Relationship of abnormalities in dental and skeletal development in the osteopetrotic (os) rabbit.

Osteopetrosis is a metabolic bone disease characterized by reduced bone resorption of heterogenous cause. The rabbit mutation is lethal and exhibits ultrastructural aberrations in osteoclasts and osteoblasts together with hypocalcemia, hypophosphatemia and failure to be cured by bone marrow transplantation. We have studied dental abnormalities in mutants from birth to 3 wk using radiographic, cytologic and autoradiographic methods. Radiographs show hypoplasia of most teeth in mutants. The maxillary incisor is smaller and more curved and the mandibular incisor thin and straight compared to normal littermates. The first 3 molars in both arches are unerupted and of distorted shape while the last 2 are less affected. Microscopically areas of ankylosis of mutant incisors and the first 3 molars were commonly encountered even at birth. Osteoclasts were numerous. Autoradiograms of 3H-proline incorporation showed strong periosteal and weak endosteal labeling of bone in both mutants and normal littermates. Dentin labeling in mutant incisors and molars was not less than that in normal rabbits and sites of ankylosis in mutants exhibited labeling. These data indicate that osteopetrotic rabbits exhibit major aberrations in shape and eruption of incisors and most molars and that these effects are not due to lack of dentin formation. Early ankylosis, perhaps secondary to congenital reduction of bone resorption, appears to be the major cause of the dental abnormalities which are less severe in the youngest (posterior) teeth.