Osteopetrosis - Pathogenesis

Pathogenesis

Normal bone growth is achieved by a balance between bone formation by osteoblasts and bone resorption (breakdown of bone matrix) by osteoclasts. In osteopetrosis, the number of osteoclasts may be reduced, normal, or increased. Most importantly, osteoclast dysfunction mediates the pathogenesis of this disease.

The exact mechanism is unknown. However, deficiency of carbonic anhydrase in osteoclasts is noted. The absence of this enzyme causes defective hydrogen ion pumping by osteoclasts and this in turn causes defective bone resorption by osteoclasts, as an acidic environment is needed for dissociation of calcium hydroxyapatite from bone matrix. Hence, bone resorption fails while its formation persists. Excessive bone is formed.