Short-course indomethacin prevents heterotopic ossification in a high-risk population following total hip arthroplasty

The efficacy of a 10-day course of indomethacin in preventing heterotopic ossification after total hip arthroplasty was studied in a consecutive series of male patients who were at increased risk for bone formation. Between September 1991 and June 1994, all male patients (123 hips in 109 patients) who underwent total hip, revision, or surface arthroplasty were placed on a 10-day course of indomethacin. Of these, 106 patients (119 hips) successfully completed the 10-day course. There was no significant formation of heterotopic ossification (Brooker grade III or IV). From a group of 45 known heterotopic bone formers following previous total hip arthroplasty, only 2 developed new heterotopic ossification. Overall there were 9 (7.6%) new cases of heterotopic ossification: 7 Brooker grade 1 (5 primary and 2 revision cases) and 2 Brooker grade II (both primary cases). A 10-day course of indomethacin prevents the more significant grades of heterotopic ossification and is effective at reducing the incidence of heterotopic ossification following total hip arthroplasty. Further, this regimen appears safe and cost effective.     

Similar effects of rofecoxib and indomethacin on the incidence of heterotopic ossification after hip arthroplasty

BACKGROUND: Although indomethacin is effective in preventing heterotopic ossification (HO) after primary total hip arthroplasty, side effects are frequently observed. In the last decade a new class of drugs--the COX-2 selective nonsteroidal anti-inflammatory drugs--has been developed. To investigate the effect of these COX-2 selective NSAIDs on heterotopic ossification (HO) after primary total hip arthroplasty (THA), we conducted a randomized controlled trial using either indomethacin or rofecoxib for 7 days. METHODS: 186 patients received either indomethacin 3 times daily, or rofecoxib twice, and 1 placebo, daily for 7 days. HO was graded according to the 1-year postoperative radiographs according to the Brooker classification. RESULTS: 12 of the 186 patients included discontinued their medication before the end of the trial due to side effects. The remaining 174 patients were included in the analysis. In the indomethacin group (n = 89), 77 patients (87%) showed no HO, 9 showed HO of grade 1 and 3 showed HO of grade 2 according to the Brooker classification. In the rofecoxib group (n = 85) 73 patients (86%) showed no ossification, 9 showed grade 1, and 3 showed grade 2. INTERPRETATION: The prophylactic effect of rofecoxib for 7 days in preventing heterotopic ossification after primary total hip arthroplasty is comparable to the effect of indomethacin given for 7 days. These results indicate that the development of HO follows a COX-2 pathway.     

Prophylaxis of heterotopic ossification after total hip arthroplasty: a prospective randomized study comparing indomethacin and meloxicam

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 x 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.     

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.     

Prophylaxis of heterotopic ossification after total hip arthroplasty: A prospective randomized study comparing indomethacin and meloxicam

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.     

Indomethacin for 3 days is not effective as prophylaxis for heterotopic ossification after primary total hip arthroplasty.

Although indomethacin is effective in preventing heterotopic ossification (HO) after total hip arthroplasty (THA) when used for 8 to 14 days, side effects are frequently observed. We conducted a prospective, nonrandomized pilot study of prophylaxis for HO in THA using indomethacin for 3 days. We used a 2-stage design for phase 2 clinical data, based on earlier studies in our department. Our study group consisted of 19 patients, of whom 14 (74%) developed HO; 7 (37%) showed grade 1, 4 (21%) grade II, and 3 (15.8%) grade III according to the Brooker classification. We compared these results with 2 historic control groups; one group received indomethacin for 7 days, and the other group received no prophylaxis. We did not see any reduction of the ossification relative to the group that received no prophylaxis. Indomethacin for 3 days seems not to be sufficient to prevent HO.     

Heterotopic ossification after uncemented hydroxyapatite-coated primary total hip arthroplasty

A total of 134 patients who had a cementless hydroxyapatite-coated total hip arthroplasty (THA) and had no recognized risk factors for heterotopic ossification (HO) were reviewed retrospectively. The average follow-up period was 83 months. Pharmacologic or radiotherapeutic prophylaxis against HO was not used. HO was seen in 90 (67.2%) of the 134 patients reviewed. HO was rated as Brooker class I in 68 (50.7%) patients, class II in 17 (12.7%) patients, class III in 3 (2.2%) patients, and class IV in 2 (1.5%) patients. The average Merle d' Aubigne score in patients with mild forms of HO (Brooker classes I and II) was 16 compared with 13.2 in patients with severe HO (Brooker classes III and IV). A statistically significant negative correlation was found between the presence of HO and the postoperative hip score. Based on our study findings and on a comparison with data in the literature, hydroxyapatite-coated cementless THA alone does not seem to increase the likelihood of HO over other types of THA. The presence of a hydroxyapatite coating does not result in more class III or IV HO, which are the only classes of HO with real clinical significance. Fear of HO should not be a factor in the choice of fixation for THA.     

Distal femoral allograft for massive proximal femoral deficiency

Background?Although indomethacin is effective in preventing heterotopic ossification (HO) after primary total hip arthroplasty, side effects are frequently observed. In the last decade a new class of drugs—the COX-2 selective nonsteroidal anti-inflammatory drugs—has been developed. To investigate the effect of these COX-2 selective NSAIDs on heterotopic ossification (HO) after primary total hip arthroplasty (THA), we conducted a randomized controlled trial using either indomethacin or rofecoxib for 7 days.

Methods?186 patients received either indomethacin 3 times daily, or rofecoxib twice, and 1 placebo, daily for 7 days. HO was graded according to the 1-year postoperative radiographs according to the Brooker classification.

Results?12 of the 186 patients included discontinued their medication before the end of the trial due to side effects. The remaining 174 patients were included in the analysis. In the indomethacin group (n = 89), 77 patients (87%) showed no HO, 9 showed HO of grade 1 and 3 showed HO of grade 2 according to the Brooker classification. In the rofecoxib group (n = 85) 73 patients (86%) showed no ossification, 9 showed grade 1, and 3 showed grade 2.

Interpretation?The prophylactic effect of rofecoxib for 7 days in preventing heteropic ossification after primary total hip arthroplasty is comparable to the effect of indomethacin given for 7 days. These results indicate that the development of HO follows a COX-2 pathway.     

Heterotopic Ossification After 2-Incision Total Hip Arthroplasty

We examined the incidence of heterotopic ossification (HO) in a consecutive series of total hip arthroplasties (THAs) performed with the so-called minimally invasive, 2-incision technique. Standard preoperative hip radiographs were used to grade the extent of degenerative arthritis, and comparable follow-up radiographs at 30 months after surgery were used to detect and classify HO formation. Of 121 patients, 32 (26.5%) developed HO, with the Brooker class distribution as follows: stage I, 16 patients; stage II, 9 patients; stage III, 6 patients; stage IV, 1 patient. In this study, HO formation after 2-incision THA occurred with nearly the same frequency as that reported in other studies after standard THA.     

Heterotopic ossification in total hip arthroplasty: the significance for clinical outcome

This study evaluates 706 patients with 835 primary total hip replacements documented in a prospective fashion in a multicenter study with respect to correlation between heterotopic ossification (HO) and clinical outcome. Only patients without prophylaxis against HO entered the study. The mean clinical and radiological follow-up was 3.1 years (+/- 0.7). Heterotopic ossification was noted in 47% of all total hips replaced. It was graded as mild (Brooker I) in 29.1%, moderate (Brooker II) in 12.7%, and severe (Brooker III and IV) in 5.2%. All clinical parameters investigated were significantly affected with the increasing amount of heterotopic ossification. The strongest correlation was found in flexion range and spreading distance. Both factors were significantly decreased with higher degrees of ossification. The other clinical parameters investigated, walking capacity, limp, and use of analgesics, were altered to a lesser extent and only with higher degrees of heterotopic bone formation. Finally, patient satisfaction was significantly influenced by the degree of heterotopic ossification and dropped from almost 90% good or excellent patient satisfaction in the non-ossification group to less than 30% in the group with severe ossification.     

Prevalence of heterotopic ossification in cemented versus noncemented total hip joint replacement in patients with osteoarthrosis: a randomized clinical trial

Objective

To determine the prevalence of heterotopic bone formation in cemented versus noncemented total hip joint replacement.

Design

A prospective randomized controlled trial. Follow-up ranged from 2 to 6 years (mean 4 years).

Setting

A university hospital.

Patients

Two hundred and twenty-six patients who had primary or secondary osteoarthrosis of the hip were stratified according to type of fixation, surgeon and age. Patients were randomized within strata: 112 received noncemented total hip prostheses and 114 received cemented prostheses. The 2 groups were similar with respect to age and sex.

Intervention

Primary total hip arthroplasty. A cemented (methylmethacrylate) or noncemented prosthesis was inserted by a lateral surgical approach.

Main outcome measure

The Brooker classification was used to grade heterotopic bone formation from postoperative radiographs.

Results

Overall, 148 (66%) hips had no heterotopic ossification, 56 (25%) were Brooker class I, 14 (6%) were class II, 8 (3%) were class III and none were class IV. In the noncemented group of patients, 76 (68%) hips had no heterotopic ossification, 25 (22%) were Brooker class I, 7 (6%) were class II, 4 (4%) were class III and none were class IV. In the cemented group of patients, 72 (63%) hips had no heterotopic ossification, 31 (27%) hips were Brooker class I, 7 (6%) were class II, 4 (4%) were class III and none were class IV.

Conclusion

There was no significant difference in the prevalence of heterotopic ossification between cemented and noncemented total hip replacements in patients with osteoarthrosis.     

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.     

Clinical and radiological results of surgical removal of periarticular ossifications after hip prosthesis implantation

The occurrence of heterotopic ossification (HO) is a well-recognized problem after total hip replacement. In a retrospective study, we investigated 32 patients who had undergone surgical excision of symptomatic HO followed by radiation with 7 Gy and nonsteroidal anti-inflammatory drug therapy between 1994 and 1999. The mean follow-up was 20 months (range: 12-60). Clinical and radiographic follow-up examinations included Harris hip score and classification according to Brooker. The preoperative Brooker class was III in 16 cases and IV in 16 patients. Comparison of the Brooker classification at follow-up revealed a statistically significant improvement (p < 0.0001; class 0:3, class I: 14, class II: 8, class III: 7 patients). In one case with symptomatic Brooker class III ossification, surgical reexcision of HO was necessary. A statistically significant increase (p < 0.05) in mean range of motion (ROM) was observed in flexion [preoperative: 57 degrees (+/- 26), follow-up: 83 degrees (+/- 21)], in abduction [preoperative: 17 degrees (+/- 12), follow-up: 24 degrees (+/- 9)], and in rotation (preoperative: 16 degrees (+/- 17), follow-up: 31 degrees (+/- 18)]. Comparison of preoperative Harris hip score (60 +/- 11) and Harris hip score at the time of follow-up examination (73 +/- 17) revealed a statistically significant increase (p < 0.0001) after treatment. At the time of follow-up examination, 18 patients (56%) assessed their pain symptoms as low but 6 patients (19%) reported strong pain symptoms. Nevertheless, the score at the time of examination (35 +/- 10) was statistically improved (p < 0.02) when compared to the preoperative score (30 +/- 8). Surgical excision of Brooker class III or IV heterotopic ossification with limited ROM followed by irradiation and anti-inflammatory prophylaxis results in significant improvement in flexion, abduction, and rotation arc and significant reduction of HO in radiographic examination at follow-up, but pain relief was only satisfactory.     

Preliminary study of rofecoxib (25 mg) in prevention of heterotopic ossification after total hip replacement

Abstract Heterotopic ossification is a well-known complication of surgical approaches to the hip that involve dissection of the gluteal muscles. Heterotopic ossification has been reported as an incidental finding on radiographs of as many as 84% of patients who have had total hip arthroplasty. This study evaluated the possibility of using rofecoxib, a COX II selective inhibitor, to prevent heterotopic bone formation after total hip replacement. Sixty consecutive patients operated by the same surgeon, using the same surgical approach (lateral approach) for total hip replacement and who were considered to be at risk for postoperative heterotopic ossification, were enrolled into this prospective study. The patients were randomly assigned to one of two treatment groups: group 1 received rofecoxib (25 mg) daily from the day after total hip replacement for three weeks; group 2 received no pharmacological treatment.The two groups were clinically and radiographically controlled at 3-monthly intervals up to 1 year after surgery with a minimum follow-up of 6 months. Three patients in group 1 were lost to follow-up and consequently were not considered in the final evaluation.In group 1, 14 patients (51.9%) showed no ossification, 9 (33.3%) showed Brooker grade I ossification, 4 (14.8%) showed grade II ossification, and no patients with grades III and IV were detected. In group 2, 15 (50.0%) of the patients showed no ossification, 6 (20.0%) showed grade I ossification, 5 (16.7%) showed grade III ossification, and no patient with grade IV ossification was detected. The difference between the two treatment groups regarding extent of heterotopic ossification was statistically significant (p=0.028) and consequently gives a rational basis for a larger successive study.     

No effective prophylaxis of heterotopic ossification with short-term ibuprofen

Ninety-five patients underwent primary total hip arthroplasty and routinely received ibuprofen for 5 days as prophylaxis for heterotopic ossification. This group was compared with a group of 99 patients who received indomethacin for 7 days as prophylaxis. After a follow-up of 1 year, the incidence of heterotopic ossification in the ibuprofen group was significantly higher than in the indomethacin group. The widespread ossification, Brooker grades III and IV, was prevented better by indomethacin than by ibuprofen. We conclude that ibuprofen for 5 days is not effective as prophylaxis for heterotopic ossification after primary total hip arthroplasty.     

Prophylaxis of heterotopic ossification in hip revisions with 7 Gy single-dose radiation

AIM OF STUDY: Radiation therapy is an established method for the prevention of heterotopic ossification. The aim of this study was to assess whether radiation therapy is also effective in revision arthroplasties. METHOD: 143 hips were irradiated with 7 Gy anterior-posterior applied single dose radiation, on one of the first four days after revision surgery. RESULTS: After an average follow-up of 18 months, 107 hips were evaluated radiographically using Brooker's criteria. In comparison to the immediate postoperative findings (26 % showed no heterotopic ossification, 66 % had Brooker I, 5 % Brooker II, and 3 % Brooker III), at final follow-up 19 % showed no heterotopic ossification, 66 % had Brooker I, and 7.5 % Brooker II and III. New ossification or an increase of one grade was found in 12 %, of two grades in 4 %. Grade 0 showed significantly more ossifications. Gender (p = 0.43), age (p = 0.43), the type of revision surgery (p = 0.36), the day of radiation (1st day vs. 2nd, 3rd, 4th day; p = 0.46) had no significant influence on this increase. There was no correlation between pain score and Brooker grades (p = 0.755). There was a significantly (p < 0.01) negative correlation (r = - 0.31) between the Brooker grades and flexion. CONCLUSION: Radiation therapy with 7 Gy single dose effectively prevents the new formation of heterotopic ossification or the progression of ossifications after revision surgery. To prevent a decrease in the range of motion due to HO after revision surgery, HO should be removed intraoperatively.     

Trochanteric heterotopic ossification after total hip arthroplasty performed using a direct lateral approach

A unique pattern and location of symptomatic heterotopic ossification (HO) was observed in patients having total hip arthroplasty (THA) performed using a direct lateral approach, situated outside the hip capsule, distal, lateral, and anterior to the greater trochanter, designated as trochanteric heterotopic ossification (THO). Radiographs of 1420 consecutive primary total hip arthroplasties were reviewed. Three hundred and seventy hips (26%) developed HO around the hip and greater trochanter. One hundred of these hips (27%) demonstrated THO, without classic HO. Of the 270 cases containing a Brooker component, 110 hips exhibited additional HO (THO). Thus, THO occurred in 210 (14.8%) of 1420 THAs. Two patients required surgical excision of the HO after maturity, gaining full relief without recurrence. Trochanteric heterotopic ossification should be considered as a possible cause of early postoperative pain after THA performed using a direct lateral approach.     

Incidence of heterotopic ossification following total hip arthroplasty in patients with prior stroke

This study reviewed the incidence of heterotopic ossification and the functional limitations in a cohort of consecutive patients with prior stroke who underwent primary total hip arthroplasty (THA). Thirty-one primary THAs were performed in 22 patients who had a cerebrovascular accident prior to THA. Mean follow-up 35 months. The overall incidence of heterotopic ossification was 36%, with significant Brooker class III and IV heterotopic ossification reported in 22% of patients. The data suggest that prior cerebrovascular accident may pose an increased risk of significant heterotopic ossification following primary THA. Consideration of prophylaxis in this subset of patients may be warranted.     

Prophylaxis for heterotopic bone formation after total hip arthroplasty using low-dose radiation in high-risk patients.

Fifteen consecutive total hip arthroplasties (THAs) in 14 patients considered at risk for developing significant heterotopic ossification (HO) were treated postoperatively with 7.5 Gy of external beam radiation in three fractions. Eight hips in eight of the patients (Group I) had developed previous Brooker Class III or IV HO after THA and were radiated after having excision of HO in conjunction with a revision THA. Three additional hips in three patients (Group II) were radiated after primary THA, because they developed significant HO on the contralateral hip after a previous THA. The remaining four hips in three patients (Group III) were radiated after primary THA because they had bilateral hypertrophic arthritis. Precision shielding was employed to minimize the volume of tissue in the radiation field and to protect the bone-implant interface around porous-coated components and the trochanteric osteotomy sites. Of the eight hips in which Class III or IV bone was excised during revision THA (Group I), no new bone formed in five hips and in the other three hips, only Class I bone formed. No heterotopic bone formed in the remaining seven hips of Groups II and III. All six trochanteric osteotomies healed. There were no wound healing problems. There were no significant radiolucencies around any of the components and there was no radiographic evidence of implant instability. This regimen using 7.5 Gy over three fractions minimizes the radiobiologic impact, whereas the use of precision shielding minimizes the total volume of tissue treated. This regimen is an effective means of preventing significant HO after THA in high-risk patients while minimizing radiation exposure.     

Celecoxib and Heterotopic Bone Formation After Total Hip Arthroplasty

We assessed the effectiveness of celecoxib in the prevention of heterotopic ossification (HO) following primary total hip replacement (THR). We studied 170 consecutive THRs. Sixty-three patients received celecoxib after surgery (200 mg twice/daily) for 28 days and 84 did not. HO was more common in non-celecoxib patients than in the celecoxib-group at 3, 6, and 12 months (P = 0.005, 0.004 and 0.01, respectively). At 1 year, fewer celecoxib recipients had Brooker classes II or III. None of the celecoxib patients developed HO Brooker class IV, while 2% in the non-celecoxib group did. No patient discontinued treatment or had revision for aseptic loosening. A short course of celecoxib for pain aids in the prevention of HO after primary THR, and could be a useful and safe option that does not interfere with anticoagulation.