Risk of fragility fracture across inflammatory conditions: a UK population study

Date of ISAC Approval: 
18/08/2015
Lay Summary: 
1 in 3 women and 1 in 5 men over 50 will break a bone (fracture), the majority of which are as a result of brittle bones (osteoporosis). Broken bones as a result of osteoporosis can dramatically affect patients quality of life and also cause a considerable financial cost to the country. However, it is possible to screen and treat people at highest risk of osteoporosis to prevent fractures. We know that inflammation is associated with increased risk of fracture in some conditions because inflammation reduces bone strength. For example, rheumatoid arthritis, ankylosing spondylosis, inflammatory bowel disease and systemic lupus erythematous have previously been linked with a higher risk of osteoporosis and fracture. However, with improvements in medical treatment in these conditions, the risk of fracture may have reduced. We also do not know if some other common inflammatory conditions, e.g. gout, polymyalgia rheumatica, giant cell arteritis and psoriasis, are linked with a higher risk of fracture. This study will use health records from a large database of UK primary care records to compare the risk of fracture in different inflammatory conditions. This will help clinicians identify and treat patients at highest risk to prevent fractures.
Technical Summary: 
Background: Inflammatory conditions such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), inflammatory bowel disease (IBD) and systemic lupus erythematous (SLE) are known to be associated with increased risk of osteoporosis and fracture. However, previous estimates of fracture risk may be outdated, especially given recent improvements in the management of these conditions. Furthermore, for common inflammatory conditions (polymyalgia rheumatica (PMR), giant cell arteritis (GCA), psoriasis and gout) limited epidemiological evidence about fracture risk exists. Primary aim: To estimate the relative effect of selected inflammatory conditions (RA, AS, SLE, IBD, gout, PMR, GCA, psoriasis) on the risk of osteoporosis and fragility fracture. Methods: A retrospective matched cohort study utilizing data from Clinical Practice Research Datalink (CPRD). Exposed individuals will be those with diagnoses of RA, AS, SLE, IBD, gout, PMR and psoriasis from 1990-2004. Incidence rates of fragility fracture and osteoporosis over 10 years of follow up will be calculated and compared in each disease group. Expected outputs and future developments: The results will impact on clinical practice by enabling screening to be targeted at those conditions with highest risk and enable accurate fracture risk estimation. The results will be presented at national and international conferences, published in high-impact medical journals, and inform (inter)national clinical guidelines.
Health Outcomes to be Measured: 
Primary outcomes of interest are time from the index date to first diagnosis of fragility fracture up to 10 years post inclusion. The secondary outcome measure will be first clinical diagnosis of osteoporosis. Fragility fractures will be defined using Read codes pertaining to fracture of the radius/ulna, femur/hip, ribs, humerus, vertebrae or clavicle.
Collaborators: 

Professor Christian Mallen - Chief Investigator - Keele University
Dr Edward Roddy - Collaborator - Keele University
Milica Blagojevic-Bucknall - Collaborator - Keele University
Rebecca Whittle - Collaborator - Keele University
Samantha Lara Hider - Collaborator - Keele University
Dr Zoe Paskins - Corresponding Applicant - Keele University