Radiological Signs in Osteopetrosis

A 7-year-old male child of nonconsanguineous parents brought to us because of swelling over left cheek, growth retardation, and fatigability. On examination, he had pallor, frontal bossing, and hepato-splenomegaly. Fundus examination showed bilateral optic atrophy and audiometry had bilateral conductive hearing loss. Hematology revealed pancytopenia with hemoglobin of 8.0 g/dL, leukocytes 3,500/mL, and platelets 14,000/mL with 3–4 nucleated red blood cells per 100 white cells on peripheral blood smear. Serum calcium was 8.4 mg/dL (reference range, 8.5–10.5), and phosphorus 5.2 mg/dL (reference range, 2.5–4.5). Serum alkaline phosphatase, thyroid hormone, parathormone, iron studies, and vitamin B12 levels were within normal range. Ultrasonography of left mandible showed destroyed bone with signs of chronic osteomyelitis. X-rays of the long bones revealed metaphyseal cupping and fraying (clubbing of metaphysis/Erlenmeyer-flask deformity) with multiple alternating dense and radiolucent transverse metaphyseal lines [Figure 1a]. X-ray of spine showed ‘Sandwich vertebral body sign’ (sclerotic bands on end plates of vertebral bodies) [Figure 1b]. Bones of the base of skull and both orbits were thickened and sclerosed showing ‘Goggle sign’ and paranasal sinuses were poorly pneumatized. [Figure 1c]. Patient was managed by supportive measures with antibiotics, platelets and blood transfusion.

Figure 1.

(a) X-rays of long bones revealed metaphyseal cupping and fraying ('Clubbing of metaphysis'/'Erlenmeyer-flask' bone deformity) with multiple alternating dense and radiolucent transverse metaphyseal lines and homogeneously dense and sclerosed pelvic bones. (b) Sclerosis of superior and inferior endplates of vertebrae with parallel bands of dense bone showing 'Sandwich Vertebrae'. (c) Thickened calvaria and sclerosis of bones of the base of skull and orbits i.e., 'Goggle sign'

Osteopetrosis (Marble bone disease or Albers-Schönberg disease or Osteitis Condensans Generalisata) is a rare heterogeneous group of metabolic bone disease in which there is impaired osteoclastic function of bone resorption resulting sclerotic bones. Osteopetrosis is categorized by clinical severity and inheritance pattern into milder or benign autosomal dominant form of adult to severe or malignant, autosomal recessive form of infants, and autosomal recessive intermediate form.[1] There is defect in acidification of bones in osteopetrosis due to three mutations. First, the most common is defect in the A3 subunit of the osteoclast vacular H+-ATPase proton pump and the two other are CLCN7 and carbonic anhydrase II defect.[2] The excessive osseous tissue in sclerotic bones compromise marrow spaces, that is responsible for cytopenias and extramedullary hematopoiesis. Anemia in osteopetrosis is leukoerythroblastic in type. Constricted cranial foraminas leads to multiple cranial nerve palsies. Rickets is a paradoxical complication of infantile osteopetrosis because of impaired osteoclastic function to maintain normal calcium phosphorus balance in extra cellular fluid, despite markedly total positive calcium balance as majority of total body calcium is sequestrated in skeleton tissue. This fall in calcium is further exacerbated by inadequate dietary intake of calcium or poor absorption from gastrointestinal tract. Persistence hypocalcemia and hypophosphatemia is responsible for decreased mineralization of newly formed chondroid and osteoid bones in osteopetrorickets.[3]

Hemotopoietic stem cell transplantation (HSCT) is reserved for severe infantile osteopetrosis. It is important to detect and treat underlying rickets in these patients for proper and adequate response of HSCT. Corticosteroids and splenectomy have benefited in some patients with hematological complications but not in all cases. The host osteoclasts cells can be stimulated with calcium restriction, calcitriol, steroids, parathormone, and interferon. Interferon gamma-1b has been tried in non-responder to HSCT or as a bridging therapy to transplantation.[1] Prognosis is poor in absence of HSCT, most of the children dies in early childhood due to anemia, infections, and bleeding manifestations.[3]

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