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Osteoarthritis and premature mortality: pathways for hand, hip, knee and foot osteoarthritis

Seale, Bethany

Osteoarthritis and premature mortality: pathways for hand, hip, knee and foot osteoarthritis Thumbnail


Bethany Seale


Martin Thomas

Ross Wilkie

Mick Bucknall


Evidence of an association between osteoarthritis (OA) and mortality is conflicting; differences in definitions and anatomical sites explain some of the discordance. The high frequency and increasing prevalence of OA highlights the need to understand its impact and potential association with premature mortality. The aims of this study were to: (i) examine the strength and direction of the association between different clinical case definitions of OA and premature mortality at different anatomical sites (hand, hip, knee and foot) (ii) identify the role of potentially modifiable factors on the pathway between OA at each site and premature mortality using mediation (path analysis) within a Cox proportional hazard model (survival analysis).

A population-based prospective cohort study was conducted using data from the North Staffordshire Osteoarthritis Project (NorStOP), in which primary care medical record data was linked to self-report information collected by questionnaire in adults aged 50 years and over (n= 8066). Different case definitions of OA at each site were derived based on whether individuals had consulted in general practice for OA, selfreported pain in the hand, hip, knee or foot in the baseline questionnaire and indicated moderate to severe pain interference. A Cox proportional hazards analysis was performed to determine the total effect of each case definition of OA on mortality with adjustment for confounders (age, gender, education, occupation, non-steroidal anti-inflammatory drug use, ischaemic heart disease, self-reported cardiovascular disease, diabetes mellitus, smoking, chronic obstructive pulmonary disease and body mass index). Within the Cox model, path analysis was used to decompose the total effects to assess the indirect and direct effects for potential mediators (walking frequency, depression, anxiety, insomnia, and social participation). Results are expressed as hazard ratios (HR); bootstrap resampling was used to generate 95% confidence intervals (95% CIs).

Mean age of participants was 65.2 (SD 9.8) years and 51.6% were female. 1515 (18.8%), 1323 (16.4%), 1774 (22.0%) and 1387 (17.2%) had disabling hand, hip, knee and foot OA respectively. Participants were followed up over 10 years during which time 1188 (14.7%) died. Disabling hand, knee and foot OA were significantly associated with premature mortality (adjusted HR 1.18 95% CI 1.02, 1.35; 1.16 95% CI1.02, 1.33; and 1.21 95% CI 1.05, 1.40 respectively); the increased HR for disabling hip OA was not significant (adjusted HR 1.06 95% CI 0.91, 1.23). Low walking frequency, depression, social participation were significant mediators of the relationship between premature mortality and OA (p<0.05). Taking knee OA to illustrate this, the indirect effects for low walking frequency, depression and social participation were 1.06 (95% CI 1.05, 1.09), 1.05 (95% CI 1.01, 1.08) and 1.09 (95% CI 1.05, 1.13) respectively.

This novel approach to understanding pathways within a survival model indicates that potentially modifiable factors explain the link between hand, knee, hip and foot OA and premature mortality. Increasing walking, exercise and activity in general may also reduce the impact of depression and improve social participation, and subsequent mortality.


Seale, B. (2019). Osteoarthritis and premature mortality: pathways for hand, hip, knee and foot osteoarthritis. (Thesis). Keele University. Retrieved from

Thesis Type Thesis
Publicly Available Date May 26, 2023
Public URL
Award Date 2019-10


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