Myositis ossificans, also known as heterotrophic ossification or ectopic ossification, is a pathologic bone formation that occurs in soft tissues that do not normally ossify. It is a rare condition of unknown pathogenesis, with the first reported case dating back to the 1740s ( 1). There are both a localized form, which is usually posttraumatic, and a widespread syndrome, which occurs in fibrodysplasia ossificans progressiva. The former initially presents as a posttraumatic and well-circumscribed lesion that frequently complicates hematoma formation of the muscles, particularly of the proximal extremities (2). It is commonly seen in the hip musculature of adolescents who are susceptible to sports trauma with contusions. Fibrodysplasia ossificans progressiva consists of skeletal abnormalities, including microdactyly of the first digits, exostosis, and the absence of 2 upper incisors, and is the most extreme manifestation of ectopic ossification (3). An autosomal dominant mutation precedes this rare disease, which results in ectopic calcifications in several muscles beginning in childhood.
A 58-year-old El Salvadorian woman presented with a 1-year history of a right hip mass. The patient initially reported bruising her hips bilaterally after a motor vehicle accident, but reported no other ill effects. Subsequently, she noticed a painful and enlarging lesion on her right hip, which became firm and gradually less painful. The patient's significant medical history was negative and she specifically denied any weight loss, malaise, anorexia, fever, or chills. On examination she had a firm 5-cm mass that was well demarcated with a soft erythematous center and coarse periphery (Figure 1A). Results of laboratory tests were unremarkable, with a white cell count of 7,300/mm3; calcium levels of 8.9 mg/dl; albumin levels of 3.1 gm/dl; and alkaline phosphatase levels of 115 units/liter. Samples of the patient's blood, sputum, and mass were sent for Gram stain and culture, and a tuberculin skin test was performed.
A right hip radiograph showed subcutaneous calcifications of the right hip with no bony involvement (Figure 1B). The patient was then admitted to the medicine service with the differential diagnosis of malignancy, tuberculosis, fungal infection, or heterotopic ossification. Examination of a fine-needle aspirate of the mass revealed nonpolarizing crystals containing calcium (Figure 1C) with no malignant cells. Stains for acid-fast bacilli, fungi, and bacteria were negative. Magnetic resonance imaging (MRI) of the pelvis demonstrated bilateral subcutaneous calcifications without osseous involvement. A diagnosis of myositis ossificans was made and the patient was referred to surgery for excision.
Posttraumatic myositis ossificans such as was seen in our patient accounts for >75% of cases ( 4). This phenomenon of unknown etiology occurs after damage to muscles with subsequent proliferation of connective tissue and differentiation into mature bone. The most frequently reported risk factor is reinjury during the early stages of recovery (5). In adolescents and young adults, the thighs and hips are most commonly involved in traumatic myositis ossificans (6). The incidence rate is 2% following closed treatment of hip dislocation and increases to 34% when open reduction is required (2). Other common sites of posttraumatic myositis ossificans are the upper arm, calf, and sole of the foot (7).
Lesions result in functionally significant deficits in only 10–20% of patients ( 8). Symptoms include localized swelling and tenderness and associated decreased range of motion in the affected extremity (9). Early in the disease, the lesion is soft and painful, and within a few weeks a firm and often painful mass develops in the affected muscles. This lesion matures over 12 months, and eventually ossifies and becomes painless.
Urist et al first observed that acid-demineralized bone matrix could induce fibroblastic cells in muscle tissue to become osteogenic and chondrogenic ( 10) and they named the associated factor bone morphogenetic protein. Other osteoinductive factors have since been recognized. Cells of connective tissue that can differentiate into bone have also been identified and named osteogenic progenitor cells (10), which have been found among blood and lymphoid cells and are believed to be part of the marrow stromal system. It has been postulated that perhaps these osteogenic progenitor cells circulate freely and are stimulated by osteoinductive factors to form osteoid tissue when tissue injury occurs.
The progressive lesion is often between 3 cm and 6 cm, with a soft erythematous center and firm periphery ( 11). The microscopic findings vary according to the age of the lesion and are mirrored by radiographic findings. Early in the disease course, the lesion is mostly cellular with fibroblastic tissue resembling a granulation tissue, and radiographs are often negative (8). As the area of ossification expands, radiographs demonstrate flocculent radiodensities or calcifications. As the lesion matures, it completely ossifies. Radionuclear scans can also be used as an adjunct for diagnosis because an increased uptake correlates accurately with ectopic bone formation (12).
Computerized axial tomography is the preferred imaging modality to demonstrate the zonal pattern in posttraumatic myositis ossificans ( 13). It optimally identifies the typical patterns of this disease, including the separation of the mass from the adjacent cortex and the decreased attenuation of the center of the mass. MRI is the technique of choice for evaluating soft-tissue lesions (14). The classic finding for myositis ossificans is a peripheral rim enhancement that correlates with calcification and ossification.
Myositis ossificans is often confused with and must be distinguished from osteosarcoma. Pain and swelling in osteosarcoma are persistent and progressive ( 4) and periosteal elevation and cortical destruction are present on bone radiographs, with anaplasia on microscopic biopsy evaluation.
Early in the disease course, rest, ice, compression, and elevation are universally recommended. Myositis ossificans is self limiting and can spontaneously resolve ( 2). Most authors recommend an initial 24–48-hour period of immobilization followed by rehabilitation to prevent reinjury. Definitive treatment for heterotopic bone formation is usually reserved for symptomatic lesions (15). Patients without any reports of pain or decreased mobility may be better off avoiding the morbidity associated with excision. Excision is only indicated if the lesion is completely ossified because removal of immature bone may cause extensive local recurrence. Some studies suggest that using prophylactic indomethacin and etidronate can be beneficial in reducing postsurgical ectopic calcification (16). The use of bisphosphonates has been bolstered by recent case reports that point to its effectiveness (17).
Myositis ossificans is a rare but significant clinical entity. Understanding its etiology and pathophysiology can save the patient from spurious medical workups and the anxiety of a suspected neoplasm.