Impact of the definition of osteoarthritis and the timing of its onset on the association between type 2 diabetes mellitus and osteoarthritis: Clinical Practice Research Datalink.

Application Number
Lay Summary

Osteoarthritis is the most important cause of pain in the United Kingdom. It is characterized by breakdown of cartilage and bone in the joint resulting in pain. Several studies have shown that patients with diabetes are more likely to have osteoarthritis. It is generally thought that this is because diabetic patients are more likely to have a higher weight, causing osteoarthritis. However, several studies found that diabetes is a risk factor for osteoarthritis regardless of weight. On the other hand, other studies did not find this result. In some studies, total joint replacement is used to define osteoarthritis since it is unknown whether a diagnosis of osteoarthritis is well recorded. However, the reliability of total joint replacement as a definition for osteoarthritis has also never been examined. Therefore, the aim of this study is to determine the risk of osteoarthritis in patients with diabetes compared to patients without diabetes using two different definitions of osteoarthritis: a clinically recorded diagnosis or total joint replacement. Additionally, studies have shown that OA is diagnosed approximately 8 years after onset of the disease. We therefore repeated the analyses looking at the effect of including periods up to 10 years during which an OA diagnosis may not occur.

Technical Summary

Several studies have proposed that type 2 diabetes mellitus (T2DM) may be an independent risk factor for osteoarthritis (OA). As it is unknown whether a diagnosis of OA is well recorded, total joint replacement (TJR) is commonly used as a proxy of OA in epidemiological studies. However, the reliability of TJR as a proxy has never been examined. The use of TJR may introduce bias due to confounding by disease severity, as severe T2DM patients may not undergo elective surgery due to contraindicating comorbidities. We therefore aim to compare different definitions (e.g. diagnosis of OA and TJR) of OA, while examining the association between T2DM and OA. All patients who received their first prescription of a non-insulin antidiabetic drug (NIAD) will be selected as T2DM patient. Each T2DM patient will be matched to one patient without a NIAD in the entire follow-up. Cox proportional hazard models will be used to estimate the risk of the outcomes. Additionally, an OA diagnosis shortly after onset of T2DM may not reflect the actual date of onset of the disease and could result in biased estimates. Therefore, additional analyses will be conducted adding a latency period up to 10 years after first NIAD prescription.

Health Outcomes to be Measured

A diagnosis of knee osteoarthritis; A diagnosis of hip osteoarthritis; Total knee replacement; Total hip replacement.


Frank de Vries - Chief Investigator - Utrecht University
Frank de Vries - Corresponding Applicant - Utrecht University
Anna Elise (Annelies) Boonen - Collaborator - Maastricht University Medical Centre
Bart JF van den Bemt - Collaborator - Sint Maartenskliniek
Johannes T.H. Nielen - Collaborator - Utrecht University
Olaf Klungel - Collaborator - Utrecht University
Pieter Dagnelie - Collaborator - Maastricht University