Heritable sclerosing bone disorders: presentation and new molecular mechanisms.
Sclerosing bone disorders can be subdivided according to their clinical presentation, the primarily affected cell type, and the cellular pathways. Osteoclast-rich osteopetrosis and related disorders have been related in most cases to mutations in genes required for osteoclast function. More recently, osteoclast-poor forms of osteopetrosis have been described as being connected to factors that govern osteoclast differentiation. However, increased bone formation can also cause osteosclerosis. Camurati-Engelman disease and osteopoikilosis are both related transforming growth factor-beta signaling. Rare recessive or dominant sclerosing disorders, such as endosteal hyperostosis, sclerosteosis, van Buchem disease, high bone-mass syndrome, and osteopathia striata, are caused by mutations in genes involved in the Wnt pathway, which regulates osteoblast differentiation. Finally, a third entity, including Ghosal syndrome and pachydermoperiostosis, is related to mutations in genes of the eicosanoid pathway. Clinical aspects and the consequences for our understanding of bone biology are discussed.
de Vernejoul
Marie-Christine
MC
University Paris 7, Federation of Rheumatology, Hospital Lariboisière, Paris, France. christine.devernejoul@lrb.aphp.fr
Kornak
Uwe
U
D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000503:physiopathology; D030342:Genetic Diseases, Inborn / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000502:physiology; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology; D010026:Osteosclerosis / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology