{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:56:30Z","timestamp":1780534590156,"version":"3.54.1"},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,12,19]],"date-time":"2017-12-19T00:00:00Z","timestamp":1513641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Heterotopic ossification (HO) is the formation of pathological bone in ectopic sites and it can have serious consequences for functional outcomes. For many years, its main clinical relevance was as a rare complication of elective joint arthroplasty or CNS injury and a number of prophylaxes were developed to mitigate against it in these settings. As a consequence of changes in patterns of wounding and survival in conflicts since the turn of the century, post\u2010traumatic HO has become much more common and case severity has increased. It represents one of the main barriers to rehabilitation in a large cohort of combat\u2010injured patients. However, extant prophylaxes have not been shown to be effective or appropriate in this patient cohort. In addition, the lack of reliable early detection or means of predicting which patients will develop HO is another barrier to effective prevention. This review examines the current state of understanding of post\u2010traumatic HO including the historical context, epidemiology, pathophysiology, clinical issues, currently prophylaxis and detection, management, and potential future approaches. Our aims are to highlight the current lack of effective means of early detection and prevention of HO after major trauma and to stimulate research into novel solutions to this challenging problem. \u00a9 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1061\u20131068, 2018.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jor.23808","type":"journal-article","created":{"date-parts":[[2017,11,29]],"date-time":"2017-11-29T17:59:58Z","timestamp":1511978398000},"page":"1061-1068","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Post\u2010Traumatic Heterotopic Ossification: An Old Problem in Need of New Solutions"],"prefix":"10.1002","volume":"36","author":[{"given":"Neil","family":"Eisenstein","sequence":"first","affiliation":[{"name":"Royal Centre for Defence Medicine Birmingham Research Park, ICT Centre, Vincent Drive Birmingham B15 2SQ United Kingdom"},{"name":"School of Chemical Engineering University of Birmingham Edgbaston B15 2TT United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Stapley","sequence":"additional","affiliation":[{"name":"Royal Centre for Defence Medicine Birmingham Research Park, ICT Centre, Vincent Drive Birmingham B15 2SQ United Kingdom"},{"name":"School of Chemical Engineering University of Birmingham Edgbaston B15 2TT United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Grover","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering University of Birmingham Edgbaston B15 2TT United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,19]]},"reference":[{"key":"e_1_2_4_2_1","unstructured":"SpinkMS LewisGL. Albucasis: on surgery and instruments: a definitive edition of the Arabic text with English translation and commentary: Wellcome Institute of the History of Medicine 1973."},{"key":"e_1_2_4_3_1","first-page":"28","article-title":"Lettres choisies defeu","volume":"1692","author":"Patin G","journal-title":"Guy Patin Coldene"},{"key":"e_1_2_4_4_1","first-page":"880","article-title":"Wounds and complications","volume":"2","author":"Otis G","year":"1883","journal-title":"The medical and surgical history of the Civil War"},{"key":"e_1_2_4_5_1","first-page":"286","article-title":"Heterotopic ossification in paraplegia","volume":"43","author":"Damanski M","year":"1961","journal-title":"Bone Joint J"},{"key":"e_1_2_4_6_1","first-page":"497","article-title":"Para\u2010osteo\u2010arthropathies des paraplegiques par lesion medullaire; etude clinique et radiographique","volume":"5","author":"Dejerne A","year":"1918","journal-title":"Ann Med"},{"key":"e_1_2_4_7_1","first-page":"399","article-title":"Para\u2010ost\u00e9o\u2010arthropathies des paraplegiques par lesion m\u00e9dullaire. Etude anatomique et histologique","volume":"26","author":"Dejerine M","year":"1919","journal-title":"Revista de Neurolog\u00eda"},{"key":"e_1_2_4_8_1","first-page":"93","article-title":"Demonstration line durch ach Hagiges Umhergehen total destruirten kniegelenkes von einem patienten mit stichverletzing des ruckans","volume":"12","author":"Riedel B","year":"1883","journal-title":"Verh Dtsch Gesellschaft Chirurg"},{"key":"e_1_2_4_9_1","first-page":"180","article-title":"Beitrag zu den parartikul\u00e4ren Verkn\u00f6cherungen nach Querschnittsl\u00e4sion des R\u00fcckenmarks","volume":"191","author":"Geldmacher M","year":"1925","journal-title":"Langenbecks Arch Surg"},{"key":"e_1_2_4_10_1","first-page":"365","article-title":"\u00dcber Myositis ossificans neurotica nach Schu\u00dfverletzung des R\u00fcckenmarks","volume":"27","author":"Israel A","year":"1920","journal-title":"Fortschr R\u00f6ntgenstr"},{"key":"e_1_2_4_11_1","first-page":"713","volume-title":"Care of the amputated in the United States","author":"Brackett EG","year":"1921"},{"key":"e_1_2_4_12_1","first-page":"192","article-title":"Blast injuries and heterotopic ossification","volume":"1","author":"Alfieri KA","year":"2012","journal-title":"Bone Joint J"},{"key":"e_1_2_4_13_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/B978-0-12-387829-8.00024-X","volume-title":"Genetics of bone biology and skeletal disease","author":"Culbert AL","year":"2013"},{"key":"e_1_2_4_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1783"},{"key":"e_1_2_4_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801681200"},{"key":"e_1_2_4_16_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2000.15.11.2084"},{"key":"e_1_2_4_17_1","doi-asserted-by":"publisher","DOI":"10.2147\/TACG.S51064"},{"key":"e_1_2_4_18_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.H.00792"},{"key":"e_1_2_4_19_1","doi-asserted-by":"crossref","first-page":"476","DOI":"10.2106\/JBJS.F.00412","article-title":"Heterotopic ossification following traumatic and combat\u2010related amputations. Prevalence, risk factors, and preliminary results of excision","volume":"89","author":"Potter BK","year":"2007","journal-title":"J Bone Joint Surg"},{"key":"e_1_2_4_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-015-4250-9"},{"key":"e_1_2_4_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2014.03.010"},{"key":"e_1_2_4_22_1","doi-asserted-by":"publisher","DOI":"10.3109\/02699052.2013.775490"},{"key":"e_1_2_4_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016632"},{"key":"e_1_2_4_24_1","doi-asserted-by":"publisher","DOI":"10.1308\/003588414X13946184904008"},{"key":"e_1_2_4_25_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.J.00845"},{"key":"e_1_2_4_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2008.03.002"},{"key":"e_1_2_4_27_1","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-200600001-00042"},{"key":"e_1_2_4_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jramc-2013-000103"},{"key":"e_1_2_4_29_1","doi-asserted-by":"crossref","first-page":"S116","DOI":"10.1097\/TA.0b013e3181e44cc7","article-title":"Comparison of development of heterotopic ossification in injured US and UK Armed Services personnel with combat\u2010related amputations: preliminary findings and hypotheses regarding causality","volume":"69","author":"Brown KV","year":"2010","journal-title":"J Trauma Acute Care Surg"},{"key":"e_1_2_4_30_1","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1097\/TA.0000000000000580","article-title":"Improved survival in UK combat casualties from Iraq and Afghanistan: 2003\u20132012","volume":"78","author":"Penn\u2010Barwell JG","year":"2015","journal-title":"J Trauma Acute Care Surg"},{"key":"e_1_2_4_31_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.J.00776"},{"key":"e_1_2_4_32_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2010.0237"},{"key":"e_1_2_4_33_1","unstructured":"ForsbergJA PotterBK. Heterotopic ossification in wartime wounds: DTIC Document 2010."},{"key":"e_1_2_4_34_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s40141-014-0063-0","article-title":"Residual limb complications and management strategies","author":"Pascale BA","year":"2014","journal-title":"Curr Phys Med Rehabil Rep"},{"key":"e_1_2_4_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOT.0b013e31819dfa04"},{"key":"e_1_2_4_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/0363546514526361"},{"key":"e_1_2_4_37_1","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1302\/0301-620X.85B5.13970","article-title":"Heterotopic ossification prophylaxis with indomethacin increases the risk of long\u2010bone nonunion","volume":"85","author":"Burd T","year":"2003","journal-title":"J Bone Joint Surg"},{"key":"e_1_2_4_38_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.4103\/0972-5229.74170","article-title":"Acute kidney injury after trauma: prevalence, clinical characteristics and RIFLE classification","volume":"14","author":"de Abreu KLS","year":"2010","journal-title":"Indian J Crit Care Med"},{"key":"e_1_2_4_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2014.08.025"},{"key":"e_1_2_4_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-005-0054-y"},{"key":"e_1_2_4_41_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.I.01435"},{"key":"e_1_2_4_42_1","first-page":"D003321","article-title":"Pharmacological interventions for treating acute heterotopic ossification","volume":"4","author":"Haran M","year":"2004","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_4_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2007.04.006"},{"key":"e_1_2_4_44_1","first-page":"CD009331","article-title":"Passive movements for the treatment and prevention of contractures","volume":"12","author":"Prabhu RKR","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_4_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2334"},{"key":"e_1_2_4_46_1","doi-asserted-by":"crossref","DOI":"10.1038\/bonekey.2014.108","article-title":"Embedded in bone, but looking beyond: osteocalcin, epigenetics and ectopic bone formation (ASBMR 2014)","volume":"11","author":"Johnson RW","year":"2014","journal-title":"IBMS BoneKEy"},{"key":"e_1_2_4_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008810"},{"key":"e_1_2_4_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2012.12.030"},{"key":"e_1_2_4_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23544"},{"key":"e_1_2_4_50_1","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1089\/neu.2007.0342","article-title":"Early excision and late excision of heterotopic ossification after traumatic brain injury are equivalent: a systematic review of the literature","volume":"24","author":"Chalidis B","year":"2007","journal-title":"J Neurotrauma"},{"key":"e_1_2_4_51_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.N.01056"},{"key":"e_1_2_4_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhsa.2013.09.029"},{"key":"e_1_2_4_53_1","first-page":"1281","article-title":"Molecular and cellular mechanisms of heterotopic ossification","volume":"29","author":"Ramirez DM","year":"2014","journal-title":"Histol Histopathol"},{"key":"e_1_2_4_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.10.020"},{"key":"e_1_2_4_55_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.H.01177"},{"key":"e_1_2_4_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-015-0034-1"},{"key":"e_1_2_4_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.20924"},{"key":"e_1_2_4_58_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060692"},{"key":"e_1_2_4_59_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf1090"},{"key":"e_1_2_4_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-014-3694-7"},{"key":"e_1_2_4_61_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOT.0b013e31825d60a5"},{"key":"e_1_2_4_62_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e318291da85"},{"key":"e_1_2_4_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-1383(02)00416-3"},{"key":"e_1_2_4_64_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e3182ab1ab5"},{"key":"e_1_2_4_65_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOT.0b013e3182724624"},{"key":"e_1_2_4_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-015-4266-1"},{"key":"e_1_2_4_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-013-3325-8"},{"key":"e_1_2_4_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-013-2801-5"},{"key":"e_1_2_4_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1691"},{"key":"e_1_2_4_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2011.06.028"},{"key":"e_1_2_4_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2015.07.016"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjor.23808","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.23808","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T13:24:24Z","timestamp":1695561864000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.23808"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,19]]},"references-count":70,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1002\/jor.23808"],"URL":"https:\/\/doi.org\/10.1002\/jor.23808","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,19]]},"assertion":[{"value":"2017-06-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}