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British Journal of Radiology 75 (2002),448-452 © 2002 The British Institute of Radiology

Full Paper

Heterotopic bone formation: irradiation of high risk patients

P G S Cornes, FRCR1, M Shahidi, FRCR1 and J P Glees, FRCR1,2

Departments of 1 Radiotherapy and Oncology, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT and 2 Department of Radiotherapy, St Georges Hospital, Blackshaw Road, London SW17 OQT, UK


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 Conclusions
 References
 
The Royal Marsden Hospital has adopted a policy for patient selection for the use of adjuvant radiotherapy to prevent heterotopic new bone formation (HTBF) limited to those at greater than 50% risk. The treatment protocol is 7 Gy post-operative megavoltage radiotherapy at mid-plane, in one fraction, given within 72 h of surgery. Since the introduction of this protocol in 1993, 26 joints have been treated in 25 patients. The majority of cases were young people with acetabular fractures resulting from road traffic accidents, often alcohol related. Follow-up studies in this group of patients has proved difficult, as many fail to attend for follow up, and others have moved out of the catchment area. Of the 14 cases for which follow-up data is available, 13 remain fully mobile. One has not mobilized since the time of treatment and continues to use crutches. There is one case of recurrent HTBF seen on X-ray after 8 months, but the joint was mobile. By 5 years, all cases have failed to attend for follow-up. The true long-term risks of this treatment policy may not be known for 30 years. The failure of patients to attend even short-term follow-up is a potential problem for clinical oncologists.


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 Conclusions
 References
 
New bone formation occurs at sites of bone fracture as part of the normal healing process. When fractures occur within joint capsules, new bone formation can occur at that site too. This heterotopic new bone formation (HTBF) can ossify normally mobile soft tissue structures, causing pain and restricting movement. In extreme cases the joint can be fused and immobilized by a bridge of new bone across the joint. HTBF follows total hip arthroplasties in 14–30% of cases [1].

Heterotopic new bone formation is an early event after surgery involving joint spaces. Most cases have occurred within 6 weeks of trauma or surgery [2]. It is classified by increasing severity from I to IV using the Brooker scale, where class III and IV indicates bone spurs that reduce the space between mobile bones to less than 1 cm [3]. This severity of HTBF is usually associated with significant pain and restricted joint movement [4, 5].

Radiotherapy has been used as an adjuvant treatment to reduce the risk of HTBF following both traumatic fractures and elective surgical procedures in joint spaces [1, 6]. A small randomized trial of 154 patients from Philipps University, Marburg, Germany has shown that adjuvant radiotherapy or indomethacin may reduce the risk of symptomatic heterotopic bone formation compared with surgery alone for prosthetic hip replacement [7]. A second small randomized trial of 75 patients from the University of Missouri Hospital and Clinics. Columbia, MO compared adjuvant indomethacin with radiation therapy for the prevention of HTBF after open reduction and internal fixation of acetabular fractures [8]. Although the rate of symptomatic HTBF was halved in the radiotherapy group, the result was not significant.

Case control studies suggest that the risk of any HTBF following surgery in high risk hip replacements falls from 32–40% to 6–7% with the addition of a single post-operative fraction of radiotherapy, and that severe cases of HTBF, Brooker grade IV, are prevented (6% vs 0%) [9–11].

Randomized trials have shown a single fraction to be as effective as multifraction schedules [12–14], and case control studies have shown that 7 Gy in a single fraction appears more effective than 5.5 Gy in a single fraction [15]. Case control studies suggest that early post-operative radiotherapy is more effective than when delayed by 4 days or more [11, 16, 17].

For low risk cases, adjuvant pre-operative radiotherapy is as effective as post-operative radiotherapy, but in high risk cases, such as patients with ipsilateral high Brooker Grade III and IV HTBF undergoing re-operation, post-operative radiotherapy appears more effective [14].

As radiotherapy for benign disease has a potential for long-term risks, local protocol restricted the use of radiotherapy to those patients at greatest risk of HTBF, to minimize the risk:benefit ratio. High risk patients were defined as patients in whom a risk of significant HTBF was 50% or greater after surgery. These included traumatic fracture through the articular surfaces of the hip and elbow joints and those undergoing elective total hip replacement with a past history of ankylosing spondylitis, hypertrophic osteoarthritis or diffuse idiopathic skeletal hyperostosis [1, 18–24]. In comparison, HTBF is seen radiographically in only 30% of elective hip replacements or arthroplasties, and only 3–10% of these will show limitation of movement caused by HTBF.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 Conclusions
 References
 
Adjuvant radiotherapy was given within 3 days of surgery. Written informed consent was obtained. The planning target volume was the entire area encompassed by the relevant joint capsule. Target volumes and shielding were planned on a treatment simulator as incorrect positioning of the block can cause loosening of a cementless prosthesis [25, 26]. Parallel opposed beams were used with shadow tray mounted shielding blocks. A dose of 7 Gy at mid-plane in one fraction was given with 6 MV photons at 100 cm source-to-skin distance (SSD) or Cobalt-60 at 80 cm SSD.

Since the introduction of this protocol at our hospital, 26 joints have been treated in 25 patients. 18 cases were male and 7 female. 17 cases (65%) were for fractures of the pelvis through the acetabulum, 5 (19%) were for established HTBF undergoing re-operation, and 4 (15%) were in the high risk category of those undergoing elective total hip replacement with a past history of ankylosing spondylitis, hypertrophic osteoarthritis or diffuse idiopathic skeletal hyperostosis.

The mean overall age was 39 years (range 19–81 years), the mean age of trauma cases being 33 years (range 19–49 years), which is low in comparison with other reported series. In a study of 67 cases at the University of Rochester Medical Center, only 3 patients under 50-years-old were treated in a 5-year period [1].


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 Conclusions
 References
 
There was no acute toxicity from radiotherapy. The transfer of patients from the trauma ward to the radiotherapy department involved interhospital ambulance transport in all cases. Several patients were transferred direct from intensive care units. Many patients were in pain, with several requiring opiate analgesia to tolerate the limb movement needed for positioning for treatment. Despite this, there were only two cases outside the protocol that required adjuvant radiotherapy to be given by the third post-operative day (mean delay 3 days). There is case control evidence that delays beyond 4 days may be associated with worse outcomes [11, 17].

Treatment benefit and late toxicity data have proved difficult to obtain because of failure to attend follow-up. The majority of cases treated were young people injured in road traffic accidents, often alcohol related. Follow-up studies in this group of patients has proved difficult, as many do not attend clinics, and others have moved out of the catchment area in the follow-up period. Young city dwellers are a mobile population. Of the 25 patients, 1 returned overseas within the first month. 10 local patients defaulted follow-up with the orthopaedic and radiotherapy services after hospital discharge (44% failure of immediate follow-up). Despite attempts at contact through hospital and primary care services, results have not been obtained for any of these 11 cases. Of the 14 cases for which follow-up data is available, 13 remain fully mobile. 1 patient has not mobilized since treatment and continues walking with crutches. There was one case of asymptomatic HTBF seen radiographically at 8 months follow-up. The joint had a full range of movement. By 5 years post treatment, all patients had been lost to follow-up. There were no radiotherapy consultations, nor any further clinical reports on patients outcomes available from the trauma, orthopaedic, family practice or other teams.

Late toxicity data is available only from this restricted follow-up. There has been one case of avascular necrosis of irradiated bone judged by radiograph criteria 7 months after treatment. In this case the patient sustained traumatic fracture through the pelvis at the acetabulum, with an ipsilateral fractured neck of femur, and had surgical reconstruction of both fracture sites. Damage to the vascular supply of the bone may explain the necrosis, but the contribution of radiation cannot be excluded. The patient is fully mobile, but a hip prosthesis may be required in the future.


   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
Conclusions
 References
 
By adopting strict criteria to limit the use of adjuvant radiotherapy for benign disease, we have selected a group of patients who appear to be at greatest risk of late toxicity but who comply poorly with attempts to follow them up. The patients selected by this policy are usually young people, injured in road traffic accidents following alcohol consumption.

These young patients have many years to live, when both the benefits and risks of adjuvant radiotherapy can be seen. Within 2 years of starting this protocol, only 14 of 25 patients treated were still being seen, a 44% loss to follow-up in 24 months. By 5 years, all patients had been lost to follow-up.

From the limited data available, adjuvant treatment has proved effective. The cases treated were all expected to have a 50% or greater risk of HTBF after surgery and this would be likely to have occurred within 6 weeks of joint trauma or surgery [2, 18, 21, 24]. Of the 14 patients followed up, joint mobility was restored and maintained in 13 cases. One patient never regained mobility after surgery, and 1 had radiological, but not clinical, evidence of HTBF.

Radiation-induced malignancies are rare, but sarcomas occur with a median latent period of more than a decade [27]. Radiation-induced malignancy seems to be a greater risk in patients irradiated when young [28, 29]. The effect of a large single fraction of irradiation, as opposed to multifraction treatments used in the past, needs to be audited, especially with respect to development of late osteonecrosis [12]. Data from the large randomized trials of single vs multifraction radiotherapy for the palliation bone metastases is not relevant.

It seems unlikely that a single radiotherapy centre can perform this audit accurately, and so cooperation will be required to ensure that the long-term risks and benefits of radiotherapy to prevent HTBF are recognized.

The University Erlangen-Nurnberg, Erlangen, Germany has randomized 410 patients with a high risk of developing HTBF following hip surgery in two trials of dose and sequencing of radiotherapy. Patients were recruited between June 1987 and December 1995. It is reassuring that there was no increase in post-operative complications, and no long-term complications were observed in these studies [14]. However, at the latest report, these studies have a maximum of only 10 years follow-up and involved patients with a greater average age than our patients.

The Henry Ford Hospital, Detroit, MI, has followed a group of 53 patients with high risk acetabular fractures treated with adjuvant radiotherapy from 1987 to 1991 [30]. They were given either 12 Gy mid-plane dose (MPD) in three daily doses or a single 7 Gy MPD dose on the first post-operative day. All patients were followed for at least 1 year post-operatively and no complications have been reported.

The UCLA Medical Center, Torrance, CA has reported a similar patient group. 68 patients with 69 acetabular fractures were followed for an average of 21 months (range 3–98 months) [22]. 20 (59%) of 34 untreated fractures developed HTBF, of which 9 (26%) were Grade III or IV, but only 5 patients had received adjuvant radiotherapy as part of their treatment.

The effects of radiotherapy on adult bone are understood poorly. Scoliosis, epiphyseal slippage, avascular necrosis and abnormalities of craniofacial growth may be observed after radiation of children [31]. Osteoporosis, medullary fibrosis and direct killing of bone cells can lead to fracture or necrosis in adults.

Radiation-induced second malignancy has been reported in many series of patients treated with radiotherapy for Hodgkin's disease [32–34]. Patients who are 24 years of age or younger appear to be at greater risk than those treated when older [28, 29]. Hodgkin's disease patients seem to be more compliant with follow-up than road traffic accident cases.

There is no doubt that radiotherapy has been an effective treatment for ankylosing spondylitis, a potentially disabling benign condition. In the UK, 13 914 patients received radiotherapy between 1935 and 1957 for this condition. By 1 January 1992 there were 60 deaths from leukemia among this group, between two and three times more than the expected rate [35]. By 35 years after first radiotherapy, cancer specific mortality was significantly greater than expected for leukaemia, non-Hodgkin's lymphoma, multiple myeloma and cancers of the oesophagus, colon, pancreas, bones, connective and soft tissue, prostate, bladder and kidneys [36].

It can be argued that these data are not applicable to heterotopic bone treatments as a greater total body exposure occurs with spinal radiotherapy for ankylosing spondylitis. Pelvic radiotherapy with limited fields has been given for metropathia haemorrhagica, with doses in the range 2.6–5.3 Gy [37]. Subsequent standardized mortality ratio was increased for bladder cancer, myeloma and leukaemia. Mortality was higher more than 30 years after radiotherapy than between 5 years and 29 years after radiotherapy. This suggests that full risks of developing cancer may not be assessed for more than 30 years.

In 2001, radiotherapy is still used in many non-malignant conditions, including orbital Graves disease, hyperthyroidism, inborn errors of metabolism, transplants, keloid scars, fasciitis, psoriasis, eczema, heterotopic bone formation, heart transplant rejection and Peyronie's disease of the penis. The alternative treatments for these conditions may have significant toxicity, including a risk of treatment induced aplastic anaemia, malignancy or death [38–42]. As an example, non-steroidal anti-inflammatory drugs prevent heterotopic new bone formation [2, 7, 8]. One in 1200 patients taking non-steroidal anti-inflammatory drugs for at least 2 months will die from gastroduodenal complications. This extrapolates to about 2000 deaths each year in the UK [42]. The corresponding acute risks from single fraction radiotherapy are not documented.

It is reassuring to note that until 1999, no single case of malignancy induced by radiotherapy for the potentially disabling condition of HTBF had been reported [43]. However, the most frequent indication for radiotherapy for HTBF, after hip replacement surgery, was first reported in only 1981 [6]. To advise patients on the best treatment choices for both short- and long-term treatment outcomes, we must undertake long-term follow-up. Our study has illustrated how difficult a task this may be in those patients who could be at greatest risk.


   Conclusions
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusions
References
 
The use of radiotherapy for benign disease can be limited to high risk patients using evidence based protocols, selecting patients who are likely to gain significant long-term benefits from radiotherapy. The guidelines for radiotherapy to prevent heterotopic bone has the unexpected outcome of selecting a group of patients who comply least with follow-up. Immediate single fraction post-operative radiotherapy does appear effective in reducing the risk of HTBF in high risk patients. The true long-term risks of this treatment policy may not be known for 30 years. The failure of patients to attend even short-term follow-up is a problem for clinical oncologists. A national database of all patients and all treatments would enable serious long-term treatment complications to be discovered, but has implications for civil liberty. We need to discuss this issue with potential patients.

Received for publication February 12, 2001. Revision received November 27, 2001. Accepted for publication December 5, 2001.


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusions
 References
 

  1. MacLennan I, Keys HM, Evarts CM, Rubin P. Usefulness of postoperative hip irradiation in the prevention of heterotopic bone formation in a high risk group of patients. Int J Radiat Oncol Biol Phys 1984;10:49–53.
  2. Moed BR, Karges DE. Prophylactic indomethacin for the prevention of heterotopic ossification after acetabular fracture surgery in high-risk patients. J Orthop Trauma 1994;8:34–9.[Medline]
  3. Brooker AF, Bowerman JW, Robinson RA, Riley LH. Ectopic ossification following total hip replacement. Incidence and a method of classification. J Bone Joint Surg Am 1973;55:1629–32.[Abstract/Free Full Text]
  4. Ahrengart L, Lindgren U. Functional significance of heterotopic bone formation after total hip arthroplasty. J Arthroplasty 1989;4:125–31.[Medline]
  5. Nollen AJ, Slooff TJ. Para-articular ossifications after total hip replacement. Acta Orthop Scand 1973;44:230–41.[Medline]
  6. Coventry MB, Scanlon PW. The use of radiation to discourage ectopic bone. A nine year study in surgery about the hip. J Bone Joint Surg Am 1981;63:201–8.[Abstract/Free Full Text]
  7. Kienapfel H, Koller M, Wust A, Sprey C, Merte H, Engenhart-Cabillic R, et al. Prevention of heterotopic bone formation after total hip arthroplasty: a prospective randomised study comparing postoperative radiation therapy with indomethacin medication. Arch Orthop Trauma Surg 1999;119:296–302.
  8. Moore KD, Goss K, Anglen JO. Indomethacin versus radiation therapy for prophylaxis against heterotopic ossification in acetabular fractures: a randomised, prospective study. J Bone Joint Surg Br 1998;80:259–63.
  9. Fingeroth RJ, Ahmed AQ. Single dose 6 Gy prophylaxis for heterotopic ossification after total hip arthroplasty. Clin Orthop 1995;317:131–40.
  10. Kennedy WF, Gruen TA, Chessin H, Gasparini G, Thompson W. Radiation therapy to prevent heterotopic ossification after cementless total hip arthroplasty. Clin Orthop 1991;262:185–91.
  11. Childs HA, Cole T, Falkenberg E, Smith JT, Alonso JE, Stannard JP, et al. A prospective evaluation of the timing of postoperative radiotherapy for preventing heterotopic ossification following traumatic acetabular fractures. Int J Radiat Oncol Biol Phys 2000;47:1347–52.[Medline]
  12. Pellegrini VD, Konski AA, Gastel JA, Rubin P, Evarts CM. Prevention of heterotopic ossification with irradiation after total hip arthroplasty. Radiation therapy with a single dose of eight hundred centigray administered to a limited field. J Bone Joint Surg Am. 1992;74:186–200.[Abstract/Free Full Text]
  13. Konski A, Pellegrini V, Poulter C, De Vanny J, Rosier R, Evarts CM, et al. Randomized trial comparing single dose versus fractionated irradiation for prevention of heterotopic bone: a preliminary report. Int J Radiat Oncol Biol Phys 1990;18:1139–42.[Medline]
  14. Seegenschmiedt MH, Keiholz L, Martus P, Goldmann A, Wolfel R, Henning F, et al. Prevention of heterotopic ossification about the hip: final results of two randomized trials in 410 patients using either preoperative or postoperative radiation therapy. Int J Radiat Oncol Biol Phys 1997;39:161–71.[Medline]
  15. Healy WL, Lo TC, DeSimone AA, Rask B, Pfeifer BA. Single-dose irradiation for the prevention of heterotopic ossification after total hip arthroplasty. A comparison of doses of five hundred and fifty and seven hundred centigray. J Bone Joint Surg Am 1995;77:590–5.[Abstract/Free Full Text]
  16. Sylvester JE, Blount LH, Selch MT. Technical considerations in the use of prophylactic radiation therapy to prevent heterotopic bone formation. Semin Arthroplasty 1992;3:167–71.[Medline]
  17. DeFlitch CJ, Stryker JA. Postoperative hip irradiation in prevention of heterotopic ossification: causes of treatment failure. Radiology 1993;188:265–70.[Abstract/Free Full Text]
  18. Haas ML, Kennedy AS, Copeland CC, Ames JW, Scarboro M, Slawson RG. Utility of radiation in the prevention of heterotopic ossification following repair of traumatic acetabular fracture. Int J Radiat Oncol Biol Phys 1999;45:461–6.[Medline]
  19. McLaren AC. Prophylaxis with indomethacin for heterotopic bone. After open reduction of fractures of the acetabulum. J Bone Joint Surg Am 1990;72:245–7.[Abstract/Free Full Text]
  20. Kaempffe FA, Bone LB, Border JR. Open reduction and internal fixation of acetabular fractures: heterotopic ossification and other complications of treatment. J Orthop Trauma 1991;5:439–45.[Medline]
  21. Schafer SJ, Schafter LO, Anglen JO, Childers M. Heterotopic ossification in rehabilitation patients who have had internal fixation of an acetabular fracture. J Rehabil Res Dev 2000;37:389–93.[Medline]
  22. Johnson EE, Kay RM, Dorey FJ. Heterotopic ossification prophylaxis following operative treatment of acetabular fracture. Clin Orthop 1994;305:88–95.
  23. Bosse MJ, Poka A, Reinert CM, Ellwanger F, Slawson R, McDevitt ER. Heterotopic ossification as a complication of acetabular fracture. Prophylaxis with low-dose irradiation. J Bone Joint Surg Am 1988;70:1231–7.[Abstract/Free Full Text]
  24. Slawson RG, Poka A, Bathon H, Salazar OM, Bromback RJ, Burgess AR. The role of post-operative radiation in the prevention of heterotopic ossification in patients with post-traumatic acetabular fracture. Int J Radiat Oncol Biol Phys 1989;17:669–72.[Medline]
  25. Blount LH, Thomas BJ, Tran L, Selch MT, Sylvester JE, Parker RG. Postoperative irradiation for the prevention of heterotopic bone: analysis of different dose schedules and shielding considerations. Int J Radiat Oncol Biol Phys 1990;19:577–81.[Medline]
  26. Jasty M, Schutzer S, Tepper J, Willett C, Stracher MA, Harris WH. Radiation-blocking shields to localize periarticular radiation precisely for prevention of heterotopic bone formation around uncemented total hip arthroplasties. Clin Orthop 1990;257:138–45.
  27. Kim JH, Chu FC, Woodard HQ, Melamed MR, Huvos A, Cantin J. Radiation-induced soft-tissue and bone sarcoma. Radiology. 1978;129:501–8.[Abstract]
  28. Metayer C, Lynch CF, Clarke EA, Glimelius B, Storm H, Pukkala E, et al. Second cancers among long-term survivors of Hodgkin's disease diagnosed in childhood and adolescence. J Clin Oncol 2000;18:2435–43.[Abstract/Free Full Text]
  29. Yasui W, Tahara E. Pediatric tumors and secondary cancer. The Ninth International Symposium of the Hiroshima Cancer Seminar, September 1999, Hiroshima, Japan. J Cancer Res Clin Oncol 2000;126:357–9.[Medline]
  30. Moed BR, Letournel E. Low-dose irradiation and indomethacin prevent heterotopic ossification after acetabular fracture surgery. J Bone Joint Surg Br 1994;76:895–900.
  31. Ramuz O, Bourhis J, Mornex F. Late effects of radiations on mature and growing bone. Cancer Radiother 1997;1:801–9.[Medline]
  32. Aref I, Cross P. Conservative surgery and radiation therapy for early stage breast cancer after previous mantle radiation for Hodgkin's disease. Br J Radiol 2000;73:905–6.[Abstract]
  33. Lee CK, Aeppli D, Nierengarten ME. The need for long-term surveillance for patients treated with curative radiotherapy for Hodgkin's disease: University of Minnesota experience. Int J Radiat Oncol Biol Phys 2000;48:169–79.[Medline]
  34. Clemons M, Loijens L, Goss P. Breast cancer risk following irradiation for Hodgkin's disease. Cancer Treat Rev 2000;26:291–302.[Medline]
  35. Weiss HA, Darby SC, Fearn T, Doll R. Leukemia mortality after X-ray treatment for ankylosing spondylitis. Radiat Res 1995;142:1–11.[Medline]
  36. Weiss HA, Darby SC, Doll R. Cancer mortality following X-ray treatment for ankylosing spondylitis. Int J Cancer 1994;59:327–38.[Medline]
  37. Darby SC, Reeves G, Key T, Doll R, Stovall M. Mortality in a cohort of women given X-ray therapy for metropathia haemorrhagica. Int J Cancer 1994;56:793–801.[Medline]
  38. Faich GA. Risks and indications of phenylbutazone: another look. Pharmacotherapy 1987;7:25–7.[Medline]
  39. Toussirot E, Wendling D. Current guidelines for the drug treatment of ankylosing spondylitis. Drugs 1998;56:225–40.[Medline]
  40. Smalley WE, Griffin MR. The risks and costs of upper gastrointestinal disease attributable to NSAIDs. Gastroenterol Clin North Am 1996;25:373–96.[Medline]
  41. Kari F, Bucher J, Haseman J, Eustis S, Huff J. Long-term exposure to the anti-inflammatory agent phenylbutazone induces kidney tumors in rats and liver tumors in mice. Jpn J Cancer Res 1995;86:252–63.[Medline]
  42. Tramer MR, Moore RA, Reynolds DJ, McQuay HJ. Quantitative estimation of rare adverse events which follow a biological progression: a new model applied to chronic NSAID use. Pain 2000;85:169–82.[Medline]
  43. Lo TCM. Radiation Therapy for Heterotopic Ossification. Semin Radiat Oncol 1999;9:163–70.[Medline]




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