Myositis ossificans

Myositis ossificans comprises two syndromes characterized by heterotopic ossification (calcification) of muscle. The World Health Organization, 2020, has grouped myositis ossificans together with fibro-osseous pseudotumor of digits as a single specific entity in the category of fibroblastic and myofibroblastic tumors.[1]

Myositis ossificans progressiva
Fibrodysplasia ossificans progressiva
SpecialtyRheumatology 
This article is about the non-genetic type of myositis ossificans. For the genetic type, see fibrodysplasia ossificans progressiva.

Classification
  • In the first, and by far most common type, nonhereditary myositis ossificans (commonly referred to simply as "myositis ossificans", as in the remainder of this article), calcifications occur at the site of injured muscle, most commonly in the arms or in the quadriceps of the thighs.
    • The term myositis ossificans traumatica is sometimes used when the condition is due to trauma.[2][3] Also myositis ossificans circumscripta is another synonym of myositis ossificans traumatica refers to the new extraosseous bone that appears after trauma.[4]
  • The second condition, myositis ossificans progressiva (also referred to as fibrodysplasia ossificans progressiva) is an inherited affliction, autosomal dominant pattern, in which the ossification can occur without injury, and typically grows in a predictable pattern. Although this disorder can be passed to offspring by those afflicted with FOP, it is also classified as nonhereditary, as it is most often attributed to a spontaneous genetic mutation upon conception.

Most (i.e. 80%) ossifications arise in the thigh or arm, and are caused by a premature return to activity after an injury. Other sites include intercostal spaces, erector spinae, pectoralis muscles, glutei, and the chest. On planar x-ray, hazy densities are sometimes noted approximately one month after injury, while the denser opacities eventually seen may not be apparent until two months have passed.

Pathophysiology

The exact mechanism of myositis ossificans is not clear. Inappropriate response of stem cells in the bone against the injury or inflammation causes inappropriate differentiation of fibroblasts into osteogenic cells. When a skeletal muscle is injured, inflammatory cytokines (Bone morphogenetic protein 2, Bone morphogenetic protein 4, and Transforming growth factor) are released. These cytokines stimulate the endothelial cells of the blood vessels to transform into mesenchymal stem cells. These mesenchymal stem cells then differentiate into chondrocytes, and osteoblasts, resulting in bone formation in soft tissues.[5]

The process of myositis ossificans can be divided into three stages: early, intermediate, and mature. The early phase occurs in the first four weeks of injury with inflammatory phase of bone formation. This is followed by intermediate phase of bone formation (four to eight weeks following injury) where calcification started to occur and is visible on X-rays. During the maturation phase, mature bone started to form. As the maturation continues, the bone will consolidate in the coming months and subsequently bone regression occurs.[5]

Diagnosis

Sonographic diagnosis

Calcification is typically depicted 2 weeks earlier by ultrasound (US) when compared to radiographs.[6] The lesion develops in two distinct stages with different presentations at US.[7] In the early stage, termed immature, it depicts a non-specific soft tissue mass that ranges from a hypoechoic area with an outer sheet-like hyperechoic peripheral rim to a highly echogenic area with variable shadowing. In the late stage, termed mature, myositis ossificans is depicted as an elongated calcific deposit that is aligned with the long-axis of the muscle, exhibits acoustic shadowing, and has no soft tissue mass associated. US may suggest the diagnosis at early stage, but imaging features need to evolve with successive maturation of the lesion and formation of the characteristic late stage changes before they become pathognomonic.[8]

The differential diagnosis includes many tumoral and nontumoral pathologies. A main concern is to differentiate early myositis ossificans from malignant soft-tissue tumors, and the latter is suggested by a fast-growing process. If clinical or sonographic findings are dubious and extraosseous sarcoma is suspected, biopsy should be performed. At histology, detection of the typical zonal phenomenon is diagnostic of myositis ossificans, though microscopic findings may be misleading during the early stage.[9]

Radiologic diagnosis

The radiological features of myositis ossificans are ‘faint soft tissue calcification within 2–6 weeks, (may have well-defined bony margins by 8 weeks) separated from periosteum by lucent zone and on CT, the characteristic feature is peripheral ossification’.[10][11][12]

Management

Since myositis ossificians is more common in those with bleeding disorders, the formation of bone in soft tissue is thought to be associated with haematoma formation. As the calcifications will typically resolve after a period of time, non-surgical treatment is encouraged to minimize the unpleasant symptoms and maximize the function of the affected limb.[5]

Following a skeletal muscle injury, the affected limb should be immobilized with bed rest, ice therapy, compression, and elevation of the affected limb. Crutches can be used for ambulation while providing adequate rest for the affected limb and minimizing the haematoma formation. Ice therapy for 15 to 20 minutes every 30 to 60 minutes is useful to reduce the skeletal muscle blood flow by 50%. Aggressive limb physiotherapy is not recommended at this stage to prevent the worsening of symptoms. After 48 to 72 hours, range of motion exercise can be introduced as long as the range of motion is not painful. If the lesion becomes more mature, active range of motion and resistance strengthening exercises are useful in maintaining joint function.[5]

Surgical excision is reserved for those who failed the non-surgical treatment, those with intolerable pain, compression of the neurovascular structures, or limitation of the range of motion of the joint which affects the activities of daily living. Surgery is only performed after 6 to 18 months following injury because surgery does not alter the bone maturation process. If a surgery is performed too early, it may predispose to recurrence. However, the optimum timing for surgery and the rate of recurrence following early surgery is controversial because some studies have shown that early surgery does reduce the rate of recurrence.[5]

For those who had total hip replacement or total hip arthroplasty, postoperative single low-dose radiation with 3 weeks of oral indomethacin regimen will be preventive for heterotopic ossification.[13][14] Radiation therapy is also effective in preventing recurrence in those who had done operative excision of heterotopic ossification of the elbow.[15]

References
  1. Sbaraglia M, Bellan E, Dei Tos AP (April 2021). "The 2020 WHO Classification of Soft Tissue Tumours: news and perspectives". Pathologica. 113 (2): 70–84. doi:10.32074/1591-951X-213. PMC 8167394. PMID 33179614.
  2. Sodl, Jeffrey F.; Bassora, Rocco; Huffman, G. Russell; Keenan, Mary Ann E. (2008). "Case Report". Clinical Orthopaedics and Related Research. 466 (1): 225–30. doi:10.1007/s11999-007-0005-6. PMC 2505309. PMID 18196398.
  3. Chadha, Manish; Agarwal, Anil (2007). "Myositis ossificans traumatica of the hand" (PDF). Canadian Journal of Surgery. 50 (6): E21–2. PMC 2386223. PMID 18067695. Archived from the original (PDF) on 2016-02-22. Retrieved 2015-07-01.
  4. Henry, D. "Myositis ossificans".
  5. Walczak, Brian E; Johnson, Christopher N; Howe, B, Matthew (October 2015). "Myositis Ossificans". Journal of the American Academy of Orthopaedic Surgeons. 23 (10): 612–622. doi:10.5435/JAAOS-D-14-00269. PMID 26320160. S2CID 40636013.
  6. Peetrons, P. (2002). "Ultrasound of muscles". European Radiology. 12 (1): 35–43. doi:10.1007/s00330-001-1164-6. PMID 11868072. S2CID 25311186.
  7. Arend, Carlos Frederico (2013). "Pectoralis Major Ultrasound: Myositis Ossificans". Ultrasound of the Shoulder. Master Medical Books.
  8. Lacout, Alexis (Jan–Mar 2012). "Myositis ossificans imaging: keys to successful diagnosis". Indian J Radiol Imaging. 22 (1): 35–39. doi:10.4103/0971-3026.95402. PMC 3354355. PMID 22623814.
  9. Mirra, Joseph M.; Picci, Piero; Gold, Richard H. (1989). "Osseous soft tissue tumors". Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger. pp. 1549–86. ISBN 978-0-8121-1156-9.
  10. Crundwell, N.; O'Donnell, P.; Saifuddin, A. (2007). "Non-neoplastic conditions presenting as soft-tissue tumours". Clinical Radiology. 62 (1): 18–27. doi:10.1016/j.crad.2006.08.007. PMID 17145259.
  11. Parikh, J; Hyare, H; Saifuddin, A (2002). "The Imaging Features of Post-traumatic Myositis Ossificans, with Emphasis on MRI". Clinical Radiology. 57 (12): 1058–66. doi:10.1053/crad.2002.1120. PMID 12475528.
  12. Gokkus, K.; Sagtas, E.; Suslu, F. E.; Aydin, A. T. (2013). "Myositis ossificans circumscripta, secondary to high-velocity gunshot and fragment wound that causes sciatica". BMJ Case Reports. 2013: bcr2013201362. doi:10.1136/bcr-2013-201362. PMC 3822215. PMID 24136914.
  13. Pakos, Emilios E.; Pitouli, Evita J.; Tsekeris, Pericles G.; Papathanasopoulou, Vasiliki; Stafilas, Kosmas; Xenakis, Theodore H. (2006). "Prevention of heterotopic ossification in high-risk patients with total hip arthroplasty: the experience of a combined therapeutic protocol". International Orthopaedics. 30 (2): 79–83. doi:10.1007/s00264-005-0054-y. PMC 2532069. PMID 16482442.
  14. Knelles, D; Barthel, T; Karrer, A; Kraus, U; Eulert, J; Kölbl, O (1997). "Prevention of heterotopic ossification after total hip replacement. A prospective, randomised study using acetylsalicylic acid, indomethacin and fractional or single-dose irradiation". The Journal of Bone and Joint Surgery. British Volume. 79 (4): 596–602. doi:10.1302/0301-620X.79B4.6829. PMID 9250745.
  15. Heyd, R; Strassmann, G; Schopohl, B; Zamboglou, N (2001). "Radiation therapy for the prevention of heterotopic ossification at the elbow". The Journal of Bone and Joint Surgery. British Volume. 83 (3): 332–4. doi:10.1302/0301-620x.83b3.11428. PMID 11341414.
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