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Joint Bone Spine 75 (2008) 667e668

Research lectures

Obesity and osteoarthritis: what are the links?

Francis Berenbaum*, Jeremie Sellam
Universite Pierre & Marie Curie Paris 6, UMR CNRS 7079, APHP Hopital Saint-Antoine, Service de Rhumatologie, 184 rue du faubourg
Saint-Antoine, 75012 Paris, France
Accepted 26 July 2008
Available online 5 November 2008

Keywords: Obesity; Osteoarthritis

Important risk factors for osteoarthritis include mechanical,

genetic, and biochemical factors. Among them, obesity plays
a key role in the involvement of both weight-bearing and nonweight-bearing joints.
1. Epidemiology

1.3. Obesity and finger osteoarthritis

Obesity is associated not only with osteoarthritis of the
weight-bearing joints, but also with finger osteoarthritis [4].
This fact suggests that obesity may act via systemic pathogenic mechanisms of osteoarthritis.

1.1. Obesity and knee osteoarthritis

2. Pathophysiology

Numerous cross-sectional and longitudinal epidemiological

studies have shown that body mass index (BMI) correlates
significantly with the incident risk of radiological and symptomatic knee osteoarthritis [1]. Each BMI increase by 1 kg/m2
above 27 is associated with a 15% risk increase. The association between obesity and knee osteoarthritis is stronger in
women than in men and is also stronger for bilateral than for
unilateral disease. It exists for all three knee compartments.
Alignment disorders further increase the risk of knee osteoarthritis in obese patients. In addition, weight loss is associated
with decreased pain and improved function, most notably
when combined with physical exercise [2].

2.1. Obesity and mechanical stress

1.2. Obesity and hip osteoarthritis

Obesity is associated with a small increase in the risk of
radiological or symptomatic hip osteoarthritis, particularly in
a bilateral distribution. Obesity is a risk factor for hip
replacement surgery [3].
* Corresponding author.
E-mail address: francis.berenbaum@sat.ap-hop-paris.fr (F. Berenbaum).

The increased mechanical loads related to obesity appear as

a logical explanation to the increased risk of osteoarthritis in
weight-bearing joints, with destruction of the cartilage and
ligaments. Repeated overloading of a normal joint can induce
abnormalities in chondrocyte and osteoblast behavior, as well
as alterations in the extracellular matrix. In addition, obesity is
associated with an increase in bone mass, which can lead to
increased rigidity of the subchondral bone, thereby promoting
rupture of the cartilage matrix. The matrix alterations are
related, at least in part, to activation of mechanoreceptors at
the chondrocyte surface, which triggers a cascade of deleterious intracellular events [5]. These mechanoreceptors include
a5b1 integrins, stretch-activated channels, and CD44.
Recently, mechanoreceptors were identified on the surface of
cilia on chondrocytes. One of the effects of mechanoreceptor
stimulation is activation of the mitogen-activated protein
kinase (MAPK) and NF-kB pathways, which leads to
increased production of several mediators of cartilage degradation (IL-1, metalloproteinases, prostaglandin E2, nitric
oxide) and to inhibition of matrix synthesis [6]. Thus,
mechanical stress induces a degradation-prone phenotype of

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F. Berenbaum, J. Sellam / Joint Bone Spine 75 (2008) 667e668

chondrocytes, as do a number of proinflammatory cytokines

and prostaglandins.
Mechanoreceptors are also present at the surface of osteoblasts. Their activation by compressive loads leads to the
production of proinflammatory mediators (IL-6, IL-8, metalloproteinases, and prostaglandin E2). This effect may
contribute to explain the early involvement of the subchondral
bone in the pathogenesis of osteoarthritis, which has been
suggested to antedate the destruction of the cartilage matrix.

Atherosclerosis is a well-established cause of impaired

blood supply. Therefore, atherosclerosis may play a role in the
pathogenesis of osteoarthritis by affecting the blood supply to
the subchondral bone [10].
In conclusion, the links between obesity and osteoarthritis
are incompletely understood. Evidence that systemic factors
may be involved broadens the spectrum of the potential
contributions of obesity to the pathophysiology of osteoarthritis. The result is an increase in potential treatment targets.

2.2. Obesity and systemic mediators

That obesity is associated with finger osteoarthritis indicates that osteoarthritis is related not only to local mechanical
factors, but also to systemic inflammation. Symptom relief
produced by weight loss is more closely associated with the
decrease in fat mass than with the total weight loss, suggesting
a systemic role for factors contained in fat tissue [7]. Fat tissue
secretes adipocytokines or adipokines. These cytokines were
first described as factors that are produced by adipocytes and
that affect sensitivity to insulin, carbohydrate metabolism, and
lipid metabolism. The best characterized adipokines are leptin,
resistin, adiponectin, and visfatin [8]. A chapter of this issue of
Joint Bone Spine is devoted to adipokines.
2.3. Indirect effects of obesity on osteoarthritis
Obesity is responsible for a number of diseases including
hypertension, atherosclerosis, and diabetes. Although there is
no convincing evidence to data that these conditions are
associated with osteoarthritis, several hypotheses deserve
consideration. Diabetes, for instance, is associated with
extracellular matrix alterations related to the build-up of
advanced glycation end-products (AGEs). AGEs increase
extracellular matrix stiffness, thereby making the matrix more
vulnerable to environmental insults. In addition, AGEs activate cells that carry receptors for AGEs (RAGE). Articular
chondrocytes express RAGE [9]. Stimulation of chondrocytes
by AGE may weaken the cartilage and induce the chondrocytes to produce mediators of inflammation and
degradation.

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