Heterotopic ossification prophylaxis with indomethacin increases the risk of long-bone nonunion

J Bone Joint Surg Br. 2003 Jul;85(5):700-5.


Indomethacin is commonly administered for the prophylaxis of heterotopic ossification (HO) after the surgical treatment of acetabular fractures. Non-steroidal anti-inflammatory drugs such as indomethacin, have been associated with delayed healing of fractures and mechanically weaker callus. Our aim was to determine if patients with an acetabular fracture, who received indomethacin for prophylaxis against HO, were at risk of delayed healing or nonunion of any associated fractures of long bones. We reviewed 282 patients who had had open reduction and internal fixation of an acetabular fracture. Patients at risk of HO were randomised to receive either radiation therapy (XRT) or indomethacin. Of these patients, 112 had sustained at least one concomitant fracture of a long bone; 36 needed no prophylaxis, 38 received focal radiation and 38 received indomethacin. Fifteen patients developed 16 nonunions. When comparing patients who received indomethacin with those who did not, a significant difference was noted in the rate of nonunion (26% v 7%; p = 0.004). Patients with concurrent fractures of the acetabulum and long bones who receive indomethacin have a significantly greater risk of nonunion of the fractures of the long bones when compared with those who receive XRT or no prophylaxis.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Acetabulum / injuries*
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Arm Injuries / physiopathology
  • Arm Injuries / surgery
  • Fracture Fixation / methods
  • Fracture Healing / drug effects
  • Fracture Healing / physiology
  • Fractures, Bone / physiopathology
  • Fractures, Bone / radiotherapy
  • Fractures, Bone / surgery*
  • Humans
  • Indomethacin / adverse effects*
  • Indomethacin / therapeutic use
  • Leg Injuries / physiopathology
  • Leg Injuries / surgery
  • Middle Aged
  • Multivariate Analysis
  • Ossification, Heterotopic / prevention & control*
  • Postoperative Complications / prevention & control*
  • Risk Factors


  • Anti-Inflammatory Agents, Non-Steroidal
  • Indomethacin