30 Osteopetrosis

Osteopetrosis

Peter L. Munk and Anthony G. Ryan

Clinical Presentation

A 32-year-old woman presented with left shoulder pain after a fall, which also resulted in left femoral neck fracture. She has a long history of fractures and is also anemic.

Figure 30A

Figure 30B

Figure 30C

All images from this 32-year-old woman show a generalized increase in bone density. The chest film (Fig. 30A) shows that all osseous elements are sclerotic and that, in addition, the left clavicle is fractured. The pelvic film (Fig. 30B) was obtained immediately after surgery to repair a left femoral neck fracture. All the bones are dense, and an old unhealed right hip fracture is present. A lamellated/arcs pattern is present within the iliac wings (bone within bone). The CT of the pelvis (Fig. 30C) once again shows diffuse increased density and no obvious marrow space.

Diagnosis

Osteopetrosis.

Differential Diagnosis

The appearance is usually characteristic; however, the differential includes

Myelofibrosis
Renal osteodystrophy
Mastocystosis
Fluorosis

Discussion

Background

Osteopetrosis is a bone dysplasia associated with deficient osteoclast activity and consequent increased bone density. Abnormal remodeling results in brittle bone that is prone to fracture. In addition, the marrow cavity becomes extremely narrowed, resulting in deficient bone marrow and secondary bone marrow failure.

Etiology

A variety of different subtypes exist with differing severity, depending on the means of transmission and penetrance. There are infantile and adult forms; the infantile severe autosomal recessive osteopetrosis (ARO) is, in part, due to mutations in the Atp6a3 (TCIRG1) and ClCN7 genes in 60% and 13%, respectively; whereas the adult autosomal dominant osteopetrosis (ADO) form (also known as tarda) is thought to be secondary to ClCN7 mutation. The degree of dominant interference with chloride channel function varies widely even in patients with identical genetic makeup. Mutations in the gene coding for an osteoclast-specific vacuolar pump have also been described, contributing to osteoclast dysfunction.