Life-course determinants of osteoporotic fracture

Lead Research Organisation: Medical Research Council
Department Name: UNLISTED

Abstract

Osteoporosis is a major public health problem through its association with fractures of the hip, spine and wrist. Although we know that a number of factors in later life influence the rate of bone loss, little is known of the way in which an individual s genetic make-up is modified by their environment during intrauterine and early postnatal life, to establish the peak bone mass that they reach in young adulthood. The studies proposed in this application will demonstrate the means whereby maternal lifestyle (smoking, nutrition, and physical activity) influence skeletal growth through modification of the expression of certain genes. This information is invaluable for two reasons: first, it enables us to modify maternal lifestyle to improve bone health in the offspring and thereby prevent osteoporotic fractures in future generations. In addition, it might permit the targeting of individuals who would benefit from measurement of bone density and pharmacological intervention, at a time when no mass screening programme for osteoporosis can be recommended.

Technical Summary

Osteoporosis is a skeletal disorder characterised by low bone mass and microarchitectural deterioration of bone tissue which predisposes to fracture. These fractures typically occur at the hip, spine and wrist. The annual cost to the NHS of managing osteoporotic fractures is #1.7 billion with over 90% of this figure attributable to hip fracture. Epidemiological evidence has accumulated that the risk of osteoporotic fracture might be modified by environmental influences acting during critical periods of intrauterine or early postnatal life. The current application proposes a series of studies to characterise the precise genetic and environmental mechanisms underlying the developmental origins of osteoporosis risk, and aims thereby to develop preventive strategies which might be targeted at mother and child. The programme will be closely linked to the MRC Epidemiology Resource Centre, and will use the two principal cohort resources maintained within the Centre (the Hertfordshire Cohort Study and the Southampton Women s Survey).

Publications

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Akesson K (2013) Capture the Fracture: a Best Practice Framework and global campaign to break the fragility fracture cycle. in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA

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Arden NK (2006) Persistence with teriparatide in patients with osteoporosis: the UK experience. in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA

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Arden NK (2006) Knee pain, knee osteoarthritis, and the risk of fracture. in Arthritis and rheumatism

 
Description National Osteoporosis Society
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact As Chairman of the Board of Trustees of this national charity, I gave evidence to the House of Lords Select Committee on Ageing, as well as contributing written responses on water fluoridation and musculoskeletal research over the period 2007-2009.
 
Description A pragmatic randomised controlled trial of the effectiveness and cost-effectiveness of screening for osteoporosis in older women for the prevention of fractures (SCOOP)
Amount £3,424,229 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 04/2007 
End 03/2014
 
Description BUPA project grant MAVIDOS
Amount £142,686 (GBP)
Organisation BUPA 
Department BUPA Foundation
Sector Private
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 10/2009 
End 09/2012
 
Description Clinical Research Fellowship
Amount £164,135 (GBP)
Organisation Arthritis Research UK 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 04/2006 
End 03/2009
 
Description Equipment grant
Amount £145,282 (GBP)
Organisation Arthritis Research UK 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 01/2009 
End 12/2009
 
Description NIHR BRU: Nutrition, Diet and Lifestyle
Amount £4,000,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 04/2008 
End 03/2012
 
Description NIHR Biomedical Research Centre in Nutrition
Amount £9,600,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 04/2012 
End 03/2017
 
Description Programme grant: A life course approach to healthy ageing: capitalizing on the value of UK life course cohorts
Amount £1,800,000 (GBP)
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 03/2008 
End 02/2012
 
Description Programme grant: Maternal and epigenetic determinants of cardiovascular structure and function
Amount £822,366 (GBP)
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 01/2007 
End 12/2012
 
Description Project grant
Amount £418,192 (GBP)
Organisation Food Standards Agency (FSA) 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 04/2006 
End 03/2010
 
Description Project grant
Amount £134,496 (GBP)
Organisation Arthritis Research UK 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 02/2006 
End 01/2008
 
Description RS Project grant
Amount £102,500 (GBP)
Organisation The Royal Society 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 01/2006 
End 12/2006
 
Description Travelling Fellowship
Amount £44,465 (GBP)
Organisation Arthritis Research UK 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 04/2006 
End 03/2007
 
Description Department of Public Health, Cambridge 
Organisation University of Cambridge
Department Department of Public Health and Primary Care
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research Colaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2008
 
Description Dr Alireza Moayyeri 
Organisation University of Cambridge
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2009
 
Description Dr Ann Prentice 
Organisation Medical Research Council (MRC)
Department MRC Human Nutrition Research Unit
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2009
 
Description Dr Barbara Boucher 
Organisation Queen Mary University of London
Department Barts and The London School of Medicine and Dentistry
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2008
 
Description Dr Brent Richards 
Organisation McGill University
Country Canada 
Sector Academic/University 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2008
 
Description Dr Francis Finucane 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Multiple 
PI Contribution Research collaboration
Collaborator Contribution Research collaboration
Impact Clinical impact
Start Year 2009
 
Description Dr Geeta Mishra 
Organisation University College London
Department MRC Unit for Lifelong Health and Ageing
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2007
 
Description Dr Jonathan Reeve 
Organisation University of Cambridge
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2006
 
Description Dr Ken Ong 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Multiple 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical impact
Start Year 2008
 
Description Dr Natascha van Schoor 
Organisation University of Amsterdam
Country Netherlands, Kingdom of the 
Sector Academic/University 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2008
 
Description Dr Rebecca Hardy 
Organisation University College London
Department MRC Unit for Lifelong Health and Ageing
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2006
 
Description Dr Ruth Loos 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Multiple 
PI Contribution Research collaboration
Collaborator Contribution Research collaboration
Impact Clinical impact
Start Year 2007
 
Description Epigenetic Studies 
Organisation University of Southampton
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Impact Research
 
Description GPRD Studies 
Organisation Utrecht University
Country Netherlands, Kingdom of the 
Sector Academic/University 
PI Contribution Research
Impact Research
 
Description Genetic Epidemiology of type 2 diabetes mellitus 
Organisation University of Cambridge
Department Department of Clinical Biochemistry
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Contribution of anonymised phenotypic data; statistical expertise
Impact Publication. PubMed ID: 17019603
Start Year 2006
 
Description HALCYON 
Organisation University College London
Department MRC Unit for Lifelong Health and Ageing
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution Provision of data from Hertfordshire Cohort Study
Collaborator Contribution Multiple publications on sarcopenia and physical frailty.
Impact 3 publications
Start Year 2010
 
Description Hertfordshire Physical Activity Intervention Trial (HPAT) 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Multiple 
PI Contribution Contribution of anonymised phenotypic data
Impact Publications. Pubmed ID: 19545359
Start Year 2006
 
Description Improving pregnancy outcome in obese women 
Organisation Guy's and St Thomas' NHS Foundation Trust
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution Intellectual input in design of study and development of protocol. On-going involvement in monitoring the study progress
Collaborator Contribution Collaboration with a well-respected group
Impact NIHR grant funding
Start Year 2008
 
Description LPIN1 genotype and diet 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Charity/Non Profit 
PI Contribution Contribution of anonymised phenotypic data
Impact Publications. Pubmed ID: 18591397
Start Year 2007
 
Description LPIN1 genotype and diet 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Multiple 
PI Contribution Contribution of anonymised phenotypic data
Impact Publications. Pubmed ID: 18591397
Start Year 2007
 
Description LifeLab Southampton 
Organisation University of Southampton
Department School of Medicine Southampton
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Our research findings have shown the importance of diet and lifestyle before children are even conceived, so we need to engage with children at schools to enable them to understand the importance of their behaviours now on their long-term health and that of their children
Collaborator Contribution Enabled us to contribute more effectively to public engagement in science by getting our research findings communicated to teenagers in and around Southampton
Impact Many public engagement activities with teenagers, with anecdotal marked improvement in the behaviour of some. Paper in preparation showing shifts in knowledge from before to after participating in the LifeLab activities.
Start Year 2007
 
Description Lung function in 6 year old children 
Organisation University of Southampton
Department School of Medicine Southampton
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Data collection, grant and paper writing
Collaborator Contribution Grant and paper writing. Data collection, analysis of samples
Impact Papers now submitted
Start Year 2007
 
Description MAVIDOS 
Organisation Medical Research Council (MRC)
Department MRC Human Nutrition Research Unit
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution Research
Impact Research
Start Year 2006
 
Description MAVIDOS 
Organisation University of Oxford
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Impact Research
Start Year 2006
 
Description MAVIDOS 
Organisation University of Sheffield
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Impact Research
Start Year 2006
 
Description MRC Epidemiology Unit (EU), University of Cambridge 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Multiple 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2006
 
Description MRC LLHA University College London 
Organisation University College London
Department MRC Unit for Lifelong Health and Ageing
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2009
 
Description MRC SCOOP Trial 
Organisation University of Birmingham
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Impact Research
Start Year 2006
 
Description MRC SCOOP Trial 
Organisation University of East Anglia
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Impact Research
Start Year 2006
 
Description MRC SCOOP Trial 
Organisation University of Manchester
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Impact Research
Start Year 2006
 
Description MRC SCOOP Trial 
Organisation University of Sheffield
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Impact Research
Start Year 2006
 
Description MRC SCOOP Trial 
Organisation University of York
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Impact Research
Start Year 2006
 
Description Metabolic syndrome in HCS 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution Contribution of anonymised phenotypic data; statistical expertise
Impact Multiple abstracts in this field
 
Description Nigel Loveridge 
Organisation University of Cambridge
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2006
 
Description Nutrition BRU 
Organisation University of Southampton
Department Faculty of Health Sciences
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Preparation of application, administration and conduct of some of the core projects
Collaborator Contribution Allowed us to conduct complementary studies arising out of the Southampton Women's Survey
Impact Grant funding
Start Year 2008
 
Description Osteoarthritis Programme 
Organisation Imperial College London
Department Department of Epidemiology and Biostatistics
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Collaborator Contribution Novel technique for grading osteoarthritis using digitised radiographs.
Impact Research
Start Year 2006
 
Description Osteoarthritis Programme 
Organisation University of Oxford
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Collaborator Contribution Novel technique for grading osteoarthritis using digitised radiographs.
Impact Research
Start Year 2006
 
Description Prof Diana Kuh 
Organisation University College London
Department MRC Unit for Lifelong Health and Ageing
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Public 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2009
 
Description Prof Kay-Tee Khaw 
Organisation University of Cambridge
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2008
 
Description Prof N Wareham 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Multiple 
PI Contribution Research collaboration
Collaborator Contribution Research collaboration
Impact Clinical impact
Start Year 2006
 
Description Prof Paul Lips 
Organisation University of Amsterdam
Country Netherlands, Kingdom of the 
Sector Academic/University 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2007
 
Description Professor Ulf Ekelund 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Multiple 
PI Contribution Research collaboration, physical activity monitoring
Collaborator Contribution Research
Impact Original papers
Start Year 2006
 
Description Relationship of aldosterone with cortisol and blood pressure 
Organisation University of Edinburgh
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Contribution of anonymised phenotypic data
Impact Publications. Pubmed ID: 19380612
Start Year 2006
 
Description Southampton Women's Survey 
Organisation Lancaster University
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Impact Research
 
Description Southampton Women's Survey 
Organisation University College London
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Impact Research
 
Description Southampton Women's Survey 
Organisation University of Bergen
Country Norway, Kingdom of 
Sector Academic/University 
PI Contribution Research
Impact Research
 
Description Southampton Women's Survey 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Multiple 
PI Contribution Research
Impact Research
 
Description Southampton Women's Survey 
Organisation University of Oslo
Country Norway, Kingdom of 
Sector Academic/University 
PI Contribution Research
Impact Research
 
Description Southampton Women's Survey 
Organisation University of Oxford
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Impact Research
 
Description Southampton Women's Survey 
Organisation University of Southampton
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research
Impact Research
 
Description University of Helsinki 
Organisation University of Helsinki
Country Finland, Republic of 
Sector Academic/University 
PI Contribution Research collaboration
Collaborator Contribution Clinical Impact
Impact Clinical impact
Start Year 2006
 
Description University of Oxford 
Organisation University of Oxford
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Research Collaboration
Collaborator Contribution Research Collaboration
Impact Clinical Impact
Start Year 2007
 
Title Phenotype Prediction: Developmental Origins of Adult Disease 
Description Phenotype prediction. 
IP Reference EP2194143 
Protection Patent granted
Year Protection Granted 2010
Licensed Yes
Impact Epigen Consortium