Clinical and epidemiological research Ann Rheum Dis 2012;71:26–32. doi:10.1136/ard.2010.144725 26 ABSTRACT Background Obesity is an important risk factor for knee osteoarthritis (OA), Weight loss can reduce the symptoms of knee OA. No prospective studies assessing the impact of weight loss on knee cartilage structure and composition have been performed. Objectives To assess the impact of weight loss on knee cartilage thickness and composition. Methods 111 obese adults were recruited from either laparoscopic adjustable gastric banding or exercise and diet weight loss programmes from two tertiary centres. MRI was performed at baseline and 12-month follow-up to assess cartilage thickness. 78 eligible subjects also underwent delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), an estimate of proteoglycan content. The associations between cartilage outcomes (cartilage thickness and dGEMRIC index) and weight loss were adjusted for age, gender, body mass index (BMI) and presence of clinical knee OA. Results Mean age was 51.7±11.8 years and mean BMI was 36.6±5.8 kg/m 2 ; 32% had clinical knee OA. Mean weight loss was 9.3±11.9%. Percentage weight loss was negatively associated with cartilage thickness loss in the medial femoral compartment in multiple regression analysis (β=0.006, r 2 =0.19, p=0.029). This association was not detected in the lateral compartment (r 2 =0.12, p=0.745). Percentage weight loss was associated with an increase in medial dGEMRIC in multiple regression analysis (β=3.9, r 2 =0.26; p=0.008) but not the lateral compartment (r 2 =0.14, p=0.34). For every 10% weight loss there was a gain in the medial dGEMRIC index of 39 ms (r 2 =0.28; p=0.014). The lowest weight loss cut-off associated with reduced medial femoral cartilage thickness loss and improved medial dGEMRIC index was 7%. Conclusions Weight loss is associated with improvements in the quality (increased proteoglycan content) and quantity (reduced cartilage thickness losses) of medial articular cartilage. This was not observed in the lateral compartment. This could ultimately lead to a reduced need for total joint replacements and is thus a finding with important public health implications. INTRODUCTION Obesity represents a major public health problem. The WHO estimates that more than one billion people are overweight and, of these, 300 million are obese. 1 In addition, the levels of extreme obe- sity (obesity grade 3, body mass index (BMI) ≥40 kg/m2) are also escalating. 2 Osteoarthritis (OA) is the most common form of arthritis and the leading cause of chronic disabil- ity among older people. Obesity is a significant risk factor for the incidence of knee OA, but the effects on disease progression are less consistent. 3–5 In an analysis of the direct costs of obesity it was estimated that the cost of OA in the USA (US$5.3 billion) was second only to the cost of diabetes in obesity-associated conditions. 6 OA has a significant negative impact on most economies—for example, in the UK economy, OA has a total cost estimated to be equivalent to 1% of Gross National Product per year. 7 Obesity-related OA is estimated to be responsible for at least 10% of this cost. 8 OA affects articular cartilage and other structures such as subchondral bone and meniscus. Loss of artic- ular cartilage is a marker of OA severity. 9 The main function of articular cartilage is to permit frictionless and pain-free movement of the joint. 10 Articular carti- lage consists of a large extracellular matrix composed of water and proteoglycans entrapped within a col- lagenous framework. Proteoglycans are made up of glycosaminoglycans (GAGs) attached to a backbone of hyaluronic acid. 11 Proteoglycans provide the carti- lage with compressive stiffness. Quantitative cartilage assessment using MRI allows the measurement of important cartilage structural features such as thickness and volume. 12 In comparison with radiography, MRI detects mor- phological changes in cartilage at a much earlier stage of the disease—that is, it allows the detection of pre-radiographic OA. 12 Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), a cartilage compositional measure, is used to assess the relative distribution of GAG in cartilage non-invasively. 13 GAGs are nega- tively charged due to abundant carboxyl and sul- fate groups that are ionised at physiological pH. The technique uses a negatively charged contrast agent, gadopentate dimeglumine (Gd-DTPA 2- ; Magnevist; Berlex Laboratories, Wayne, New Jersey, USA) which, when given time to penetrate cartilage tissue, distributes within the cartilage matrix in an inverse relationship to the concentra- tion of negatively charged GAG. 11 14 15 The concen- tration of Gd-DTPA will therefore be relatively low in normal (GAG-abundant) cartilage and relatively high in degraded cartilage (GAG loss). This allows calculation of the dGEMRIC index, with a low GAG content resulting in a low dGEMRIC index and a high GAG content yielding a high dGEMRIC ▶ Additional data are published online only. To view the files please visit the journal online (http://ard.bmj.com/ content/71/1.toc). 1 Institute of Bone and Joint Research, Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney, New South Wales, Australia 2 Rheumatology, Concord Hospital, Sydney, Australia 3 University of Sydney, Sydney, New South Wales, Australia 4 Royal North Shore Hospital, Sydney, Department of Surgery, New South Wales, Australia 5 Human Nutrition, University of Sydney, Sydney, New South Wales, Australia 6 Radiology, Royal North Shore Hospital, Sydney, New South Wales, Australia 7 Clinical and Rehabilitation Sciences Research Group, University of Sydney, Sydney, New South Wales, Australia Correspondence to Professor L March, Department of Rheumatology, Royal North Shore Hospital, University of Sydney, Building 35, Level 4, St Leonards, Sydney, NSW 2065, Australia; lynmar@med.usyd.edu.au Accepted 14 August 2011 EXTENDED REPORT Weight loss in obese people has structure-modifying effects on medial but not on lateral knee articular cartilage A Anandacoomarasamy, 1–3 S Leibman, 3,4 G Smith, 3,4 I Caterson, 5 B Giuffre, 3,6 M Fransen, 7 P N Sambrook, 1,3 L March 1,3 group.bmj.com on February 19, 2013 - Published by ard.bmj.com Downloaded from