VOL. 88-B, No. 12, DECEMBER 2006 1613 Indometacin as prophylaxis for heterotopic ossification after the operative treatment of fractures of the acetabulum M. A. Karunakar, A. Sen, M. J. Bosse, S. H. Sims, J. A. Goulet, J. F. Kellam From The University of Michigan, Ann Arbor, Michigan, and Carolinas Medical Centre, Charlotte, North Carolina, USA  M. A. Karunakar, MD, Assistant Professor  J. A. Goulet, MD, Professor Department of Orthopaedic Surgery  A. Sen, PhD, Associate Research Scientist Center for Statistical Consultation and Research The University of Michigan, Ann Arbor, Michigan 48109- 03278, USA.  M. J. Bosse, MD, Orthopaedic Traumatologist  S. H. Sims, MD, Orthopaedic Traumatologist  J. F. Kellam, MD, Orthopaedic Traumatologist Department of Orthopaedic Surgery Carolinas Medical Centre, Charlotte, North Carolina 28232, USA. Correspondence should be sent to Dr M. A. Karunakar; e-mail: mkarun@umich.edu ©2006 British Editorial Society of Bone and Joint Surgery doi:10.1302/0301-620X.88B12. 18151 $2.00 J Bone Joint Surg [Br] 2006;88-B:1613-17. Received 17 May 2006; Accepted 26 July 2006 Our study was designed to compare the effect of indometacin with that of a placebo in reducing the incidence of heterotopic ossification in a prospective, randomised trial. A total of 121 patients with displaced fractures of the acetabulum treated by operation through a Kocher-Langenbeck approach was randomised to receive either indometacin (75 mg) sustained release, or a placebo once daily for six weeks. The extent of heterotopic ossification was evaluated on plain radiographs three months after operation. Significant ossification of Brooker grade III to IV occurred in nine of 59 patients (15.2%) in the indometacin group and 12 of 62 (19.4%) receiving the placebo. We were unable to demonstrate a statistically significant reduction in the incidence of severe heterotopic ossification with the use of indometacin when compared with a placebo (p = 0.722). Based on these results we cannot recommend the routine use of indometacin for prophylaxis against heterotopic ossification after isolated fractures of the acetabulum. Heterotopic ossification (HO) is commonly described as a complication after the operative treatment of fractures of the acetabulum. 1-12 The incidence ranges from 24% to 90% with greater frequency and severity with posterior or extensile approaches to the acetabulum. 7-13 Large amounts of ectopic bone around the hip have been shown to result in severe limitation of the range of movement of the hip with a decreased functional outcome. 2-5 Indometacin has been used as prophylaxis for HO with several retrospective studies showing a reduction in bone formation of clin- ical significance. 3-5 The results of recent studies are mixed, with some authors showing a dra- matic decrease in the incidence of HO and others finding little or no effect. 5,8-11 The null hypothesis of our study was that there was no difference in the development of severe HO between patients receiving indometacin and those having a placebo. Patients and Methods We performed a prospective double-blind con- trolled clinical trial with the approval of the Institutional Review Boards at two level-I trauma centres to evaluate the efficacy of indometacin compared with a placebo for prophylaxis against HO after the operative treatment of fractures of the acetabulum. Between January 1999 and June 2003, 232 patients with such fractures were treated by operation through a posterior approach. The criteria for exclusion were: age under 18 years, injury to the spinal cord, ankylosing spondylitis, burns, gastro-intestinal bleeding, Glasgow coma scale < 15, cerebrovascular accident and the use of other non-steroidal anti-inflammatory drugs. 14 There were 157 patients who were eligible, and 127 were enrolled in the trial, and under- went operative stabilisation of their acetabu- lar fractures through a posterior Kocher- Langenbeck approach. 9 After fixation and before wound closure, any devitalised muscle was excised. 12 The patients were randomised to receive either indometacin (Merck Inc., Whitehouse Station, New Jersey) or a placebo using a computer-generated list. Indometacin (75 mg) sustained release and the placebo were admin- istered to the patients in a blinded fashion by the investigational drug pharmacy. The sus- tained-release formulation was selected for our study to improve patient compliance since it is given in a single daily dose, and to reduce the costs associated with formulating the placebo. The manufacturer (Merck Inc.) states that “when measured over a 24-hour period, the cumulative amount and time-course of indometacin absorption from a single capsule of Indocin SR are comparable to those of three doses of 25 mg capsules of Indocin”. Trauma