Endocrine Abstracts

An large number of clinical entities are associated with abnormal bone mineral density. On one end of the spectrum, the sclerosing bone dysplasias are characterized by an excess of bone tissue. These conditions are, in most cases, monogenic diseases with involvement of one gene resulting in a clear mode of inheritance. Molecular genetic studies over the last decennia revealed the underlying genetic causes for many of them. The pathogenic mechanism can either be a decreased bone resorption, as in different forms of osteopetrosis, or an increased bone formation. The latter cases were for example very instrumental in illustrating the essential role of canonical Wnt signaling in the process of bone formation.

On the other end of the spectrum osteoporosis is the best known example of a condition with decreased bone mass resulting in an increased risk for low trauma fractures in the elderly. The risk for osteoporosis is influenced by both environmental and genetic factors and is determined both by the peak bone mass reached at young age and by the subsequent bone loss later on in life. Especially genome wide association studies in the last years have been very useful for dissecting the genetic basis for the regulation of bone mineral density. However, despite extremely large scale studies by very extended consortia, the obtained results so far can explain only a small percentage of the assumed genetic variability and further studies are needed. But these genome wide association studies definitely contributed to our current understanding of bone homeostasis by the identification of novel genes of relevance, as was the case by the study of monogenic sclerosing bone dysplasias.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.