High Doses of the Diphosphonate EHDP for the Prevention of Heterotopic Ossification

Abstract

The effect of Ethane-1-Hydroxy-1, 1-Diphosphonate (EHDP) on experimental and clinical heterotopic ossification was studied. Demineralized cortical bone matrix was implanted in the abdominal wall of three groups of adult male rats. Two groups received injections amounting to 5 and 20 mg/kg/day of EHDP, respectively, and a control group received placebo. The lower dose of EHDP had no effect on bone formation, whereas the higher dose resulted in a marked reduction in ash content and ⁴⁵Ca uptake in the implants. Inhibitory effects on heterotopic bone and serum alkaline phosphatase activity were observed when treating with high doses (50 mg/kg/day) a paraplegic patient following resection of para-articular ossifications around the hips. The effect of EHDP on bone formation is interpreted as reflecting a dose-dependent interference with the deposition of hydroxyapatite crystals in the bone matrix.