ABSTRACT
Osteogenesis imperfecta is one of the most commonly recognized inheritable disorders of the connective tissue leading to bone fragility. Usually it is associated to a genetic mutation inducing a reduction in collagen quality and entity production. It involves either modification in dentin formation or multiple bone fractures. The authors reviewed the clinical aspects of these disorders, focusing on oral and orthopaedic concerns, especially related to the histological features of the fracture callus, with respect to new trends in pharmacological and surgical treatments of bone fractures. Surgical treatment varies, according to the age of the patient. In children, surgical orthopaedic procedures include multiple osteotomies and the use of telescopic rods. Medical therapy has always to be associated to surgery and is designed to reduce the incidence of fractures, to increase growth velocity and to ally pain in order to improve mobility and independence. Bisphosphonates (BP) are considered potent inhibitors of bone resorption decreasing the osteoclast population and its activity and bone turn over.
Subject(s)
Bones of Lower Extremity/abnormalities , Fractures, Bone/pathology , Fractures, Bone/therapy , Osteogenesis Imperfecta/pathology , Osteogenesis Imperfecta/therapy , Tooth Abnormalities/pathology , Tooth Abnormalities/therapy , Bone Resorption/genetics , Bone Resorption/metabolism , Bone Resorption/pathology , Bone Resorption/therapy , Bones of Lower Extremity/metabolism , Bony Callus/abnormalities , Bony Callus/metabolism , Bony Callus/pathology , Child , Child, Preschool , Collagen/genetics , Collagen/metabolism , Dentin , Fractures, Bone/genetics , Fractures, Bone/metabolism , Humans , Mutation , Osteogenesis Imperfecta/genetics , Osteogenesis Imperfecta/metabolism , Tooth Abnormalities/genetics , Tooth Abnormalities/metabolismABSTRACT
Mutations in the zebrafish connexin43 (cx43) gene cause the short fin phenotype, indicating that direct cell-cell communication contributes to bone length. Three independently generated cx43 alleles exhibit short segments of variable sizes, suggesting that gap junctional intercellular communication may regulate bone growth. Dye coupling assays showed that all alleles are capable of forming gap junction channels. However, ionic coupling assays revealed allele-specific differences in coupling efficiency and gating. For instance, oocyte pairs expressing the weakest allele exhibited much higher levels of coupling than either of the strong alleles. Therefore, measurable differences in Cx43 function may be correlated with the severity of defects in bone length.
