Generalized myositis ossificans This disease, first described by Munchmeyer in 1869, has since been referred to by his name or as myositis ossificans progressiva. It is rare, although Lutwak, in 1964, was able to collect 264 cases from the literature. The cause is unknown, but the disease is probably inherited as an autosomal dominant trait. It consists of widespread bone formation along the fascial planes of muscles and has its onset in infancy and childhood in 90 percent of cases. Biopsies of indurated swellings have revealed extensive proliferation of interstitial connective tissue in which little inflammatory cell reaction is found. Within a few weeks, the connective tissue becomes less cellular and retracts, compressing the adjacent muscle fibers. Osteoid and cartilage formation occur at a later stage, developing in the connective tissue and enclosing relatively intact muscle fibers.
Nearly 75 percent of all reported cases have been associated with congenital anomalies, the most frequent of which is a failure of development of the great toes or thumbs and less often, other digits. Less frequently, there is hypogenitalism, deafness, and an absence of upper incisors. The first symptom is often a firm swelling and tenderness in a paravertebral or cervical muscle. There is, in addition, a mild discomfort during muscle contraction, and the overlying skin may be reddened and slightly swollen. Trauma may be recalled as the initiating factor, but as the months pass, other muscles not injured in any recognizable way become similarly involved. At first, radiographs reveal no important changes, but within 6 to 12 months, calcium deposits are observed, and one can feel stony-hard masses within the muscles. As the disease advances, limitation of movement and deformities become increasingly evident. Calcified bridges between adjacent muscles and across joints lead to rigidity of the spine, jaw, and limbs; scoliosis; and limited expansion of the thorax. Ultimately, the patient is virtually “changed to stone.” A genetic basis for one type, fibrodysplasia ossificans progressiva, has been determined.
The principal problem in diagnosis is to differentiate generalized myositis ossificans from calcinosis universalis. The latter usually occurs in relation to scleroderma or polymyositis and is characterized by calcium deposits in the skin, subcutaneous tissues, and connective tissue sheaths around the muscles; in myositis ossificans, there is actual bone formation within the muscles. The pathologic data are often too meager to justify this sharp distinction. The prolonged ingestion of large doses of vitamin D may also result in the deposition of masses of calcium salts around muscles, joints, and subcutaneous tissue.
Calcific deposits, perhaps true ossification, may occur in the soft tissues around the hips and knees of paraplegics and rarely following a hemiplegia (“paralytic myositis ossificans”) or other causes of prolonged immobilization such as casting.
Myositis ossificans may undergo spontaneous remissions and may stabilize for many years, during which the patient is capable of adequate function. In other cases, progression leads to marked debilitation and respiratory embarrassment, the final illness often being a terminal pneumonia or other infection.
The molecular basis for myositis ossificans is unknown, but it has been suggested that one causative defect is the overexpression of bone morphogenic protein. In mice, the forced expression of this protein induces heterotopic bone formation. It is likely that the primary problem arises either because of inappropriate expression of one element of the protein or of excessive binding between signaling proteins and their receptors.