Abstract
Heterotopic ossification is the formation of lamellar bone outside the skeletal system and in the soft tissue. This may occur in the skin, subcutaneous tissue, fibrous tissue adjacent to joints, ligaments, walls of blood vessels, and skeletal muscle. While new bone formation may occur secondary to genetic, neurogenic, or postsurgical factors, trauma also plays a role. Traumatic heterotopic ossification may occur secondary to acetabular fracture; fracture and fracture/dislocation of the elbow, knee, or shoulder; contusions; strains; sprains; blast injuries; and burns. This chapter will review traumatic heterotopic ossification, along with specific clinical entities including myositis ossificans, heterotopic ossification of the hip, heterotopic ossification after elbow trauma, Pellegrini-Stieda syndrome, heterotopic ossification of the tibiofibular syndesmosis, and heterotopic ossification following blast injury.
Key Concepts
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Refers to abnormal deposition of lamellar bone in soft tissue structures; often associated with trauma but may result from a number of other etiologies
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First described nearly 1000 years ago in the healing of fractures.
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Formation closely resembles the physiology of fracture healing.
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Tissues with a heightened or prolonged inflammatory response to injury are prone to heterotopic ossification.
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The true mechanism for the development of heterotopic ossification is uncertain, although prerequisites needed for development include
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A signaling protein (bone morphogenic protein) secreted from cells of injured tissue or inflammatory cells
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A supply of mesenchymal cells that can differentiate into osteoblasts or chondroblasts
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An appropriate environment conducive to osteogenesis
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Posttraumatic heterotopic ossification occurs most frequently in the hip. Elbow injuries are the second leading cause.
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More common in males
Imaging
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Radiographic abnormalities can be seen within 18 to 21 days but may take 4 to 5 weeks to develop and should be present by 8 weeks.
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Nuclear medicine bone scan is the most sensitive imaging modality for early heterotopic ossification and can be used to indicate whether the lesion is active or has matured. It is usually positive by 2 to 4 weeks and can be used to predict the optimal timing for surgical resection.
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Ultrasound can detect heterotopic ossification sooner than radiographs, computed tomography, or magnetic resonance imaging, and enables early identification and treatment.
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Magnetic resonance imaging is not typically used but can identify a nonspecific soft-tissue mass within the first few weeks. Magnetic resonance imaging may be useful in the preoperative setting to help describe relationships to other structures.
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Computed tomography can delineate zonal pattern of calcification and can be diagnostic before radiographs.
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Computed tomography with three-dimensional reconstruction may be used for preoperative planning.
Additional Tests
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Sedimentation rate may be elevated in the early stages.
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Alkaline phosphatase elevates after 3 weeks, reaches 3.5 times normal at 4 weeks, peaks at 11 to 12 weeks, and normalizes when the bone matures.
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Calcium decreases briefly and then normalizes when serum alkaline phosphatase increases.
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Prostaglandin E 2 excretion in a 24-hour urine collection may be increased.
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Creatinine kinase may be elevated.
Differential Diagnosis
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Clinically the early inflammatory stage may be confused with cellulitis, deep venous thrombosis, thrombophlebitis, or osteomyelitis.
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An early lesion may be misdiagnosed as a soft-tissue osteosarcoma, whereas a late lesion may be mistaken for parosteal osteosarcoma.
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Differential diagnosis may also include abscess, soft tissue recurrence of giant cell tumor of bone, extraskeletal osteosarcoma, and melorheostosis.
Treatment
Early (Prevention After Injury)
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Gentle range of motion within a pain-free zone
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Nonsteroidal antiinflammatory drugs have been effective after total hip arthroplasty. The mechanism of action includes inhibition of differentiation of mesenchymal cells into osteogenic cells and suppression of the prostaglandin-mediated inflammatory response.
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Indomethacin often used for 2 to 6 weeks
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Selective cyclooxygenase (COX)-2 inhibitors may be equally effective
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Radiation
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Has been effective prophylactically for perioperative care of total hip arthroplasty
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May inhibit the differentiation of pluripotent mesenchymal cells into osteoblasts
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Complications include soft tissue contracture, delayed wound healing, and theoretically malignancy
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Equally effective as nonsteroidal antiinflammatory drugs
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Later (If Heterotopic Ossification Develops)
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Physical Therapy
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Bisphosphonates
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Have been effective in neurogenic heterotopic ossification
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May be effective in other forms of heterotopic ossification including burns and spinal cord injury
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Mechanisms include
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Inhibition of precipitation of calcium phosphate
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Delaying aggregation of hydroxyapatite crystals
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Blocking conversion of calcium phosphate into hydroxyapatite
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May develop rebound and bone growth after discontinuation due to resumption of osteoid mineralization while osteoclast function remains suppressed
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May need long-term treatment (at least 6 months)
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Radiation has been used in heterotopic ossification related to spinal cord injury and in conjunction with removal of heterotopic ossification
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Extracorporeal shock wave therapy has been used successfully
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Surgery
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Indications
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Peripheral nerve compromise due to compression
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Persistent pain
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Impaired range of motion not amenable to conservative measures
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Need to combine with nonsteroidal antiinflammatory drugs and/or radiation
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Resection can generally be performed after 6 to 9 months and usually after bone matures.
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Earlier resection with secondary prophylaxis with single-dose radiation or nonsteroidal antiinflammatory medications may be safe.
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Early surgical intervention may provide more effective rehabilitation and dramatic improvements in patient function.
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