5th International Workshop on Advances in the Molecular Pharmacology and Therapeutics of Bone Disease: Oxford Workshop 2012

Abstract

Musculoskeletal Sciences at the University of Oxford, was aimed at bringing academic and industry scientists together to discuss disease mechanisms and current and prospective molecular targets for development of drugs for metabolic bone diseases. As in the previous meetings, this benefited by having strong representation from industry as well as academic scientists, with the sessions held in an atmosphere of very open discussion. The topic was covered broadly and in depth, with 200 participants in the 4-day meeting. It was preceded by a 2-day instructional course for PhD students, organized by the European Calcified Tissue Society, and with more than 60 graduate student participants. This report outlines only some aspects of a most successful meeting, made possible, as with the previous meetings, by the excellent help provided by Janet Crompton as Conference Organiser. Further details about the program and speakers, sponsors and other information can be found on the website www.oxfordbonepharm.org/ . GeneticsSeveral views of genetics were discussed, reflecting the many advances in skeletal biology provided by both human and mouse genetics, and beginning with a review by Stuart Ralston (Edinburgh). He pointed out that collagen gene mutations accounted for most cases of osteogenesis imperfecta, but the relatively recent discovery of osteogenesis imperfecta caused by abnormal hydroxylation of collagen despite normal collagen secretion 1 shows that primary structure alone is not the only determinant. For osteoporosis, twin studies show us that the heritability of bone mineral density (BMD) is 50 -80 % , of bone turnover is 40 -70 % , but total fractures only 0 -68 % . Despite the heterogeneity of fractures indicated by the latter figures, earlyage fractures show a stronger inheritance. Improved appreciation of the genetic basis of low BMD and osteoporosis has come from several genome-wide association studies and next gene sequencing (predominantly exome sequencing) in the past several years. From the beginning of these studies, genes in the RANKL / RANK and Wnt pathways featured, and were repeated in later studies. 2 A 2012 study revealed 56 new gene loci linked to BMD, which include the RANK, Wnt and NOTCH pathways. 3