Abstract
Introduction: non steroidal anti‐inflammatory drugs ((NSAIDs) and prophylactic radiotherapy can prevent ectopic bone formation around the hip after total hip arthroplasty. Methods: We retrieved from Medline, Embase and the Cochrane Register (clinical)) trials and other relevant literature on the prevention of heterotopic ossification (HO) from 1990‐2002 for further review.Results: Review of these clinical trials shows that HO is effectively prevented by a postoperative NSAID treatment with indomethacin for at least seven days. The best evidence is available for indomethacin, although naproxen, diclofenac and ibuprofen are also well documented. Short term use of ibuprofen is not effective. If NSAIDs are contraindicated, preoperative or postoperative radiotherapy is a very effective therapeutic option to prevent HO. Discussion and conclusion: Because of the potential of serious gastrointestinal side effects of NSAIDs and their interaction with anticoagulant drugs, rofecoxib and other COX‐2 specific NSAIDs may be a safer option for the treatment of HO. However, randomised controlled studies are needed to confirm the results of the rofecoxib study.
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References
Toom A, Haviko T, Rips L. Heterotopic ossification after total hip arthroplasty. Int Orthop 2001; 24: 323–6.
McMahon JS, Waddell JP, Morton J. Effect of short-course indomethacin on hetertopic bone formation after uncemented total hip arthroplasty. J Arthroplasty 1991; 6: 259–64.
McLaren AD. Prophylaxis with indomethacin for heterotopic bone after open reduction of fractures of the acetabulum. J Bone Joint Surg 1990; 72A: 245–7.
Nayak KNK, Mulliken B, Rorabeck CH, Bourne RB, Woolfrey MR. Prevalence of heterotopic ossification in cemented versus noncemented total hip joint replacement in patiens with osteoarthrosis: a randomized clinical trial. Can J Surg 1997; 40: 368–74.
Kjærsgaard-Andersen P, Sletgård J, Gerløff C, Lund F. Heterotopic bone formation after noncemented total hip arthroplasty. Location of ectopic bone and the influence of postoperative antiinflammatory treatment. Clin Orthop Rel Res 1990; 252: 156–62.
Purtill JJ, Eng K, Rothman RH, Hozack WJ. Heterotopic ossification: incidence in cemented versus cementless total hip arthroplasty. J Arthroplasty 1996; 11: 58–63.
Knelles D, Barthel T, Karrer A, Kraus U, Eulert J, Köbl O. Prevention of heterotopic ossifcation after total hip replacement. A prospective randomised study using acetylsalicylic acid, indomethacin and fractional or single-dose irradiation. J Bone Joint Surg 1997; 79B: 569–602.
Randelli G, Romanò C. Prophylaxis with indomethacin for heterotopic ossification after chiari osteotomy of the pelvis. J Bone Joint Surg 1992; 74A:1344–6.
Reis HJ, Küsswetter W, Schellinger T. The suppression of heterotopic ossification after total hip arthroplasty. Int Orthop 1992; 16:140–145.
Bosse A, Sprockhoff SD, Diedeggen A, Ekkernkamp A, Müller KM. Heterotope Ossifikationen - Morphologie, Differentialdiagnose, Klinik. Akt Traumatol 1996; 26: 237–44.
Kienapfel H, Koller M, Wüst A. 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.
Ahrengard L. Periarticular heterotopic ossification after total hip arthroplasty. Clin Orthop 1991; 263: 49–57.
Vastel L, Kerboull L, Anract P, Kerboull M. Heterotopic ossification after total hip arthroplasty: risk factors and prevention. Rev Rheum 1998; 65: 238–44.
Kjærsgaard-Andersen P, Nafei A, Teichert G Indomethacin for prevention of heterotopic ossification. A randomized controlled study in 41 hip arthroplasties. Acta Orthop Scand 1993; 64: 639–42.
Köbl O, Knelles D, Barthel T, Raunecker F, Flentje M, Eulert J. Preoperative irradiation versus the use of nonsteroidal antiinflammatory drugs for prevention of heterotopic ossification following total hip replacement: the results of a randomized trial. Int J Radiat Oncol Biol Phys 1998; 42: 397–401.
Guillemin F, Mainard D, Rolland H, Delagoutte JP. Antivitamin K prevents heterotopic ossification after hip arthroplasty in diffuse idiopathic skeletal hyperostosis. A retrospective study in 67 patients. Acta Orthop Scand 1995; 66: 123–6.
Moed BR, Letournel E. Low-dose irradiation and indomethacin prevent heterotopic ossification after acetabular fracture surgery. J Bone Joint Surg 1994; 76B: 895–900.
Köbl O, Knelles D, Barthel T, Kraus U, Flentje M, Eulert J. Randomized trial comparing early postoperative irradiation versus the use of nonsteroidal antiinflammatory drugs for prevention of heterotopic ossification following prosthetic total hip replacement. Int J Radiat Oncol Biol Phys 1997; 39: 961–6.
Seegenschmiedt M, Keilholz L, Martus P. 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.
Garrett WR, Abbey PA. The use of fat grafts to prevent heterotopic bone formation in the temporomandibular joint. J Oral Maxillofac Surg 1997; 55: 1037.
Duriez J, Flautre B, Blary MC, Duriez R. The effect of the calciumantagonist verapamil in the prevention of heterotopic bone formation in rats. Int Orthop 1990; 14: 415–21.
Sodemann B, Persson PE, Nilsson OS. Nonsteroid anti-inflammatory drugs prevent the recurrence of heterotopic ossification after excision. Arch Orthop Trauma Surg 1990; 109: 53–6.
Sudanese A, Tabarroni M, Busanelli L The use of cobalt therapy to prevent heterotopic ossification after total hip arthroplasty. Chir Organi Mov 1996; 81: 89–106.
Anglen JO, Moore KD. Prevention of heterotopic bone formation after acetabular fracture fixation by single-dose radiation therapy. J Orthop Trauma 1996; 10: 258–63.
Wurnig C, Auersperg V, Boehler N Short term prophylaxis against heterotopic bone after cementless hip replacement. Clin Orthop Rel Res 1997; 334: 175–83.
Jockheck M, Willms R, Volkmann R, Sell S, Weller S, Küsswetter W. Prevention of heterotopic ossification after endoprosthetic hip joint replacement by means of diclofenac. Arch Orthop Trauma Surg 1998; 117: 337–40.
Seegenschmidt MH, Makoski HB, Micke O. Radiation prophylaxis for heterotopic ossification about the hip joint-a multi centre study Int J Radiat Oncol Biol Phys 2001; 51: 756–65.
Gregoritch SJ, Chadha M, Pelligrini VD, Rubin P, Kantorowitz DA. Randomized trial comparing preoperative versus postoperative irradiation for prevention of heterotopic ossification following prosthetic total hip replacement. Int J Rad Oncol Biol Phys 1994; 30: 55–62.
Bontke CF. Should we use etidronate disodium as prophylaxis in patients with brain injury at risk for heterotopic ossification? J Head Trauma Rehabil 1996; 11: 80–8.
Biering-Sørensen F, Tøndevold E. Indomethacin and disodium etidronate for the prevention of recurrence of heterotopic ossifcation after surgical resection. Paraplegia 1993; 31: 513–5.
Buschbacher R, McKinley W, Buschbacher L, Devaney CW, Coplin B. Warfarin in the prevention of heterotopic ossification. Am J Phys Med Rehabil 1992; 71: 86–91.
Vielpeau C, Joubert JM, Hulet C. Naproxen in the prevention of heterotopic ossification after total hip replacement. Clin Orthop Rel Res 1999; 369: 279–88.
Risto O, Wahlström O, Abdiu A. The effect of low dose diclofenac sodium administered locally on heterotopic bone formation in rats. Int Orthop 1995; 19: 392–5.
Neal BC, Rodgers A, Clark T. A systematic survey of 13 randomized trials of non-steroidal anti-inflammatory drugs for the prevention of heterotopic bone formation after major hip surgery. Acta Orthop Scand 2000; 71: 122–8.
Kjærsgaard-Andersen P, Ritter MA. Prevention of formation of heterotopic bone after total hip arthroplasty. J Bone Joint Surg 1991; 73: 942–7.
Amstutz HC, Fowble VA, Schmalzried TP, Dorey FJ. Shortcourse indomethacin prevents heterotopic ossification in a high-risk population following total hip arthroplasty. J Arthroplasty 1997; 12: 126–32.
Koorevaar CT, Hu HP, Lemmens A, van Kampen A. No effective prophylaxis of heterotopic ossification with short-term ibuprofen. Arch Orthop Trauma Surg 1999; 119: 183–5.
Sahin-Akkoc Y, Kirazli Y, Aydogdu S, Sur H, Sabah D. Indomethacin in the prevention of heterotopic ossification following total hip arthroplasty. J Rheumatol Med Rehabil 1999; 10: 69–73.
Gebuhr P, Sletgård J, Dalsgård J. Heterotopic ossification after hip arthroplasty: a randomized trial. Acta Orthop Scand 1996; 67: 29–32.
Dorn U, Grethen C, Effenberger H, Berka H, Ramsauer T, Drekonja T. Indomethacin for prevention of heterotopic ossification after hip arthroplasty. A randomized comparison between 4 and 8 days of treatment. Acta Orthop Scand 1998; 69: 107–10.
Gebuhr P, Wilbek H, Soelberg M. Naproxen for 8 days can prevent heterotopic ossification after hip arthroplasty. Clin Orthop Rel Res 1995; 314: 166–9.
Gebuhr P, Soelberg M, Orsnes T, Wilbek H. Naproxen prevention of heterotopic ossification after hip arthroplasty. A prospective control study of 55 patients. Acta Orthop Scand 1991; 62: 226–9.
Burssens A, Thiery J, Kohl P, Molderez A, Haazen L. Prevention of heterotopic ossification with tenoxicam following total hip arthroplasty: a double-blind, placebo-controlled dose-finding study. Acta Orthop Belg 1995; 61: 205–11.
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.
Freiberg AA, Cantor R, Freiberg RA. The use of aspirin to prevent heterotopic ossification after total hip arthroplasty. Clin Orthop Rel Res 1991; 267: 93–6.
Hoikka V, Lindholm TS, Eskola A. Flurbiprofen inhibits heterotopic bone formation in total hip arthroplasty. Arch Orthop Trauma Surg 1990; 109: 224–6.
Persson PE, Sodemann B, Nilsson OS. Preventive effects of ibuprofen on periarticular heterotopic ossification after total hip arthroplasty. A randomized double-blind prospective study of treatment time. Acta Orthop Scand 1998; 69: 111–5.
Naraghi FF, DeCoster TA, Moneim TA, Miller RA, Rivero D. Heterotopic ossification. Orthopedics 1996; 19: 145–52.
Neal BC, Rodgers A, Gray H. No effect of low-dose aspirin for the prevention of heterotopic bone formation after total hip replacement. A randomized trial of 2,649 patients. Acta Orthop Scand 2000; 71: 129–34.
Kjærsgaard-Andersen P, Schmidt AS. Total hip arthroplasty: the role of antiinflammatory medications in the prevention of heterotopic ossification. Clin Orthop Rel Res 1991; 263: 78–86.
Weinreb M, Kelner A, Keila S. Inhibition of cyclo-oxygenase-2 activity does not abolish the anabolic effect of prostaglandin E2 in vivo or in vitro. J Endocrinol 2002; 174: 127–35.
Tozun R, Pinar H, Yesiller E, Hamzaoglu A. Indomethacin for prevention of heterotopic ossification after total hip arthroplasty. J Arthroplasty 1992; 7: 57–61.
Wahlström O, Risto O, Djerf K, Hammerby S. Heterotopic bon formation prevented by diclofenac. Prospective study of 100 hip arthroplasties. Acta Orthop Scand 1991; 62: 419–21.
Neal BC, Rodgers A, Dunn L, Fransen M. Non-steroidal antiinflammatory drugs for preventing heterotopic bone formation after hip arthroplasty. Cochrane Database Syst Rev 2000; 3: CD001160.
Zacher J, Walther E, Gursche A. Prevention of periarticular ossification after total hip replacement with rofecoxib 25mg (Abstract OP0127). Ann Rheum Dis 2001; 6: 79.
Van Dijk KN, Plat AW, Van Dijk AAC, Piersma-Wichers M, de Jong-van den Berg LTW et al. Potential interaction between acenocoumarol and diclofenac, naproxen and ibuprofen and the role of CYP2C9 genotype. Pharmacoepidemiol Drug Saf 2002; 11(S1): 73–4.
Cohen AT, Bailey CS, Alikhan R, Cooper DJ. Extended thromboprophylaxis with low molecular weight heparin reduces symptomatic venous thromboembolism following lower limb arthroplasty. A meta-analysis. Thromb Haemost 2001; 85: 940–1.
Burd TA, Lowry KJ, Anglen JO. Indomethacin compared with localized irradiation for the prevention of heterotopic ossification following surgical treatment of acetabular fractures J Bone Joint Surg 2001; 83; 1783–8.
Matta JM, Siebenrock KA. Does indomethacin reduce heterotopic bone formation after operations for acetabular fractures? J Bone Joint Surg 1997; 79B: 959–63.
Martini F, Sell S, Reize P, Jani R, Küsswetter W. Perioperative side effects of preventative measures against heterotopic ossification. Diclofenac versus irradiation. Akt Rheumatol 1995; 20: 61–5.
Vastel L, Kerboull L, Dejean O, Courpied JP, Kerboull M. Prevention of heterotopic ossification in hip arthroplasty. The influence of the duration of treatment. Int Orthop 1999; 23: 107–10.
Hofmann S, Trnka HJ, Metzenroth H, Frank E, Ritschl P, Salzer M. General short-term indomethacin prophylaxis to prevent heterotopic ossification in total hip arthroplasty. Orthopedics 1999; 22: 207–11.
Sell S, Willms R, Jany R. The suppression of heterotopic ossifications: radiation versus NSAID therapy. A prospective study. J Arthroplasty 1998; 13: 854–9.
Bremen-Kuhne R, Stock D, Franke C. Indomethacin short term therapy versus single low doseage radiation for prevention of periarticular ossifications after total hip endoprothesis. Z Orthop Ihre Grenzgeb 1997; 135(5): 422–9.
Gierse H, Eisebitt R, Bernard I. Prevention of periarticular ossification with results of randomised double blind study comparing acemetacin versus indomethacin. Z Orthop Ihre Grenzgeb 1997; 135(5): 417–21.
Gunal I, Hazer B, Seber S, Gokturk E, Turgut A, Kose N. Prevention of heterotopic ossification after total hip replacement: a prospective comparison of indomethacin and salmon calcitonin in 60 patients. Acta Orthop Scand 2001; 72(5): 467–9.
Hochheim B, Wunsche F. Indomethacin in the prevention of para-articular ossification following total hip endoprothesis. Beitr Orthop Traumatol 1990; 37(6): 330–4.
van der Heide HJ, Koorevaar RTh, Schreurs BW, van Kampen A, Lemmens A. Indomethacin for 3 days is not effective as prophylaxis for heterotopic ossification after primary hip arthroplasty. J Arthroplasty 1999; 14: 796–9.
Iotov A. Heterotopic ossification in surgically treated patients with acetabular fractures and indomethacin prophylaxis for its prevention. Ortop Travmatol 2000; 36(1): 367–73.
D'Lima DD, Venn-Watson EJ, Trippuraneni P, Colwell CW. Indomethacin versus radiation therapy for heterotopic ossification after hip arthoplasty Orthopedics 2001; 24(12): 1139–43.
McMahon JS, Waddell JP, Morton J. Effect of short course indomethacin on heterotopic bone formation after uncemented total hip arthroplasty. J Arthroplasty 1991; 6(3): 259–64.
Moed BR, Maxey JW. The effect of incdomethacin on heterotopic ossification following acetabular fracture surgery. J Orthop Trauma 1993; 7(1): 33–8.
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(2): 259–63.
Weissinger M, Keppel A, Helmreich C. Retrospective study of heterotopic ossification with and without prophylactic indomethacin therapy. Acta Chir Orthop Traumatol Cech 1994; 61(2): 87–91.
Wick M, Muller EJ, Hahn MP, Muhr G. Surgical excision of heterotopic bone after hip surgery followed by oral indomethacin application: is there a clinical benefit for the patient? Arch Orthop Trauma Surg 1999; 119(3–4): 151–5.
Wurnig C, Eyb R, Auersperg V. Indomethacin for prevention of ectopic ossification in cementless hip arhtroplasties: aprospective 1 year study of 100 cases. Acta Orthop Scand 1992; 63(6): 628–30.
Wurnig C, Schwameis E, Bitzan P, Kainberger F. Six-year results of a cementless stem with prophylaxis against heterotopic bone. Clin Orthop 1999; 361: 150–8.
Pagnani MJ, Pellicci PM, Salvati EA. Effect of aspirin on heterotopic ossification after total hip arthroplasty in men who have osteoporosis. J Bone Joint Surg Am 1991; 73(6: 924–9.
Ahrengart L, Blomgren G, Tornkvist H. Short-term ibuprofen to prevent ossification after hip arthroplasty. No effects in a prospective randomised study of arthrosis cases. Acta Orthop Scand 1994; 65(2): 139–141.
Pritchett JW. Ketorolac prophylaxis against heterotopic ossification after hip replacement. Clin Orthop 1995; 314: 162–5.
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Fijn, R., Koorevaar, R. & Brouwers, J. Prevention of heterotopic ossification after total hip replacement with NSAIDs. Pharm World Sci 25, 138–145 (2003). https://doi.org/10.1023/A:1024830213832
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DOI: https://doi.org/10.1023/A:1024830213832