A 49-Year-Old Man With Pain at the Site of a Previous Fracture

Maria Romanova, MD


January 14, 2016

Infantile and intermediate osteopetrosis are inherited in an autosomal recessive fashion; they carry a poor prognosis and high mortality. These forms of the disease are diagnosed early in life. Bone marrow failure often results, with associated bony abnormalities, hydrocephalus, proptosis, delayed dentition, blindness due to retinal detachment, and extreme bone fragility. Failure to thrive and growth retardation are also symptoms.

Nasal stuffiness caused by mastoid and paranasal sinus malformation is often the presenting feature. Neuropathies related to cranial nerve entrapment occur because the foramina of the skull fail to widen completely, with manifestations that include deafness, proptosis, and hydrocephalus. Normal dentition may be delayed, and osteomyelitis of the mandible is commonly seen because of an abnormal blood supply. The bones are fragile and can fracture easily.[1]

Bone marrow tends to be replaced by defective osseous tissue, which leads to bone marrow failure with resultant pancytopenia. Patients may have anemia, a tendency to bruise easily, and bleeding resulting from thrombocytopenia; recurrent infections may occur because of inherent defects in the immune system. Extramedullary hematopoiesis may also be seen, with resultant hepatosplenomegaly, hypersplenism, and hemolysis. Other physical findings include short stature, frontal bossing, a large head, nystagmus, and genu valgum. Laboratory findings in infantile osteopetrosis include hypocalcemia, elevated parathyroid hormone levels (secondary hyperparathyroidism), and high acid phosphatase and creatinine kinase levels.[1]

Plain radiographs are usually diagnostic and reveal generalized osteosclerosis, although findings may vary by subtype. The cranium is usually thickened and dense, especially at the base, and the paranasal and mastoid sinuses are underpneumatized. On lateral views, vertebral radiographs may show a "bone-in-bone" (endobone) configuration or end-plate sclerosis causing a "rugger-jersey" appearance. Similarly, other bones may also be uniformly sclerotic, but alternating sclerotic and lucent bands may be noted in the iliac wings and near the ends of the long bones. The radiographs may also show evidence of frequent fractures or osteomyelitis.

MRI can be used to assess bones over time, especially after bone marrow transplantation. On histologic examination, failure of osteoclasts to resorb skeletal tissue is the pathognomonic feature of osteopetrosis. Remnants of mineralized primary spongiosa can be seen as islands of calcified cartilage within mature bone. Woven bone is commonly seen. The number of osteoclasts can be increased, normal, or even decreased.


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