Kirsten M Leyland1,2, Lucy S Gates2,3, Maria T Sanchez-Santos4, Michael C Nevitt5, David Felson6, Graeme Jones7, Joanne M Jordan8, Andrew Judge2,9, Dani Prieto-Alhambra4, Noriko Yoshimura10, Julia L Newton2, Leigh F Callahan8, Cyrus Cooper2,11, Mark E Batt12, Jianhao Lin13, Qiang Liu13, Rebecca J Cleveland8, Gary S Collins4, Nigel K Arden14,15. 1. MRC Integrated Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, UK. 2. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. 3. Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, University of Southampton, Southampton, UK. 4. Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. 5. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA. 6. Boston University School of Medicine, Boston, MA, USA. 7. Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia. 8. Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. 9. Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. 10. Department of Preventive Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, Japan. 11. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK. 12. Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, Nottingham University Hospitals, Nottingham, UK. 13. Peking University People's Hospital, Arthritis Clinic and Research Centre, Beijing, China. 14. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. nigel.arden@ndorms.ox.ac.uk. 15. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK. nigel.arden@ndorms.ox.ac.uk.
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.
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.
Authors: K M Leyland; L S Gates; M Nevitt; D Felson; S M Bierma-Zeinstra; P G Conaghan; L Engebretsen; M Hochberg; D J Hunter; G Jones; J M Jordan; A Judge; L S Lohmander; E M Roos; M T Sanchez-Santos; N Yoshimura; J B J van Meurs; M E Batt; J Newton; C Cooper; N K Arden Journal: Osteoarthritis Cartilage Date: 2018-02-07 Impact factor: 6.576
Authors: R J Cleveland; C Alvarez; T A Schwartz; E Losina; J B Renner; J M Jordan; L F Callahan Journal: Osteoarthritis Cartilage Date: 2018-12-22 Impact factor: 6.576
Authors: Ross Wilkie; Simran Singh Parmar; Milica Blagojevic-Bucknall; Diane Smith; Martin J Thomas; Bethany Jane Seale; Gemma Mansell; George Peat Journal: RMD Open Date: 2019-11-13