the study was to assess the efficacy and the safety of pamidronate (APD) in recalcitrant reflex sympathetic dystrophy (RSD). Ten women and 13 men with a mean (+/-standard deviation, SD) age of 44 +/- 11 years were included. The involved sites were: the ankle (n = 10), the foot (n = 7), the hand (n = 3), the hip (n = 2), the knee (n = 2) and the shoulder (n = 1). Some patients had more than one site involved. Mean (+/-SD) duration of the disease was 15 +/- 13 months. RSD was in pseudo-inflammatory phase in 16 patients and in ischaemic phase in 7 patients. RSD was post-traumatic in 17 cases; 11 patients have been previously treated unsuccessfully by sympathetic blockades. APD was administered intravenously (perfusion) to a dose of 1 mg/kg/day during 3, 2 or one day. Fourteen patients received APD during 3 consecutive days whereas 7 patients have been treated during 2 consecutive days and 2 patients only during 1 day mainly due to adverse events. Efficacy was assessed by a decrease of pain = visual analogic scale (VAS, 0-100 mm) and verbal scale (PVS, range 0-3). Moreover, the patient and the observer have estimated the efficacy of the treatment on a verbal scale (EVS, range 0-3). Measurements of these parameters were performed immediately before the treatment and 7, 30, 60 and 90 days later. The maximum duration after treatment was 9 months. A significant decrease of VAS and PVS were observed between D0 and D30 (p = 0.0002 and p = 0.0002 respectively), D0 and D60 (p = 0.0004, p = 0.0004 respectively), and D0 and D90 (p = 0.00003, p = 0.0001 respectively). A significant increase of EVS was only observed between D0 and D90 (p = 0.03). Adverse events were noted in 14 patients: transient fever (n = 6), venous inflammation (n = 2), transient symptomless hypocalcaemia (n = 3), nausea (n = 1), lymphopenia (n = 1), transient hypertension (n = 1). These results suggest an efficacy of APD in recalcitrant RSD. Double-blind placebo controlled studies are required to back up these preliminary results.