Disodium etidronate in the prevention of heterotopic ossification following spinal cord injury (preliminary report)

Abstract

Heterotopic ossification is a frequent complication following spinal cord injury with 16 per cent to 53 per cent of patients developing varying degrees of pathologic ossification. The diphosphonates are known to block the transformation of amorphous calcium phosphate into crystalline hydroxyapatite. Therefore, one of the diphosphonates, disodium etidronate (generic name of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was selected fro clinical trials to study the effectiveness of EHDP in preventing heterotopic ossification following spinal cord injury. In a double-blind, clinical study of 149 spinal cord injury patients, disodium etidronate has proven its effectiveness in the prevention of heterotopic ossification. The extent of heterotopic ossification development as measured by the total heterotopic ossification X-ray grade was significantly less in EHDP-treated patients compared to placebo-treated patients (P less than 0-05). For maximal effectiveness, EHDP treatment must be started before the onset of the pathological process initiating the development of heterotopicossification. Further studies are necessary to determine the optimal time to institute EHDP treatment, length of treatment, and minimal effective dose. EHDP is the first hterapeutic agent known to alter the formation of heterotopic ossification after spinal injury and may prove useful in other conditions where heterotopic ossification prevention is clinically indicated.

Neurogenic heterotopic ossification in spinal cord injury

“…172 ± 175 However, operative resection of NHO has been associated with severe complications and poor outcome. 171 These complications include deep (2 ± 5%) 174,175 or super®cial infection (7 ± 38%), 45,49,174,175 post-operative haemorrhage (5 ± 38%), 45,173 and excessive intra-operative bleeding requiring (multiple) blood transfusions (9 ± 83%). 49,174 ± 176 Moreover, intra-and post-operative fracturation of bone may occur in the case of severe osteoporosis.…”

“…The post-operative recurrence of NHO depends on the de®nition used and the followup period. Radiographic signs of NHO recurrence have been mentioned in 82 ± 100% of the operated SCI patients, 45,49,173,174 although clinically signi®cant NHO would develop in only 17 ± 58% of the cases. 10,45,49,173,174,176 It has been suggested that the recurrence after resection can be reduced if NHO is removed only once the ®rst and second phase of the bone scan have normalized.…”

“…Radiographic signs of NHO recurrence have been mentioned in 82 ± 100% of the operated SCI patients, 45,49,173,174 although clinically signi®cant NHO would develop in only 17 ± 58% of the cases. 10,45,49,173,174,176 It has been suggested that the recurrence after resection can be reduced if NHO is removed only once the ®rst and second phase of the bone scan have normalized. 10,52,115,129,132 However, such a maturity rating does not guarantee that NHO recurrence is unlikely.…”

Prevention of heterotopic ossification after spinal cord injury with indomethacin

“…The prevention of HO with etidronate after SCI had an e ect mainly on the reduction of progression of ectopic bone than on the incidence of this complication. 18,19 The e ect of NSAIDs on the prevention of HO following total hip arthroplasty (THA) is well accepted. 20,21 In only a few patients with SCI these drugs have been used as a`secondary' prevention after surgical removal of HO.…”

Evaluation and management of heterotopic ossification in patients with spinal cord injury

“…13,14,20,21 In the present study we report an e ective management of HO which was based on the screening of asymptomatic patients by bone scintigraphy, consequently resulting in considerable better prevention of HO than reported in previous studies where the diagnosis of HO was based on the radiographic examination. 17,19 …”