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Objective: Metabolic osteoarthritis (OA) is one of the proposed clinical phenotypes defined by the existence of metabolic syndrome (MetS). This study aimed to (1) investigate whether MetS and its components are associated with progression of knee OA magnetic resonance imaging (MRI) features, and (2) to evaluate the interaction of MetS with menopause and progression of MRI features., Method: 682 women from the Rotterdam Study who participated in a sub-study with knee MRI data available and 5-year follow-up were included. Tibiofemoral (TF) and patellofemoral (PF) OA features were assessed with the MRI Osteoarthritis Knee Score. MetS was quantified by the MetS severity Z-score. Generalized estimating equations were used to evaluate associations between MetS and menopausal transition and progression of MRI features., Results: MetS severity at baseline was associated with progression of osteophytes in all compartments, bone marrow lesions (BMLs) in the PF compartment, and cartilage defects in the medial TF compartment. Waist circumference was associated with progression of osteophytes in all compartments and cartilage defects in the medial TF compartment. High-density lipoprotein (HDL)-cholesterol levels were associated with progression of osteophytes in the medial and lateral TF compartment and glucose levels with osteophytes in the PF and medial TF compartment. No interactions were found between MetS with menopausal transition and MRI features., Conclusion: Women with higher MetS severity at baseline showed progression of osteophytes, BMLs, and cartilage defects, indicating more structural knee OA progression after 5 years. Further studies are required to understand whether targeting MetS components may prevent the progression of structural knee OA in women., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Obesity is the most important modifiable risk factor for knee osteoarthritis (KOA). Especially in an early stage of the disease, weight loss is important to prevent further clinical and structural progression. Since 2019, general practitioners (GPs) in the Netherlands can refer eligible patients to a combined lifestyle intervention (GLI) to promote physical activity, healthy nutrition and behavioural change. However, GPs scarcely refer patients with KOA to the GLI potentially due to a lack of evidence about the (cost-)effectiveness. The aim of this study is to determine the (cost-)effectiveness of the GLI for patients with early-stage KOA in primary care., Methods and Analysis: For this pragmatic, multi-centre randomised controlled trial, 234 participants (aged 45-70 years) with National Institute for Health and Care Excellence (NICE) guideline diagnosis of clinical KOA and a body mass index above 25 kg/m 2 will be recruited using a range of online and offline strategies and from general practices in the Netherlands. Participants will receive nine 3-monthly questionnaires. In addition, participants will be invited for a physical examination, MRI assessment and blood collection at baseline and at 24-month follow-up. After the baseline assessment, participants are randomised to receive either the 24-month GLI programme in addition to usual care or usual care only. Primary outcomes are self-reported knee pain over 24 months, structural progression on MRI at 24 months, weight loss at 24 months, as well as societal costs and Quality-Adjusted Life-Years over 24-month follow-up. Analyses will be performed following the intention-to-treat principle using linear mixed-effects regression models., Ethics and Dissemination: Ethical approval was obtained through the Medical Ethical Committee of the Erasmus MC University Medical Center Rotterdam, The Netherlands (MEC-2020-0943). All participants will provide written informed consent. The results will be disseminated through publications in peer-reviewed journals, presentations at international conferences and among study participants and healthcare professionals., Trial Registration Number: Netherlands Trial Registry (NL9355)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)