Abstract
Heterotopic ossification is the abnormal formation of mature lamellar bone within extraskeletal soft tissues where bone does not exist. Heterotopic ossification has been classified into posttraumatic, nontraumatic or neurogenic, and myositis ossificans progressiva or fibrodysplasia ossificans progressive. The pathophysiology is unknown. Anatomically, heterotopic ossification occurs outside the joint capsule without disrupting it. The new bone can be contiguous with the skeleton but generally does not involve the periosteum. Three-phase technetium-99m (99mTc) methylene diphosphonate bone scan is the most sensitive imaging modality for early detection and assessing the maturity of heterotopic ossification. Nonsurgical treatment with indomethacin and radiation therapy is appropriate for prophylaxis or early treatment of heterotopic ossification. Although bisphosphonates are effective prophylaxis if initiated shortly after the trauma, mineralization of the bone matrix resumes after drug discontinuation. During the acute inflammatory stage, the patient should rest the involved joint in a functional position; once acute inflammatory signs subside, passive range of motion exercises and continued mobilization are indicated.
Surgical indications for excision of heterotopic ossification include improvement of function, standing posture, sitting or ambulation, independent dressing, feeding and hygiene, and repeated pressure sores from underlying bone mass. The optimal timing of surgery has been suggested to be a delay of 12 to 18 months until radiographic evidence of heterotopic ossification maturation and maximal recovery after neurological injury. The ideal candidate for surgical treatment before 18 months should have no joint pain or swelling, a normal alkaline phosphatase level, and 3-phase bone scan indicating mature heterotopic ossification.
- 1.Dejerne A, Ceillier A. Para-osteo-arthropathies des paraplegiques par lesion medullaire; etude clinique et radiographique. Ann Med. 1918; (5):497. Google Scholar
- 2.Nuovo MA, Norman A, Chumas J, Ackerman LV. Myositis ossificans with atypical clinical, radiographic, or pathologic findings: a review of 23 cases. Skeletal Radiol. 1992; 21(2):87–101.
10.1007/BF00241831 Crossref Medline, Google Scholar - 3.Garland DE. A clinical perspective on common forms of acquired heterotopic ossification. Clin Orthop Relat Res. 1991; (263):13–29. Medline, Google Scholar
- 4.Singer BR. Heterotopic ossification. Br J Hosp Med. 1993; 49(4):247–255. Medline, Google Scholar
- 5.Thomas BJ. Heterotopic bone formation after total hip arthroplasty. Orthop Clin North Am. 1992; 23(2):347–358. Crossref Medline, Google Scholar
- 6.Allard MM, Thomas RL, Nicholas RW. Myositis ossificans: an unusual presentation in the foot. Foot Ankle Int. 1997; 18(1):39–42. Crossref Medline, Google Scholar
- 7.Jacobs JE, Birnbaum BA, Siegelman ES. Heterotopic ossification of midline abdominal incisions: CT and MR imaging findings. AJR Am J Roentgenol. 1996; 166(3):579–584. Crossref Medline, Google Scholar
- 8.Reardon MJ, Tillou A, Mody DR, Reardon PR. Heterotopic calcification in abdominal wounds. Am J Surg. 1997; 173(2):145–147.
10.1016/S0002-9610(96)00415-1 Crossref Medline, Google Scholar - 9.Haque S, Eisen RN, West AB. Heterotopic formation in the gastrointestinal tract. Arch Pathol Lab Med. 1996; 120(7):666–670. Medline, Google Scholar
- 10.Naraghi FF, DeCoster TA, Moneim MS, Miller RA, Rivero D. Heterotopic ossification. Orthopedics. 1996; 19(2):145–151. Link, Google Scholar
- 11.Thomas BJ, Amstutz HC. Prevention of heterotopic bone formation: clinical experience with diphosphonates. Hip. 1987: 59–69. Medline, Google Scholar
- 12.Rossier AB, Bussat P, Infante F, Current facts of para-osteo-arthropathy (POA). Paraplegia. 1973; 11(1):38–78. Medline, Google Scholar
- 13.Subbarao JV, Garrison SJ. Heterotopic ossification: diagnosis and management, current concepts and controversies. J Spinal Cord Med. 1999; 22(4):273–283. Crossref Medline, Google Scholar
- 14.Gibson CJ, Poduri KR. Heterotopic ossification as a complication of toxic epidermal necrolysis. Arch Phys Med Rehabil. 1997; 78(7):774–776.
10.1016/S0003-9993(97)90088-5 Crossref Medline, Google Scholar - 15.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. Medline, Google Scholar
- 16.Inan M, Chan G, Dabney K, Miller F. Heterotopic ossification following hip osteotomies in cerebral palsy: incidence and risk factors. J Pediatr Orthop. 2006; 26(4):551–556. Crossref Medline, Google Scholar
- 17.Benetos IS, Mavrogenis AF, Themistocleous GS, Kanellopoulos AD, Papagelopoulos PJ, Soucacos PN. Optimal treatment of fibrodysplasia ossificans progressiva with surgical excision of heterotopic bone, indomethacin, and irradiation. J Surg Orthop Adv. 2006; 15(2):99–104. Medline, Google Scholar
- 18.Kaplan FS, Xu M, Glaser DL, Early diagnosis of fibrodysplasia ossificans progressiva. Pediatrics. 2008; 121(5):e1295–1300.
10.1542/peds.2007-1980 Crossref Medline, Google Scholar - 19.Bosch P, Musgrave DS, Lee JY, Cummins J, Osteoprogenitor cells within skeletal muscle. J Orthop Res. 2000; 18(6):933–944.
10.1002/jor.1100180613 Crossref Medline, Google Scholar - 20.Clifton GL, Ziegler MG, Grossman RG. Circulating catecholamines and sympathetic activity after head injury. Neurosurgery. 1981; 8(1):10–14.
10.1227/00006123-198101000-00003 Crossref Medline, Google Scholar - 21.Fisher LA, Kikkawa DO, Rivier JE, Stimulation of noradrenergic sympathetic outflow by calcitonin gene-related peptide. Nature. 1983; 305(5934):534–536.
10.1038/305534a0 Crossref Medline, Google Scholar - 22.De Bastiani G, Mosconi F, Spagnol G, Nicolato A, Ferrari S, Aprili F. High calcitonin levels in unconscious polytrauma patients. J Bone Joint Surg Br. 1992; 74(1):101–104. Crossref Medline, Google Scholar
- 23.Jensen LL, Halar E, Little JW, Brooke MM. Neurogenic heterotopic ossification. Am J Phys Med. 1987; 66(6):351–363. Medline, Google Scholar
- 24.Kurer MH, Khoker MA, Dandona P. Human osteoblast stimulation by sera from paraplegic patients with heterotopic ossification. Paraplegia. 1992; 30(3):165–168. Medline, Google Scholar
- 25.Billings PC, Fiori JL, Bentwood JL, Dysregulated BMP signaling and enhanced osteogenic differentiation of connective tissue progenitor cells from patients with fibrodysplasia ossificans progressiva (fibrodysplasia ossificans progressive). J Bone Miner Res. 2008; 23(3):305–313.
10.1359/jbmr.071030 Crossref Medline, Google Scholar - 26.Bodley R, Jamous A, Short D. Ultrasound in the early diagnosis of heterotopic ossification in patients with spinal injuries. Paraplegia. 1993; 31(8):500–506. Medline, Google Scholar
- 27.Snoecx M, De Muynck M, Van Laere M. Association between muscle trauma and heterotopic ossification in spinal cord injured patients: reflections on their causal relationship and the diagnostic value of ultrasonography. Paraplegia. 1995; 33(8):464–468. Medline, Google Scholar
- 28.Wittenberg RH, Peschke U, Bötel U. Heterotopic ossification after spinal cord injury. Epidemiology and risk factors. J Bone Joint Surg Br. 1992; 74(2):215–218. Crossref Medline, Google Scholar
- 29.Downing MR, Knox D, Gibson P, Reid DM, Potter A, Ashcroft GP. Impact of trochanteric heterotopic ossification on measurement of femoral bone density following cemented total hip replacement. J Orthop Res. 2008; 26(10):1334–1339.
10.1002/jor.20636 Crossref Medline, Google Scholar - 30.Macfarlane RJ, Ng BH, Gamie Z, Pharmacological treatment of heterotopic ossification following hip and acetabular surgery. Expert Opin Pharmacother. 2008; 9(5):767–786.
10.1517/14656566.9.5.767 Crossref Medline, Google Scholar - 31.Garland DE, Blum CE, Waters RL. Periarticular heterotopic ossification in head-injured adults. Incidence and location. J Bone Joint Surg Am. 1980; 62(7):1143–1146. Crossref Medline, Google Scholar
- 32.Bradleigh LH, Perkash A, Linder SH, Sullivan GH, Bhatt HK, Perkash I. Deep venous thrombosis associated with heterotopic ossification. Arch Phys Med Rehabil. 1992; 73(3):293–294. Medline, Google Scholar
- 33.Varghese G, Williams K, Desmet A, Redford JB. Nonarticular complication of heterotopic ossification: a clinical review. Arch Phys Med Rehabil. 1991; 72(12):1009–1013. Medline, Google Scholar
- 34.Ragone DJ, Kellerman WC, Bonner FJ. Heterotopic ossification masquerading as deep venous thrombosis in head-injured adult: complications of anticoagulation. Arch Phys Med Rehabil. 1986; 67(5):339–341. Medline, Google Scholar
- 35.Sarafis KA, Karatzas GD, Yotis CL. Ankylosed hips caused by heterotopic ossification after traumatic brain injury: a difficult problem. J Trauma. 1999; 46(1):104–109.
10.1097/00005373-199901000-00017 Crossref Medline, Google Scholar - 36.Aboulafia AJ, Brooks F, Piratzky J, Weiss S. Osteosarcoma arising from heterotopic ossification after an electrical burn. A case report. J Bone Joint Surg Am. 1999; 81(4):564–570. Crossref Medline, Google Scholar
- 37.Sawyer JR, Myers MA, Rosier RN, Puzas JE. Heterotopic ossification: clinical and cellular aspects. Calcif Tissue Int. 1991; 49(3):208–215.
10.1007/BF02556120 Crossref Medline, Google Scholar - 38.Orzel JA, Rudd TG. Heterotopic bone formation: clinical, laboratory, and imaging correlation. J Nucl Med. 1985; 26(2):125–132. Medline, Google Scholar
- 39.Garland DE, Orwin JF. Resection of heterotopic ossification in patients with spinal cord injuries. Clin Orthop Relat Res. 1989; (242):169–176. Medline, Google Scholar
- 40.Tibone J, Sakimura I, Nickel VL, Hsu JD. Heterotopic ossification around the hip in spinal cord-injured patients. A long-term follow-up study. J Bone Joint Surg Am. 1978; 60(6):769–775. Crossref Medline, Google Scholar
- 41.Singh RS, Craig MC, Katholi CR, Jackson AB, Mountz JM. The predictive value of creatine phosphokinase and alkaline phosphatase in identification of heterotopic ossification in patients after spinal cord injury. Arch Phys Med Rehabil. 2003; 84(11):1584–1588.
10.1053/S0003-9993(03)00347-2 Crossref Medline, Google Scholar - 42.Sherman AL, Williams J, Patrick L, Banovac K. The value of serum creatine kinase in early diagnosis of heterotopic ossification. J Spinal Cord Med. 2003; 26(3):227–230. Crossref Medline, Google Scholar
- 43.Estrores IM, Harrington A, Banovac K. C-reactive protein and erythrocyte sedimentation rate in patients with heterotopic ossification after spinal cord injury. J Spinal Cord Med. 2004; 27(5):434–437. Crossref Medline, Google Scholar
- 44.Schurch B, Capaul M, Vallotton MB, Rossier AB. Prostaglandin E2 measurements: their value in the early diagnosis of heterotopic ossification in spinal cord injury patients. Arch Phys Med Rehabil. 1997; 78(7):687–691.
10.1016/S0003-9993(97)90074-5 Crossref Medline, Google Scholar - 45.Mysiw WJ, Tan J, Jackson RD. Heterotopic ossification. The utility of osteocalcin in diagnosis and management. Am J Phys Med Rehabil. 1993; 72(4):184–187.
10.1097/00002060-199308000-00002 Crossref Medline, Google Scholar - 46.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(8):1629–1632. Crossref Medline, Google Scholar
- 47.Schmidt J, Hackenbroch MH. A new classification for heterotopic ossification in total hip arthroplasty considering the surgical approach. Arch Orthop Trauma Surg. 1996; 115(6):339–343.
10.1007/BF00420328 Crossref Medline, Google Scholar - 48.Bressler EL, Marn CS, Gore RM, Hendrix RW. Evaluation of ectopic bone by CT. AJR Am J Roentgenol. 1987; 148(5):931–935. Crossref Medline, Google Scholar
- 49.Amendola MA, Glazer GM, Agha FP, Francis IR, Weatherbee L, Martel W. Myositis ossificans circumscripta: computed tomographic diagnosis. Radiology. 1983; 149(3):775–779. Crossref Medline, Google Scholar
- 50.Ehara S, Nakasato T, Tamakawa Y, Yamataka H, Murakami H, Abe M. MRI of myositis ossificans circumscripta. Clin Imaging. 1991; 15(2):130–134.
10.1016/0899-7071(91)90162-O Crossref Medline, Google Scholar - 51.Kransdorf MJ, Meis JM, Jelinek JS. Myositis ossificans: MR appearance with radiologicpathologic correlation. AJR Am J Roentgenol. 1991; 157(6):1243–1248. Crossref Medline, Google Scholar
- 52.De Smet AA, Norris MA, Fisher DR. Magnetic resonance imaging of myositis ossificans: analysis of seven cases. Skeletal Radiol. 1992; 21(8):503–507. Crossref Medline, Google Scholar
- 53.Drane WE. Myositis ossificans and the three-phase bone scan. AJR Am J Roentgenol. 1984; 142(1):179–180. Crossref Medline, Google Scholar
- 54.Freed JH, Hahn H, Menter R, Dillon T. The use of three-phase bone scan in the early diagnosis of heterotopic ossification (heterotopic ossification) and in the evaluation of Didronel therapy. Paraplegia. 1982; 20(4):208–216. Medline, Google Scholar
- 55.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. Crossref Medline, Google Scholar
- 56.Muheim G, Donath A, Rossier AB. Serial scintigrams in the course of ectopic bone formation in paraplegic patients. Am J Roentgenol Radium Ther Nucl Med. 1973; 118(4):865–869. Crossref Medline, Google Scholar
- 57.Tanaka T, Rossier AB, Hussey RW, Ahnberg DS, Treves S. Quantitative assessment of para-osteo-arthropathy and its maturation on serial radionuclide bone images. Radiology. 1977; 123(1):217–221. Crossref Medline, Google Scholar
- 58.Cipriano CA, Pill SG, Keenan MA. Heterotopic ossification following traumatic brain injury and spinal cord injury. J Am Acad Orthop Surg. 2009; 17(11):689–697. Crossref Medline, Google Scholar
- 59.Blokhuis TJ, Frölke JP. Is radiation superior to indomethacin to prevent heterotopic ossification in acetabular fractures?: a systematic review [published online ahead of print September 27, 2008]. Clin Orthop Relat Res. 2009; 467(2):526–530.
10.1007/s11999-008-0532-9 Crossref Medline, Google Scholar - 60.Hamid N, Ashraf N, Bosse MJ, Radiation therapy for heterotopic ossification prophylaxis acutely after elbow trauma: a prospective randomized study. J Bone Joint Surg Am. 2010; 92(11):2032–2038.
10.2106/JBJS.I.01435 Crossref Medline, Google Scholar - 61.Haran MJ, Bhuta T, Lee BS. WITHDRAWN: Pharmacological interventions for treating acute heterotopic ossification. Cochrane Database Syst Rev. 2010; (5):CD003321. Medline, Google Scholar
- 62.Banovac K, Williams JM, Patrick LD, Haniff YM. Prevention of heterotopic ossification after spinal cord injury with indomethacin. Spinal Cord. 2001; 39(7):370–374.
10.1038/sj.sc.3101166 Crossref Medline, Google Scholar - 63.Banovac K, Williams JM, Patrick LD, Levi A. Prevention of heterotopic ossification after spinal cord injury with COX-2 selective inhibitor (rofecoxib). Spinal Cord. 2004; 42(12):707–710.
10.1038/sj.sc.3101628 Crossref Medline, Google Scholar - 64.Haran M, Bhuta T, Lee B. Pharmacological interventions for treating acute heterotopic ossification. Cochrane Database Syst Rev. 2004; (4):CD003321. Medline, Google Scholar
- 65.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(2):107–110.
10.1007/s002640050319 Crossref Medline, Google Scholar - 66.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 Am. 2001; 83(12):1783–1788. Crossref Medline, Google Scholar
- 67.Knelles D, Barthel T, Karrer A, Kraus U, Eulert J, Kölbl O. Prevention of heterotopic ossification after total hip replacement. A prospective, randomized study using acetyl-salicylic acid, indomethacin and fractional or single dose irradiation. J Bone Joint Surg Br. 1997; 79(4):596–602.
10.1302/0301-620X.79B4.6829 Crossref Medline, Google Scholar - 68.Amstutz HC, Fowble VA, Schmalzreid TP, Dorey FJ. Short-course indomethacin prevents heterotopic ossification in a high-risk population following total hip arthroplasty. J Arthroplasty. 1997; 12(2):126–132.
10.1016/S0883-5403(97)90058-9 Crossref Medline, Google Scholar - 69.Romanò CL, Duci D, Romanò D, Mazza M, Meani E. Celecoxib versus indomethacin in the prevention of heterotopic ossification after total hip arthroplasty. J Arthroplasty. 2004; 19(1):14–18.
10.1016/S0883-5403(03)00279-1 Crossref Medline, Google Scholar - 70.Karunakar MA, Sen A, Bosse MJ, Sims SH, Goulet JA, Kellam JF. Indometacin as prophylaxis for heterotopic ossification after the operative treatment of fractures of the acetabulum. J Bone Joint Surg Br. 2006; 88(12):1613–1617.
10.1302/0301-620X.88B12.18151 Crossref Medline, Google Scholar - 71.Shafer DM, Bay C, Caruso DM, Foster KN. The use of etidronate disodium in the prevention of heterotopic ossification in burn patients [published online ahead of print September 14, 2007]. Burns. 2008; 34(3):355–360.
10.1016/j.burns.2007.04.006 Crossref Medline, Google Scholar - 72.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 [published online ahead of print January 30, 2008]. Int J Radiat Oncol Biol Phys. 2008; 71(5):1460–1464.
10.1016/j.ijrobp.2007.12.006 Crossref Medline, Google Scholar - 73.Sautter-Bihl ML, Liebermeister E, Nanassy A. Radiotherapy as a local treatment option for heterotopic ossifications in patients with spinal cord injury. Spinal Cord. 2000; 38(1):33–36. Crossref Medline, Google Scholar
- 74.Padgett DE, Holley KG, Cummings M, 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.
10.1016/S0883-5403(03)00265-1 Crossref Medline, Google Scholar - 75.Esenwein SA, Sell S, Herr G, Superior efficacy in suppression of heterotopic bone formation using fractionated irradiation of 5 x 2 Gy compared to a single dose of 7 Gy. An experimental study in rats. Acta Orthop Belg. 2003; 69(2):119–126. Medline, Google Scholar
- 76.Hastings H, Graham TJ. The classification and treatment of heterotopic ossification about the elbow and forearm. Hand Clin. 1994; 10(3):417–437. Crossref Medline, Google Scholar
- 77.Ring D, Jupiter JB. Operative release of complete ankylosis of the elbow due to heterotopic bone in patients without severe injury of the central nervous system. J Bone Joint Surg Am. 2003; 85(5):849–857. Crossref Medline, Google Scholar
- 78.Shehab D, Elgazzar AH, Collier DB. Heterotopic Ossification. J Nucl Med. 2002; (43):346–353. Medline, Google Scholar
- 79.Summerfield SL, DiGiovanni C, Weiss AP. Heterotopic ossification of the elbow. J Shoulder Elbow Surg. 1997; 6(3):321–332.
10.1016/S1058-2746(97)90025-2 Crossref Medline, Google Scholar - 80.Vince KG, Miller JE. Cross-union complicating fracture of the forearm. Part I: Adults. J Bone Joint Surg Am. 1987; 69(5):640–653. Crossref Medline, Google Scholar
- 81.Djurickovic S, Meek RN, Snelling CFT, Range of motion and complications after postburn heterotopic bone excision about the elbow. J Trauma. 1996; 41(5):825–830.
10.1097/00005373-199611000-00010 Crossref Medline, Google Scholar - 82.Lundborg G. Surgical treatment for ulnar nerve entrapment at the elbow. J Hand Surg Br. 1992; 17(3):245–247.
10.1016/0266-7681(92)90106-C Crossref Medline, Google Scholar - 83.Hoffer MM, Brody G, Ferlic F. Excision of heterotopic ossification about elbows in patients with thermal injury. J Trauma. 1978; 18(9):667–670.
10.1097/00005373-197809000-00009 Crossref Medline, Google Scholar - 84.Viola RW, Hastings H. Treatment of ectopic ossification about the elbow. Clin Orthop Relat Res. 2000; (370):65–86.
10.1097/00003086-200001000-00008 Crossref Medline, Google Scholar - 85.Finerman GAM, Krengel WF, Lowell JD, Role of diphosphonate EHDP in the prevention of heterotopic ossification after total hip arthroplasty: preliminary report.
Proceedings of the Fifth Open Scientific Meeting of the Hip Society .St Louis, MO : 2008; 222–234. Google Scholar - 86.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(2):201–208. Crossref Medline, Google Scholar
- 87.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. Medline, Google Scholar
- 88.Stover SL, Hahn HR, Miller JM. Disodium etidronate in the prevention of heterotopic ossification following spinal cord injury (preliminary report). Paraplegia. 1976; 14(2):146–156. Medline, Google Scholar
- 89.Khan FA. Bilateral ankylosis of the hips following heterotopic ossification of the iliopsoas in a child. Int Orthop. 1992; 16(2):202–204.
10.1007/BF00180219 Crossref Medline, Google Scholar
