• Abstract 1759: Impact of Small Weight Loss on OA Symptoms
• Abstract 397: Impact of Obesity in Lupus
• Abstract 753: Weight Loss: An Underutilized Approach in OA Care
• Abstract 1872: Musculoskeletal Findings Following Gastric Bypass Surgery

Introduction Rates of overweight an obesity are increasing at such alarming rates in US adults in the past decade that the Centers for Disease Control and Prevention in Atlanta has termed this an 'epidemic.' Results of the National Health and Nutrition Examination Survey (NHANES) 1999-2000 indicated that nearly 2 out of 3 U.S adults aged 20 years and older were either overweight or obese. Nearly 1 in 3 adults - nearly 59 million people - were obese. In response to public health consequences of obesity, the National Institutes of Health formed an Obesity Research Task Force in 2003 to accelerate efforts at reducing and preventing obesity. (For more information visithttp://obesityresearch.nih.gov/index.htm or the CDC website at http://www.cdc.gov/nccdphp/dnpa/obesity/index.htm.)

Excess body weight has been implicated in the development and progression of osteoarthritis (OA). Initial results from a prospective study we are conducting at the Johns Hopkins Arthritis Center that were presented at the 2004 ACR Meeting suggest that weight loss may indeed be a promising approach to managing OA. Beyond this, new evidence also suggests that excess body fat may also play an important role in the development and maintenance of autoimmune diseases. Achieving and maintaining a health body weight is one of the most important health behaviors for all adults, and especially among patients with arthritis and other rheumatic diseases. However, as you will also read, it also appears that we are not using opportunities to reinforce this critical message often enough. What follows is a summary of several presentations and posters addressing the latest findings related to overweight and obesity in OA and autoimmune disorders.

Abstract 1759: Small Weight Losses Can Yield Significant Improvements in Knee OA Symptoms
Susan J. Bartlett, Steffany Haaz, Peggy Wrobleski, Joan M. Bathon, Kevin R. Fontaine, Claire Ruffing

Background: Small reductions in weight (10%) have been associated with significant improvements in hypertension, diabetes, and dyslipidemias. While weight reduction has been identified by ACR and EULAR as a promising intervention for treating pain and improving function in persons with knee osteoarthritis (OA), little is known about how much is needed to improve symptoms.

Objectives: To evaluate the long-term impact of weight loss on pain, stiffness and functioning in overweight and obese adults with knee OA in a RCT of immediate vs. delayed intervention.

Participants: Data are from the initial 24 participants enrolled in a 16 month RCT comparing weight loss and exercise against delayed intervention for persons with knee OA. Eligibility criteria included: met ACR criteria for knee OA; reported pain on > 50 % of days in one or both knees; experienced difficulty with ADLs; had radiographic grade 2-3 K-L; and of body mass index (BMI) 27 - 35 kg/m2 . Men (n=5) had a mean age of 63.6 + 7.4 and women (n=19) were 58.2 + 6.8 years (p = .133). Men and women were mildly obese (BMI 33.9 + 2.4) at baseline and mostly white (i.e., 83%; 13% black; 4% Hispanic). Results are from the first 24 individuals who completed the weight loss intervention; 7 individuals also served as controls.

Methods: Participants attended weight-loss classes that met in small groups each week for 4 months. Classes emphasized changes in nutrition, physical activity, eating behaviors and incorporating lifestyle exercise to facilitate permanent weight reduction. Women were advised to eat a balanced diet of 12-1400 kcal/d while men were prescribed 16-1800 kcal/day. Participants were instructed to accumulate 30 minutes of moderate-intensity physical activity most days of the week, consistent with the Surgeon General and others' guidelines for physical activity. Participants wore pedometers each day to help them meet physical activity targets and to quantify daily physical activity.

Results: Men lost an average of 9.0 2.5 kg and women lost 7.1 4.8 kg over 4 months. This reflects an 8.7% and 7.8% loss (of initial weight) for men and women, respectively. At week 16, participants reported significant (p's = .001) reductions in pain (40%), stiffness (45%) and improvements in physical functioning (51%) as compared with baseline WOMAC scores. Among individuals in the delayed intervention condition, there was no significant difference between baseline and follow-up.

Conclusions: These preliminary data suggest that in obese persons with mild-moderate knee OA, small weight losses (8% or ~18 lbs) are associated with significant improvements in pain, stiffness and physical function. These losses may equal or exceed the symptom reduction associated with commonly prescribed arthritis medications and viscosupplement injections. In addition, accumulating 30-minutes of moderate-intensity physical activity (i.e., brisk walking) is feasible and enjoyable to knee OA patients. Participants will be evaluated over one full year of follow-up to assess the maintenance of weight and improvements in symptoms.

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Abstract 397: Obesity, a Modifiable Risk Factor, is a Major Determinant of Quality of Life, Functional Capacity and Inflammatory Markers in Systemic Lupus Erythematosus (SLE)
Annette Oeser, Cecilia P. Chung, Yu Asanuma, C. Michael Stein

Purpose: Obesity is a major cause of morbidity in the general population, but little is known about its effect in chronic illnesses such as SLE. Therefore, we examined the relationship between obesity and functional capacity, quality of life, and inflammatory markers in patients with SLE.

Methods: Ninety four patients fulfilling criteria for SLE were divided into 3 groups based upon body mass index (BMI, weight in kg/height in m2 ) - BMI < 25 (normal), BMI 25-29.99 (overweight) and BMI =30 (obese). We compared functional capacity (8 and 10 question Modified Health Assessment Questionnaire (MHAQ8 and MHAQ10), Fatigue Severity Scale (FSS), walking distance), quality of life (QL index, Spitzer, 1980), disease activity (SLEDAI), disease damage (SLICC), use of steroids and inflammatory markers (C-reactive protein (CRP), Interleukin-6 (IL-6)) among the three groups, using ANOVA, Mann-Whitney or Chi-squared test as appropriate.

Results: There was a striking relationship between obesity and decreased functional capacity, lower quality of life scores, more fatigue and increased concentrations of CRP and IL-6 (Table). BMI was not significantly related to SLEDAI, SLICC or use of corticosteroids.

Conclusions: Obesity is a major determinant of functional capacity, quality of life, and inflammatory markers in patients with SLE. Weight management could be an important tool to improve functional capacity and quality of life and decrease cardiovascular risk factors such as IL-6 and CRP concentrations.

Editorial Comments: Overweight and obesity status (and in particular abdominal obesity, or having an apple shape) is linked with higher levels of inflammatory markers. For example, about 25% of IL-6 is released into the body from subcutaneous fat.⁽¹⁾ Higher body mass index (a marker of body composition and excess fat) is associated with elevated CRP levels.⁽²⁾ Overweight and obesity are also independently associated with impairments in physical functioning, quality of life and energy.^(3;4)

To date, very little has been reported about the prevalence of obesity among SLE patients and its consequences. Thus, the results of this study, while not surprising, add to the growing body of literature that underscores that negative synergistic effect that excess body weight has in persons with rheumatic diseases.

Beyond the social, physical and psychological burdens overweight and obese individuals endure in western society, preliminary evidence also suggests that excess adipose tissue has important physiological consequences related to autoimmune diseases. For example, leptin, a fat hormone that influences food intake and metabolic and endocrine function, has also been shown to influence immunity, inflammation, hematopoiesis, and adrenal androgen secretion.^(5;6)

Animal studies for human diseases have suggested a determining role for leptin in the development and/or maintenance of autoimmune diseases like inflammatory bowel disease (IBD), rheumatoid arthritis (RA), multiple sclerosis (MS) and type 1 diabetes.⁽⁷⁾ Leptin levels are elevated in obese individuals; similarly, in 41 women with systemic lupus erythematosus, serum leptin levels were significantly higher than in an age-, sex- and BMI-matched control group.⁽⁸⁾ Findings such as these are leading some to suggest that overweight and obesity is a low-grade systemic inflammatory disease, characterized by increased concentrations of pro-inflammatory cytokines like IL-6, TNF-aand leptin.^(2;7) While adequate body fat is required for health immune functioning, perhaps excess body fat (and resulting higher leptin levels) over the long-term may result problematic immune reactions such as those observed in autoimmune diseases.⁽⁷⁾

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Abstract 753: Weight Loss and Exercise: Opportunities for Quality Improvement in Osteoarthritis
Sarah L. Sampsel, Catherine H. MacLean, Teresa Brady, Khaled Saleh, Daniel H. Solomon, Jeffrey Susman, Kenneth G. Saag, Russell Mardon, Philip Renner

In osteoarthritis of the hip and knee, weight loss and exercise/physical activity are the cornerstones of treatment and have been shown to reducing disability. Though weight loss is recommended in ACR guidelines, it is unclear how often this information may be communicated to patients.

The investigators conducted an observational study in two health plans with total population exceeding one million members. Patient-level administrative and medical record data were collected to assess documentation of recommendations for weight loss and exercise in health plan members with OA of the hip or knee. Patients were identified based on diagnostic coding for OA of the hip or knee. For a random sample of 150 patients from each plan, medical records were obtained and abstracted to ascertain recommendations for weight loss and exercise over the one-year period 2001-2002.

In this sample, 1284 (.0012%) non-Medicare and 1101 (.017%) Medicare patients had a diagnosis of OA. (The low prevalence of OA in these health plans raises questions about the case ascertainment method used in this study.) However, among patients with OA for whom medical records were reviewed, 33 % were overweight as defined by BMI > 27 kg/m2; there was documentation of a recommendation for weight loss for 48% of these patients. A recommendation for physical activity/therapeutic exercise was documented for only 43% of patients with an OA diagnosis.

Editorial comments: The prevalence of overweight and obesity are high among US adults. In persons with knee OA, obesity is a potentially modifiable factor that may improve symptoms and attenuate disease progression. However, these data suggest that behavioral approaches to managing knee and hip OA (i.e., advice to lose weight and exercise) are either not addressed or not documented in medical records for many patients.

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Abstract 1872: Musculoskeletal Findings in Morbidly Obese Subjects Before and After Weight Loss Due to Gastric Bypass Surgery
Michele M. Hooper, Thomas A. Stellato, Peter T. Hallowell, Roland W. Moskowitz

The prevalence of musculoskeletal (MSK) complaints and their response to weight loss were assessed in morbidly obese subjects before and after gastric bypass surgery and weight loss. Individuals were consecutively recruited from a bariatric surgery program. Twenty percent declined to participate and 54 were subsequently enrolled. A total of 48 were available for follow-up at 6-12 months (mean 201 + 50 days).

Subjects completed the London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ), the WOMAC questionnaire and were examined by a rheumatologist or trained rheumatology nurse. MSK signs and symptoms including description of pain and location; joint, tendon, bursal exams and trigger points were recorded, along with comorbid diseases.

There were 52 women, 2 men; 70% Caucasian, 28% African American, 2% Hispanic. Mean age 44 + 9 years. Mean weight (women) before surgery was 292 + 42 lbs (BMI 51 + 8) and 202 + 50 lbs (BMI 36 + 7) nearly seven months later. At baseline, the most common comorbid conditions were hypertension (52%), sleep apnea (46%), GERD (31%), type II diabetes (30%), asthma (30%), bladder incontinence (22%). There was a decrease of 52% in the number of sites of MSK complaints (as shown in Table 1) and a 92% reduction in FMS (by LFESSQ and ACR criteria). The WOMAC scores indicate a significant magnitude of improvement (Table 2).

Table 1

Table 2

Conclusion: Morbid obesity was associated with a high frequency of MSK complaints before surgery, including non-weight bearing sites, which decreased significantly following weight loss. The dramatic resolution of FMS may be due to a decrease in comorbid syndromes (sleep apnea, GERD) and an increase in physical activity. These benefits may improve further, as weight loss may continue for up to 24 months. This highly motivated group of individuals may not reflect the general obese population, but the benefits seen with weight loss indicate that prevention and treatment of obesity can improve MSK health and function.

Editorial comments: These data suggest that the substantial weight loss (i.e., 32%) associated with gastric bypass surgery were associated with significant improvements in pain (49%), stiffness (64%) and physical function (74%) on the WOMAC scales. Further musculoskeletal complaints were also significantly reduced.

However, the authors' conclusions regarding resolution of FMS with weight loss appear unfounded and potentially misleading. The London Fibromyalgia Epidemiology Study Screening Questionnaire was designed to "assess the distribution and predictive ability of fibromyalgia (FM) tender points (TP) in adults with chronic widespread pain.⁽⁹⁾ The instrument tested pain criteria using four questions and fatigue criteria with 2 questions. While the screening test has been shown to have high positive predictive value in a general population,⁽¹⁰⁾ it has not been validated in a morbidly obese population. Complaints of pain and fatigue are common^(11;12) among overweight and obese individuals and have been shown to improve with weight loss^(4;13). The 92% reduction in FMS may more accurately reflect significant improvements in quality of life suggested by the WOMAC scales than resolution of fibromyalgia syndrome.

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Reference List
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2. Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA 1999; 282(22):2131-2135.

3. Fontaine KR, Bartlett SJ. Estimating health-related quality of life in obese individuals. Disease Management and Health Outcomes 1998; 3(2):61-70.

4. Fontaine KR, Bartlett SJ, Barofsky I. Health-related quality of life among obese persons seeking and not currently seeking treatment. Int J Eat Disord 2000; 27(1):101-105.

5. Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 2004; 92(3):347-355.

6. Harle P, Pongratz G, Weidler C, Buttner R, Scholmerich J, Straub RH. Possible role of leptin in hypoandrogenicity in patients with systemic lupus erythematosus and rheumatoid arthritis. Ann Rheum Dis 2004; 63(7):809-816.

7. Peelman F, Waelput W, Iserentant H, Lavens D, Eyckerman S, Zabeau L et al. Leptin: linking adipocyte metabolism with cardiovascular and autoimmune diseases. Progress in Lipid Research 2004; 43(4):283-301.

8. Garcia-Gonzalez A, Gonzalez-Lopez L, Valera-Gonzalez IC, Cardona-Muoz EG, Salazar-Paramo M, Gonzalez-Ortiz M et al. Serum leptin levels in women with systemic lupus erythematosus. Rheumatology International 2002; 22(4):138-141.

9. White KP, Harth M, Speechley M, Ostbye T. Testing an instrument to screen for fibromyalgia syndrome in general population studies: the London Fibromyalgia Epidemiology Study Screening Questionnaire. J Rheumatol 1999; 26(4):880-884.

10. White KP, Harth M, Speechley M, Ostbye T. A general population study of fibromyalgia tender points in noninstitutionalized adults with chronic widespread pain. J Rheumatol 2000; 27(11):2677-2682.

11. Fontaine KR, Barofsky I, Andersen RE, Bartlett SJ, Wiersema L, Cheskin LJ et al. Impact of weight loss on health-related quality of life. Qual Life Res 1999; 8(3):275-277.

12. Barofsky I, Fontaine KR, Cheskin LJ. Pain in the obese: impact on health-related quality-of-life. Ann Behav Med 1997; 19(4):408-410.

13. Larsson UE. Influence of weight loss on pain, perceived disability and observed functional limitations in obese women. Int J Obes Relat Metab Disord 2004; 28(2):269-277.

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