Molecular genetics of too much bone

Bone remodelling is an important process both throughout growth and in adult life. The homeostasis of bone tissue is maintained by the balanced processes of bone resorption and formation. Imbalance can give rise to a broad spectrum of skeletal pathologies, of which osteoporosis, characterized by a decrease in bone density leading to increased fracture risk, is the best known because of its high prevalence and consequently high socio-economic impact. At the opposite end of the spectrum, several genetic conditions displaying too much bone are situated. Mainly because of their monogenic nature—in contrast to the multifactorial character of osteoporosis—the underlying molecular genetic causes for several of these conditions have been revealed recently. In this review, the most important gene identifications of the last years and their impact on the understanding of bone biology are discussed. Bone tissue, the major constituent of the human skeleton, has many metabolic and mechanical functions. Abnormalities affecting this tissue can therefore lead to an extended number of pathological conditions. Many osteochondrodysplasias involve a disturbed skeletal morphogenesis due to abnormal-ities in bone patterning and growth during development. In a