Prevention of heterotopic ossification about the hip: Final results of two randomized trials in 410 patients using either preoperative or postoperative radiation therapy

Purpose: Experimental and clinical data support effectiveness of perioperative radiotherapy to prevent heterotopic ossification after hip surgery or trauma. Since 1987, two prospectively randomized trials were performed in patients with high-risk factors to develop heterotopic ossification: the first (HOP 1) to assess the prophylactic efficacy of postoperative low vs. medium dose radiotherapy, and the second (HOP 2) to assess the prophylactic efficacy of pre vs. postoperative radiotherapy. Methods and Material: 410 patients with high risk to develop heterotopic ossifications about the hip following hip surgery were recruited. Between June 1987 and June 1992, 249 patients were randomized in HOP 1 to postoperative ''low dose'' (5 x 2 Gy; total: 10 Gy) or ''medium dose'' (5 x 3.5 Gy; total: 17.5 Gy) radiotherapy. Between July 1992 and December 1995, 161 patients were randomized in HOP 2 to either 1 x 7 Gy preoperatively (less than or equal to 4 h before surgery) or 5 x 3.5 Gy (total: 17.5 Gy) postoperatively(less than or equal to 96 h after surgery). With exception of age and type of implant (cemented vs. uncemented prosthesis) all confounding patient variables (gender, prior surgery) and predisposing risk factors were similarly distributed between both trials and treatment arms. Portals encompassed the periacetabular and intertrochanteric soft tissues. Radiographs were obtained prior and immediately after surgery and at least 6 months after surgery to assess the extent of ectopic bone formation about the hip. Modified Brooker grading was used to score the extent of heterotopic ossification. Harris scoring was applied to evaluate the functional hip status. If the scores decreased from immediate post or preoperative status, respectively, to the last follow-up, radiological or functional failures were assumed. Results: Effective prophylaxis was achieved in 227 (91%) hips of HOP 1 and in 142 (88%) of HOP 2. In HOP 1, 15 (11%) radiological failures were observed in the law-dose group compared to 7 (6%) in the medium dose group (p > 0.05). In HOP 2, 4 (5%) radiological failures were observed in the postoperative and 11 (19%) in the preoperative group (p < 0.05). Subgroup analysis of the preoperative group revealed that the highest failure rate occurred in patients with prophylactic radiotherapy prior to removal of ipsilateral Brooker Grade III and IV ossification (39%) (p < 0.001), while all other patients in the preoperative group had a failure rate that was comparable to postoperative treatment groups. In multivariate logistic regression analysis the number of high-risk factors for development of heterotopic ossification (p = 0.03) and the time to RT initiation (p = 0.05) were independent prognostic factors in the HOP I study. For the HOP 2 study, the multivariate logistic regression analysis revealed the number of high-risk factors for development of heterotopic ossification (p = 0.003), the preoperative HO grade (p = 0.001) and the RT dose concept (p = 0.05) as independent prognostic factors. Other factors including type of implant( cemented vs. uncemented) did not affect the prophylactic efficacy of radiotherapy. There were no increased intra-and postoperative complications seen in the preoperative group, and no long-term complications were observed in both HOP studies. For functional failures (decrease of Harris score) no statistically prognostic factors were found. There were less functional failures in HOP 1 (18 = 7%) than in HOP 2 (23 = 14%, but this difference was not statistically significant. Only patients with high Brooker Grade III and TV at last FU achieved a lower Harris score than those with low Brooker Grade 0, I and II (p < 0.05). Conclusion: With the exception of a small subgroup of patients with ipsilateral high Brooker Grade III and IV, pre-and postoperative radiotherapy are equally effective to prevent heterotopic ossification about the hip after hip surgery and total hip arthroplasty. Fractionated medium dose radiotherapy resulted in the lowest failure rate. (C) 1997 Elsevier Science Inc.