The gastrointestinal (GI) tract is home to a community of microorganisms called the microbiome. It has been shown that the gut microbiome can influence the immune system and impact distant sites like joints. The classic inflammatory musculoskeletal disorders rheumatoid arthritis and ankylosing spondylitis have recently been linked to microbial imbalance in the GI microbiome.
Tendinopathy and osteoarthritis (OA) are common musculoskeletal disorders that have an immune component to their initiation and progression, whereas osteoporosis is a condition caused by a mismatch between bone breakdown and building, regulated by the immune system. We suggest the microbiome may be partly responsible for these conditions by interacting with the immune system, and we note the association between the microbiome and these disorders has not been well studied. Therefore, the purpose of this study is to determine whether there is an association between microbial imbalance (caused by medications which alter the microbiome) and the risk of OA, tendinopathy and osteoporosis to patients.
We plan to use data from NHS records of 6.5 million people. Using these records, we will study use of microbiome-altering drugs in patients who develop severe OA, tendinopathy or osteoporosis and also any links between these conditions and inflammatory bowel diseases.
Aims. To study the association between gastrointestinal microbiome altering drug (GMAD) treatment and osteoarthritis, osteoporosis, tendinopathy via dysbiosis.
To confirm the association between dysbiosis and rheumatoid arthritis and ankylosing spondylitis.
Data sources: Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES).
Population/Sample size: Minimum of 480,000 patients aged 18 and over in CPRD with a minimum of 1 year prior to the index date. The study has been powered to detect an association with an OR of 1.1.
Study Type: Nested case-control study. Sub analysis with inflammatory bowel disease will be considered.
Control: Five age, gender and practice matched patients.
Outcomes: Osteoarthritis, osteoporosis and tendinopathy, RA and ankylosing spondylitis identified by read codes.
Exposures: GMAD treatment
Statistical analysis: Conditional logistic regression, Propensity score analysis.
Navraj Nagra - Chief Investigator - University of Oxford
Navraj Nagra - Corresponding Applicant - University of Oxford
Andrew Carr - Collaborator - University of Oxford
Antonella Delmestri - Collaborator - University of Oxford
Daniel Prieto-Alhambra - Collaborator - University of Oxford
Sanni Ali - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Sarah Snelling - Collaborator - University of Oxford
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation