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Early Excision of Heterotopic Ossification about the Elbow followed by Radiation Therapy*

JOHN A. McAULIFFE, M.D., FORT LAUDERDALE and AARON H. WOLFSON, M.D., MIAMI, FLORIDA

Investigation performed at the University of Miami Jackson Memorial Medical Center, Miami

	Abstract

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We reviewed the results, in eight patients, of excision of heterotopic ossification about the elbow performed three to ten months (average, seven months) after the initial injury and followed by radiation therapy to prevent recurrence. The etiology of the heterotopic ossification included a neurological (head or spinal cord) injury in five patients and a local injury (fracture or fracture-dislocation) of the elbow in three patients. The average preoperative arc of motion of the three joints that were capable of motion was 12 degrees (5, 10, and 20 degrees); the remaining five joints were fixed in an average of 56 degrees (range, 10 to 90 degrees) of flexion. All of the patients received a total dose of radiation of 1000 centigray, divided into five fractions. The radiation therapy was instituted on the first postoperative day, and at least three of the remaining four treatments were administered on consecutive days. Radiation therapy was not performed on the weekend, so the five fractions were administered over the course of seven days. At an average of forty-six months (range, twenty-five to seventy-two months), the arc of motion averaged 103 degrees, which compared favorably with the 121-degree arc of motion that had been attained intraoperatively. Two patients who had residual motor deficits in the involved extremity had an arc of motion of 50 and 70 degrees at the latest follow-up evaluation; those who had normal motor function fared considerably better, averaging 118 degrees of motion. There was no substantial recurrence of ossification either radiographically or that limited motion, and no complications attributable to the radiation therapy were noted. On the basis of this experience, it seems that the generally recommended twelve to eighteen-month delay between injury and excision, to allow for maturation of heterotopic bone and thus to lessen the likelihood of recurrence, may be eliminated. Additional studies are needed to define the relative risk of recurrence in the various clinical settings in which heterotopic ossification is seen and to determine whether radiation therapy is necessary to prevent recurrence after early excision in each of these instances.

	Introduction

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Heterotopic ossification is a poorly understood phenomenon characterized by the formation of bone in periarticular regions. Although the pathogenesis of heterotopic ossification is unknown, it is clearly associated with certain clinical situations, including local injury, neurological injury (to the brain or the spinal cord), and wounds caused by thermal or electrical burns^7-9,19. Heterotopic ossification can lead to severe limitation of motion and sometimes to total loss of motion of the affected joint.

There is no completely effective or well accepted regimen for prophylaxis against heterotopic ossification at the time of an acute injury^9,19. Despite early dissatisfaction with operative treatment³¹, gratifying results have been reported after excision of heterotopic bone about the elbow^13,17,23,25. Most authors have suggested a waiting period of twelve to eighteen months before excision^13,17,23,25, during which time function of the elbow is considerably impaired. Even with this delay, recurrence after excision of heterotopic bone is distressingly frequent, particularly in neurologically injured patients¹³.

The effectiveness of radiation therapy in preventing heterotopic ossification after total hip arthroplasty in patients known to be at risk has been well established^2,6,16. Mention has been made of similar success in the treatment of heterotopic ossification about the elbow with excision followed by radiation therapy, although this technique has not been reported in detail^1,8,15,26. We describe our experience with eight patients who were managed in this fashion.

	Materials and Methods

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Since 1989, we have treated a total of twenty elbows with radiation therapy after excision of heterotopic bone. We excluded from the study patients who had had excision of heterotopic bone more than one year after the initial injury, those who had had a simultaneous interposition arthroplasty of the elbow, and those who had been followed for less than two years after the operation.

The eight patients who form the basis of this report had had excision of heterotopic bone about the elbow an average of seven months (range, three to ten months) after the initial injury. The etiology of the heterotopic ossification was a neurological injury (of the head in two patients and of the spinal cord in three) or a local injury of the elbow (a fracture in two patients and a fracture-dislocation in one). There were five men and three women. The average age at the time of the excision of the heterotopic bone was forty-two years (range, twenty-seven to seventy-one years). The duration of follow-up averaged forty-six months (range, twenty-five to seventy-two months).

Plain radiographs were used to determine the extent and localization of abnormal bone, which was predominantly posteromedial in all patients (Figs. 1-A and 1-B). Conventional tomography in the lateral projection was helpful in four patients. Three of them had the study so that the congruity of the articular surfaces after local injury of the elbow could be better assessed, and one, to delineate a smaller focus of heterotopic bone laterally. Radionuclide bone scans and measurements of levels of serum alkaline phosphatase were not routinely performed. The four patients for whom radionuclide bone images were made had marked uptake in the region of the affected elbow. However, the uptake was diffuse, and these studies therefore were not helpful in localizing the abnormal ossification or in planning the operative approach.

View larger version (123K): [in this window] [in a new window]   Figs. 1-A and 1-B: Case 5. Fig. 1-A: Lateral radiograph of the elbow, made seven months after an incomplete injury of the cervical spinal cord and immediately before excision of heterotopic bone. There is marked heterotopic bone posteromedially, resulting in fixation of the joint. The heterotopic bone is radiographically immature, particularly peripherally.

View larger version (139K): [in this window] [in a new window]   Fig. 1-B: Lateral radiograph of the same elbow, made eighteen months postoperatively. The range of motion of the elbow was 0 to 135 degrees.

The radiation therapy involved anteroposterior/posteroanterior four-megavolt photon irradiation, to a total dose of 1000 centigray in five 200-centigray fractions. The radiation therapy was begun on the first postoperative day, and a minimum of three of the subsequent four treatments were administered on consecutive days. The total of five fractions was given over a seven-day period, as radiation therapy was not performed on the weekend.

For the irradiation, splints were removed and the elbow routinely was placed in the prone position and was flexed approximately 45 to 60 degrees. The patient was placed in the position in which the radiation therapy subsequently would be administered. A radiograph was made with the patient in this position to confirm osseous landmarks, and the isocenter of the treatment beam was indicated with use of a permanent marker on the skin. During subsequent therapy, on at least the first occasion, a portal radiograph was made to confirm the positioning as seen on the simulation radiograph and to verify the field placement of the treatment beam. The radiation therapist verified the setup and the position on the treatment table daily with use of a light field. Five-half-value-layer anteroposterior/posteroanterior blocking was used to spare a strip of skin on the radial aspect of the elbow. This technique is commonly used in radiation therapy of the extremities to spare a portion of lymphatic drainage in an effort to prevent distal edema. The operative incisions were not excluded from the field.

Active and assisted range-of-motion exercises were begun under the supervision of a therapist on the first postoperative day. Extension of the elbow tends to be the most severely limited motion preoperatively and the most difficult motion for the patient to achieve and maintain postoperatively. The elbow generally was splinted in as much extension as possible at the end of the operation, and static elbow-extension splints were used, between periods of exercise and while the patient was sleeping, for approximately two to four weeks postoperatively. As functional control returned, the patient was progressively weaned from the splints during waking hours. Prescription of the splints was individualized to the needs of the particular patient; a patient sometimes may need a balance between flexion and extension splinting, as did six patients in the current series. Dynamic splinting can be a helpful adjunct after soft-tissue equilibrium has been reached at two to four weeks postoperatively, although it cannot be used effectively for patients who have spasticity. Continuous-passive-motion devices were not used, although subsequent experience has shown that they can be helpful in preventing the patient from beginning periods of therapy or exercise from a position of relative stiffness.

The medical records and radiographs of all patients were reviewed. All patients returned for follow-up examination and radiographs for the purposes of this study.

	Results

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All patients had had functional limitation of the involved elbow preoperatively. The average preoperative (humero-ulnar) arc of the three elbows that were capable of motion was 12 degrees (5, 10, and 20 degrees). Five joints were fixed preoperatively in an average of 56 degrees (range, 10 to 90 degrees) of flexion. In all patients, most of the heterotopic bone was located posteromedially. One of two patients who had a fracture of the olecranon and the patient who had the fracture-dislocation needed both a medial and a lateral incision, one of the three patients who had a spinal cord injury needed both a medial and a lateral incision, and neither patient who had a closed head injury needed a lateral incision. Thus, patients who had sustained a direct injury of the elbow seemed somewhat more likely to have additional foci of abnormal bone on the lateral side of the joint, although the numbers in the present study were too small for us to comment on the importance of this finding.

The arc of motion that was attained intraoperatively averaged 121 degrees (range, 95 to 135 degrees) in the seven patients for whom it was recorded; at the latest follow-up evaluation, it averaged 103 degrees (range, 50 to 135 degrees). Two patients had residual motor deficits in the involved extremity. One of these patients (Case 4) had a spinal cord injury with poor motor control and spasticity; a static neurological lesion was noted seven months after the injury. The other patient (Case 7), who had a head injury, had an injury of the ipsilateral brachial plexus that resulted in loss of function of the biceps; this function was not recovered despite exploration of the brachial plexus and neurolysis. The patient who had spasticity was the only one who had an intraoperative arc of motion that was less than 115 degrees; the motion was limited because of secondary musculotendinous contracture. The arc of motion in these two patients was only 70 and 50 degrees at the latest follow-up evaluation. The six patients who had normal motor function of the involved extremity fared considerably better, averaging 118 degrees (range, 90 to 135 degrees) of motion at the latest follow-up evaluation (Table I).

Therapy directed specifically at maintaining the range of motion of the elbow was continued for an average of four months postoperatively. The neurologically injured patients often participated in an ongoing rehabilitation program for longer periods, during which motion of the elbow was monitored but was not specifically treated. The range of motion of the elbow in the patients who had normal motor function remained stable after the cessation of formal therapy. The two patients who had poor motor control gradually lost motion after therapy was discontinued, before reaching an apparently steady state eighteen to twenty-four months postoperatively. These patients were followed for fifty-four and seventy-two months, respectively, and had no additional change in the arc of motion during this time.

There was no substantial recurrence of heterotopic ossification either radiographically or that limited motion, although minor calcifications, usually in the vicinity of the collateral ligaments or the tip of the coronoid or the olecranon process, as commonly seen after injury of the elbow^18,24, were frequently observed (Fig. 2). We did not attempt to use the classification of heterotopic ossification that was proposed by Brooker et al.⁵, as it was believed to be insufficiently sensitive to describe the functional realities of loss of motion of the elbow in any meaningful way.

View larger version (101K): [in this window] [in a new window]   Fig. 2 Case 8. Anteroposterior radiograph of the elbow, made twenty-six months after excision of heterotopic bone. There is excellent healing of the site of the epicondylar osteotomy, and there are small flecks of mineralization adjacent to the medial epicondyle. The range of motion of the elbow was 5 to 125 degrees. The joint had been fixed preoperatively.

No patient reported pain that limited function of the elbow, although two patients who had had a local injury of the elbow occasionally used non-prescription anti-inflammatory agents for discomfort associated with strenuous use of the arm. One of these patients worked as a painting contractor, and the other was an aviation mechanic. All patients were satisfied with the result of the procedure and stated that they would choose to be operated on again in similar circumstances. This included the two patients who had limited motion and poor motor control; they found the improved capabilities for passive positioning of the affected joints to be beneficial.

One patient (Case 1) had symptoms of causalgia in the distribution of the ulnar nerve preoperatively. After anterior transposition of the nerve at the time of excision of a mass of posteromedial heterotopic bone, these symptoms resolved completely. Four patients reported mild-to-moderate ulnar-nerve paresthesias in the early postoperative period, particularly when flexion of the elbow was emphasized in therapy. These symptoms were attributed to traction neuritis caused by local swelling about the ulnar nerve at the elbow and by the increasing amount of flexion of the elbow. These symptoms resolved spontaneously within eight weeks postoperatively in all four patients, and there were no long-lasting problems in this regard.

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

 
The prevention of heterotopic ossification would clearly be preferable to its treatment; however, there are many inherent challenges in this endeavor. It is difficult to decide which patients should receive prophylaxis in light of the fact that a relatively small percentage of individuals have any measure of clinically meaningful heterotopic ossification. Approximately 1 per cent of patients who have sustained burns (eighteen of 1478)²³, 3 per cent of patients who have had local injury of the elbow (forty-one of 1314)³¹, and 11 per cent of adults who have sustained a head injury (fifty-seven of 496)¹² have been found to have heterotopic ossification. Unfortunately, after the process of heterotopic ossification has begun, it is questionable whether any of the available methods of prevention can influence the outcome^3,9,19. In the treatment of patients who apparently are at greatest risk—for example, patients who have a fracture of the elbow in association with a head injury¹⁰ or in association with severe soft-tissue injuries of the elbow¹⁹—a major concern is that available methods of prophylaxis will adversely affect wound or fracture-healing^3,9.

Pharmacological agents used to inhibit heterotopic ossification have the disadvantage of causing systemic effects. Both diphosphonates and non-steroidal agents can interfere with fracture-healing, and the former, when used for prolonged periods of as long as six months as suggested, can result in osteomalacia¹⁹. There is continued concern that diphosphonates, which inhibit mineralization, have no effect on the deposition of osteoid matrix and that ultimately this matrix may mineralize with the same result after therapy has been discontinued^9,19.

Radiation therapy is the only local measure available for the prevention and treatment of heterotopic ossification. Systemic effects on mineralization, as in the case of diphosphonates, or an inability to tolerate the medication due to gastrointestinal or hematological side effects, as occurs with non-steroidal anti-inflammatory agents, are not seen^1,3. Limited-field irradiation has been used with success after total hip arthroplasty³. This technique limits the amount of radiation delivered to the bone adjacent to the porous-coated surfaces of the prosthesis so as not to delay bone ingrowth (a process similar to fracture-healing) and also avoids direct exposure of the incision to radiation, thus avoiding problems with wound-healing³. Unfortunately, the tighter anatomical confines of the elbow region make such limited portals impractical. The blocking required to spare the medial skin incision would leave the bed of resection untreated because of the limited distance from bone to skin. Blocking of normal bone also would prevent irradiation of areas from which heterotopic bone was excised. However, the patients whom we have managed with this technique, including those who were excluded from the present study, have had no difficulty with wound-healing (with the exception of the patient [Case 7] in whom erythema developed), and both epicondylar osteotomies healed uneventfully.

One of the major concerns in the consideration of the treatment of heterotopic bone relates to the timing of the excision. Most authors have recommended a delay of twelve to eighteen months after the injury to allow for maturation of the heterotopic bone^13,17,23,25. Despite our best efforts to determine the maturity of the aberrant bone, we have not found bone scans, levels of alkaline phosphatase, or the radiographic appearance of the heterotopic ossification to be reliable predictors of recurrence^8,9,11,19. Thus, these studies were not performed routinely in the present series. It would seem that the proclivity for recurrence of heterotopic ossification is variable and, to some extent, related to its etiology⁹. Some authors have suggested that the twelve to eighteen-month waiting period is unnecessary for patients who have an isolated injury of the elbow without accompanying neurological injury^9,15,19, although, to the best of our knowledge, clinical reports documenting the safety of this approach have not been published. The present study suggests that low-dose postoperative radiation therapy may prevent recurrence of heterotopic ossification; additional clinical studies will be needed to determine which patients need such preventive measures.

Early excision, as performed in the current series, has substantial benefits. The operative procedure is greatly simplified; immature bone can be peeled atraumatically from tissue planes with ease, reducing the likelihood of injury to stabilizing structures about the joint. The single greatest advantage of early excision, particularly in patients who have neurological injury, is that function of the elbow can be incorporated into therapy during the initial rehabilitation process, enhancing function and independence. Early restoration of motion also may prove beneficial to the articular cartilage of the affected joint and may help to prevent secondary soft-tissue contracture and atrophy, maximizing functional recovery¹⁵.

We have found no major contraindication to the technique of early excision followed by radiation therapy. Patients who have normal motor function have achieved and maintained a nearly normal range of motion. As Garland et al. noted, patients who have motor deficits do not fare nearly as well¹³. Despite the fact that the intraoperative arc of motion was not maintained as completely in the two patients who had residual motor deficits in the present series, heterotopic bone did not recur, in contrast to the 30 per cent (seven of twenty-three) rate of recurrence reported by Garland et al.¹³. Although the numbers are small, it is encouraging to think that radiation therapy prevented recurrence even in this challenging subset of patients. A potential disadvantage of early excision of heterotopic bone is the fact that the prediction of useful motor recovery in neurologically injured patients is less certain in the months immediately after the injury¹³. However, both of our motor-impaired patients, who had had ankylosis of the elbow preoperatively, believed that the improved capabilities for passive positioning were of considerable functional benefit.

Fortunately, the prevalence of radiation-induced sarcoma is low; however, this hazard must be considered carefully when the desirability of elective radiation therapy for benign conditions is evaluated for patients who have a long life expectancy^4,15. Retrospective studies of bomb survivors, radiologists, and patients who had irradiation for treatment of ankylosing spondylitis, as well as studies of patients who were diagnosed with a radiation-induced sarcoma, documented no radiation-induced malignant lesions at doses of less than 3000 centigray over a three-week period^4,20. This consideration does, however, limit the prophylactic role of radiation therapy at the time of the injury, particularly in patients who have neurological injury, in whom involvement of multiple joints is the rule rather than the exception^13,28,29.

The pain and dysfunction after irradiation of the brachial plexus in the treatment of breast carcinoma is well known. These effects have been seen after high-dose and fractionation regimens with use of older orthovoltage and cobalt irradiation techniques, which are no longer employed^21,30. The relative resistance of peripheral nerves to radiation²⁷, combined with modern low-dose megavoltage techniques that deliver doses in multiple fractions, seems to offer considerable protection against this possibility. Irradiation of the femoral and sciatic nerves during treatment of the hip during the last quarter of a century has not, to our knowledge, resulted in a single reported case of radiation-induced neuritis, attesting to the apparent safety of this technique.

On the basis of the findings of the present study, it seems that long delays of a year or more before excision of heterotopic ossification can be eliminated. Radiation therapy has proved effective in the prevention of heterotopic ossification at other anatomical sites, particularly about the hip^2,3,6. This effect is postulated to be due to radiation injury to rapidly dividing mesenchymal cells, which prevents their differentiation into osteoblasts²⁶. This protective effect may prevent heterotopic ossification from recurring about the elbow after early excision.

Additional studies are needed to define the relative risk of recurrence in the various clinical settings in which heterotopic ossification is seen and to determine whether radiation therapy is necessary to prevent recurrence after early excision in each of these instances. Additional experience with single-dose and preoperative radiation-therapy protocols, as are being attempted in conjunction with total hip arthroplasty³, may improve and simplify this technique even more. It should be noted, however, that fractionated or multiple-dose protocols have less of a biological effect than the same amount of radiation given as a single dose and may serve to increase the margin of safety²². The clinically ideal treatment would be an effective single low-dose radiation protocol that could be administered preoperatively.

	Footnotes

 

*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.

Read in part at the Annual Meeting of the American Society for Surgery of the Hand, San Francisco, California, September 13, 1995.

Cleveland Clinic Florida, 3000 West Cypress Creek Road, Fort Lauderdale, Florida 33309.

Department of Radiation Oncology (D-31), University of Miami School of Medicine, 1475 N. W. 12 Avenue, Miami, Florida 33136.

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