Heterotopic Ossification

Heterotopic ossification (HO) is a common complication following acetabular surgery and can jeopardize the functional outcome of patients. Overall, rates of HO have been reported to vary from 45% to 100%, with the rate of severe HO between 14% and 50% when no prophylaxis is used (2,3,57,62,149,150-152). When nonoperative treatment is selected, HO is rare (50). A direct relationship between the severity of HO and loss of function has been demonstrated, thus making prophylaxis routine for most surgeons (151). Significant reported potential risk factors for HO development include head injury, type and severity of the fracture, time delay to surgery, trochanteric osteotomy, and associated injuries to the abdomen and chest (50,153-155). The most commonly reported and convincing risk factor for HO is the surgical approach, with the extended iliofemoral and the Kocher-Langenbeck approaches having the highest rate of HO and the ilioinguinal approach the lowest (50,63,152,154). The major difference in approaches involves the stripping of the gluteal muscles off the external iliac fossa. Unless the ilioinguinal approach is extended onto the external fossa, no HO prophylaxis is recommended (2,3,43,62). Unfortunately, without a clear understanding of the etiology of HO, multiple methods of prophylaxis currently are in use, all with literature to support and refute their effectiveness.

Heterotopic bone experimentally occurs with soft tissue trauma, with transplantation of cells which form bone, and with undifferentiated mesenchymal cells that are exposed to bone growth factors (156). These theories support the idea that, with tissue injury and/or dissection, the process of HO is more likely to occur, especially in situations that displace bony fragments into the surrounding soft tissue. The process of HO formation is thought to begin within 16 hours of the injury/surgery and is maximal at 36 to 48 hours (50,152,157,158). Therefore, whatever treatment selected, the optimal time for initiation of preventative treatment is within the first 48 hours following the surgery.

Heterotopic ossification is usually evident on radiographs by six weeks and has shown little likelihood of progression after three months (57,63). Once identified on radiographs, the classification of HO has been described by Brooker, which is based on a single AP pelvic radiograph. Although commonly used, the classification system has been modified by Moed, and most published articles refer to the modified Brooker classification system. The modified system uses two additional radiographic views to identify the extent of HO formation (159). The views are the iliac oblique and obturator oblique (Judet views) views of the acetabulum. The modified system allows for better correlation with hip motion (159). Ultimately, HO formation is only important if it affects the range of motion of the hip, and as the grade of HO increases the range of motion diminishes, thus the importance for prevention rather than treatment after formation (50,62,63,149,154,159-162).

Various prophylactic treatments have been attempted in the past, much of which was based on the literature for HO prevention in total hip arthroplasty. In the 1970s, ethyl hydroxydiphosphonate was thought to prevent osteoid mineralization, but not osteoid production (163,164). Unfortunately, diphosphonates only delayed the mineralization of osteoids, rather than preventing HO. In subsequent experimental animal studies and in patients after surgery about the hip, diphosphonates have been shown to be ineffective (165,166).

Indomethacin, a nonsteroidal antiinflammatory drug (NSAID), has been shown to diminish the incidence of HO after pelvic surgery (2,57,62,63). The pathway for indo-methacin's use in HO prevention is felt to be related to its ability to affect the inflammatory process by acting through an inhibitory action on prostaglandin synthesis (167). Therefore, early administration of the medication for prophylaxis, usually within the first 24 to 48 hours of surgery, is important. Current recommended prophylactic dose is 25 mg three times a day, administered orally or by rectal suppository, beginning on the first postoperative day and continuing for three to six weeks (26). Specific to acetabular surgery, the incidence of HO with indomethacin prophylaxis is 5% to 47% with significant ectopic bone formation in up to 22% of the patients (57,62,63,155). The benefits of indomethacin include both cost and ease of administration. However, a randomized, prospective study in 1997, using three-dimensional CT reconstruction to assess the HO, determined that indomethacin was not effective as a prophylactic agent, raising again the question of its use. Patient compliance can be an issue, with a reported noncompliance rate as high as 33% (168). Furthermore, although rarely reported in most studies, indomethacin can have serious complications, including gastric ulcerations, decreased platelet function, renal toxicity, impaired fracture healing, and increased risk of long bone nonunion (162,169-171).

Radiation has been proven effective in reducing the severity and overall incidence of HO after acetabular surgery (50,57,62,149,151). Irradiation acts by altering DNA transcription. This affects rapidly dividing cells and prevents osteoblastic precursor cells from multiplying and forming active osteoblasts (149,172). Several studies noted that the timing of the radiation may effect the success, and therefore recommend the radiation be given within 48 to 72 hours of the surgery, if not preoperatively (50,149,155). Following the fourth postoperative day, the success of HO prevention fell from 98% to 33% in one study (155). Treatment recommendations vary from as little as 500 to 1000 cGy in a one time single low-dose to 1000 to 1200 cGy given in five or six divided doses daily over five to six days. A major benefit of the radiation is that prophylactic treatment is administered while still in the hospital, eliminating compliance issues. However, radiation therapy is not always available and may be costly at some institutions, but considering the complexity of such cases, and the trend for such patients to be transferred to tertiary institutions or trauma centers, as well as the increasing level of oncologic services at such centers, obtaining radiation therapy is not very difficult. It would not be justified to transfer a multiply injured patient in the rare case that it is not available; other methods should be employed. Radiation therapy has major risks, including induction of malignancy, genetic alterations of offspring, and sterility. However, these risks are dose-related, and none have been shown to occur with the recommended single low-dose treatment, although its long-term effects have not been determined (50,62,149,156,160,173).

A more aggressive prophylactic treatment for HO includes a combination therapy, of both indomethacin and radiation (160). This has reported results as good as the best individual treatments, but carries the risks of both treatments.

Another recommendation for prevention of HO is resection of the necrotic muscle at the time of surgery, specifically resection of the damaged/necrotic gluteus minimus and medius muscles. One study reports a decrease in the incidence of significant HO with resection of the necrotic muscle and no adjuvant treatment (156). The obvious advantages include no compliance issues and no complications related to radiation or NSAIDs; however, most surgeons already remove necrotic muscle, bringing into question the ultimate success of this treatment alone.

Even with prophylactic treatment, HO does occur and in some instances can become disabling for the patient by limiting hip motion. Surgical excision should only be considered if hip motion is limited and even then must be decided upon on a case-by-case basis. Verification that the ossification process has subsided is important since resection in the active phase can result in an even more significant recurrence. Monitoring blood alkaline phosphatase and bone scan activity for stabilization are two accepted methods for determing the appropriate timing of resection, should it be contemplated. If resection is planned, a preoperative CT is helpful for preoperative planning. Resection of the bone is usually done through the original approach used for fracture fixation. Care must be taken when resecting bone because the sciatic and superior gluteal nerves can be entrapped in the bone or surrounding scar tissue. If done carefully, excision of the HO can result in an improved range of motion in the hip. After excision, HO prophylaxis is recommended using NSAIDs, or a combination of both.

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