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Meta-Analysis
. 2021 Mar;33(3):529-545.
doi: 10.1007/s40520-020-01762-2. Epub 2021 Feb 15.

Knee osteoarthritis and time-to all-cause mortality in six community-based cohorts: an international meta-analysis of individual participant-level data

Kirsten M Leyland  1   2 , Lucy S Gates  2   3 , Maria T Sanchez-Santos  4 , Michael C Nevitt  5 , David Felson  6 , Graeme Jones  7 , Joanne M Jordan  8 , Andrew Judge  2   9 , Dani Prieto-Alhambra  4 , Noriko Yoshimura  10 , Julia L Newton  2 , Leigh F Callahan  8 , Cyrus Cooper  2   11 , Mark E Batt  12 , Jianhao Lin  13 , Qiang Liu  13 , Rebecca J Cleveland  8 , Gary S Collins  4 , Nigel K Arden  14   15 ; PCCOA Steering Committee
Collaborators, Affiliations
Meta-Analysis

Knee osteoarthritis and time-to all-cause mortality in six community-based cohorts: an international meta-analysis of individual participant-level data

Kirsten M Leyland et al. Aging Clin Exp Res. 2021 Mar.

Abstract

Background: Osteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population.

Methods: Seven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung-Knapp modification for random-effects meta-analysis.

Findings: 10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA.

Discussion: Participants with POA or PROA had a 35-37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality.

Funding: Versus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International.

Keywords: Knee; Meta-analysis; Mortality; Osteoarthritis.

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Conflict of interest statement

Dr Leyland reports grants from the Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, during the conduct of the study. Dr Gates is funded by the Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis. Professor Arden reports grants from the Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, grants from Merck, and personal fees from Merck, Pfizer/Lilly. Professor Cooper reports personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda, and UCB. Professor Hunter reports personal fees from Merck Serono, Pfizer, Lilly, and TLCBio. Professor Jordan reports grants from National Institutes of Health, Centers for Disease Control and Prevention, American College of Rheumatology, personal fees from Samumed, Flexion, Osteoarthritis Research Society International, and National Institutes of Health. Professor Judge reports personal fees from Anthera Pharmaceuticals Ltd, Freshfields, Bruckhaus, and Derringer. Professor Jones reports personal fees from BMS, Roche, Abbvie, Amgen, Lilly, Novartis, Jannsen, and grants from Covance. Professor Felson has nothing to disclose.

Figures

Fig. 1
Fig. 1
a–c Forest plots of univariable models: a ROA; b POA; c PROA compared to Pain-/ROA-
Fig. 2
Fig. 2
a–c Forest plots of fully adjusted models: a ROA; b POA; c PROA compared to Pain-/ROA-
See this image and copyright information in PMC

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