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
Hereditary Expansile Osteolysis; McCabe Disease; Familial
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 18q21.1-q22. 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.
Airway assessment should be done in
those patients with craniofacial involvement. Assess dentition condition and
note presence of loose teeth. If a central neuraxial anesthetic technique is
planned, carefully document the presence of any vertebral fractures.
Patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) or salicylates should have
the platelet function assessed. ...