The effect of etidronate on late development of heterotopic ossification after spinal cord injury

Forty patients with spinal cord injury (SCI) and heterotopic ossification (HO) were treated with etidronate and followed after therapy to determine the effects of long-term medication on heterotopic bone formation. Eighteen patients had tetraplegia and 22 had paraplegia. Early diagnosis of HO (positive bone scintigraphy and negative radiographic findings of HO) was established by 3-phase bone scintigraphy using 99m technetium-labeled methylene diphosphonate. All patients underwent treatment with etidronate, first with intravenous administration of 300 mg/day for 3 days followed by an oral administration of 20 mg/kg/day for 6 months. Eleven patients (27.5%) developed radiographic evidence of HO from 1.5 to 6 years after therapy. A low degree of HO was found in these patients; 8 had grade I and 3 had grade II ectopic ossification (Brooker's scale). The analysis of data showed that 2 different types of ectopic bone may form in the later stages after SCI. In 5% of patients, HO was found in the same anatomical site initially and finally, suggesting a "rebound" in mineralization of bone matrix not prevented by the administration of etidronate. The other type of HO was found in the majority of patients (95%) where the localization of HO showed different involvement of joints than initially, indicating de novo appearance of HO following SCI. The data suggest that etidronate given for a prolonged period in higher doses has, in addition to an inhibitory effect on crystal formation, a cellular effect on bone-forming cells.