osteopetrosi

Osteopetrosis, also known as marble bone disease, is a rare inherited disorder characterized by increased bone density caused by defective osteoclast-mediated bone resorption. The bones become abnormally dense but structurally brittle, and the condition is most often genetic. It presents in infancy or childhood, though milder forms may be diagnosed in adulthood. Two major clinical forms are described: an autosomal recessive malignant infantile form with severe early symptoms, and an autosomal dominant milder adult form.

Cause and pathophysiology: Mutations affecting osteoclast function disrupt normal bone remodeling, leading to diffuse osteosclerosis and reduced marrow spaces. This can cause anemia, thrombocytopenia, and increased susceptibility to infections. Thickened skull bones may compress cranial nerves, producing vision or hearing problems. Dental abnormalities and growth delays are common. The disease reflects an imbalance between bone formation and resorption, with bone that is dense but often fragile.

Diagnosis and imaging: Radiographs show generalized increases in bone density, a “bone in bone” appearance, Erlenmeyer flask deformities of the long bones, and “sandwich” vertebrae. Blood tests may reveal cytopenias; alkaline phosphatase levels can be normal or elevated. Genetic testing identifies causative variants in genes involved in osteoclast function (for example, TCIRG1, CLCN7, among others). Bone marrow examination may show reduced hematopoietic activity.

Treatment and prognosis: Management is largely supportive. This includes treating anemia and infections, fracture care, dental management, and monitoring calcium balance. Hematopoietic stem cell transplantation can cure certain autosomal recessive forms by restoring functional osteoclasts. Prognosis varies by form; the infantile malignant type often has a poor outcome without transplant, while milder adult forms may have normal life expectancy with appropriate care.