Session III - Polytrauma

Heterotopic Ossification Prophylaxis with Indomethacin Increases the Risk of Long Bone Nonunion

Timothy A. Burd, MD; Michael S Hughes, BS; Jeffrey O. Anglen, MD; University of Missouri, Columbia, Missouri, USA

Purpose: Indomethacin is commonly administered for heterotopic ossification bone prophylaxis after acetabular fracture surgery. Nonsteroidal antiinflammatory drugs (NSAIDs) such as Indomethacin have been associated with retarded fracture healing as well as mechanically weaker fracture callus. The purpose of this study was to determine whether patients with acetabular fractures who receive Indomethacin for heterotopic ossification prophylaxis (HOP) have a greater risk for developing healing problems in associated long bone fractures.

Methods: A retrospective review was performed of the records of 282 acetabular fracture patients who underwent open reduction and internal fixation (ORIF) between July 1992 and January 2001. Patients at risk for heterotopic ossification because of the use of a posterior or extensile surgical approach were randomized to receive one of two methods for HOP: radiation therapy or Indomethacin. One hundred twelve of the patients sustained at least one concomitant long bone fracture. Of these, 36 patients received no HOP, 38 received focal radiation (XRT), and 38 patients received Indomethacin. The medical records and radiographs of these patients were reviewed for any evidence of healing problems and the treatments required. Patients who required treatment (either surgical or nonsurgical) to re-start a stalled healing process were counted.

Results: Fifteen of the 112 patients developed 16 nonunions of 190 associated long bone fractures. Patients receiving Indomethacin had a 26% incidence of long bone nonunion (11 nonunions in 10 of 38 patients) compared with an 8% incidence in the radiation group (3 of 38). The group not receiving either treatment for HOP had a 6% nonunion rate (2 of 36). The difference between the no-treatment and XRT groups was not significant (P = 0.708). Patients who received Indomethacin compared with those who did not had a significantly higher rate of nonunion: 26% vs. 7% (P = 0.004). Among total long bone fractures at risk, there were 11 nonunions in 72 fractures of patients who received Indomethacin (15%), and 5 nonunions in 118 fractures of patients who did not receive Indomethacin (4%) (P = 0.029). Post hoc power analysis was determined (power = 0.80 with _ set at 0.05). No acetabular nonunions were identified. Multivariate analysis demonstrated that age, smoking, ISS score, the presence of an open fracture, and alcohol use did not independently affect whether or not nonunion developed in long bones.

Discussion/Conclusions: Patients with concurrent acetabular and long bone fractures who receive Indomethacin for HOP have a significantly greater risk of developing a nonunion in the associated long bone fractures compared with patients receiving XRT or no HOP. Although Indomethacin treatment is much cheaper and has been shown to be approximately equally effective, consideration should be given to radiation when the patient has concomitant long bone fractures and requires HOP.