Osteopetrosis (marble bone disease) results from defective osteoclast function. Mutations have been identified in the following genes:
- TCIRG1 (proton pump)
- CLCN7 (chloride channel)
- CAII (carbonic anhydrase II)
- gl/gl (unknown function)
Each of these gene abnormalities lead to the inability of osteoclasts to create an acidic environment in the resorption pit under its ruffled border, which is needed for the dissociation of calcium hydroxyapatite from bone matrix. The impaired bone resorption produces dense, chalky, fragile bones and bone marrow replacement.
Skeletal x-rays show generalized osteosclerosis. The diagnosis is made by genetic testing. Bone marrow transplantation to provide normal osteoclasts may be needed in severe cases whereas high-dose calcitriol to stimulate osteoclasts can be effective in the milder forms.