Heritable sclerosing bone disorders: presentation and new molecular mechanisms

• Published in: Annals of the New York Academy of Sciences Vol. 1192; no. 1; pp. 269 - 277
• Main Authors: de Vernejoul, Marie-Christine, Kornak, Uwe
• Format: Journal Article
• Language: English
• Published: United States 01.03.2010
• Subjects: Animals; Bone Resorption - genetics; Bone Resorption - physiopathology; Genetic Diseases, Inborn - diagnosis; Genetic Diseases, Inborn - genetics; Genetic Diseases, Inborn - physiopathology; Humans; Models, Biological; Mutation - physiology; Osteoclasts - metabolism; Osteoclasts - physiology; Osteogenesis - physiology; Osteosclerosis - diagnosis; Osteosclerosis - genetics; Osteosclerosis - physiopathology
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2009.05244.x

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.