Download View Presentation Slides - Osteoarthritis Action Alliance

Jonathan T. Bravman, MD
CU Sports Medicine
Division of Sports Medicine and Shoulder Surgery
University of Colorado Department of Orthopedics
Denver, Colorado
Journal of the American Academy of Orthopaedic Surgery, March 2013
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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
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Osteoarthritis is strongly correlated with
high BMI
Biomechanical
Systemic
Theories
Theories
OA
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The intuitive theories
Most studies involve the knee
Surprising lack of data to support them
(presented evidence here is weak)
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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)
=
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Obesity increases subchondral bone density
and stiffness
Load is redistributed on cartilage causing
increased wear
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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 loading
Increased WEAR
 Increased variability in loading
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
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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”
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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

Important members:
 Leptin
 Resistin
 Adiponectin
 Visfatin
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Active in cartilage regulation
Exact role of each is unclear but many studies
are currently underway
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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
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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!!
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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
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Adipocyte-derived hormone with known antidiabetic 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
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Hand xrays compared at baseline and 6 years
Serum adipokines measured at baseline
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Increased levels of adipokines
Elevated inflammatory markers in obese:
 CRP, ESR, IL-6, and TNF
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Inflammation plays a role in OA, cardiovascular
disease, DM, dyslipidemia, respiratory disorders,
autoimmune disorders, and cancer
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Development of OA is both mechanical and metabolic
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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
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Is OA an inflammatory arthropathy?
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Leptin and adiponectin are key mediators in
inducing cartilage breakdown
Work with MMPs, nitric oxide, and
interleukins
Therapeutic targets for OA treatment??
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“a cluster of conditions…that occur together
increasing your risk of heart disease, stroke, and
diabetes”
1.
2.
3.
4.
excess body fat around the waist
increased blood pressure
elevated insulin levels
abnormal cholesterol levels
Being overweight and inactive are “major
contributors”
 Treatment: exercise, weight loss, eat healthy, and
stop smoking
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Predominant theory behind OA now is that it
occurs from local mechanical factors acting in
the context of systemic susceptibility
Black box
Obesity and overweight are associated with
increased musculoskeletal pain
 The impact of pain on functional status and healthrelated 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)
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There is a strong relationship:
55%
obesity
depression
58%
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Is the patient’s knee pain caused by obesity or
osteoarthritis or both?
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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?
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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
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48 morbidly obese subjects → bariatric surg
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Lost avg 90 lbs
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MSK pain complaints:
100% preop
23% postop
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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
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Exercise increases production of myokines
from muscles → induces lypolysis + inhibits
TNF + decreases insulin resistance
• 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
References available:
[email protected]
Jonathan T. Bravman, MD
[email protected]
Talk to
him…please