Osteoporosis

Introduction

Research on the pathogenesis of osteoporosis is jointly led by Professor Stuart H Ralston, Dr Omar M E Albagha and Dr Philip Riches. Osteoporosis is a multifactorial condition which can be caused by several factors such as poor diet, lack of exercise, smoking and excessive alcohol intake. One of the most important factors is heredity, which is a major focus of our research in this area. We have also recently found that osteoporosis in patients with inflammatory diseases may develop as the result of “autoantibodies” to an essential bone protein called Osteoprotegerin (Riches et al. N Engl J Med 2009;361:1459-1465). The normal function of osteoprotegerin is to inhibit bone resorption, but in the presence of these antibodies this function is impaired leading in some cases to severe osteoporosis with high bone turnover. So far we have detected these antibodies in patients with coeliac disease and research is now in progress to determine if they also occur in other inflammatory diseases.

People a family history of osteoporosis are at increased risk of suffering osteoporosis themselves and it has been estimated that between 75%-85% of the variation in bone mineral density (BMD) is genetically determined. The genetic basis of osteoporosis is incompletely understood, but it is currently considered that the condition is determined by the combined effects of several genes, each with a relatively small effect on disease risk, rather than a small number of genes with large effects. Please follow this link (Ralston J Clin Endocrinol Metab 2002) for a review article on the role of genetic factors in osteoporosis.

Several approaches have been used to try and identify the genetic variants that regulate BMD and susceptibility to osteoporotic fractures. Using a candidate gene approached we have identified functional polymorphisms in the regulatory region of the COL1A1 gene that seem to predispose to osteoporosis by regulating gene expression (Jin et al Hum Mol Gen 2009;18:2729-2738). Using linkage studies we conducted a genome wide scan in 3691 individuals from 715 families with a family a history of osteoporosis (the FAMOS consortium). This led to the identification of several susceptibility loci for regulation of BMD and showed that different loci for regulation of BMD are involved in men and women (Ralston et al. Hum Mol Gen 2005). Recently genome wide association studies have been performed to define the genes that predispose to osteoporosis and a meta-analysis of these studies involving Professor Ralston and other members of the GEFOS consortium (www.gefos.org ) has identified 20 genes and loci with robust evidence of association with osteoporosis (Rivadeniera et al Nature Genetics 2009;41:1119-1206. The loci so far identified only explain a small proportion of the heritability of osteoporosis however and additional genes remain to be discovered.

	Introduction Projects Publications Biography Contact	Osteoporosis Introduction Research on the pathogenesis of osteoporosis is jointly led by Professor Stuart H Ralston, Dr Omar M E Albagha and Dr Philip Riches. Osteoporosis is a multifactorial condition which can be caused by several factors such as poor diet, lack of exercise, smoking and excessive alcohol intake. One of the most important factors is heredity, which is a major focus of our research in this area. We have also recently found that osteoporosis in patients with inflammatory diseases may develop as the result of “autoantibodies” to an essential bone protein called Osteoprotegerin (Riches et al. N Engl J Med 2009;361:1459-1465). The normal function of osteoprotegerin is to inhibit bone resorption, but in the presence of these antibodies this function is impaired leading in some cases to severe osteoporosis with high bone turnover. So far we have detected these antibodies in patients with coeliac disease and research is now in progress to determine if they also occur in other inflammatory diseases. People a family history of osteoporosis are at increased risk of suffering osteoporosis themselves and it has been estimated that between 75%-85% of the variation in bone mineral density (BMD) is genetically determined. The genetic basis of osteoporosis is incompletely understood, but it is currently considered that the condition is determined by the combined effects of several genes, each with a relatively small effect on disease risk, rather than a small number of genes with large effects. Please follow this link (Ralston J Clin Endocrinol Metab 2002) for a review article on the role of genetic factors in osteoporosis. Several approaches have been used to try and identify the genetic variants that regulate BMD and susceptibility to osteoporotic fractures. Using a candidate gene approached we have identified functional polymorphisms in the regulatory region of the COL1A1 gene that seem to predispose to osteoporosis by regulating gene expression (Jin et al Hum Mol Gen 2009;18:2729-2738). Using linkage studies we conducted a genome wide scan in 3691 individuals from 715 families with a family a history of osteoporosis (the FAMOS consortium). This led to the identification of several susceptibility loci for regulation of BMD and showed that different loci for regulation of BMD are involved in men and women (Ralston et al. Hum Mol Gen 2005). Recently genome wide association studies have been performed to define the genes that predispose to osteoporosis and a meta-analysis of these studies involving Professor Ralston and other members of the GEFOS consortium (www.gefos.org ) has identified 20 genes and loci with robust evidence of association with osteoporosis (Rivadeniera et al Nature Genetics 2009;41:1119-1206. The loci so far identified only explain a small proportion of the heritability of osteoporosis however and additional genes remain to be discovered.
	Updated: Wed, 22nd September, 2010