summary Osteopetrosis is a congenital metabolic bone disease caused by defective osteoclastic resorption of immature bone that presents with increased frequency of long bone fractures, cranial nerve palsies, and low back pain. Diagnosis is made radiographically with increased cortical thickening, increased overall bone density, and loss of medullary canal diameter. Treatment is multidisciplinary approach to address fracture management, and cranial nerve abnormalities. Epidemiology Prevalence approximately 1 in 20,000 for autosomal dominant form approximately 1 in 200,000 for autosomal recessive form Demographics genetic inheritance (3 types) malignant autosomal recessive intermediate autosomal recessive benign autosomal dominant (most common) Penetrance may skip generations 75% gene penetrance Etiology Pathophysiology pathoanatomy osteoclast dysfunction leads to dense bone and obliterated medullary canals login to view 2 more bullets leads to predisposition to fracture login to view 2 more bullets Associated conditions head login to view 7 more bullets spine login to view 2 more bullets pelvis login to view 3 more bullets extremities login to view 5 more bullets Classification Classification of Osteopetrosis Type Genetic Clinical Presentation Malignant Autosomal recessive Proton pump or chloride channel dysfunction Pancytopenia, hepatosplenomegaly and infection Fatal at an early age without bone marrow transplant Intermediate Autosomal recessive Carbonic anhydrase II dysfunction or chloride channel dysfunction Usually live into adulthood Benign Autosomal dominant Chloride channel dysfunction Type I does not have increased fracture risk Type II is known as Albers-Schonberg disease (anemia, pathologic fractures, and premature osteoarthritis) General health, life span, mental function, and physique are normal Most common form to be managed by orthopaedic surgeon Presentation Autosomal recessive forms symptoms frequent fractures progressive deafness and blindness severe anemia (caused by encroachment of bone on marrow) beginning in early infancy or in utero login to view 2 more bullets physical exam macrocephaly hepatosplenomegaly (caused by compensatory extramedullary hematopoiesis) dental abscesses and osteomyelitis of the mandible Autosomal dominant form symptoms usually asymptomatic fractures login to view 2 more bullets anemia (fatigue) joint pain login to view 2 more bullets physical exam general login to view 2 more bullets range of motion login to view 1 more bullet head and neck login to view 1 more bullet Imaging Radiographs recommended views AP and lateral of bone of interest general findings increased cortical thickening increased overall bone density loss of medullary canal diameter login to view 1 more bullet additional findings "erlenmeyer flask" proximal humerus and distal femur "rugger jersey spine" with very dense bone block femoral metaphysis coxa vara Studies Histology histology shows defective osteoclasts lack ruffled border and clear zone islands of calcified cartilage within mature trabeculae empty lacunae and plugging of the haversian canals also seen Laboratory studies autosomal recessive increases acid phosphatase may have increased PTH +/- calcium autosomal dominant usually normal Treatment Medical management bone marrow transplant indications login to view 1 more bullet high dose calcitriol (1,25 dihydroxy vitamin D), bone marrow transplant indications login to view 1 more bullet interferon gamma-1beta indications login to view 1 more bullet Cranial nerve impingment Neurosurgical decompression Fracture management nonoperative indications login to view 2 more bullets techniques login to view 2 more bullets outcomes login to view 3 more bullets operative indications login to view 1 more bullet techniques login to view 4 more bullets outcomes login to view 3 more bullets Degenerative joint disease total hip arthroplasty indication login to view 1 more bullet techniques login to view 8 more bullets total knee arthroplasty indication indications login to view 1 more bullet technique login to view 1 more bullet Complications Refracture caused by hard brittle bones hardware failure Infection increased risk due to reduced tissue vascularity Malunion Non-union