Neurogenic heterotopic ossification: A review. Part 2

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

BACKGROUND: Neurogenic heterotopic ossification is characterized by the formation of bone tissue in the soft tissues of the body caused by severe brain or spinal cord injury of various etiologies. In neurogenic heterotopic ossification, the hip joints are most often affected.

AIM: To analyze publications on the instrumental diagnosis, surgical and nonsurgical methods of treatment, and prevention of neurogenic heterotopic ossification of the hip joints.

MATERIALS AND METHODS: In the second part of our review, we analyzed the literature on modern diagnostics, surgical and conservative methods of treatment, prevention of the formation and recurrence of neurogenic heterotopic ossification of the hip joints. Data were searched in scientific literature databases, namely, PubMed, Google Scholar, Cochrane Library, CrossRef, and eLibrary, without language restrictions.

RESULTS: Modern diagnostic methods allow the screening of hip neurogenic heterotopic ossification in patients at high risk of their formation, with further verification of the diagnosis by computed tomography or magnetic resonance imaging. Despite the lack of consensus on the timing of hip neurogenic heterotopic ossification removal at present, surgical treatment is the most effective method, which allows the removal or reduction of the volume of neurogenic heterotopic ossification. Most cases require controlling the pain syndrome and improving the quality of life of the patients. Despite the common etiologic factor (damage to the central nervous system), nonsurgical methods of the prevention and treatment of patients with neurogenic heterotopic ossification of the hip joints have different effectiveness because of spinal cord injury, cerebral trauma, and cerebral palsy.

CONCLUSIONS: Randomized controlled trials will help to establish the efficacy of conservative treatment methods to prevent the formation and recurrence of hip joint neurogenic heterotopic ossification, taking into account the cause of central nervous system lesions.

About the authors

Vladimir A. Novikov

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: novikov.turner@gmail.com
ORCID iD: 0000-0002-3754-4090
SPIN-code: 2773-1027

MD, PhD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Alina M. Khodorovskaya

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Author for correspondence.
Email: alinamyh@gmail.com
ORCID iD: 0000-0002-2772-6747
SPIN-code: 3348-8038

MD, Research Associate

Russian Federation, Saint Petersburg

Valery V. Umnov

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: umnovvv@gmail.com
ORCID iD: 0000-0002-5721-8575
SPIN-code: 6824-5853

MD, PhD, Dr. Sci. (Med.)

Russian Federation, Saint Petersburg

Evgenii V. Melchenko

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Email: emelchenko@gmail.com
ORCID iD: 0000-0003-1139-5573
SPIN-code: 1552-8550

MD, PhD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Dmitry V. Umnov

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: dmitry.umnov@gmail.com
ORCID iD: 0000-0003-4293-1607
SPIN-code: 1376-7998

MD, PhD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

References

  1. Deev RV, Bersenev AV. Rol’ stvolovykh stromal’nykh (mezenkhimal’nykh) kletok v formirovanii geterotopicheskikh ossifikatov. Kletochnaya transplantologiya i tkanevaya inzheneriya. 2005;(1):46–48. (In Russ.)
  2. Meyers C, Lisiecki J, Miller S, et al. Heterotopic ossification: a comprehensive review. JBMR Plus. 2019;3(4). doi: 10.1002/jbm4.10172
  3. Brady RD, Shultz SR, McDonald SJ, et al. Neurological heterotopic ossification: Current understanding and future directions. Bone. 2018;109:35–42. doi: 10.1016/j.bone.2017.05.015
  4. Garland DE, Orwin JF. Resection of heterotopic ossification in patients with spinal cord injuries. Clin Orthop Relat Res. 1989;(242):169–176. doi: 10.1097/00003086-198905000-00016
  5. Ippolito E, Formisano R, Caterini R, et al. Operative treatment of heterotopic hip ossification in patients with coma after brain injury. Clin Orthop Relat Res. 1999;(365):130–138. doi: 10.1097/00003086-199908000-00018
  6. Wong KR, Mychasiuk R, O’Brien TJ, et al. Neurological heterotopic ossification: novel mechanisms, prognostic biomarkers and prophylactic therapies. Bone Res. 2020;8(1):42. doi: 10.1038/s41413-020-00119-9
  7. Arduini M, Mancini F, Farsetti P, Piperno A, Ippolito E. A new classification of peri-articular heterotopic ossification of the hip associated with neurological injury: 3D CT scan assessment and intra-operative findings. Bone Joint J. 2015;97-B(7):899–904. doi: 10.1302/0301-620X.97B7.35031
  8. de l’Escalopier N, Denormandie P, Gatin L, et al. Resection of neurogenic heterotopic ossification (NHO) of the hip, lessons learned after 377 procedures. Annals of Physical and Rehabilitation Medicine. 2018;61. doi: 10.1016/j.rehab.2018.05.385
  9. Zielinski E, Chiang BJL, Satpathy J. The role of preoperative vascular imaging and embolisation for the surgical resection of bilateral hip heterotopic ossification. BMJ Case Rep. 2019;12(8). doi: 10.1136/bcr-2019-230964.
  10. Cholok D, Chung MT, Ranganathan K, et al. Heterotopic ossification and the elucidation of pathologic differentiation. Bone. 2018;109:12–21. doi: 10.1016/j.bone.2017.09.019
  11. Svircev JN, Wallbom AS. False-negative triple-phase bone scans in spinal cord injury to detect clinically suspect heterotopic ossification: a case series. J Spinal Cord Med. 2008;31(2):194–196. doi: 10.1080/10790268.2008.11760711
  12. van Kuijk AA, Geurts AC, van Kuppevelt HJ. Neurogenic heterotopic ossification in spinal cord injury. Spinal Cord. 2002;40(7):313–326. doi: 10.1038/sj.sc.3101309
  13. Denormandie P, de l’Escalopier N, Gatin L, et al. Resection of neurogenic heterotopic ossification (NHO) of the hip. Orthop Traumatol Surg Res. 2018;104(1S):S121–S127. doi: 10.1016/j.otsr.2017.04.015
  14. Mujtaba B, Taher A, Fiala MJ, et al. Heterotopic ossification: radiological and pathological review. Radiol Oncol. 2019;53(3):275–284. doi: 10.2478/raon-2019-0039
  15. Wang H, Nie P, Li Y, et al. MRI findings of early myositis ossificans without calcification or ossification. Biomed Res Int. 2018;2018. doi: 10.1155/2018/4186324
  16. Stefanidis K, Brindley P, Ramnarine R, et al. Bedside ultrasound to facilitate early diagnosis and ease of follow-up in neurogenic heterotopic ossification: a pilot study from the intensive care unit. J Head Trauma Rehabil. 2017;32(6):E54–E58. doi: 10.1097/HTR.0000000000000293
  17. Wang Q, Zhang P, Li P, et al. Ultrasonography monitoring of trauma-induced heterotopic ossification: guidance for rehabilitation procedures. Front Neurol. 2018;9:771. doi: 10.3389/fneur.2018.00771
  18. Rosteius T, Suero EM, Grasmücke D, et al. The sensitivity of ultrasound screening examination in detecting heterotopic ossification following spinal cord injury. Spinal Cord. 2017;55(1):71–73. doi: 10.1038/sc.2016.93.
  19. Garland DE. A clinical perspective on common forms of acquired heterotopic ossification. Clin Orthop Relat Res. 1991;(263):13–29. doi: 10.1097/00003086-199102000-00003
  20. Mavrogenis AF, Guerra G, Staals EL, et al. A classification method for neurogenic heterotopic ossification of the hip. J Orthop Traumatol. 2012;13(2):69–78. doi: 10.1007/s10195-012-0193-z
  21. Della Valle AG, Ruzo PS, Pavone V, et al. Heterotopic ossification after total hip arthroplasty: a critical analysis of the Brooker classification and proposal of a simplified rating system. J Arthroplasty. 2002;17(7):870–875. doi: 10.1054/arth.2002.34819
  22. Brooker AF, Bowerman JW, Robinson RA, et al. Ectopic ossification following total hip replacement. Incidence and a method of classification. J Bone Joint Surg Am. 1973;55(8):1629–1632.
  23. Genet F, Marmorat JL, Lautridou C, et al. Impact of late surgical intervention on heterotopic ossification of the hip after traumatic neurological injury. J Bone Joint Surg Br. 2009;91(11):1493–1498. doi: 10.1302/0301-620X.91B11.22305
  24. Genêt F, Jourdan C, Schnitzler A, et al. Troublesome heterotopic ossification after central nervous system damage: a survey of 570 surgeries. PLoS One. 2011;6(1). doi: 10.1371/journal.pone.0016632
  25. Taunton MJ. Heterotopic Ossification. In: Complications after primary total hip arthroplasty: a comprehensive clinical guide. Ed. by M.P. Abdel, C.J. Della Valle. Springer Cham; 2017. P. 213–224.
  26. Cobb TK, Berry DJ, Wallrichs SL, et al. Functional outcome of excision of heterotopic ossification after total hip arthroplasty. Clin Orthop Relat Res. 1999;(361):131–139. doi: 10.1097/00003086-199904000-00018
  27. Moore TJ. Functional outcome following surgical excision of heterotopic ossification in patients with traumatic brain injury. J Orthop Trauma. 1993;7(1):11–14. doi: 10.1097/00005131-199302000-00003
  28. Almangour W, Schnitzler A, Salga M, et al. Recurrence of heterotopic ossification after removal in patients with traumatic brain injury: a systematic review. Ann Phys Rehabil Med. 2016;59(4):263–269. doi: 10.1016/j.rehab.2016.03.009
  29. Chalidis B, Stengel D, Giannoudis PV. Early excision and late excision of heterotopic ossification after traumatic brain injury are equivalent: a systematic review of the literature. J Neurotrauma. 2007;24(11):1675–1686. doi: 10.1089/neu.2007.0342
  30. Macheras GA, Lepetsos P, Leonidou A, et al. Results from the surgical resection of severe heterotopic ossification of the hip: a case series of 26 patients. Eur J Orthop Surg Traumatol. 2017;27(8):1097–1102. doi: 10.1007/s00590-017-1980-2
  31. Behery OA, Dai AZ, McLaurin TM. Posttraumatic heterotopic ossification of the hip. J Orthop Trauma. 2018;32(1):S18–S19. doi: 10.1097/BOT.0000000000001197
  32. Meiners T, Abel R, Böhm V, et al. Resection of heterotopic ossification of the hip in spinal cord injured patients. Spinal Cord. 1997;35(7):443–445. doi: 10.1038/sj.sc.3100415
  33. Dilling CF, Wada AM, Lazard ZW, et al. Vessel formation is induced prior to the appearance of cartilage in BMP-2-mediated heterotopic ossification. J Bone Miner Res. 2010;25(5):1147–1156. doi: 10.1359/jbmr.091031
  34. Kim JH, Park C, Son SM, et al. Preoperative arterial embolization of heterotopic ossification around the hip joint. Yeungnam Univ J Med. 2018;35(1):130–134. doi: 10.12701/yujm.2018.35.1.130
  35. Papalexis N, Peta G, Errani C, et al. Preoperative arterial embolization for heterotopic ossification of the hip. J Vasc Interv Radiol. 2023;34(4):608–612. doi: 10.1016/j.jvir.2022.11.030
  36. Koulouvaris P, Tsailas P, Tsiavos K, et al. Clinical observations on surgical details of resection of heterotopic ossification at the hip in traumatic brain-injured adult. J Surg Orthop Adv. 2010;19(3):177–180.
  37. Gatin L, Genêt F, Dinh A, et al. Postoperative infections after excision of neurogenic heterotopic ossifications at the hip: Risk factors and causative organisms. Orthop Traumatol Surg Res. 2017;103(3):357–361. doi: 10.1016/j.otsr.2017.02.001
  38. Stover SL, Niemann KM, Tulloss JR. Experience with surgical resection of heterotopic bone in spinal cord injury patients. Clin Orthop Relat Res. 1991;(263):71–77.
  39. Xu Y, Huang M, He W, et al. Heterotopic ossification: clinical features, basic researches, and mechanical stimulations. Front Cell Dev Biol. 2022;10. doi: 10.3389/fcell.2022.770931
  40. Huber AK, Patel N, Pagani CA, et al. Immobilization after injury alters extracellular matrix and stem cell fate. J Clin Invest. 2020;130(10):5444–5460. doi: 10.1172/JCI136142
  41. Jones NA, Bentley BC, Wahl L. Nonsurgical management of heterotopic ossification in a runner. J Orthop Sports Phys Ther. 2019;49(9):676. doi: 10.2519/jospt.2019.8491
  42. Crawford CM, Varghese G, Mani MM, et al. Heterotopic ossification: are range of motion exercises contraindicated? J Burn Care Rehabil. 1986;7(4):323–327. doi: 10.1097/00004630-198607000-00005
  43. Daud O, Sett P, Burr RG, et al. The relationship of heterotopic ossification to passive movements in paraplegic patients. Disabil Rehabil. 1993;15(3):114–118. doi: 10.3109/09638289309166001
  44. Craven PL, Urist MR. Osteogenesis by radioisotope labelled cell populations in implants of bone matrix under the influence of ionizing radiation. Clin Orthop Relat Res. 1971;76:231–243. doi: 10.1097/00003086-197105000-00030
  45. Wang Y, Zhu G, Wang J, et al. Irradiation alters the differentiation potential of bone marrow mesenchymal stem cells. Mol Med Rep. 2016;13(1):213–223. doi: 10.3892/mmr.2015.4539
  46. Pohl F, Hassel S, Nohe A, et al. Radiation-induced suppression of the Bmp2 signal transduction pathway in the pluripotent mesenchymal cell line C2C12: an in vitro model for prevention of heterotopic ossification by radiotherapy. Radiat Res. 2003;159(3):345–350. doi: 10.1667/0033-7587(2003)159[0345:risotb]2.0.co;2
  47. Georhakopoulos I, Kouloulias V, Kougiountzopoulou A, et al. Radiation therapy for the prevention of heterotopic ossification: efficacy and toxicity of single fraction radiotherapy. Orthop Rev (Pavia). 2020;12(2). doi: 10.4081/or.2020.8577
  48. Davis E, Williams K, Matheney TH, et al. Radiation prophylaxis for hip salvage surgery in cerebral palsy: can we reduce the incidence of heterotopic ossification? J Pediatr Orthop. 2019;39(5):e386–e391. doi: 10.1097/BPO.0000000000001314
  49. Müseler AC, Grasmücke D, Jansen O, et al. In-hospital outcomes following single-dose radiation therapy in the treatment of heterotopic ossification of the hip following spinal cord injury-an analysis of 444 cases. Spinal Cord. 2017;55(3):244–246. doi: 10.1038/sc.2016.112
  50. Schincariol CYN, Echauri EMI, Silvestre OF, et al. Heterotopic ossification after spinal cord injury: prevention and treatment – a sistematic review. Acta Ortop Bras. 2023;31(3). doi: 10.1590/1413-785220233103e267451
  51. Lee CH, Shim SJ, Kim HJ, et al. Effects of radiation therapy on established neurogenic heterotopic ossification. Ann Rehabil Med. 2016;40(6):1135–1139. doi: 10.5535/arm.2016.40.6.1135
  52. Hu ZH, Chen W, Sun JN, et al. Radiotherapy for the prophylaxis of heterotopic ossification after total hip arthroplasty: a systematic review and meta-analysis of randomized controlled trails. Med Dosim. 2021;46(1):65–73. doi: 10.1016/j.meddos.2020.07.010
  53. Milakovic M, Popovic M, Raman S, et al. Radiotherapy for the prophylaxis of heterotopic ossification: A systematic review and meta-analysis of randomized controlled trials. Radiother Oncol. 2015;116(1):4–9. doi: 10.1016/j.radonc.2015.05.022
  54. Ebinger T, Roesch M, Kiefer H, et al. Influence of etiology in heterotopic bone formation of the hip. J Trauma. 2000;48(6):1058–1062. doi: 10.1097/00005373-200006000-00010.
  55. Padgett DE, Holley KG, Cummings M, et al. The efficacy of 500 CentiGray radiation in the prevention of heterotopic ossification after total hip arthroplasty: a prospective, randomized, pilot study. J Arthroplasty. 2003;18(6):677–686. doi: 10.1016/s0883-5403(03)00265-1
  56. Honore T, Bonan I, Salga M, et al. Effectiveness of radiotherapy to prevent recurrence of heterotopic ossification in patients with spinal cord injury and traumatic head injury: a retrospective case-controlled study. J Rehabil Med. 2020;52(5). doi: 10.2340/16501977-2692
  57. Cipriano C, Pill SG, Rosenstock J, et al. Radiation therapy for preventing recurrence of neurogenic heterotopic ossification. Orthopedics. 2009;32(9). doi: 10.3928/01477447-20090728-33
  58. Mourad WF, Packianathan S, Shourbaji RA, et al. Radiation-induced sarcoma following radiation prophylaxis of heterotopic ossification. Pract Radiat Oncol. 2012;2(2):151–154. doi: 10.1016/j.prro.2011.06.005
  59. Farris MK, Chowdhry VK, Lemke S, et al. Osteosarcoma following single fraction radiation prophylaxis for heterotopic ossification. Radiat Oncol. 2012;7:140. doi: 10.1186/1748-717X-7-140
  60. Liu H, Zhao JG, Li Y, et al. Non-steroidal anti-inflammatory drugs for preventing heterotopic bone formation after hip arthroplasty. Cochrane Database Syst Rev. 2019;2019(7). doi: 10.1002/14651858.CD012861.pub2
  61. Banovac K, Williams JM, Patrick LD, et al. Prevention of heterotopic ossification after spinal cord injury with indomethacin. Spinal Cord. 2001;39(7):370–374. doi: 10.1038/sj.sc.3101166
  62. Banovac K, Williams JM, Patrick LD, et al. Prevention of heterotopic ossification after spinal cord injury with COX-2 selective inhibitor (rofecoxib). Spinal Cord. 2004;42(12):707–710. doi: 10.1038/sj.sc.3101628
  63. Zakrasek EC, Yurkiewicz SM, Dirlikov B, et al. Use of nonsteroidal anti-inflammatory drugs to prevent heterotopic ossification after spinal cord injury: a retrospective chart review. Spinal Cord. 2019;57(3):214–220. doi: 10.1038/s41393-018-0199-3
  64. Yolcu YU, Wahood W, Goyal A, et al. Pharmacologic prophylaxis for heterotopic ossification following spinal cord injury: a systematic review and meta-analysis. Clin Neurol Neurosurg. 2020;193. doi: 10.1016/j.clineuro.2020.105737
  65. Dartnell J, Paterson JM, Magill N, Norman-Taylor F. Proximal femoral resection for the painful dislocated hip in cerebral palsy: does indomethacin prevent heterotopic ossification? J Pediatr Orthop. 2014;34(3):295–299. doi: 10.1097/BPO.0000000000000146
  66. Borgeat A, Ofner C, Saporito A, et al. The effect of nonsteroidal anti-inflammatory drugs on bone healing in humans: a qualitative, systematic review. J Clin Anesth. 2018;49:92–100. doi: 10.1016/j.jclinane.2018.06.020
  67. Stover SL, Hahn HR, Miller JM 3rd. Disodium etidronate in the prevention of heterotopic ossification following spinal cord injury (preliminary report). Paraplegia. 1976;14(2):146–156. doi: 10.1038/sc.1976.25
  68. Teasell RW, Mehta S, Aubut JL, et al.; SCIRE Research Team. A systematic review of the therapeutic interventions for heterotopic ossification after spinal cord injury. Spinal Cord. 2010;48(7):512–521. doi: 10.1038/sc.2009.175
  69. Spielman G, Gennarelli TA, Rogers CR. Disodium etidronate: its role in preventing heterotopic ossification in severe head injury. Arch Phys Med Rehabil. 1983;64(11):539–542.
  70. Banovac K. The effect of etidronate on late development of heterotopic ossification after spinal cord injury. J Spinal Cord Med. 2000;23(1):40–44. doi: 10.1080/10790268.2000.11753507
  71. Shafer DM, Bay C, Caruso DM, et al. The use of eidronate disodium in the prevention of heterotopic ossification in burn patients. Burns. 2008;34(3):355–360. doi: 10.1016/j.burns.2007.04.006
  72. Thomas BJ, Amstutz HC. Results of the administration of diphosphonate for the prevention of heterotopic ossification after total hip arthroplasty. J Bone Joint Surg Am. 1985;67(3):400–403. doi: 10.2106/00004623-198567030-00008
  73. Ploumis A, Donovan JM, Olurinde MO, et al. Association between alendronate, serum alkaline phosphatase level, and heterotopic ossification in individuals with spinal cord injury. J Spinal Cord Med. 2015;38(2):193–198. doi: 10.1179/2045772314Y.0000000213
  74. Schuetz P, Mueller B, Christ-Crain M, et al. Amino-bisphosphonates in heterotopic ossification: first experience in five consecutive cases. Spinal Cord. 2005;43(10):604–610. doi: 10.1038/sj.sc.3101761

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2023 Эко-Вектор

Creative Commons License
This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.
 


Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».