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Published in: Clinical Orthopaedics and Related Research® 12/2009

01-12-2009 | Original Article

Prophylaxis of Heterotopic Ossification of the Hip: Systematic Review and Meta-Analysis

Authors: Patrick Vavken, MD, MSc, Lorenzo Castellani, MD, Thomas P. Sculco, MD

Published in: Clinical Orthopaedics and Related Research® | Issue 12/2009

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Abstract

Heterotopic ossification (HO) is a potentially severe, if infrequent, complication in hip surgery, and uncertainty exists regarding whether to use NSAIDs or radiation in its prevention. Thus, we systematically reviewed the literature in MedLine, EMBASE, CINAHL, and the Cochrane Controlled Trial Register and, after ruling out publication bias and data heterogeneity, performed a meta-analysis of randomized, controlled trials to assess effectiveness and complications of NSAIDs and radiation in the prevention of HO. We identified nine studies reporting on effectiveness and complications including a total of 1295 patients. The pooled risk ratio for the effectiveness in HO prevention was 0.96 (95% confidence interval, 0.88–1.06) and was independent of the type of surgery (THA or open reduction and internal fixation). There was no association with gender, age, length of followup, or year of publication. The risk ratio for associated complications was 0.79 (95% confidence interval, 0.45–1.41), and, again, was independent of the aforementioned factors. We found no evidence for a statistically significant or clinically important difference between NSAIDs or radiation in preventing HO.
Literature
1.
go back to reference Back DL, Smith JD, Dalziel RE, Young DA, Shimmin A. Incidence of heterotopic ossification after hip resurfacing. ANZ J Surg. 2007;77:642–647.CrossRefPubMed Back DL, Smith JD, Dalziel RE, Young DA, Shimmin A. Incidence of heterotopic ossification after hip resurfacing. ANZ J Surg. 2007;77:642–647.CrossRefPubMed
2.
go back to reference Birrell F, Lohmander S. Non-steroidal anti-inflammatory drugs after hip replacement. BMJ. 2006;333:507–508.CrossRefPubMed Birrell F, Lohmander S. Non-steroidal anti-inflammatory drugs after hip replacement. BMJ. 2006;333:507–508.CrossRefPubMed
3.
go back to reference Board TN, Karva A, Board RE, Gambhir AK, Porter ML. The prophylaxis and treatment of heterotopic ossification following lower limb arthroplasty. J Bone Joint Surg Br. 2007;89:434–440.CrossRefPubMed Board TN, Karva A, Board RE, Gambhir AK, Porter ML. The prophylaxis and treatment of heterotopic ossification following lower limb arthroplasty. J Bone Joint Surg Br. 2007;89:434–440.CrossRefPubMed
4.
go back to reference Bremen-Kühne R, Stock D, Franke C. [Indomethacin: short-term therapy vs. single low dosage radiation for prevention of periarticular ossifications after total hip endoprosthesis] [in German]. Z Orthop Ihre Grenzgeb. 1997;135:422–429.CrossRefPubMed Bremen-Kühne R, Stock D, Franke C. [Indomethacin: short-term therapy vs. single low dosage radiation for prevention of periarticular ossifications after total hip endoprosthesis] [in German]. Z Orthop Ihre Grenzgeb. 1997;135:422–429.CrossRefPubMed
5.
go back to reference Burd T, Lowry K, Anglen J. Indomethacin compared with localized irradiation for the prevention of heterotopic ossification following surgical treatment of acetabular fractures. J Bone Joint Surg Am. 2001;83:1783–1788.PubMed Burd T, Lowry K, Anglen J. Indomethacin compared with localized irradiation for the prevention of heterotopic ossification following surgical treatment of acetabular fractures. J Bone Joint Surg Am. 2001;83:1783–1788.PubMed
6.
7.
go back to reference Duval S, Tweedie R. A nonparametric “trim and fill” method of accounting for publication bias in meta-analysis. J Am Stat Assoc. 2000;95:89–98.CrossRef Duval S, Tweedie R. A nonparametric “trim and fill” method of accounting for publication bias in meta-analysis. J Am Stat Assoc. 2000;95:89–98.CrossRef
8.
go back to reference Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634.PubMed Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634.PubMed
9.
go back to reference Fransen M, Anderson C, Douglas J, MacMahon S, Neal B, Norton R, Woodward M, Cameron ID, Crawford R, Lo SK, Tregonning G, Windolf M, Group HC. Safety and efficacy of routine postoperative ibuprofen for pain and disability related to ectopic bone formation after hip replacement surgery (HIPAID): randomised controlled trial. BMJ. 2006;333:519.CrossRefPubMed Fransen M, Anderson C, Douglas J, MacMahon S, Neal B, Norton R, Woodward M, Cameron ID, Crawford R, Lo SK, Tregonning G, Windolf M, Group HC. Safety and efficacy of routine postoperative ibuprofen for pain and disability related to ectopic bone formation after hip replacement surgery (HIPAID): randomised controlled trial. BMJ. 2006;333:519.CrossRefPubMed
10.
go back to reference Fransen M, Neal B. Non-steroidal anti-inflammatory drugs for preventing heterotopic bone formation after hip arthroplasty. Cochrane Database Syst Rev. 2004;3:CD001160.PubMed Fransen M, Neal B. Non-steroidal anti-inflammatory drugs for preventing heterotopic bone formation after hip arthroplasty. Cochrane Database Syst Rev. 2004;3:CD001160.PubMed
11.
go back to reference Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560.CrossRefPubMed Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560.CrossRefPubMed
12.
go back to reference Higo T, Mawatari M, Shigematsu M, Hotokebuchi T. The incidence of heterotopic ossification after cementless total hip arthroplasty. J Arthroplasty. 2006;21:852–856.CrossRefPubMed Higo T, Mawatari M, Shigematsu M, Hotokebuchi T. The incidence of heterotopic ossification after cementless total hip arthroplasty. J Arthroplasty. 2006;21:852–856.CrossRefPubMed
13.
go back to reference Ince A, Sauer U, Wollmerstedt N, Hendrich C. No migration of acetabular cups after prophylaxis for heterotopic ossification. Clin Orthop Relat Res. 2007;461:125–129.PubMed Ince A, Sauer U, Wollmerstedt N, Hendrich C. No migration of acetabular cups after prophylaxis for heterotopic ossification. Clin Orthop Relat Res. 2007;461:125–129.PubMed
14.
go back to reference Johnson RT, Dickersin K. Publication bias against negative results from clinical trials: three of the seven deadly sins. Nat Clin Pract Neurol. 2007;3:590–591.CrossRefPubMed Johnson RT, Dickersin K. Publication bias against negative results from clinical trials: three of the seven deadly sins. Nat Clin Pract Neurol. 2007;3:590–591.CrossRefPubMed
15.
go back to reference Kienapfel H, Koller M, Wüst A, Sprey C, Merte H, Engenhart-Cabillic R, Griss P. 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.CrossRefPubMed Kienapfel H, Koller M, Wüst A, Sprey C, Merte H, Engenhart-Cabillic R, Griss P. 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.CrossRefPubMed
16.
go back to reference Kim JH, Chu FC, Woodward HQ, Huvos A. Radiation induced sarcomas of bone following therapeutic radiation. Int J Radiat Oncol Biol Phys. 1983;9:107–110.PubMed Kim JH, Chu FC, Woodward HQ, Huvos A. Radiation induced sarcomas of bone following therapeutic radiation. Int J Radiat Oncol Biol Phys. 1983;9:107–110.PubMed
17.
go back to reference Kim JH, Chu FC, Woodward HQ, Melamed MR, Huvos A, Cantin J. Radiation-induced soft-tissue and bone sarcoma. Radiology. 1978;129:501–508.PubMed Kim JH, Chu FC, Woodward HQ, Melamed MR, Huvos A, Cantin J. Radiation-induced soft-tissue and bone sarcoma. Radiology. 1978;129:501–508.PubMed
18.
go back to reference Knelles D, Barthel T, Karrer A, Kraus U, Eulert J, Kolbl O. Prevention of heterotopic ossification after total hip replacement: a prospective, randomised study using acetylsalicylic acid, indomethacin and fractional or single-dose irradiation. J Bone Joint Surg Br. 1997;79:596–602.CrossRefPubMed Knelles D, Barthel T, Karrer A, Kraus U, Eulert J, Kolbl O. Prevention of heterotopic ossification after total hip replacement: a prospective, randomised study using acetylsalicylic acid, indomethacin and fractional or single-dose irradiation. J Bone Joint Surg Br. 1997;79:596–602.CrossRefPubMed
19.
go back to reference Kölbl O, Knelles D, Barthel T, Raunecker F, Flentje M, Eulert J. Preoperative irradiation versus the use of nonsteroidal anti-inflammatory 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.PubMed Kölbl O, Knelles D, Barthel T, Raunecker F, Flentje M, Eulert J. Preoperative irradiation versus the use of nonsteroidal anti-inflammatory 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.PubMed
20.
go back to reference Martini F, Sell S, Reize P, Jani R, Küsswetter W. Perioperative side effects of preventative measures against heterotopic ossification: diclofenac versus irradiation. Aktuelle Rheumatol. 1995;20:61–65.CrossRef Martini F, Sell S, Reize P, Jani R, Küsswetter W. Perioperative side effects of preventative measures against heterotopic ossification: diclofenac versus irradiation. Aktuelle Rheumatol. 1995;20:61–65.CrossRef
21.
go back to reference 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;80:259–263.CrossRefPubMed 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;80:259–263.CrossRefPubMed
22.
go back to reference Neal B. Effects of heterotopic bone formation on outcome after hip arthroplasty. ANZ J Surg. 2003;73:422–426.CrossRefPubMed Neal B. Effects of heterotopic bone formation on outcome after hip arthroplasty. ANZ J Surg. 2003;73:422–426.CrossRefPubMed
23.
go back to reference Neal B, Gray H, MacMahon S, Dunn L. Incidence of heterotopic bone formation after major hip surgery. ANZ J Surg. 2002;72:808–821.CrossRefPubMed Neal B, Gray H, MacMahon S, Dunn L. Incidence of heterotopic bone formation after major hip surgery. ANZ J Surg. 2002;72:808–821.CrossRefPubMed
24.
go back to reference Okike K, Kocher MS, Mehlman CT, Heckman JD, Bhandari M. Publication bias in orthopaedic research: an analysis of scientific factors associated with publication in the Journal of Bone and Joint Surgery (American Volume). J Bone Joint Surg Am. 2008;90:595–601.CrossRefPubMed Okike K, Kocher MS, Mehlman CT, Heckman JD, Bhandari M. Publication bias in orthopaedic research: an analysis of scientific factors associated with publication in the Journal of Bone and Joint Surgery (American Volume). J Bone Joint Surg Am. 2008;90:595–601.CrossRefPubMed
25.
go back to reference Pakos E, Ioannidis J. Radiotherapy vs. nonsteroidal anti-inflammatory drugs for the prevention of heterotopic ossification after major hip procedures: a meta-analysis of randomized trials. Int J. Radiat Oncol Biol Phys. 2004;60:888–895.PubMed Pakos E, Ioannidis J. Radiotherapy vs. nonsteroidal anti-inflammatory drugs for the prevention of heterotopic ossification after major hip procedures: a meta-analysis of randomized trials. Int J. Radiat Oncol Biol Phys. 2004;60:888–895.PubMed
26.
go back to reference Persson PE, Nilsson OS, Berggren AM. Do non-steroidal anti-inflammatory drugs cause endoprosthetic loosening? A 10-year follow-up of a randomized trial on ibuprofen for prevention of heterotopic ossification after hip arthroplasty. Acta Orthop. 2005;76:735–740.CrossRefPubMed Persson PE, Nilsson OS, Berggren AM. Do non-steroidal anti-inflammatory drugs cause endoprosthetic loosening? A 10-year follow-up of a randomized trial on ibuprofen for prevention of heterotopic ossification after hip arthroplasty. Acta Orthop. 2005;76:735–740.CrossRefPubMed
27.
go back to reference Schafer SJ, Schafer LO, Anglen JO, Childers M. Heterotopic ossification in rehabilitation patients who have had internal fixation of an acetabular fracture. J Rehabil Res Dev. 2000;37:389–393.PubMed Schafer SJ, Schafer LO, Anglen JO, Childers M. Heterotopic ossification in rehabilitation patients who have had internal fixation of an acetabular fracture. J Rehabil Res Dev. 2000;37:389–393.PubMed
28.
go back to reference Sell S, Willms R, Jany R, Esenwein S, Gaissmaier C, Martini F, Bruhn G, Burkhardsmaier F, Bamberg M, Küsswetter W. The suppression of heterotopic ossifications: radiation versus NSAID therapy - a prospective study. J Arthroplasty. 1998;13:854–859.CrossRefPubMed Sell S, Willms R, Jany R, Esenwein S, Gaissmaier C, Martini F, Bruhn G, Burkhardsmaier F, Bamberg M, Küsswetter W. The suppression of heterotopic ossifications: radiation versus NSAID therapy - a prospective study. J Arthroplasty. 1998;13:854–859.CrossRefPubMed
29.
go back to reference Strauss JB, Chen SS, Shah AP, Coon AB, Dickler A. Cost of radiotherapy versus NSAID administration for prevention of heterotopic ossification after total hip arthroplasty. Int J Radiat Oncol Biol Phys. 2008;71:1460–1464.PubMed Strauss JB, Chen SS, Shah AP, Coon AB, Dickler A. Cost of radiotherapy versus NSAID administration for prevention of heterotopic ossification after total hip arthroplasty. Int J Radiat Oncol Biol Phys. 2008;71:1460–1464.PubMed
30.
go back to reference Thompson SG. Why and How Sources of Heterogeneity Should Be Investigated. Ed 2. London, England: BMJ Publishing Group; 2001. Thompson SG. Why and How Sources of Heterogeneity Should Be Investigated. Ed 2. London, England: BMJ Publishing Group; 2001.
31.
go back to reference Vavken P, Culen G, Dorotka R. Management of confounding in controlled orthopaedic trials: a cross-sectional study. Clin Orthop Relat Res. 2008;466:985–989.CrossRefPubMed Vavken P, Culen G, Dorotka R. Management of confounding in controlled orthopaedic trials: a cross-sectional study. Clin Orthop Relat Res. 2008;466:985–989.CrossRefPubMed
Metadata
Title
Prophylaxis of Heterotopic Ossification of the Hip: Systematic Review and Meta-Analysis
Authors
Patrick Vavken, MD, MSc
Lorenzo Castellani, MD
Thomas P. Sculco, MD
Publication date
01-12-2009
Publisher
Springer-Verlag
Published in
Clinical Orthopaedics and Related Research® / Issue 12/2009
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-009-0924-5

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