Sclerosing bone disorders: a lot of knowns but still some unknowns

In the last decade, many advances have been made in understanding how osteoclasts and osteoblasts work and communicate by elucidation of the molecular genetic causes of many rare bone dysplasias. The relationship between the clinical findings and the molecular defects underlying these aberrant bone phenotypes has given new insights into the molecular machinery of the different bone cell types, and into how they act and interact to regulate bone mass. The study of sclerosing bone dysplasias caused by a disturbance of the balance between bone formation and bone resorption has had an especially high impact. Furthermore, it has also become clear that genetic variation within several of the identified genes contributes to the risk to develop osteoporosis and that in some cases the metabolic pathways involved provide interesting targets for the development of novel treatments for osteoporosis. In this review, some of the sclerosing bone diseases are discussed, focusing on the underlying mechanisms and the broader implications of the insights gained.