Osteopetrosis

Osteopetrosis (Albers-Schonberg disease, marble bone disease) is a bone disease caused by osteoclast failure and impared bone resorption. The primary event can be an osteoclast-autonomous defect or microenvironmental changes that affect ability of osteoclast progenitors to mature, resorb bone, or both. It is a rare condition with autosomal recessive and dominant modes of inheritance.

• Autosomal dominant form:
  • Type 1: Not currently classified as osteopetrosis, because the defect has been shown to be due to an osteoblast defect that enhances bone formation. There is generalized mild osteosclerosis and normal hematological findings. Fractures are uncommon.
  • Type 2 (ADO): The most common form of osteopetrosis. The course is heterogeneous, ranging from asymptomatic to fatal (rare). Patients present with hematological and neural defects with a range of disease severity. Generally seen in adults, it is characterized by sclerosis of the skull base and pelvis and a typical "bone-within-bone" appearance of the vertebral bodies due to endplate sclerosis ("sandwich" spine").
    
    A variant, centrifugal osteopetrosis, presents with sclerosis of the distal appendicular skeleton and the skull.
• Autosomal recessive:
  • Severe form (ARO): Also known as malignant osteopetrosis, this form usually results in stillbirth or early death. Infants who survive present in early childhood with fractures, as well as diffuse marrow space obliteration leading to pancytopaenia. Patients also commonly have neurological complications due to increased intracranial pressure from calvarial expansion, as well as cranial nerve, spinal cord, and vascular compression due to narrowing of cranial and spinal foramina.
  • Intermediate severity form (IRO): Infantile osteopetrosis with distal renal tubular acidosis and cerebral calcifications ("marble brain syndrome"). Patients present with mental retardation, muscle weakness, hypotonia, and fractures.
• X-linked: Rare. Associated with osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency (OL-EDA-ID syndrome).

The images above are from a young woman with autosomal dominant osteopetrosis. There is sclerosis and widening of the diploic space and a hair-on-end appearance of the skull. The spine images show the classic sandwich vertebrae sign (differentiate by some from the rugger jersey spine). The femur demonstrates increased sclerosis and an Erlenmeyer flask deformity.

References

• Butteriss DJ, Clarke M, Birchall D. The angel in the marble. Br J Radiol. 2006 Apr;79(940):359-61.
• Del Fattore A, Cappariello A, Teti A. Genetics, pathogenesis and complications of osteopetrosis. Bone. 2008 Jan;42(1):19-29.
• Del Fattore A, Peruzzi B, Rucci N, Recchia I, Cappariello A, Longo M, Fortunati D, Ballanti P, Iacobini M, Luciani M, Devito R, Pinto R, Caniglia M, Lanino E, Messina C, Cesaro S, Letizia C, Bianchini G, Fryssira H, Grabowski P, Shaw N, Bishop N, Hughes D, Kapur RP, Datta HK, Taranta A, Fornari R, Migliaccio S, Teti A. Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment. J Med Genet. 2006 Apr;43(4):315-25.
• Vanhoenacker FM, De Beuckeleer LH, Van Hul W, Balemans W, Tan GJ, Hill SC, De Schepper AM. Sclerosing bone dysplasias: genetic and radioclinical features. Eur Radiol. 2000;10(9):1423-33.