Osteopetrosis

Definition

Osteopetrosis (‘marble bone disease’) is a rare hereditary disorder of defective osteoclast function: because osteoclasts cannot resorb bone, bone is laid down but not remodelled, so it becomes abnormally dense but brittle. The paradox is that this very dense bone fractures easily and is mechanically weak.

Clinical Features

Severe (infantile, autosomal-recessive) forms present early with bone marrow failure (anaemia, infections, bleeding — because dense bone crowds out the marrow), cranial nerve compression (blindness, deafness) from narrowed foramina, hepatosplenomegaly (extramedullary haematopoiesis) and failure to thrive. The milder (adult, autosomal-dominant / Albers-Schönberg) form may present with fractures or be found incidentally.

Management

The milder adult form needs mainly supportive care and fracture management. The severe infantile form is life-threatening and may be treated with haematopoietic stem-cell transplantation (which provides functional osteoclasts), together with management of the marrow failure and complications.

Complications

The consequences of unremodelled, marrow-crowding bone dominate the severe form: progressive anaemia, thrombocytopenia and immunodeficiency from marrow failure, with compensatory hepatosplenomegaly; cranial nerve palsies (optic and facial nerves, deafness) as skull foramina narrow; and, throughout the skeleton, fractures that heal poorly and osteomyelitis (classically of the mandible) because the dense, poorly vascularised bone resists infection clearance.

Bones are dense yet brittle — they fracture easily.

• Defective osteoclast resorption → dense but brittle bone (‘marble bone’).
• Severe infantile form: marrow failure, cranial nerve compression, failure to thrive.
• X-ray: very dense bones, ‘bone-within-bone’, sandwich vertebra; still fractures easily.
• Adult form supportive; severe infantile form may need stem-cell transplant.