Endocrine Abstracts

Osteoporosis is a common, age-related disease with a strong genetic component. Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are known to cause rare bone-related syndromes including loss-of-function mutations with decreased bone mineral density (BMD) and gain-of-function mutations with high bone mass. The initial discovery of lipoprotein involvement in bone metabolism was surprising, but revealed a strong regulatory pathway by the Wnt-signalling cascade. In addition, several attempts to investigate the genetic background of osteoporosis by whole genome investigations resulted in the affirmation of the lipoprotein receptor gene loci in association with bone fractures and BMD.

Recent studies demonstrate the LRP6 coreceptor as a key element of the PTH signalling that regulates osteoblast activity. Furthermore, lipoproteins and the respective genes regulate atherogenesis and bone properties – more investigations are on the way to elucidate their involvement in bone metabolism using new insights in the calcification of bone and vasculature.

Defining targets for investigating new therapies and possible individual pharmacogenomics in osteoporosis patients by lipoprotein research will expand our repertoire in diagnosis and treatment of this widespread disease.