Mapping phenotypic to genetic variability in the High Bone Mass Study
Disease - Osteopetrosis, osteoporosis
Lead applicant - Dr Celia Gregson
Organisation - Royal United Hospital
Type of grant - Clinician Scientist Fellowship
Status of grant - Active
Amount of the original award - £355,256.70
Start date - 28 January 2013
Reference - 20000
What are the aims of this research?
Thin brittle bones are common and cause osteoporosis, whereas thick dense bones are rare and those affected are known as having ‘High Bone Mass. High Bone Mass (HBM) runs in families and yet the genes causing HBM are largely unknown. This study aims to firstly identify HBM-causing genes in a rare collection of people in England and Wales. Secondly this research will establish the effect of these genes on specific bone characteristics such as shape, density and function.
Why is this research important?
Osteoporosis is very common and leads to progressive bone thinning with advancing age. Half of British women and 1 in 5 men over the age of 50 will break a bone in their lifetime; health consequences can be severe. Our current treatments mostly focus on preventing further bone thinning, rather than building new bone. There is currently only one treatment for building new bone which is very expensive and hence rarely used. New, better and cost-efficient medicines are needed to tackle the growing problem of osteoporosis in our ageing society.
Bone density is largely determined by the genes we inherit from our parents. Recent studies have identified many genetic factors affecting bone density within the general population, yet we still only know a fraction of the genes involved. Understanding the genes behind a rare condition in which bones naturally grow to be extremely dense is an alternative approach to understanding controls over bone growth. It is hoped that by finding the genes which cause HBM, we can better understand the ways in which bones can develop to be thicker and stronger. Ultimately it is intended that this knowledge will enable the development of new osteoporosis treatments, which act to mimic the action of these HBM genes.
This research will use cutting-edge genetic techniques, so called next-generation re-sequencing, in order to find HBM genes. Once identified it will be important to understand how HBM genes affect different components of bone, for example cortical (ie. the outer layer of bone) and trabecular (ie. the inner meshwork of bone) bone and this study will use detailed research scans in order to measure these structures.
How will the findings benefit patients?
It is intended that this research will lead to the identification of new genes controlling bone density and strength. Through understanding how these genes function, we can develop new treatments for osteoporosis, which will work by mimicking the action of these naturally occurring, but rare HBM genes. This research will increase our understanding of bone structure and function, for example, the interactions between bone and fat tissue, which has relevance for a society with rising levels of obesity.