A disorder characterized by congenital fibrous bone remodeling leading to painful, disabling bone deformity, early conductive hearing loss, early dentition loss, and tendency to pathological bone fracture.
McCabe Disease; Hereditary Expansile Osteolysis; Familial Expansile Osteolysis.
An inherited bone dysplasia first described in 1989 by Wallace and Osterberg. It has some histologic similarity to Paget disease.
Rare; only a few kindreds have been reported in people of Northern Irish, German, or American ancestry.
An autosomal dominant inheritance. The gene is mapped to 18q21. The gene TNFRSF11A encodes the receptor activator of nuclear factor-kappa-B (RANK), which is essential for osteoclast formation.
The primary feature is one of active remodeling. The bone matrix is abundant and dense in the early stages, but with increased numbers of osteoblasts lining the bone trabeculae and focal collections of multinucleated osteoclasts at areas of active resorption. As the disease progresses, the matrix becomes scantier with osteoblastic activity becoming intense in advanced cases. Subsequently, there is a reduction in the amount of bone matrix associated with an increasingly disorganized arrangement of bone trabeculae. There is a corresponding increase in the prominence of fibrous tissue with more extensive vascularity. In the end stage of the disease, there is almost complete fatty replacement of the bone, with few remaining features of the original nature of the tissue.
Bone biopsies obtained from affected patients show focal concentrations of multinuclear osteoclasts containing viral-like microcylindrical inclusions. The radiographic features are distinctive. Generalized features are either altered trabecular pattern or modeling abnormalities. Focal features comprise lytic areas that progressively enlarge, producing expansion of the bone and its eventual disintegration because of fibrous and, finally, fatty replacement of the normal medulla. Almost 90% of these lesions occur in the appendicular skeleton. The radiographic features in combination with the histopathology render the condition unique. The serum alkaline phosphatase and urinary hydroxyproline are elevated to a variable degree.
The initial symptom may be early-onset hearing loss in the first decade, which is typically conductive in nature, but may progress to a mixed type. Skeletal changes manifest in the second decade of life and are predominantly distributed in the extremities as severe bone pain, deformity, and pathologic fractures. There are also dental abnormalities with bizarre and extensive resorption of the cervical region of the teeth and the root apex resulting in loss of dentition. There is an initial rapid but nonsustained biochemical response to parenteral dichloromethylene-diphosphonate. Current treatment is based on the drugs used in the treatment of Paget disease (calcitonin, etidronate sodium). None has had any significant sustained effect.