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 caused by osteoclast inability to acidify Howship's lacuna due to defective carbonic anhydrase II or chloride channel dysfunction leads to predisposition to fracture lower extremity > upper extremity > axial skeleton lifelong prevalence of fracture ~ 40-50% Associated conditions head cranial nerve palsies from overgrowth of skull foramina optic n. > auditory n. > trigeminal n. > facial n. osteomyelitis due to lack of marrow vascularity and impaired WBC function caffey disease infantile cortical hyperostosis affecting mandible in addition to clavicle, ribs, and scapulae spine lower lumbar pain increased prevalence of spondylolysis pelvis coxa vara commonly due to femoral neck fracture nonunion or repeated stress fractures increased risk of degenerative joint arthritis extremities increased tendency for long bone fractures often low energy transverse increased risk of delayed union and malunion carpal tunnel syndrome 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 bleeding risk frequent infections physical exam macrocephaly hepatosplenomegaly (caused by compensatory extramedullary hematopoiesis) dental abscesses and osteomyelitis of the mandible Autosomal dominant form symptoms usually asymptomatic fractures first learn of disease after fracture usually a low energy pathologic fracture to lower extremity anemia (fatigue) joint pain lower back pain common early hip osteoarthritis physical exam general normal height and appearance generalized osteosclerosis range of motion usually normal unless underlying osteoarthritis head and neck high risk of cranial nerve palsy 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 bone-in-bone appearance 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 autosomal recessive (infantile-malignant) form high dose calcitriol (1,25 dihydroxy vitamin D), bone marrow transplant indications autosomal recessive (infantile-malignant) form interferon gamma-1beta indications autosomal dominant form Cranial nerve impingment Neurosurgical decompression Fracture management nonoperative indications diaphyseal long bone fractures upper extremity fractures techniques prolonged casting and non-weight bearing acceptable bone alignment, rotation and length outcomes healing may be delayed fracture remodeling limited increased risk of malunion and refracture operative indications proximal femur fractures techniques plate and screws avoid intramedullary devices slow steady drilling constant cooling and change of drill bit outcomes increased risk of hardware failure higher union rates and lower malunion rates compared to non-operative management decreased risk of coxa vara Degenerative joint disease total hip arthroplasty indication end stage osteoarthritis techniques femur cannulated reamers under fluoroscopy short stemmed implants usually uncemented components are used acetabulum small, sharp reamers irrigation multiple screws total knee arthroplasty indication indications end stage osteoarthritis technique consider navigation Complications Refracture caused by hard brittle bones hardware failure Infection increased risk due to reduced tissue vascularity Malunion Non-union