Available online at

www.sciencedirect.com

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 faubourgSaint-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 playsa key role in the involvement of both weight-bearing and non-weight-bearing joints.

1. Epidemiology

1.1. Obesity and knee osteoarthritis

Numerous cross-sectional and longitudinal epidemiologicalstudies have shown that body mass index (BMI) correlatessignificantly with the incident risk of radiological and symp-tomatic knee osteoarthritis [1]. Each BMI increase by 1 kg/m2

above 27 is associated with a 15% risk increase. The associ-ation between obesity and knee osteoarthritis is stronger inwomen than in men and is also stronger for bilateral than forunilateral disease. It exists for all three knee compartments.Alignment disorders further increase the risk of knee osteo-arthritis in obese patients. In addition, weight loss is associatedwith decreased pain and improved function, most notablywhen combined with physical exercise [2].

1.2. Obesity and hip osteoarthritis

Obesity is associated with a small increase in the risk ofradiological or symptomatic hip osteoarthritis, particularly ina bilateral distribution. Obesity is a risk factor for hipreplacement surgery [3].

* Corresponding author.

E-mail address: francis.berenbaum@sat.ap-hop-paris.fr (F. Berenbaum).

1297-319X/$ - see front matter � 2008 Elsevier Masson SAS. All rights reserved

doi:10.1016/j.jbspin.2008.07.006

1.3. Obesity and finger osteoarthritis

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

2. Pathophysiology

2.1. Obesity and mechanical stress

The increased mechanical loads related to obesity appear asa logical explanation to the increased risk of osteoarthritis inweight-bearing joints, with destruction of the cartilage andligaments. Repeated overloading of a normal joint can induceabnormalities in chondrocyte and osteoblast behavior, as wellas alterations in the extracellular matrix. In addition, obesity isassociated with an increase in bone mass, which can lead toincreased rigidity of the subchondral bone, thereby promotingrupture of the cartilage matrix. The matrix alterations arerelated, at least in part, to activation of mechanoreceptors atthe chondrocyte surface, which triggers a cascade of delete-rious intracellular events [5]. These mechanoreceptors includea5b1 integrins, stretch-activated channels, and CD44.Recently, mechanoreceptors were identified on the surface ofcilia on chondrocytes. One of the effects of mechanoreceptorstimulation is activation of the mitogen-activated proteinkinase (MAPK) and NF-kB pathways, which leads toincreased production of several mediators of cartilage degra-dation (IL-1, metalloproteinases, prostaglandin E2, nitricoxide) and to inhibition of matrix synthesis [6]. Thus,mechanical stress induces a degradation-prone phenotype of

.

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

chondrocytes, as do a number of proinflammatory cytokinesand prostaglandins.

Mechanoreceptors are also present at the surface of osteo-blasts. Their activation by compressive loads leads to theproduction of proinflammatory mediators (IL-6, IL-8, metal-loproteinases, and prostaglandin E2). This effect maycontribute to explain the early involvement of the subchondralbone in the pathogenesis of osteoarthritis, which has beensuggested to antedate the destruction of the cartilage matrix.

2.2. Obesity and systemic mediators

That obesity is associated with finger osteoarthritis indi-cates that osteoarthritis is related not only to local mechanicalfactors, but also to systemic inflammation. Symptom reliefproduced by weight loss is more closely associated with thedecrease in fat mass than with the total weight loss, suggestinga systemic role for factors contained in fat tissue [7]. Fat tissuesecretes adipocytokines or adipokines. These cytokines werefirst described as factors that are produced by adipocytes andthat affect sensitivity to insulin, carbohydrate metabolism, andlipid metabolism. The best characterized adipokines are leptin,resistin, adiponectin, and visfatin [8]. A chapter of this issue ofJoint Bone Spine is devoted to adipokines.

2.3. Indirect effects of obesity on osteoarthritis

Obesity is responsible for a number of diseases includinghypertension, atherosclerosis, and diabetes. Although there isno convincing evidence to data that these conditions areassociated with osteoarthritis, several hypotheses deserveconsideration. Diabetes, for instance, is associated withextracellular matrix alterations related to the build-up ofadvanced glycation end-products (AGEs). AGEs increaseextracellular matrix stiffness, thereby making the matrix morevulnerable to environmental insults. In addition, AGEs acti-vate cells that carry receptors for AGEs (RAGE). Articularchondrocytes express RAGE [9]. Stimulation of chondrocytesby AGE may weaken the cartilage and induce the chon-drocytes to produce mediators of inflammation anddegradation.

Atherosclerosis is a well-established cause of impairedblood supply. Therefore, atherosclerosis may play a role in thepathogenesis of osteoarthritis by affecting the blood supply tothe subchondral bone [10].

In conclusion, the links between obesity and osteoarthritisare incompletely understood. Evidence that systemic factorsmay be involved broadens the spectrum of the potentialcontributions of obesity to the pathophysiology of osteoar-thritis. The result is an increase in potential treatment targets.

References

[1] Anderson JJ, Felson DT. Factors associated with osteoarthritis of the

knee in the first national Health and Nutrition Examination Survey

(HANES I). Evidence for an association with overweight, race, and

physical demands of work. Am J Epidemiol 1988;128:179e89.

[2] Messier SP, Gutekunst DJ, Davis C, et al. Weight loss reduces knee-joint

loads in overweight and obese older adults with knee osteoarthritis.

Arthritis Rheum 2005;52:2026e32.

[3] Karlson EW, Mandl LA, Aweh GN, et al. Total hip replacement due to

osteoarthritis: the importance of age, obesity, and other modifiable risk

factors. Am J Med 2003;114:93e8.

[4] Cicuttini FM, Baker JR, Spector TD. The association of obesity with

osteoarthritis of the hand and knee in women: a twin study. J Rheumatol

1996;23:1221e6.

[5] McGlashan SR, Cluett EC, Jensen CG, et al. Primary cilia in osteoar-

thritic chondrocytes: from chondrons to clusters. Dev Dyn 2008;237:

2013e20.

[6] Gosset M, Berenbaum F, Levy A, et al. Prostaglandin E2 synthesis in

cartilage explants under compression: mPGES-1 is a mechanosensitive

gene. Arthritis Res Ther 2006;8:R135.

[7] Toda Y, Toda T, Takemura S, et al. Change in body fat, but not body

weight or metabolic correlates of obesity, is related to symptomatic relief

of obese patients with knee osteoarthritis after a weight control program.

J Rheumatol 1998;25:2181e6.

[8] Gosset M, Berenbaum F, Salvat C, et al. Crucial role of visfatin/pre-B

cell colony-enhancing factor in matrix degradation and prostaglandin

E(2) synthesis in chondrocytes: possible influence on osteoarthritis.

Arthritis Rheum 2008;58:1399e409.

[9] Loeser RF, Yammani RR, Carlson CS, et al. Articular chondrocytes

express the receptor for advanced glycation end products: potential role

in osteoarthritis. Arthritis Rheum 2005;52:2376e85.

[10] Conaghan PG, Vanharanta H, Dieppe PA. Is progressive osteoarthritis an

atheromatous vascular disease? Ann Rheum Dis 2005;64:1539e41.