1. Jonathan T. Bravman, MD CU Sports Medicine Division of Sports Medicine and Shoulder Surgery University of Colorado Department of Orthopedics Denver, Colorado

2. Journal of the American Academy of Orthopaedic Surgery, March 2013

3.  Present data available in 2013 regarding:  The effect of obesity on osteoarthritis  The effect of weight loss and exercise for treatment of osteoarthritis in obese patients

5. OA Biomechanical Theories Systemic Theories  Osteoarthritis is strongly correlated with high BMI

6.  The intuitive theories  Most studies involve the knee  Surprising lack of data to support them (presented evidence here is weak)

7.  Increased load = increased wear = increased pain  Load exerted on knee: 3x body weight with walking 5x body weight with stairs 200 lb 1000 lb (1/2 ton) =

8.  Obesity increases subchondral bone density and stiffness  Load is redistributed on cartilage causing increased wear

9.  Obese are generally deconditioned  Relative quadriceps weakness, muscle imbalance, and impaired control have been observed in adults with OA vs. none  Decreased muscle mass is associated with increased knee cartilage (Arthritis Rheum. 2005 Feb;52(2):461-7)  Reduced muscle strength relative to body weight causes early quadriceps fatigue in the obese:  Reduced shock attenuation  Increased loadingIncreased WEAR  Increased variability in loading

10.  BMI is associated with severity of joint space narrowing of the knee in varus malalignment (but not valgus)  Increased adduction moment increases medial compartment wear  Adduction moment increases with age in the obese but not in normal-weight individuals

11.  Malalignment  smaller role than originally thought  mediates other risk factors such as obesity  “The clinician should focus on what is definitively modifiable…obesity, in particular”

12.  Less intuitive, newer, possibly more important  Adipose tissue is not just an energy depot  White adipose tissue = immunologically active organ  Cytokines: small cell-signaling peptides  Adipokines: pro-inflammatory cytokines derived primarily from adipose tissue

13.  Important members:  Leptin  Resistin  Adiponectin  Visfatin  Active in cartilage regulation  Exact role of each is unclear but many studies are currently underway

14.  Leptin  Present in synovial fluid of joints with OA  levels in both synovial fluid and plasma correlate closely with BMI  Marked expression in OA cartilage and osteophytes compared to minimal in normal cartilage  First to suggest that leptin plays an important role in pathophysiology of OA

15.  Acts on hypothalamus to decrease food intake and increase energy expenditure  Closely linked to the immune system  Synovial fluid levels strongly linked to radiographic severity of OA!!

16.  Cartilage taken from TKA procedures  Leptin upregulated multiple MMPs in cartilage  Leptin levels correlate with multiple MMPs in synovial fluid from OA pts  Conclusion: Leptin has a catabolic effect in OA joints

17.  Adipocyte-derived hormone with known anti- diabetic and anti-atherogenic properties  Found in OA synovial fluid and chondrocytes  Upregulates TIMP-2 and downregulates MMP-13  Researchers feel it is critically involved in pathogenesis of OA

18.  Hand xrays compared at baseline and 6 years  Serum adipokines measured at baseline

19.  Increased levels of adipokines  Elevated inflammatory markers in obese:  CRP, ESR, IL-6, and TNF  Inflammation plays a role in OA, cardiovascular disease, DM, dyslipidemia, respiratory disorders, autoimmune disorders, and cancer

20.  Development of OA is both mechanical and metabolic  Mechanoreceptors on chondrocyte surfaces may detect obesity load and trigger intracellular signaling cascades  Adiposity is highly metabolic and inflammatory  Development of OA appears strongly correlated with disordered glucose and lipid metabolism  Adipokines may cause direct cartilage degredation Is OA an inflammatory arthropathy?

21.  Leptin and adiponectin are key mediators in inducing cartilage breakdown  Work with MMPs, nitric oxide, and interleukins  Therapeutic targets for OA treatment??

22.  “a cluster of conditions…that occur together increasing your risk of heart disease, stroke, and diabetes” 1. excess body fat around the waist 2. increased blood pressure 3. elevated insulin levels 4. abnormal cholesterol levels  Being overweight and inactive are “major contributors”  Treatment: exercise, weight loss, eat healthy, and stop smoking

24.  Predominant theory behind OA now is that it occurs from local mechanical factors acting in the context of systemic susceptibility Black box

25.  Obesity and overweight are associated with increased musculoskeletal pain  The impact of pain on functional status and health- related quality of life is greater in the the obese  The metabolic syndrome is associated with chronic pain  Central obesity is the metabolic syndrome component most directly associated with pain (beyond OA or neuropathy)

26.  There is a strong relationship: obesity depression 55% 58%

27.  Is the patient’s knee pain caused by obesity or osteoarthritis or both?  How do we figure this out? 1. Weight loss trial 2. Surgical trial (knee scope vs. TKA) Is the risk of surgery justifiable to answer this?

28.  Weight loss is difficult for physician and patient  Unfortunately, few studies have looked at MSK outcomes after weight loss:  Wt loss reduces risk of symptomatic OA  Bariatric surgery: decreases overall joint pain

29.  48 morbidly obese subjects → bariatric surg  Lost avg 90 lbs  MSK pain complaints: 100% preop 23% postop

30.  Few new risk factors for OA have been identified in the past few years  The only 2 modifiable risk factors with sufficient evidence to support intervention for preventing OA:  Weight loss  Avoiding traumatic injury

31.  Exercise increases production of myokines from muscles → induces lypolysis + inhibits TNF + decreases insulin resistance

32. Obesity is an epidemic in the US Osteoarthritis is not just “wear and tear” and adipose tissue is not just an energy storage organ The medical risk:benefit ratio for weight loss in obese patients approaches ZERO Orthopaedic surgery is not a cure for obesity, but weight loss has potential to cure orthopaedic conditions

33. References available: ryanckoonce@gmail.com Talk to him…please Jonathan T. Bravman, MD Jonathan.Bravman@UCDenver.edu