Amino-bisphosphonates in heterotopic ossification: first experience in five consecutive cases

Abstract

Study design: Retrospective, observational study in five consecutive cases. Objectives: The management of heterotopic ossification (HO), a frequent complication after spinal cord injury (SCI) and after orthopaedic surgery, is a therapeutic challenge with high recurrence rates of over 50%. Conflicting data were reported for Etidronate. The use of the more potent new generation of amino-bisphosphonates has been put forward in different inflammatory, dysmorphogenic bone disease. In order to try and halt the underlying dysfunctional bone metabolism we have studied the action of pamidronate in five consecutive high-risk patients with established HO of different etiology undergoing surgical removal. Setting: University Hospital of Basel, Switzerland, Division of Endocrinology, Diabetology and Clinical Nutrition and the Department of Orthopedic Surgery. Methods: In all five patients, ranging from 47 to 68 years of age, we used continuous pamidronate infusions perioperatively at a dosage of 120 mg in the first 12 h and subsequent reduction to 75-60-30-15 mg/12 h over a period of 10-14 days. Results: None of these patients showed clinical, radiographical and laboratory signs of HO recurrence or new forming HO in the follow-up 5-54 month after surgery. Potential side effects of high-dose bisphosphonate therapy such as osteoporosis and osteomalacia were not reported in any case. Conclusion: We postulate that pamidronate might have pronounced beneficial effects in highrisk patients with established HO undergoing excision surgery. Since the therapeutic window of amino-bisphosphonates has not yet been defined and the minimal necessary doses for preventing new HO are unknown, further studies are encouraged to confirm our findings and to identify the necessary dosage and duration of treatment and to pinpoint, which patients will benefit most from this treatment.Spinal Cord (2005) 43, 604-610.

A systematic review of the therapeutic interventions for heterotopic ossification after spinal cord injury

“…There were 13 studies that met the inclusion criteria; this included four prophylaxis 1,3,22,23 and nine treatment [24][25][26][27][28][29][30][31][32][33][34][35] studies of HO. Three of these intervention studies had Level 1,3,22,23 two Level 2, 24,25 seven Level 4 [26][27][28][29][32][33][34][35] and one Level 5 1 evidence.…”

“…Three of these intervention studies had Level 1,3,22,23 two Level 2, 24,25 seven Level 4 [26][27][28][29][32][33][34][35] and one Level 5 1 evidence.…”

“…Subbarao et al 28 used disodium edridonate before and after surgical hip wedge resection, whereas Schuetz et al 29 used pamidronate before and after HO surgical removal.…”

“…There was Level 4 (at a case series level) evidence that bisphosphonates effectively halt secondary HO progression after surgical resection of HO. 28,29 Radiotherapy. Radiotherapy involves the irradiation of pluripotential mesencymal cells, which may be responsible for the formation of heterotopic bone.…”

“…34,35 There was Level 4 evidence that resection combined with bisphosphonate treatment halts the recurrence of HO. 28,29 …”