Indomethacin prophylaxis for heterotopic ossification after acetabular fracture surgery increases the risk for nonunion of the posterior wall

J Orthop Trauma. 2014 Jul;28(7):377-83. doi: 10.1097/BOT.0000000000000049.


Objectives: To determine if indomethacin has a positive clinical effect for the prophylaxis of heterotopic ossification (HO) after acetabular fracture surgery. To determine whether indomethacin affects the union rate of acetabular fractures.

Design: Prospective randomized double-blinded trial.

Setting: Level 1 regional trauma center.

Patients: Skeletally mature patients treated operatively for an acute acetabular fracture through a Kocher-Langenbeck approach.

Intervention: Patients were randomly allocated to 1 of 4 groups comparing placebo (group 1) to 3 days (group 2), 1 week (group 3), and 6 weeks (group 4) of indomethacin treatment.

Main outcome measurements: Factors analyzed included the overall incidence, Brooker class and volume of HO, radiographic union of the acetabular fracture, and pain. Patients were followed clinically and radiographically at 6 weeks, 3 months, 6 months, and 1 year. Serum levels of indomethacin were drawn at 1 month to assess compliance. Computed tomographic scans were performed at 6 months to assess healing and volume of HO.

Results: Ninety-eight patients were enrolled into this study, 68 completed the follow-up and had the 6-month computed tomographic scan, and there was a 63% compliance rate with the treatment regimen. Overall incidence of HO was 67% for group 1, 29% for group 2 (P = 0.04), 29% for group 3 (P = 0.019), and 67% for group 4. The volume of HO formation was 17,900 mm for group 1, 33,800 mm for group 2, 6300 mm for group 3 (P = 0.005), and 11,100 mm for group 4. The incidence of radiographic nonunion was 19% for group 1, 35% for group 2, 24% for group 3, and 62% for group 4 (P = 0.012). Seventy-seven percent of the nonunions involved the posterior wall segment. Pain visual analog scores (VASs) were significantly higher for patients with radiographic nonunion (VAS 4 vs. VAS 1, P = 0.002).

Conclusions: Treatment with 6 weeks of indomethacin does not appear to have a therapeutic effect for decreasing HO formation after acetabular fracture surgery and appears to increase the incidence of nonunion. Treatment with 1 week of indomethacin may be beneficial for decreasing the volume of HO formation without increasing the incidence of nonunion.

Level of evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetabulum / diagnostic imaging
  • Acetabulum / injuries
  • Acetabulum / surgery*
  • Adolescent
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Female
  • Fracture Healing / drug effects
  • Fractures, Bone / complications
  • Fractures, Bone / diagnostic imaging
  • Fractures, Bone / surgery*
  • Fractures, Ununited / chemically induced*
  • Humans
  • Indomethacin / adverse effects*
  • Indomethacin / pharmacology
  • Indomethacin / therapeutic use
  • Male
  • Middle Aged
  • Ossification, Heterotopic / diagnostic imaging
  • Ossification, Heterotopic / etiology
  • Ossification, Heterotopic / prevention & control*
  • Prospective Studies
  • Radiography
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal
  • Indomethacin