NDORMS DPhil & MSc by Research
Maternal health, offspring growth and risk of fracture: A population-based investigation in 700,000 individuals
Fractures (broken bones) constitute an enormous burden to health both in childhood and adulthood. In the UK 30% boys and 19% girls will have experienced a fracture before the age of 18 years.(1) From the age of 50 years a woman has a 50% chance, and a man a 20% chance, of sustaining an osteoporotic fracture in their remaining lifetime, with such events in adulthood associated with a 20% reduction in relative survival, in addition to substantial morbidity, and a total cost across the UK of £4.4 billion annually.(2) Although traditionally clinicians have focused on identifying those individuals most at risk of fracture, there is increasing evidence to support a public health approach, aimed at optimising bone health across the population, and across the lifecourse.(3) Poor early growth is associated with reduced bone mass at peak bone mass (achieved in early adulthood, and strongly predictive of the later fracture risk), and bone mass in old age.(3) More detailed studies of growth during early and later childhood have demonstrated that poor infant and childhood growth is associated with increased risk of hip fracture,(4,5) and that this might be mediated through altered femoral neck geometry.(6) Consistent with these findings, work in the Southampton Women's Survey demonstrated that slower growth in late gestation and early infancy is associated with lower childhood bone mass, and a narrower femoral neck, an indicator of greater fracture risk in later life.(7,8) Work thus far has been undertaken within relatively modest cohorts for whom birth records exist, and it has not been possible to explore in detail components of childhood growth, such as the timing of the adiposity rebound (which has been associated with later cardiometabolic health) and of peak height velocity (giving an indicator of pubertal maturation) in relation to overall patterns of growth, factors which might influence growth rates (both in childhood, and those acting early in life via maternal health before and during pregnancy), and fracture outcomes.
The overarching aim is to establish patterns of growth from birth to adolescence associated with increased fracture risk in childhood. Within this overall plan, there will be four secondary aims:
- To elucidate key attributes such as timing and magnitude of peak height velocity, and of adiposity rebound, in relation to fracture risk.
- To investigate the maternal determinants of patterns of offspring growth (for example, maternal age, anthropometry, health, medications, family history, lifestyle, ethnicity).
- To establish fracture risk associated with common and rare morbidities of childhood, exploring interactions with their effects on growth.
- To elucidate the effect of maternal medication use before and during pregnancy, and medication use by the child, on childhood fracture risk and whether this is independent of childhood growth.
This project will use data from the "Healthy Child Programme" in the SIDIAP information system for Research in primary care database, Catalonia, Spain. Commencing in 2002, all babies born since 2002 are enrolled in a comprehensive and longitudinal assessment programme until 14 years. Linked information on incident events and critically, maternal health before and during pregnancy will be available.
1 Moon et al (2016) Bone;85:9-14; 2 Harvey et al (2009) NatRev Rheumatol;260:10.1038; 3 Harvey et al (2014) J Bone Miner Res;29(9):1917-25; 4Cooper et al (2001) Osteoporos Int JID – 9100105;12(8):623-9; 5Javaid et al (2011) OsteoporosInt;22(1):69-73; 6 Javaid et al (2006) J Bone Miner Res;21(4):508-12; 7 Harvey et al (2012) PaediatrPerinatEpidemiol;2012;26(1):34-44; 8Harvey et al (2013) Pediatr Res; 74(4):450-6; 9 Clark et al (2007) Rheumatology;46(Supplement 1):i3-i4
Details of the research group
Prof Daniel Prieto-Alhambra is recognised internationally as an authority on use of routine data for musculoskeletal pharmaco- and device epidemiology. He will be the primary supervisor for this project.
Dr Victoria Strauss’ research interests include growth modelling. She will be the statistical supervisor.
Prof Nick Harvey’s (MRC Lifecourse Epidemiology Unit, University of Southampton) work has focused on investigating the factors which influence bone development early in life. This DPhil project is closely linked to Prof Harvey’s research.
Associate Prof Kassim Javaid’s research focus is the epidemiology of osteoporosis and rare bone disease. He will provide clinical support for this project.
Prof Cyrus Cooper is an expert in the epidemiology of musculoskeletal diseases. This DPhil project is closely link to research undertaken in the MRC lifecourse epidemiology unit which is led by him. He will provide clinical guidelines to this project.
The Botnar Research Centre plays host to the University of Oxford's Institute of Musculoskeletal Sciences, which enables and encourages research and education into the causes of musculoskeletal disease and their treatment. The proposed project would be part of the work of the pharmaco- and device epidemiology group, centre for Statistics in Medicine (CSM), NDORMS. CSM has more than 20 years’ experience in medical statistics, and has teams of statisticians, epidemiologists, methodologists and systematic review specialists. The pharmaco- and device epidemiology group is led by Prof Daniel Prieto-Alhambra and has seven doctoral researchers, two post-doctoral researchers and four senior post-doctoral researchers.
Training will be provided in techniques including lifecourse epidemiology and advanced statistical techniques. Attendance at formal training courses will be encouraged, and will include the "Real world epidemiology Oxford summer school" and advanced statistics courses. In addition, courses from the Oxford Learning Institute and the Oxford University Computer Sciences on key skills for the completion of a successful DPhil thesis will be available. Additional on the job training opportunities will arise, and the supervisors will encourage the student to pursue such opportunities. A core curriculum of lectures will be taken in the first term to provide a solid foundation in a broad range of subjects including musculoskeletal biology, inflammation, epigenetics, translational immunology, data analysis and the microbiome. Students will attend regular seminars within the department and those relevant in the wider University.
Students will be expected to present data regularly in the departmental PGR seminars, the pharmaco- and device epidemiology group and to attend external conferences to present their research globally.
Students will also have the opportunity to work closely with the pharmaco- and device epidemiology group and MRC Lifecourse Epidemiology Unit (University of Southampton). Students will have access to various courses run by the Medical Sciences Division Skills Training Team and other departments. All students are required to attend a 2 - day Statistical and Experimental Design course at NDORMS.
How to Apply
The department accepts applications throughout the year but it is recommended that, in the first instance, you contact the relevant supervisors or the Graduate Studies Officer, Sam Burnell (Samuel.email@example.com), who will be able to advise you of the essential requirements.
Interested applicants should have or expect to obtain a first or upper second class BSc degree or equivalent, and will also need to provide evidence of English language competence. The application guide and form are found online and the DPhil will commence in October 2019.
For further information, please visit http://www.ox.ac.uk/admissions/graduate/applying-to-oxford and/or contact Associate Prof Daniel Prieto-Alhambra (firstname.lastname@example.org)