The more severe autosomal recessive form (malignant osteopetrosis, occurring in 1 in 300,000 births) is usually noted shortly after birth; death occurs in the first few years secondary to faulty hematopoiesis, in the absence of a bone transplant. The milder autosomal dominant form (tarda osteopetrosis) may not be evident until adulthood. The extent of bone involvement varies widely. The thickening of the bones at the base of the skull may cause impingement on the foramina at the base of the skull, leading to entrapment of the optic nerve (blindness) or acoustic nerves (deafness).

Pathologic fractures are a significant complication of osteopetrosis because, despite its dense appearance on radiographs, the bone is structurally weak. Normal callus formation occurs in the early stages of fracture healing but is unable to reorganize into normal trabecular bone.

Clinical Manifestations. The abnormal bone encroaches on the metaphyses and medullary canals, leaving no space for the hematopoietic marrow. This results in severe aplastic anemia, secondary enlargement of the liver and spleen, and increased susceptibility to infection (i.e., osteomyelitis). Narrowing of canals that harbor cranial nerves can rarely lead to blindness or deafness.

Radiographic Findings. The most striking characteristic is the extreme density (increased radiopacity) of the bone. On radiographs, the abnormal bone lacks an obvious trabecular pattern, cortex, or medullary canal. Occasionally, there may be transverse or longitudinal streaking. The chalklike density is caused by the persistence of irregularly shaped trabeculae of calcified cartilage surrounded by bone. Spine films show a classic “rugger jersey” appearance, with sclerotic end plates sandwiching the relatively radiolucent midportion of the vertebral bodies.

Treatment. In patients with mild-to-moderate involvement, the focus is on the management of secondary complications with good medical and surgical methods. Fractures should be treated with standard modalities. Severe secondary anemia necessitates blood transfusions, whereas bone marrow transplantation has been helpful in carefully selected patients with severe forms of the condition. Owing to the successful ability to diagnose osteopetrosis in utero, umbilical cord blood transplantation has been shown to be successful in congenital cases. In severe cases, such as threatening or impending blindness, bone marrow transplant, coupled with cranial nerve surgical decompression, has proven successful in preventing further progression. Medical treatments vary, but include corticosteroids, interferon-gamma, thyroid hormone, and erythropoietin therapies.

OSTEOPOIKILOSIS

Osteopoikilosis (“spotted bone disease”) is an asymptomatic dysplasia of bone in which tiny foci of dense bone form in the spongiosa of the epiphyses and metaphyses of the long bones and the small bones of the hands and feet. Although the spine, sacrum, ribs, and sternum can be involved, occurrences in these locations are less common. The overall incidence is 0.1 per 1 million.

Dermatofibrosis lenticularis disseminata (Buschke-Ollendorf syndrome), a congenital disorder characterized by small, yellow nodular foci of subcutaneous connective tissue hyperplasia, is occasionally (~10%) associated with osteopoikilosis.

Radiographic Findings. Radiographs reveal small, rounded spots of increased density, usually less than 10 mm in diameter. The foci consist of rounded areas of normal-appearing, densely compacted bone in the spongiosa. The trabeculae in the bone surrounding the ossification center are either decreased in number or more slender than usual. The pathologic structure of each focus is identical to that of the common hyperostotic lesion called a bone island. It is important to distinguish these lesions from metastatic bony lesions, particularly in adults. Family history may help distinguish the two.

In a closely related dysplasia called osteopathia striata, radiographs show parallel and straight-lined striations that represent slender streaks of normal bone. These striations are most common in the metaphyses of long bones and in the pelvis. The hands are rarely affected, and the clavicle is never involved. A small minority of patients may have concurrent features of osteopathia striata or melorheostosis. Existence of concurrent sclerosing conditions is known as “mixed sclerosing bone dysplasia.”

Treatment. No medical or surgical treatment is indicated, because these patients are largely asymptomatic.