The prevention of heterotopic ossification in high-risk patients by low-dose radiation therapy after total hip arthroplasty

A prospective study was done to evaluate the efficacy of treatment with 1,000 rads of radiation in the prevention of heterotopic ossification after total hip arthroplasty in patients who are at high risk. In a previous prospective study, patients who were at high risk for heterotopic ossification after total hip arthroplasty were identified and an effective regimen for its prevention was established. It was demonstrated that treatment with 2,000 rads of radiation that was initiated within four days after the total hip arthroplasty was highly effective in the prevention of heterotopic ossification and in the prevention of recurrence after resection of existing ossification. In the present study, 1,000 rads of radiation was administered in increments of 200 rads over a period of five to seven days and was as effective as treatment with 2,000 rads. The protocol of 1,000 rads is preferable because it reduces the risk of malignancy and the duration of hospitalization.     

Prophylaxis of heterotopic ossification after total hip arthroplasty

We performed a randomized, prospective study on the prophylaxis of heterotopic ossification (HO) after total hip arthroplasty (THR), comparing indomethacin and the selective COX-2 inhibitor meloxicam. From the day after surgery, 272 patients were treated with 7.5 mg meloxicam, 15 mg meloxicam, or 2 × 50 mg indomethacin a day, for 14 days. After 6 months, radiographs of patients treated with 7.5 mg meloxicam showed that HO had occurred in one third. This treatment was therefore stopped after 26 patients have been assigned to this group. According to the intention-to-treat principle, patients given 15 mg meloxicam developed HO in 25% (20% Brooker grade I,4% grade II and 1 % grade III) and those given indomethacin in 10% (7% Brooker grade I,1% grade II and 2% grade III), a statistically significant difference.     

Functional significance of heterotopic bone formation after total hip arthroplasty

The effects of heterotopic bone formation on hip function after arthroplasty was studied in 145 cases of total hip arthroplasty. Hip muscle strength was determined 1.8-2.9 years after the operation, using a Cybex II dynamometer. Heterotopic bone formation was seen after 75% of the operations, and in 21% significant amounts developed (Brooker's classes III and IV). The gain in range of motion after surgery was significantly less in the groups with class III or IV heterotopic bone than in those without heterotopic bone formation. Heterotopic bone did not cause pain or Trendelenburg's limp after surgery; in fact, patients with trochanteric pain had less heterotopic bone than those without this pain. Hip flexion strength was greater in men with heterotopic bone than in those without heterotopic bone. Also, men with heterotopic bone formation had a higher mean maximum strength in extension but lower mean strength in abduction than did men without heterotopic bone (NS). When only patients with unilateral hip disease were considered, the same differences were found around the healthy hip; men with heterotopic bone formation had greater strength in flexion and extension than men without heterotopic bone formation and the same tendencies were seen in women. Accordingly, heterotopic bone had no serious impact on hip muscle strength in this study.     

Flurbiprofen inhibits heterotopic bone formation in total hip arthroplasty

Summary A double-blind prospective parallel group study comparing slow-release flurbiprofen with placebo in the control of ectopic bone formation was carried out in 68 patients undergoing total hip arthroplasty. Eight weeks after surgery there was evidence, significant at the 1% level, that the incidence and extent of periarticular calcification was lower in the flurbiprofen group. At an early phase, serum calcium level decreased and after 8 weeks serum alkaline phosphatase level increased more in the placebo group than in the flurbiprofen group, indicating an effect of flurbiprofen on bone mineral metabolism. Six patients were withdrawn in each treatment group, four due to side effects in the flurbiprofen group and three due to side effects in the placebo group. Overall, five patients in each group reported side effects, the nature and severity of the side effects being very similar in each group. We conclude that flurbiprofen is an efficient and safe drug in limiting ectopic bone formation following total hip arthroplasty. Heterotopic bone formation is a frequent complication after total hip replacement [1, 2, 4–6, 8–16]. Heterotopic bone reduces the extent of hip motion, reduction being more evident in cases with extensive ectopic bone formation around the hip joint [3, 10, 11]. Various treatment regimens have been proposed for discouraging heterotopic bone formation. Anti-inflammatory agents such as indomethacin and ibuprofen have turned out effective [11, 12, 14]. Local irradiation also prevents ectopic bone formation [4], but diphosphonates seem not be effective in this respect [15]. The aim of the present study was to assess the efficacy of flurbiprofen, a new anti-inflammatory agent, in limiting heterotopic bone formation, and to note the frequency and severity of any side effects of the treatment.     

Erythrocyte sedimentation rate and heterotopic bone formation after cemented total hip arthroplasty

The erythrocyte sedimentation rate (ESR) was analyzed in 176 patients treated with cemented total hip arthroplasty (THA) for primary osteoarthritis and correlated with the degree of heterotopic bone formation (HBF) one year after the THA. Ninety patients were treated with indomethacin in the first six postoperative weeks, and 86 patients had no antiinflammatory treatment during that same period. The ESR was measured with the Westergren method and estimated preoperatively and six and 12 weeks after THA. Patients treated with indomethacin had no or only Grade I HBF and no significant elevation in the six- and 12-week ESR. In the placebo group, 44 patients (51%) developed Grade II or Grade III HBF, and six weeks after THA, patients with Grade III HBF had a significant elevated ESR when compared with patients without or with Grade I HBF. Moreover, in patients not treated with indomethacin in the first six postoperative weeks, an ESR above 35 mm/hour 12 weeks after THA was found to be a reliable predictor for the development of severe HBF.     

Heterotopic bone formation after total hip arthroplasty.

Formation of heterotopic bone can cause pain and limit motion, thus ruin what would otherwise have been an excellent result after total hip arthroplasty. The cause of bone formation remains controversial, and diphosphonates have been ineffective in its prevention. Radiotherapy and nonsteroidal anti-inflammatory drugs, however, are effective preventative agents. Once the bone is formed, however, surgical excision is the only effective treatment.     

Heterotopic bone formation after total hip arthroplasty.

Heterotopic bone formation is a common complication of total hip arthroplasty. A certain degree of heterotopic bone formation occurs in about one-half of the patients in degrees ranging from very mild to moderate involvement. The patients do not necessarily have any clinical disability; only 2 per cent of the patients developed severe heterotopic bone radiographically, and unsatisfactory functional results. There is no sex predilection for heterotopic bone formation except that the condition appears more severe in females. All ages are equally affected. The underlying disease process in the hip does not influence the occurrence of heterotopic bone. The incidence was significantly greater in patients who developed postoperative hematomas, prolonged wound drainage, or superficial infection. When surgical exposure is difficult and retraction of soft tissue aand soft tissue damage takes place, the incidence is much greater. Patients who have undergone previous surgical procedures about the hip present a greater risk in regards to development of disabling heterotopic bone formation.The etiology of heterotopic bone formation is not known. The following steps should be taken to avoid or greatly minimize the development of heterotopic bone: meticulous exposure with most careful retraction, copious irrigation with antibiotic solution, debridement of devitalized tissue prior to closure, instillation of drainage tubes, intraoperative and postoperative antibiotics, and carefully controlled postoperative anticoagulation.     

Effect of short-course indomethacin on heterotopic bone formation after uncemented total hip arthroplasty

One hundred consecutive total hip arthroplasties (THA) were allocated into two groups: 92 patients received 25 mg of indomethacin three times daily for 10 days starting on the first postoperative day; 108 patients received no prophylactic treatment. Clinical examination and radiographs were evaluated by an independent observer at 3, 6, 12, and 24 postoperative months. No difference was noted at the bone-prosthesis interface between the two groups. Short-course indomethacin was felt to deter heterotopic bone formation significantly, while having no deleterious effect on stabilization of the St. Michael's madreporic system. Clinical examination and radiographs were evaluated by an independent observer at 3 and 6 postoperative months; all patients have continued to be observed, with an average follow-up period of 2 years following surgery.     

Extensive spinal osteophytosis as a risk factor for heterotopic bone formation after total hip arthroplasty

Observations on 54 patients present circumstantial evidence of a relationship between an underlying spinal ossifying diathesis and the heterotopic bone formation following total hip arthroplasty. This relationship should be investigated in a larger patient population to determine whether a spine-hip diathesis exists and could account for some patients with this complication. If it can be statistically substantiated, spinal roentgenograms may provide a preoperative screening procedure for the identification of "a population at risk" of heterotopic bone formation who might benefit from a prophylactic medical regimen.     

Ectopic bone formation after total hip arthroplasty

Ectopic bone formation (EBF) is a well-known complication of total hip arthroplasty (THA). The etiology and pathogenesis are still obscure. An analysis of 119 consecutive patients with 129 primary THAs was performed to identify factors predisposing to ectopic bone formation, its frequency, and its effect on the results. Gender (male) and the duration of the operative procedure were statistically significant factors in the development of ectopic bone, which occurred in 63% of hips. The effect of grade III EBF on THA was a limited range of movement. Both local and systemic factors seem to play a role in the development of ectopic bone. Gentle handling of tissues may be important if the rate of ectopic bone is to be reduced.     

Single-dose radiation therapy for prevention of heterotopic ossification after total hip arthroplasty

Single-dose radiation therapy was prospectively evaluated for its efficacy in prevention of heterotopic ossification in patients at high risk after total hip arthroplasty. Thirty-one patients (34 hips) were treated between 1981 and 1988. Risk factors for inclusion in the protocol included prior evidence of heterotopic ossification, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis. Patients with hypertrophic osteoarthritis or traumatic arthritis with osteophytes were not included. Operations on 34 hips included 19 primary total and 11 revision total hip arthroplasties and 4 excisions of heterotopic ossification. All patients received radiotherapy to the hip after operation with a single dose of 700 centigray. Radiotherapy is recommended on the first postoperative day. After this single-dose radiation treatment, no patient had clinically significant heterotopic ossification. Recurrent disease developed in two hips (6%), as seen on radiography (grades 2 and 3). This series documents a 100% clinical success rate and a 94% radiographic success rate in preventing heterotopic ossification in patients at high risk after total hip arthroplasty. Single-dose radiotherapy is as effective as other radiation protocols in preventing heterotopic ossification after total hip arthroplasty. It is less expensive and easier to administer than multidose radiotherapy.     

Excision of heterotopic bone followed by irradiation after total hip arthroplasty.

Twelve patients who had had a total hip arthroplasty had extensive excision of heterotopic bone, followed by prompt, low-dose irradiation, between 1983 and 1990. Volumes of as much as 900 milliliters of heterotopic bone tissue were resected. Of these patients, eleven had excellent relief of pain, and all twelve gained an average of 45 degrees of flexion and 25 degrees of abduction. Two patients had a recurrence of heterotopic bone (Brooker et al. class II); however, only one of these patients was symptomatic and had a result that was considered a failure.     

Effects of heterotopic bone formation on outcome after hip arthroplasty

Background: Heterotopic bone formation (HBF) is well established as a frequent complication of major hip surgery, but its importance as a cause of impaired postoperative outcome is uncertain. Methods: A systematic overview of all studies that reported the association of HBF with the risk of impaired range of movement, pain or poor function, late after hip arthroplasty. Results: A computer‐based search identified 37 relevant studies that included 10 826 individuals. There were 30 studies (8305 participants) that assessed the association between HBF and range of movement, 14 studies (7420 participants) that assessed the association between HBF and pain and 16 studies (5918 participants) that assessed the association between HBF and function. Overall, there was a clear positive association of HBF with the risk of an impaired range of movement at the hip joint and with the risk of a poor functional outcome. The association of HBF with pain was unclear. There was evidence of effects of mild‐to‐moderate HBF on the postoperative range of movement. Conclusions: These results suggest that mild‐to‐moderate HBF, not just severe HBF, can influence outcome after major hip ­surgery. HBF may therefore be a more frequent cause of postoperative symptomatology than is generally believed. It is possible that effective prophylactic regimens will improve outcomes in large numbers of patients.     

Prophylactic indomethacin for the prevention of heterotopic bone formation following total hip arthroplasty

In July 1977, prophylactic indomethacin for "high-risk" total hip arthroplasty candidates was adopted for the prevention of heterotopic bone formation. A total of 1053 patients were included in this retrospective study. Five hundred twenty-five patients were operated on before July 1977, whereas 528 patients had a total hip arthroplasty after July 1977, when the indomethacin program was initiated. Eighty-one of the 528 patients operated on after July 1977 were identified as high-risk surgical candidates and therefore received prophylactic coverage. None of the 81 patients treated with indomethacin developed the functionally disabling Grade II or III ectopic ossification. Statistical analysis revealed a marked different (p less than .001) between the overall incidence of heterotopic bone formation in patients operated on before July 1977 and that of patients who had hip procedures after July 1977, when the indomethacin program began. Surprisingly, the action of indomethacin on bone metabolism did not seem to retard fusion of the greater trochanter with the femur or alter the frequency of nonunion.     

Prophylaxis for heterotopic ossification after primary total hip arthroplasty. A cohort study between indomethacin and meloxicam

The authors have conducted a prospective cohort study of the efficacy of a 7 days administration of Indomethacin (n = 89) versus Meloxicam (n = 92), in the prophylaxis of heterotopic ossification (HO) in primary total hip arthroplasty. To assess the interobserver variability of the Brooker classification, all radiographs were evaluated by three investigators. In the Indomethacin group 25 patients developed HO (grade I: 22, grade III: 2 and grade IV: 1). In the Meloxicam group 34 developed HO (grade I: 30, grade II: 1 and grade III: 3). We were not able to show any difference between Indomethacin and Meloxicam in preventing heterotopic ossification after primary hip arthroplasty. We found a high interobserver variability in the grading system according to Brooker, in particular for the higher grades(grade II, III and IV).     

Prophylaxis against venous thrombosis after total hip arthroplasty.

Venous thrombosis rates were compared in 200 patients undergoing total hip arthroplasty and randomized to receive either fixed mini-dose warfarin (1 mg daily) or adjusted-dose warfarin to maintain an international normalized prothrombin ratio (INR) of 2.0-4.0. Bilateral lower limb venography was performed between days 11 and 13 inclusive. Fixed mini-dose warfarin was associated with a significantly higher rate of total thrombosis (P less than 0.05). General anaesthesia was associated with a significantly higher rate of thrombosis than spinal anaesthesia (P less than 0.05). Adjusted-dose warfarin was associated with more bleeding complications than mini-dose warfarin although these were not attributable to excessive anticoagulation. A single death from pulmonary embolus occurred in the early postoperative period in a patient receiving adjusted-dose warfarin.     

Indomethacin for prevention of heterotopic ossification after total hip arthroplasty.

Twenty-four patients (29 hips) undergoing total hip arthroplasty were routinely given 75 mg of indomethacin daily for 4 weeks after operation and reviewed radiographically for heterotopic ossification (HO) for a minimum of 6 months. A comparison group of 25 patients (27 hips) without indomethacin treatment was formed and studied in the same manner. This group of patients received the usual postoperative analgesic treatment, which is diclofenac sodium twice daily parenterally for 5-10 days. The indomethacin group also received the same treatment. In the indomethacin group no patient had grade II, III, and grade IV HO and the incidence of grade I HO was 31% (nine patients). In the comparison group one patient (3%) had grade I, three (11%) grade II, and eight (30%) grade III HO. These findings suggested that indomethacin effectively prevented higher grades of HO following total hip arthroplasty. Two patients not included in the study had gastrointestinal bleeding and recovered after withdrawal of the drug.     

Indomethacin versus radiation therapy for heterotopic ossification after hip arthroplasty.

This study compared the efficacy and cost of radiation therapy with indomethacin in the prophylaxis of heterotopic ossification following total hip replacement. Twenty-two patients received a radiation dose of 10 Gy in five fractions, 28 patients 8 Gy in one fraction, and 27 patients 25 mg oral indomethacin three times a day for either 7 or 21 days. Patients at higher risk for heterotopic ossification were more likely to receive radiation therapy than indomethacin. At a mean follow-up of 2 years, there were no differences in failure rates between the high-risk patients treated with radiation and the low-risk patients treated with indomethacin. Currently, the patient-billed cost of radiation is $1400 whereas the cost for indomethacin is approximately $100. Indomethacin appears to be as effective as radiation therapy in patients at low to moderate risk for heterotopic ossification and offers significant cost savings.     

Radiation prophylaxis of heterotopic bone formation following total hip arthroplasty: current status

Differentiation of pluripotential stem cells into osteogenic precursors is exquisitely sensitive to ionizing radiation. Radiation prophylaxis effectively prevents ectopic ossification if delivered to the operative site within 5 days following total hip arthroplasty. Continued efforts at dose reduction over the last decade have demonstrated efficacy with as little as 6,000 to 8,000 rad; no soft tissue sarcomas have been reported in this low dose range following treatment of malignant disease. Precise limitation of the treatment field is necessary for application of this modality to cementless implants dependent on bony ingrowth for stable fixation. Trochanteric nonunion is reported in 25% of hips following radiation prophylaxis, but this is as likely related to the high proportion of revision surgery in these series as it is a direct consequence of the radiation.