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Benefits of massive weight loss on symptoms,
systemic inflammation and cartilage turnover in
obese patients with knee osteoarthritis
Pascal Richette, Christine Poitou, Patrick Garnero, et al.
Ann Rheum Dis 2011 70: 139-144 originally published online October 26,

doi: 10.1136/ard.2010.134015

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7 ± 7.18–22 In those studies. Paris. 2010 . Accepted 11 August 2010 Published Online First 26 October 2010 ABSTRACT Objective To investigate the effect of massive weight loss on (1) knee pain and disability. Hôtel-Dieu Hospital.9 Jean-Marc Lacorte.12–15 Additionally. Endocrinology and Oncology Biochemistry Department. reduced the serum concentrations of C reactive protein (CRP). Assistance Publique Hôpitaux de Paris. France 11Assistance Publique-Hôpitaux de Paris. Changes in COMP concentration were correlated with changes in insulin levels (p=0.70:139–144.0001).1 Christine Poitou. (2) lowgrade inflammation and metabolic status and (3) joint biomarkers in obese patients with knee osteoarthritis (OA). Centre de Recherche des Cordeliers.03). INTRODUCTION Obesity is the main modifiable risk factor for the onset of knee osteoarthritis (OA). Créteil. tumour necrosis factor α. Pitié-Salpêtrière Hospital. Nutrition and Endocrinology Department. Change in levels of joint biomarkers with weight loss suggests a structural effect on cartilage.10 11 In vitro and in vivo studies have shown that all these adipokines could affect cartilage homoeostasis.006) and Helix-II (p=0. Nutriomique Team 7. high levels of leptin.26 27 PATIENTS AND METHODS Ethics statement The ethics committee of the Hôtel-Dieu Hospital approved the clinical investigations. France (past affiliation) 8Université Paris 7.2–5 Karine Clément. p< on December 22. 75475 Paris cedex 10. Paris.Published by group. Hôpital Lariboisière. releasing several proinflammatory mediators and adipokines in blood that Ann Rheum Dis 2011. Surgery resulted in substantial decrease in BMI (−20%).6. a biomarker of cartilage turnover.2 kg/m2). Paris. ranging from 5% to 11%. interleukin 6 (IL-6) levels were correlated with levels of high-sensitivity C reactive protein (hsCRP) (p=0. Adipose tissue may act as an endocrine organ.02) and insulin resistance (p=0.bmj.001).05).6 mm. hsCRP (p<0. Knee pain decreased after surgery (24. UMRS 872. cartilage turnover and systemic inflammation.7 Eric Vicaut. Levels of insulin and insulin resistance were decreased at 6 months.6–9 With mass enlargement of fat. serum amyloid A.134015 may participate in cartilage alteration in obese patients. Unité de Recherche Clinique. alone or in combination with exercise. UFR médicale. France 10Assistance Publique-Hôpitaux de Paris.001). some studies have suggested that metabolic risk factors such as diabetes mellitus. Pitié-Salpêtrière Hospital. doi:10. Methods 140 patients involved in a gastric surgery programme were screened for painful knee OA. Surgery Department. and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score (p=0. Hôpital Lariboisière.bmj. Paris Cedex. France 5Université Pierre et Marie Curie-Paris 6. Weight loss resulted in a significant increase in N-terminal propeptide of type IIA collagen levels (+32%. and secretes inflammatory cytokines such as interleukin 6 (IL-6).1–3 The strong association between body mass index (BMI) and OA of the knee is thought to be mainly due to an increase in mechanical loads to the tibiofemoral cartilage. a biomarker of cartilage synthesis. Hôpital Fernand Widal. Clinical data and biological samples were collected before and 6 months after surgery.04) were decreased after surgery. leading to significant metabolic changes with improvement in insulin sensitivity and lipid parameters and systemic inflammation. knee joint loads and metabolic status impairment to demonstrate a benefit on cartilage turnover. 2 Rue Ambroise Paré.3 Extended report Benefits of massive weight loss on symptoms.2–5 Thomas Bardin. systemic inflammation and cartilage turnover in obese patients with knee osteoarthritis Pascal Richette.2–5 Patrick Garnero. which results in drastic weight loss. orosomucoid (p<0.10 Arnaud Basdevant. France Correspondence to Dr Pascal Richette.0001). U872. the magnitude of the weight loss was mild to moderate. a biomarker of cartilage degradation. IL-6 and tumour necrosis factor α soluble receptor 125 but did not attenuate OA progression. to a lesser extent.19 24 25 A 5% weight loss over 18 months. Lyon. Conclusion Massive weight loss improves pain and function and decreases low-grade inflammation. as assessed by sequential measurements of joint space width of the knee. Lyon.002).16 17 Randomised controlled trials have evaluated the effects of diet weight loss on pain and function in overweight patients with knee OA. p<0. France 4INSERM. A recent meta-analysis of pooled data from four of these randomised controlled trials demonstrated that a moderate weight loss of about 5% in obese patients reduces functional disability and. UFR médicale. Paris.01). We chose the model of gastric surgery. We aimed to investigate the effect of weight loss >10% in obese patients with knee OA on pain.5 ± 21 mm vs 50 ± 26. France 7Synarc. Hôpital Henri-Mondor.24 One explanation for these somewhat disappointing results might be that the magnitude of weight loss in these studies (5–10%) was not enough to sufficiently reduce systemic inflammation. p=0.19 The effect of exercise and a weight-loss intervention on the serum levels of joint biomarkers yielded inconclusive results. resistin and visfatin.8 Jean-Luc Bouillot. pain. and a significant decrease in cartilage oligomeric matrix protein (COMP) (−36%.0001) and fibrinogen (p=0.1 Xavier Chevalier11 1Université Paris 7. and low levels of adiponectin.1136/ard. knee OA structural progression and joint biomarkers.4 The observation that obesity is also a risk factor for OA of non-weightbearing joints such as the hand5 has suggested that the link between overweight and OA might also occur through systemic inflammation. body mass index (BMI) 50. France 9Assistance Publique-Hopitaux de Paris. pascal. Results Before The first two authors contributed equally to this work. adipose tissue accumulates inflammatory cells. particularly macrophages.richette@lrb. France. Paris Cedex.aphp.23 Few studies have explored the effects of moderate diet weight loss on systemic inflammation. Fédération de Rhumatologie. increased levels of triglycerides and/or cholesterol might also be associated with OA. Paris.Downloaded from ard. France 6INSERM Research Unit 664 and Cisbio Bioassays. Fédération de Rhumatologie. All subjects 139 . France 2Assistance Publique-Hôpitaux de Paris. France 3Center of Research on Human Nutrition Ile de France. and scores on all WOMAC subscales were improved. Paris. Assistance PubliqueHôpitaux de Paris. and 44 were included (age 44 ± 10.2010. disability. Levels of IL-6 (p<0.

France). Patients’ weight had to be stable (ie. France). Colorado. respectively. Measurements of body composition Fat-free body mass and adiposity were determined by dual energy x-ray absorptiometry (GE Lunar Prodigy.2 (http://www. variation within ±2 kg) for at least 3 months before surgery. France).02 and 35 mg/dl. who were prospectively recruited between 2006 and 2007 in the Department of Nutrition. Center of Reference for Medical and Surgical Care of Obesity. the HOMA represents a useful index for study of morbidly obese individuals in whom the evaluation of insulin sensitivity with the clamp technique has understandable technical limitations because of extreme BMI. Immunoassays for joint biomarkers Serum cartilage oligomeric matrix protein (COMP) is a biomarker of cartilage degradation and a potential prognostic indicator of joint OA damage. cancer and/or known alcohol consumption (>20 g/day).ac. USA). respectively.and interassay CVs are < Extended report gave their written informed consent before their inclusion in the study.134015 .and interassay CVs are both <15%. Intra. Intra. 44 met the inclusion criteria and were enrolled. Lille. respectively. respectively. Pitié Salpêtrière Hospital (Paris. intra. The sensitivity is 0. dyslipidaemia. Synarc. Sweden) with two monoclonal antibodies raised against different antigenic determinants of the COMP molecule. Intra. respectively. Patients met the criteria for obesity surgery: BMI ≥40 kg/m2. chondrocalcinosis of the knee.8 μg/ml for leptin and adiponectin.31 was measured by competitive ELISA (human PIIANP ELISA. USA). USA) before and 6 months after surgery. Multiple regression 140 Ann Rheum Dis 2011. Other outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscores for pain. patients had to have radiographically confirmed knee OA (Kellgren/Lawrence (K/L) grade 2–4) with symptoms for at least 1 on December 22. AnaMar Medical. and intra. a marker of type II collagen synthesis.and interassay CVs are <10% and 12%. the radiographic evidence of knee OA and eligibility criteria were verified by the same investigator (PR). New Jersey. Immunoassays for adipokines and inflammatory markers Serum leptin and adiponectin were determined with a radioimmunoassay kit from Linco Research (St Louis.28 Therefore. Serum levels of fibrinogen were measured with use of a Star Diagnostica Stago system by FibriPrest (Parsippany. California. Homoeostasis model assessment (HOMA) of insulin resistance (IR) was determined using the HOMA Calculator v2. obstructive sleep apnoea syndrome).32 was measured by competitive ELISA (SYNCART.2. Exclusion criteria were a K/L grade of 1.04 pg/ml. Intra. France) by the glucose oxidase method and an IMMULITE 2000 system (Siemens.and interassay CVs are <8% and 14%. viscosupplementation within the past 6 months and oral corticosteroid treatment or intra-articular corticosteroid injection into any joint within the last month before the bariatric surgery. Lipid profile and insulin sensitivity calculation Statistical analysis Plasma glucose and insulin were measured on a Modular Hitachi system (Roche Diagnostics.bmj. Subjects did not demonstrate acute or chronic inflammatory disease. High-sensitivity CRP (hsCRP) and orosomucoid levels were measured with an IMMAGE automatic immunoassay system (Beckman–Coulter. a marker of synovial metabolism. Serum hyaluronic acid (HA). Serum levels of IL-6 were measured by a high-sensitivity ELISA system (Quantikine US. Preoperative evaluation included medical history and physical.16 29 It was measured by ELISA (COMP ELISA Kit. Subjects and study design We screened 140 patients involved in a gastric surgery programme. For all patients. or ≥35 kg/m2 with at least one comorbidity (hypertension. for hsCRP and 4% and 6% for orosomucoid. Meylan. To be included. USA). doi:10. Of the 140 screened patients. infectious diseases.2010.Published by group. viral infection. stiffness and disability.Downloaded from ard. current use of symptomatic slow-acting drugs. clinical outcomes or changes in metabolic status and systemic inflammation were tested with the non-parametric Spearman correlation test. metabolic. Intra. Linco. baseline) and at 6 months after surgery. respectively. a marker of cartilage collagen turnover. inflammatory joint disease. Wisconsin. When both knees were painful. France). nutritional. This index has been validated in different populations in comparison with Data are reported as mean (SD) or median (range) depending on distribution. Texas.70:139–144.5%. cardiopulmonary and psychological assessments. Missouri.bmj.1136/ard.dtu. only the most painful knee was selected for the evaluation. The sensitivity of this assay is <0. Lyon. The Wilcoxon test was used for comparisons between clinical outcomes and biological marker levels before and after weight loss. clinical data and biological samples were collected just before surgery (ie. El Paso. and the patient global assessment of the severity of knee OA measured on a 100 mm VAS. defined by a knee pain score of at least 30 mm on a 0–100 mm visual analogue scale (VAS). Fullerton. La Garenne Colombe. Lund. The surgical procedure was laparoscopic Roux-en-Y gastric bypass (RYGB) (n=38) or laparoscopic adjustable gastric banding (n=6) and was performed in the department of surgery of Hôtel-Dieu Hospital.ox. USA) with a specific HA binding protein isolated from bovine cartilage.and interassay coefficients of variation (CVs) are <4% and 9% for leptin and adiponectin. 2010 . USA) with a polyclonal antibody raised against recombinant human type II procollagen exon 2 fusion protein. respectively. Serum N-terminal propeptide of type IIA collagen (PIIANP). Serum collagen helical peptide (Helix-II). diabetes mellitus. Correlations between relative changes in joint biomarker levels. Venous blood was collected in the morning (between 08:00 and 10:00) after a 12 h overnight fast.5 ng/ml and 0. according to the manufacturer’s recommendations.and interassay CVs are <7% and 9%. Assays for joint biomarkers were performed in a central specialised laboratory (Synarc) in batches. with the two samples for the same subject in the same run to reduce analytical variation. the euglycaemic-hyperinsulinaemic clamp values. regardless of the circumstances over the previous 48 h. Broomfield. Outcomes for knee OA The severity of the knee OA pain was evaluated using a continuous 100 mm VAS assessing the global level of pain in the target knee. Blood sampling and clinical evaluation For all was measured by ELISA (Corgenix. Madison. Serum samples were stored at −80°C for biological assays.and interassay CVs are <5% and 7. R&D Systems Europe. The sensitivity is 0.

0001).8 ± 1. BMI. hsCRP.2 ± 0. p=0. body weight (−20%.9 < ± 2.1). interleukin 6.6 years.1136/ard. WOMAC.03 <0.2 kg/m2 and was 50. p<0.7 ± 6.1 ± 10. male/female. p<0. stiffness (−47%.1±0. osteoarthritis.2±24. were significantly decreased 6 months after surgery (p<0.001) (table 4 and figure 1). p<0.0001).6±257.bmj. p=0.7 ± 3. homoeostasis model assessment estimate of insulin resistance.48.2 4.3 15. 35%. None of the other joint biomarkers correlated with inflammatory biomarkers or with outcomes for knee OA at baseline. p<0. IL-6.6 NA NA 40.2 ± 0. mg/dl Orosomucoid (g/l) Fibrinogen (g/l) Baseline 6 Months p Value 63.2 UI/l (p<0.0001 <0.0 ± 0.134015 Correlation between biochemical markers and clinical outcomes at baseline We searched for correlations between markers of systemic inflammation or joint biomarkers and symptoms (pain or disability) at baseline. A two-sided significance level was fixed at 5%.Downloaded from ard. Effect of weight loss on knee OA symptoms Massive weight loss greatly improved both pain and function in these obese patients with knee OA.4±239.2 3.0001 0. orosomucoid (−20%. p=0. p<0.6±26.3 years.03).4 ± 9. the relationship between changes in COMP levels and changes in insulin levels or HOMA-IR score was not Table 3 Serum levels of adipokines and inflammatory biomarkers at baseline and 6 months Leptin.7 μg/ml. p=0.Published by group. p<0.0001) and fibrinogen (−5%.6 2. p=0.7 9.5 ng/ml vs 586.0001 0. kg Fat mass (kg) Free fat mass (kg) Total cholesterol (mmol/l) HDL cholesterol (mmol/l) Triglycerides (mmol/l) Glucose (mmol/l) Insulin (IU/l) HOMA-IR Baseline 6 Months p Value 44 ± 10. NA.1 0. levels of circulating total cholesterol.0001 <0. p<0. systemic inflammation and metabolic status Variation in COMP concentration was significantly correlated with changes in pain (VAS) (r=0. Moreover.0001 0.6 ± 10.0±2. Additionally. IL-6 level was also correlated with levels of hsCRP (r=0.2 kg/m2 just before surgery (table 1).2 ± 24.2 ± 11. and serum level of adiponectin was increased by 21% (7. triglycerides and insulin were significantly decreased after surgery (all p<0.7 ng/ml.5±3. high-density lipoprotein. not applicable.4 ng/ml vs 33±16. 15%). Patient global assessment of the severity of the target knee OA was significantly decreased (−50%. By contrast. OA.2 ± 1.6±289 <0.2 (SAS Institute. p=0.8 ± 0.37.001).0001 <0.006) and Helix-II (r=0.33.5 0.2 94.0001 <0. Duration of knee OA symptoms was 5.9±4.0001 187.6 1.2 ± 4.6 51. Bariatric surgery resulted in a substantial decrease in BMI (−20% of baseline values.4 7. As expected.1 ± 0.42. p<0. µg/ml IL-6. Our study population consisted of 44 obese patients (mean age 44 ± 10.001 <0.9 36.001).03). whereas serum levels of Helix-II and HA were unchanged (p=0.5 ± 21 mm (−51%. 141 . 50%.0001 Values are the mean ± SD.0001). Mean BMI at age 20 was 31.6 5.05.6±0.9±4.2 1. Effect of weight loss on adipokine levels and systemic inflammation Changes in joint biomarkers with massive weight loss Weight loss resulted in a significant increase (+32%) in serum level of PIIANP (443.0001 <0.0 0. hsCRP (−46%.33.4 ng/ml. Cary.9±7.4 ± 6.31.8 33±16.01).3 1.9 272. ng/ml Adiponectin.8 8.4±41.7 ± 7.2 ± 20.0001) and fat free mass (−9%. p=0. visual analogue scale.002).0001 <0.0001 < on December 22.8 643. grade 4.04). p<0. table 1).001) and function (−57%. HOMA-IR. doi:10.1±93. fat mass (−21%. respectively).3 8/36 Extended report analysis was used to assess the independent association and contributions of changes in BMI. high-sensitivity C reactive protein.9 NA NA <0. kg/m2 Weight.001) (table 2).0001 0. p=0.0001.5 UI/l vs 6.0±0.2010. p=0.9 4. We also found a significant correlation between Helix II and hsCRP (r=0. A two-tailed p value <0. Western Ontario and McMaster Universities Osteoarthritis Index. p<0.6 μg/ml vs 9. at 6 months.4 4.3±20. Level of high-density lipoprotein cholesterol did not change (p=0. glycaemic status and insulin resistance. However.bmj. VAS.5±21 25. We found a significant correlation between level of IL-6 and WOMAC function score (r=0.5 1.001). p=0. Change in COMP concentration was also correlated with change in BMI (r=0.8±0. p=0.04 Values are the mean ± SD.9±7. grade 3.05 was considered statistically significant. pg/ml hsCRP. Levels of leptin or adiponectin were not correlated with clinical outcomes or joint biomarker levels. After surgery.4 68. knee OA pain scores on the VAS decreased from 50 ± 26. p<0.9 <0.2 ± 0.001).0001 <0. USA).0 64. HDL.6 47.5 24.0001).0 ± 9. the serum level of COMP was significantly decreased (−36%) after surgery: 10. n BMI. Table 2 Effect of massive weight loss on knee osteoarthritis symptoms Pain score (100 mm VAS) Patient global assessment of the severity of knee OA (100 mm VAS) WOMAC pain score WOMAC stiffness score WOMAC function score Baseline 6 Months p Value 50±26. body mass index.9±424.1±0.02) and HOMA-IR score (r=0.8 1.7 3. p<0.6 6.2 138.9 4.2±53. All analyses involved use of SAS v9. 36 women) with moderate to severe knee OA (K/L grade 2.9±0. Correlation between changes in COMP or PIIANP levels and changes in clinical outcomes.5 58.3±124.70:139–144.7 1.1 ± 0.0001). North Carolina. p=0.5 59. RESULTS Demographic characteristics of patients and effects of weight loss on metabolic status The changes in levels of inflammation biomarkers after gastric surgery are shown in table 3. Finally. values are mean ± SD.6 to 24.03).0001) and orosomucoid (r=0.63. the serum levels of IL-6 (−26%.3 ± 10.98 and p=0.04) were all significantly decreased after surgery. subscales were improved: pain (−50%. insulin and HOMA-IR with the dependant variable COMP.0001) at 6 months. weight loss was associated with changes in adipokine levels: mean serum leptin concentration was decreased by 48% (63.03) and WOMAC stiffness score (r=0.7 ± 7.0001 <0. insulin level (r=0.01).0001 Unless otherwise indicated.7±2. as evaluated by HOMA-IR.8 ± 23.0001 <0. years Sex.05) (table 5). p<0. and scores on all WOMAC Table 1 Demographic characteristics of obese patients with knee osteoarthritis and variation in metabolic marker levels before and after bariatric surgery Age.3 1. p<0. 2010 .8 110. Ann Rheum Dis 2011.36.

2 3. cartilage oligomeric matrix protein.35 36 Hooper et al.0 10. here we found a significant correlation at baseline between circulating levels of IL-6 and WOMAC function score.2 36. and result in a change in cartilage turnover as assessed by systemic biochemical markers.39) and 0. found that obese patients with knee OA who lost 29% of body weight between 6 and 12 months after bariatric surgery showed improved WOMAC pain.5±3. they suggest that the greater the weight loss. The reductions in WOMAC pain. hyaluronan.70:139–144.5 5. one recent study also found a positive correlation between moderate weight loss and changes in COMP levels.39 As expected. a biomarker of cartilage turnover.0 586.134015 .24 The mechanism by which weight loss decreases COMP levels is unknown.1 kg were 0. Figure 1 Serum levels of N-terminal propeptide of type IIA collagen (PIIANP). hepatic and cardiovascular diseases.bmj. 74% and 64%. Behavioural and pharmacological treatments of obesity usually result in short-term weight loss of approximately 5–10% body weight.8 377.9±5.43 44 Ann Rheum Dis 2011. which suggests that the decrease in low-grade inflammation has no role or is of little importance in clinical improvement related to weight loss. Boxes represent the interquartile range. decrease levels of metabolic parameters and low-grade inflammation.4±220.27 40 However. type II collagen helical peptide (Helix-II).6 10.23 (95% CI 0.41 Values are mean ± SD or median ± IQR.5 31. We also observed that the level of IL-6.7±35. hsCRP. Helix-II. cartilage-oligomeric matrix protein (COMP) and hyaluronan (HA) in obese patients with knee osteoarthritis (OA) before (M0) and 6 months after (M6) bariatric surgery.4 6.42.9±4.5 6. stiffness and function were significantly correlated among themselves and the WOMAC function correlated best with the patient global assessment of the severity of knee OA (data not shown). HA. respectively.34 Trials that have assessed the efficacy of surgically induced massive weight loss on knee OA symptoms are scarce and have not specifically included patients with well-defined radiographic evidence of knee OA.002 0.33 According to a recent meta-analysis. type II collagen helical peptide. Our findings extend the results of recent work showing a significant association of IL-6 circulating levels and the prevalence and incidence of knee OA. doi:10.bmj. and a decrease in that of COMP (−36%).001 0.3 0. By contrast. according to the BIPED classification.3±6.7±2. independent of changes in BMI because BMI was the only significant regressor found on multivariate regression analysis (β=0.38 was correlated with Helix-II.04 to 0. COMP.3±26.41 Massive weight loss resulted in a significant increase in the level of PIIANP (+32%).6±257.42). Weight loss alone of <5% seems ineffective or poorly effective in alleviating OA knee pain in obese patients. PIIANP.4±242.9 27. a 20% weight loss over 6 months decreased scores for pain by 50%. the pooled effect sizes for improvement in pain and physical disability in patients with knee OA who lost an average of 6.5 6. p=0. because this protein has been shown to be mechanosensitive. ng/ml Helix-II.2±34.36 In 142 our study.10 Interestingly. UI/l HA.4± Extended report Table 4 Serum levels of joint biomarkers at baseline and 6 months after bariatric surgery Baseline PIIANP.1±2. change in the PIIANP level was not correlated with changes in clinical outcomes or biological marker levels. a marker of type II collagen synthesis. 2010 . IL-6. Of note. IL-6 has been shown to be secreted substantially by adipose tissue and its level correlates with metabolic complications in some studies. no other inflammatory protein or adipokine level or BMI were correlated with clinical outcomes before surgery. as in our study. which mainly originates from adipose tissue in obese patients but which is also produced by infrapatellar fat pad within the joint.8±5. DISCUSSION Our study shows that a surgically induced mean weight loss of 20% in patients with severe obesity and knee OA can improve pain and function.0 538. bariatric surgery resulted in a significant increase in the serum level of adiponectin and a significant decrease in that of leptin. we used biochemical markers of joints as surrogate markers to assess cartilage turnover. using a single-arm open study design. N-terminal propeptide of type IIA collagen. lines inside boxes represent the median.9 20.Downloaded from ard. and lines outside boxes indicate 95% CI. Elevated inflammatory protein levels in obese individuals suggest that inflammation may have a determinant role in connecting obesity to metabolic. none of the changes in these inflammatory biomarkers was correlated with changes in clinical outcomes.30 These results are the first to suggest a benefit of weight loss on both cartilage anabolism and catabolism. ng/ml COMP.2 (95% CI 0 to 0. orosomucoid and fibrinogen.1136/ard. as assessed by a VAS or the WOMAC subscore and for function by 57%. the greater the benefit for pain and function.6 on December 22.98 <0.4±38. A decrease in knee joint load with weight loss42 may modulate the release of COMP. a marker of cartilage degradation.Published by group.4±4.04). Obesity is now recognised as a low-grade inflammatory disease. Finally. respectively.37 Among a myriad of inflammatory mediators.10 11 Whether this systemic inflammatory state has a role in the genesis of OA in obese patients is a subject of growing interest. Because the morphology of our patients precluded carrying out repeated MRI or standard x-ray examinations for structural evaluation. function and stiffness scores. by 51%. ng/ml 6 Months Mean±SD Median±IQR Mean±SD Median±IQR p Value 443. Although these data should be cautiously compared.

France). Osteoarthr Cartil 2005. Astrup A. several experimental data suggest a detrimental effect of insulin resistance on cartilage. Hart DJ. Spearman rank correlation coefficient.16 0. Serum amyloid A: a marker of adiposityinduced low-grade inflammation but not of metabolic status. Jr. 24. Lago F. Effect of an exercise and dietary intervention on serum biomarkers in overweight and obese adults with osteoarthritis of the knee. 16. 3.25:2181–6. Knee osteoarthritis in obese women with cardiometabolic clustering. Lago F. Bliddal H.60:2858–60.58:1399–409. Association between weight or body mass index and hand osteoarthritis: a systematic review.44 0. Christensen R.13:20–7. COMP Change in Patient consent Obtained. hsCRP. Diet. J Rheumatol 1998. doi:10. Nicklas BJ. J Mol Endocrinol 2009. Arthritis Rheum 2004. The relatively small sample size may have missed some weak associations. 12. Clément K.25 0.4:e7905. Astrup A. Biorheology 2008. COMP. Kraus VB. our findings need to be replicated in confirmatory studies. et al. obese adults: a randomized controlled clinical trial.bmj. 20. Berenbaum F.001 0. Dieguez C. Ma K. BJOG 2006. which promoted and supported the clinical investigation.61:1328–36. The effect of changes in insulin resistance related to weight loss on cartilage homoeostasis needs further investigation. The strengths of this study include the assessment of severely obese patients recruited from a centre of reference for medical and surgical care of obesity. Exercise and dietary weight loss in overweight and obese older adults with knee osteoarthritis: the Arthritis. hip and/ or hand: an epidemiological study in the general population with 10 years follow-up. Arthritis Rheum 2009. 26. Legault C. 11.53 0. BMC Musculoskelet Disord 2008.17 0. Messier SP. J Am Geriatr Soc 2000. Griffin TM. Arthritis Res Ther 2009. Terlain B. 5.21 0. Arthritis Rheum 2009.113:1141–7. Thus. Ambrosius W. 19. Diet-induced weight loss. Although there is no formal clinical evidence for a link between diabetes mellitus and OA. Woolf AD.006 Ethics approval The ethics committee of the Hôtel-Dieu Hospital approved the clinical investigations. Loeser RF. 7. Grotle M. 15. Miller GD. 10. 2010 . Bariatric surgery resulted in a sharp decrease in levels of cholesterol and triglycerides and insulin resistance. HOMA-IR. et al. our data show that massive weight loss (20%) in patients with symptomatic knee OA improves pain and function. data collection and sampling at the Center of Research on Human Nutrition.43:11–18.10 0. Our trial was conducted as an open exploratory study.36 0.20 −0.36 0. Obesity (Silver Spring) 2006. and thus should be carefully interpreted. Controlling the obesity epidemic is important for maintaining musculoskeletal health.35 0. PIIANP. et al.04 −0. Jeffery A. Natvig B. Obesity and osteoarthritis: is leptin the link? Arthritis Rheum 2009. Griffin TM. interleukin 6. Coussieu C.53 0. 21.05 0. 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