LRP receptor family member associated bone disease.

Abstract

A dozen years ago the identification of causal mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene involved in two rare bone disorders propelled research in the bone field in totally new directions. Since then, there have been an explosion in the number of reports that highlight the role of the Wnt/β-catenin pathway in the regulation of bone homeostasis. In this review we discuss some of the most recent reports (in the past 2 years) highlighting the involvement of the members of the LRP family (LRP5, LRP6, LRP4, and more recently LRP8) in the maintenance of bone and their implications in bone diseases. These reports include records of new single nucleotides polymorphisms (SNPs) and haplotypes that suggest variants in these genes can contribute to subtle variation in bone traits to mutations that give rise to extreme bone phenotypes. All of these serve to further support and reinforce the importance of this tightly regulated pathway in bone. Furthermore, we discuss provocative reports suggesting novel approaches through inhibitors of this pathway to treat rarer diseases such as Osteoporosis-Pseudoglioma Syndrome (OPPG), Osteogenesis Imperfecta (OI), and Sclerosteosis/Van Buchem disease. It is hoped that by understanding the role of each component of the pathway and their involvement in bone diseases that this knowledge will allow us to develop new, more effective therapeutic approaches for more common diseases such as post-menopausal osteoporosis, osteoarthritis, and rheumatoid arthritis as well as these rarer bone diseases.