osteopetrosis

Osteopetrosis, also known as marble bone disease, refers to a group of rare inherited disorders characterized by defective osteoclast-mediated bone resorption. The resulting impairment of normal bone remodeling leads to diffuse skeletal sclerosis with abnormally dense yet brittle bones.

Most cases are autosomal recessive and present in infancy, with autosomal dominant forms seen in later childhood or adulthood. Key disease genes include TCIRG1, CLCN7, OSTM1, SNX10, and PLEKHM1; mutations disrupt osteoclast formation or function, impairing bone resorption.

Dense, brittle bones narrow the marrow cavities, causing anemia and thrombocytopenia and raising infection risk. Thickened skull bones can compress cranial nerves, leading to vision or hearing loss, facial palsy, or dental problems. Skeletal deformities and growth delay may occur.

Radiographs show generalized osteosclerosis, with signs such as bone-in-bone appearance and sandwich vertebrae, along with Erlenmeyer flask deformities of the long bones and thickened skull base.

Diagnosis uses clinical features, radiographs, and confirmation by genetic testing. Treatment depends on form; hematopoietic stem cell transplantation can cure malignant infantile osteopetrosis by supplying functional osteoclasts, but is not universally effective. Supportive care includes managing anemia and infections, transfusions when needed, fracture care, dental management, and monitoring for cranial nerve impairment.

Osteopetrosis is rare. Prognosis varies by form, with the infantile malignant type carrying high mortality without transplantation, while milder autosomal dominant forms may allow near-normal life expectancy with proper management.