THE EFFECT OF INDOMETHACIN FOR PROPHYLAXIS OF HETEROTOPIC OSSIFICATION AFTER OPERATIVE TREATMENT OF ACETABULAR FRACTURES

Participants: M. Karunakar, J. Goulet, T. Le, J.M. Hall

Keywords: acetabular fracture, heterotopic ossification, indocin

Introduction

Heterotopic ossification (HO) is a commonly reported complication following surgical treatment of acetabular fractures. The reported incidence ranges from 24%-90% with an increased incidence and severity reported with posterior or extensile approaches to the acetabulum. Large amounts of ectopic bone around the hip have been shown to result in severe limitations of range of motion and a decreased functional outcome for patients.

Both indomethacin and low-dose radiation have been studied for prophylaxis after acetabular fractures. Indomethacin is a non-steroidal anti-inflammatory agent which has been shown to decrease heterotopic ossification in animal models. Indomethacin affects inflammation by inhibiting the conversion of arachidonic acid to prostaglandins through the cyclooxygenase pathway. It is also believed to exert an inhibitory effect on mesenchymal cell proliferation.

The results of clinical studies with prophylactic indomethacin are mixed, with some authors showing dramatic decreases in the incidence and others showing little or no effect. The only prospective randomized trial published to date found that indomethacin was not effective in preventing ectopic bone formation after acetabular fractures. However, half of the patients in that study underwent the ilioinguinal approach, which has a much lower incidence of HO complication. Low-dose radiation has been reported to be effective for prophylaxis of heterotopic ossification after acetabular fractures. However since many acetabular injuries occur in younger patients, radiation is not widely used because of potential long-term side effects.

The specific aim of this study is to determine whether indomethacin effectively prevents heterotopic ossification following surgical repair of acetabular fractures.

Materials and Methods

A double-blind placebo controlled trial is being conducted jointly with Carolinas Medical Center. One hundred and eighteen consecutive patients with acetabular fractures treated operatively through a posterior approach will be enrolled in the study. Patients will be randomly assigned to receive either 75 mg indomethacin once daily or a placebo. Patients, surgeons and all clinical personnel will be blind to whether the subjects receive indomethacin or placebo. Indomethacin serum levels will be checked at 2 week follow-up to determine patient compliance. Follow-up assessment will include radiographs (AP and Judet) and range of motion measurements. Statistical analysis will be performed to determine the incidence and severity of heterotopic ossification in the two treatment groups.

Progress

IRB approval has been obtained for this study and sixty patients have been enrolled (26 at the University of Michigan, and 34 at Carolinas). Recruitment will continue until at least 118 patients have completed the trial.