Review Question - QID 309

Inactivation of the osteoclast carbonic anhydrase enzyme is responsible for the intermediate-type osteopetrosis.

Osteopetrosis, or marble bone disease, is caused by a defect in the osteoclast, normally responsible for bone resorption and remodeling. There are three types of osteopetrosis: malignant, intermediate and benign. The malignant form, results in early life fatality and is associated with a defect with the proton pump or chloride channel. The cellular mechanism responsible for intermediate-type osteopetrosis is related to inactive osteoclast carbonic anhydrase, the enzyme responsible for acidification and bone resorption within Howship's lacunae (Illustration A). Lastly, the benign form is caused by dysfunctional chloride channel and patients typically live a normal life. Patients with osteopetrosis develop anemia, hearing loss, and frequent fractures because of the defective osteoclast. Two characteristic radiographs are shown in the illustrations below. Illustration B shows the classic "rugger jersey" spine lateral radiograph and illustration C shows the classic "erlenmeyer flask" distal femur radiograph, both diagnostic for osteopetrosis.

Armstrong et al review the literature and discuss their survey of the Pediatric Orthopedic Society of North America, looking at 57 surgeons treating 79 patients with osteopetrosis. While many patients with osteopetrosis require intervention for orthopaedic manifestations of the disease, these authors findings indicate a very high complication rate with operative management of deformity or fractures related to osteopetrosis. Patients in this study treated in traction or with casting had good clinical results with lower complication rates.

Incorrect answers:
Answer 1: Mutation of Gs alpha subunit of the G-protein coupled receptor is responsible for fibrous dysplasia, however it occurs in more than just the osteoclast.
Answer 2: The mitochondria is involved in osteoclast differentiation
Answer 3: The osteoblast doesn't have a ruffled border, the osteoclast does
Answer 4: RunX2 (aka CBFA-1) is invovled in cleidocranial dysplasia