Top

Published in:

01-10-2005 | Review Article

Heterotopic ossification: a review

Authors: E. F. McCarthy, M. Sundaram

Published in: Skeletal Radiology | Issue 10/2005

Abstract

Heterotopic ossification is the formation of bone in the soft tissues. Soft tissue bone deposition may range from the minimal and inconsequential to massive and clinically significant. In some clinical settings it is a predictable finding with an unpredictable course and in other settings it may be diagnostically confounding. Heterotopic ossification may be encountered in clinically disparate disease processes and circumstances. We review the genetic, neurogenic, post-traumatic, post-surgical and “reactive” causes of heterotopic ossification and discuss some current concepts of its pathogenesis.

Bostrom K, Watson KE, Horn S, Wortham C, Herman IM, Demer LL. Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest 1993; 91:1800–1809.PubMed

Wilson JD, Montague CJ, Salcuni P, Bordi C, Rosai J. Heterotopic mesenteric ossification (“intraabdominal myositis ossificans”): report of five cases. Am J Surg Pathol 1999; 23:1464–1470.CrossRefPubMed

Kaplan FS, Glaser DL, Hebela N, Shore EM. Heterotopic ossification. J Am Acad Orthop Surg 2004; 12:116–125.PubMed

Urist MR. Bone: formation by autoinduction. 1965. Clin Orthop 2002;395:4–10.PubMed

Kaplan FS. Skin and bones. Arch Dermatol 1996; 132:815–818.CrossRefPubMed

Kingsley DM. The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev 1994; 8:133–146.PubMed

Wozney JM, Rosen V, Byrne M, Celeste AJ, Moutsatsos I, Wang EA. Growth factors influencing bone development. J Cell Sci Suppl 1990; 13:149–56.PubMed

Jones CM, Lyons KM, Hogan BL. Involvement of Bone Morphogenetic Protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse. Development 1991; 111:531–542.PubMed

Nakase T, Nomura S, Yoshikawa H, Hashimoto J, Hirota S, Kitamura Y, et al. Transient and localized expression of bone morphogenetic protein 4 messenger RNA during fracture healing. J Bone Miner Res 1994; 9:651–659.PubMed

10.

Shore EM, Glaser DL, Gannon FH. Osteogenic induction in hereditary disorders of heterotopic ossification. Clin Orthop 2000; 374:303–316.CrossRefPubMed

11.

DeWitt LM. Myositis ossificans with a report of two cases. Am J Med Sci 1900; 120:295–309.

12.

Munchmeyer. Ueber myositis ossificans progressiva. Zeitschr Rationelle Med 1869; 34:9.

13.

Cohen RB, Hahn GV, Tabas JA, Peeper J, Levitz CL, Sando A, et al. The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients. J Bone Joint Surg Am 1993; 75:215–219.PubMed

14.

Campbell RK. Myositis ossificans progressiva. Radiol Rev 1933; 55:153.

15.

Smith R, Russell RG, Woods CG. Myositis ossificans progressiva. Clinical features of eight patients and their response to treatment. J Bone Joint Surg Br 1976; 58:48–57.PubMed

16.

Shafritz AB, Shore EM, Gannon FH, Zasloff MA, Taub R, Muenke M, et al. Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva. N Engl J Med 1996; 335:555–561.CrossRefPubMed

17.

Feldman G, Li M, Martin S, Urbanek M, Urtizberea JA, Fardeau M, et al. Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27–31. Am J Hum Genet 2000; 661:128–135.CrossRef

18.

Semonin O, Fontaine K, Daviaud C, Ayuso C, Lucotte G. Identification of three novel mutations of the noggin gene in patients with fibrodysplasia ossificans progressiva. Am J Med Genet 2001; 102:314–317.CrossRefPubMed

19.

Gazzerro E, Gangji V, Canalis E. Bone morphogenetic proteins induce the expression of noggin, which limits their activity in cultured rat osteoblasts . J Clin Invest 1998; 102:2106–2114.PubMed

20.

Ahn J, Serrano DLP, Shore EM, Kaplan FS. Paresis of a bone morphogenetic protein-antagonist response in a genetic disorder of heterotopic skeletogenesis. J Bone Joint Surg Am 2003; 85:667–674.PubMed

21.

Gannon FH, Kaplan FS, Olmsted E, Finkel GC, Zasloff MA, Shore E. Bone morphogenetic protein 2/4 in early fibromatous lesions of fibrodysplasia ossificans progressiva. Hum Pathol 1997; 28:339–343.CrossRefPubMed

22.

Kaplan FS, Tabas JA, Gannon FH, Finkel G, Hahn GV, Zasloff MA. The histopathology of fibrodysplasia ossificans progressiva. An endochondral process. J Bone Joint Surg Am 1993; 75:220–230.PubMed

23.

Kaplan FS, Craver R, MacEwen GD, Gannon FH, Finkel G, Hahn G, et al. Progressive osseous heteroplasia: a distinct developmental disorder of heterotopic ossification. Two new case reports and follow-up of three previously reported cases. J Bone Joint Surg Am 1994; 76:425–436.PubMed

24.

Kaplan FS, Shore EM. Progressive osseous heteroplasia. J Bone Miner Res 2000; 15:2084–2094.PubMed

25.

Eddy MC, De Beur SM, Yandow SM, McAlister WH, Shore EM, Kaplan FS, et al. Deficiency of the alpha-subunit of the stimulatory G protein and severe extraskeletal ossification. J Bone Miner Res 2000; 15:2074–2083.PubMed

26.

Weinstein LS, Chen M, Liu J. Gs(alpha) mutations and imprinting defects in human disease. Ann N Y Acad Sci 2002; 968:173–197.PubMed

27.

Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med 1991; 325:1688–1695.PubMed

28.

Heifetz SA, Galliani CA, DeRosa GP. Myositis (fasciitis) ossificans in an infant. Pediatr Pathol 1992; 12:223–229.PubMed

29.

DeSmet AA, Norris MA, Fisher DR. Magnetic resonance imaging of myositis ossificans: analysis of seven cases. Skeletal Radiol 1992; 21:503–507.PubMed

30.

Cvitanic O, Sedlak J. Acute myositis ossificans. Skeletal Radiol 1995; 24:139–141.CrossRefPubMed

31.

Ehara S, Shiraishi H, Abe M, Mizutani H. Reactive heterotopic ossification ITS patterns on MRI. Clin Imaging 1998; 22:292–296.CrossRefPubMed

32.

Ogilvie-Harris DJ, Fornasier VL. Pseudomalignant myositis ossificans: heterotopic new-bone formation without a history of trauma. J Bone Joint Surg Am 1980; 62:1274–1283.PubMed

33.

Lagier R, Cox JN. Pseudomalignant myositis ossificans. A pathological study of eight cases. Hum Pathol 1975; 6:653–665.PubMed

34.

Kaplan FS, Gannon FH, Hahn GV, Wollner N, Prauner R. Pseudomalignant heterotopic ossification. Differential diagnosis and report of two cases. Clin Orthop 1998; 346:134–140.PubMed

35.

Mody BS, Patil SS, Carty H, Klenerman L. Fracture through the bone of traumatic myositis ossificans. A report of three cases. J Bone Joint Surg Br 1994; 76:607–609.PubMed

36.

Amir G, Mogle P, Sucher E. Case report 729. Myositis ossificans and aneurysmal bone cyst. Skeletal Radiol 1992; 21:257–259.CrossRefPubMed

37.

Konishi E, Kusuzaki K, Murata H, Tsuchihashi Y, Beabout JW, Unni KK. Extraskeletal osteosarcoma arising in myositis ossificans. Skeletal Radiol 2001; 30:39–43.CrossRefPubMed

38.

Damanski M. Heterotopic ossification in paraplegia. J Bone Joint Surg Br 1961; 43:286–299.

39.

Botte MJ, Keenan MAE, Abrams RA, von Schroeder HP, Gellman H, Mooney V. Heterotopic ossification in neuromuscular disorders. Orthopedics 1997; 20:335–341.PubMed

40.

Garland DE. A clinical perspective on common forms of acquired heterotopic ossification. Clin Orthop 1991; 263:13–29.PubMed

41.

Goodman TA, Merkel PA, Perlmutter G, Doyle MK, Krane SM, Polisson RP. Heterotopic ossification in the setting of neuromuscular blockade. Arthritis Rheum 1997; 40:1619–1627.PubMed

42.

Taly AB, Nair KP, Kumar MV, Jayakumar PN, Vasudev MK, Ravishankar D, et al. Heterotopic ossification in non-traumatic myelopathies. Spinal Cord 1999; 37:47–49.CrossRefPubMed

43.

Milgram J. (1990) Myositis ossificans and heterotopic bone. In: Gruhn J, ed. Radiologic and histologic pathology of nontumorous diseases of bones and joints. Illinois: Northbrook Publishing, 1990:454.

44.

Riegler HF, Harris CM. Heterotopic bone formation after total hip arthroplasty. Clin Orthop 1976; 117:209–216.PubMed

45.

Thomas BJ. Heterotopic bone formation after total hip arthroplasty. Orthop Clin North Am 1992; 23:347–358.PubMed

46.

Brooker AF, Bowerman JW, Robinson RA, Riley LH, Jr. Ectopic ossification following total hip replacement. Incidence and method of classification. J Bone Joint Surg Am 1973; 55:1629–1632.PubMed

47.

Kjaersgaard-Andersen P, Ritter MA. Prevention of formation of heterotopic bone after total hip arthroplasty. J Bone Joint Surg Am 1991; 73:942–947.PubMed

48.

Nilsson OS, Persson PE. Heterotopic bone formation after joint replacement. Curr Opin Rheumatol 1999; 11:127–131.CrossRefPubMed

49.

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; 21:87–101.CrossRefPubMed

50.

Johnson MK, Lawrence JF. Metaplastic bone formation (myositis ossificans) in the soft tissues of the hand. J Bone Joint Surg AM 1975; 57:999–1000.PubMed

51.

Yuen M, Friedman L, Orr W, Cockshott WP. Proliferative periosteal processes of phalanges: a unitary hypothesis. Skeletal Radiol 1992; 21:301–303.CrossRefPubMed

52.

Sundaram M, Wang L, Rotman M, Howard R, Saboeiro AP. Florid reactive periostitis and bizarre parosteal osteochondromatous proliferation: pre-biopsy imaging evolution, treatment and outcome. Skeletal Radiol 2001; 30:192–198.CrossRefPubMed

53.

Wissinger HA, McClain EJ, Boyes JH. Turret exostosis. Ossifying hematoma of the phalanges. J Bone Joint Surg Am 1966; 48:105–110.PubMed

54.

Abramovici L, Steiner GC. Bizarre parosteal osteochondromatous proliferation (Nora’s lesion): a retrospective study of 12 cases, 2 arising in long bones. Hum Pathol 2002; 33:1205–1210.CrossRefPubMed

55.

Meneses MF, Unni KK, Swee RG. Bizarre parosteal osteochondromatous proliferation of bone (Nora’s lesion). Am J Surg Pathol 1993; 17:691–697.PubMed

56.

Helliwell TR, O’Connor MA, Ritchie DA, Feldberg L, Stilwell JH, Jane MJ. Bizarre parosteal osteochondromatous proliferation with cortical invasion. Skeletal Radiol 2001; 30:282–285.CrossRefPubMed

57.

Nora FE, Dahlin D, Beabout JW. Bizarre parosteal osteochondromatous proliferations of the hands and feet. Am J Surg Pathol 1983; 7:245–250.PubMed

58.

Spjut HJ, Dorfman HD. Florid reactive periostitis of the tubular bones of the hands and feet. A benign lesion which may simulate osteosarcoma. Am J Surg Pathol 1981; 5:423–433.PubMed

59.

Landon GC, Johnson KA, Dahlin DC. Subungual exostoses. J Bone Joint Surg Am 1979; 61:256–259.PubMed

60.

Zambrano E, Nose V, Perez-Atayde AR, et al. Distinct chromosomal rearrangements in subunqual (Dupuytren’s) exostosis and bizarre parosteal osteochondromatous proliferation (Nora lesion), Am J Surg Pathol 2004, 8:1033–1039.

Title: Heterotopic ossification: a review
Authors: E. F. McCarthy
M. Sundaram
Publication date: 01-10-2005
Publisher: Springer-Verlag
Published in: Skeletal Radiology / Issue 10/2005
Print ISSN: 0364-2348
Electronic ISSN: 1432-2161
DOI: https://doi.org/10.1007/s00256-005-0958-z

At a glance: The STEP trials

Springer Medicine

Heterotopic ossification: a review

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 10/2005

Multifocal osseous involvement as the sole manifestation of Rosai-Dorfman disease

Extranodal Rosai-Dorfman disease of bone, subcutaneous tissue and paranasal sinus mucosa with a review of its pathogenesis

Dynamic contrast-enhanced perfusion MR imaging of diseased vertebrae: analysis of three parameters and the distribution of the time-intensity curve patterns

The crescent sign: dissociation of the polyethylene liner from a modular acetabular component in total hip arthroplasty

Abstracts of the Society of Skeletal Radiology. Meeting held in Orlando, Florida, 13-16 March 2005

Semi-automated digital image analysis of patellofemoral joint space width from lateral knee radiographs