Bisphosphonate therapy of reflex sympathetic dystrophy syndrome

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Ann Rheum Dis 1997;56:201-204 ( March )
Concise reports

Bisphosphonate therapy of reflex sympathetic dystrophy syndrome
S Adami,a V Fossaluzza, D Gatti,a E Fracassi,a V Bragaa

a COC di Valeggio, University of Verona, Valeggio, Verona, Italy , b Ospedale di Udine, Italy

Correspondence to: Professor S Adami, Ospedale di Valeggio,37067 Valeggio s/M, Verona, Italy.

Accepted for publication 27 November 1996


OBJECTIVE—The reflex sympathetic dystrophy syndrome (RSDS) is a painful limb disorder, for which a consistently effective treatment has not yet been identified. The disease is associated with increased bone resorption and patchy osteoporosis, which might benefit from treatment with bisphosphonates, powerful inhibitors of bone resorption.
METHODS—Twenty patients with RSDS of foot and hand, were randomly assigned to blind administration of either alendronate intravenously (Istituto Gentili, Pisa, Italy) 7.5 mg dissolved in 250 ml saline solution or placebo saline infusions daily for three days. Two weeks later all patients had an identical treatment course with open labelled alendronate (7.5 mg/day for three days), independent from the results of the first blind treatment.
RESULTS—In the patients treated with blind alendronate the diminution in spontaneous pain, tenderness, and swelling (circumference of the affected limb) and the improvement in motion were significantly different from baseline (p<0.001), from those observed within the first two weeks in the control group (p<0.01), and from week 2 to week 4 (p<0.01). In the patients given blind placebo infusions no relevant symptomatic changes were observed after the first two weeks of follow up, but they responded to the open alendronate therapy given afterwards. In 12 patients with RSDS of the hand the ultradistal bone mineral content (BMC) of the affected arm was considerably lower than that of the controlateral arm (mean (SD)) (426(82) mg/cm versus 688(49)). Six weeks after the beginning of the trial BMC rose by 77(12) mg/cm (p<0.001) in the affected arm, but it did not change in the controlateral.
CONCLUSIONS—These results indicate that bisphosphonates should be considered for the treatment of RSDS, producing consistent and rapid remission of the disease.
(Ann Rheum Dis 1997;56:201-204)


The reflex sympathetic dystrophy syndrome (RSDS) is a painful limb disorder characterised by swelling, autonomic dysfunction, patchy osteoporosis and, later, contracture formation. Some of the symptoms might not be present or a particular feature is more apparent; this has been responsible for the myriad of terms applied to partial descriptions and designations of RSDS.1

Various methods of treatment have been tried, including physiotherapy, calcitonin, corticosteroids, sympathetic blockade, non-steroidal anti-inflammatory drugs. The results of these attempts are inconsistent2-4 and they produce slow improvements that cannot be easily distinguished from spontaneous remission.

The bone disease is characterised by increased bone resorption,5 which might benefit from treatment with bisphosphonates, powerful inhibitors of bone resorption.6 In preliminary studies we observed rapid and persistent remission of the symptoms in several patients treated with intravenous clodronate or alendronate. Our preliminary results together with other positive uncontrolled findings with intravenous pamidronate7 8 prompted us to undertake a double blind study in patients with RSDS with intravenous alendronate, a powerful bisphosphonate, which was extensively investigated in our unit for several years.9 10

*** Editor’s Note: This article is very long. If you’d like to view the remainder… please click here for the original version online


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