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Contents
Pathogenesis of osteoarthritis
Topic Outline
SUMMARY
INTRODUCTION
ROLE OF INFLAMMATION
OVERVIEW OF PATHOLOGY
MULTIPLE PATHWAYS TO OSTEOARTHRITIS
o Risk factors
o Aging
o Inflammatory mediators
o Proteases
o Other pathways
CLINICAL IMPLICATIONS
SOCIETY GUIDELINE LINKS
SUMMARY
ACKNOWLEDGMENT
REFERENCES
GRAPHICS
FIGURES
o - Pathogenesis of osteoarthritis
RELATED TOPICS
Clinical manifestations and diagnosis of osteoarthritis
Investigational approaches to the management of osteoarthritis
Management of hand osteoarthritis
Management of knee osteoarthritis
Overview of surgical therapy of knee and hip osteoarthritis
Overview of the management of osteoarthritis
Society guideline links: Osteoarthritis
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Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Feb 2018. | This topic last updated: Feb 02,
2018.
This topic will review the pathogenesis of OA. The diagnosis, treatment, and other
issues related to OA are discussed separately. (See "Overview of surgical therapy
of knee and hip osteoarthritis" and "Investigational approaches to the management
of osteoarthritis" and "Clinical manifestations and diagnosis of osteoarthritis" and
"Management of knee osteoarthritis" and "Overview of the management of
osteoarthritis" and "Management of hand osteoarthritis".)
The order in which particular joint tissues are affected may depend on the initiating
factors. With the exception of posttraumatic OA that starts with an acute injury to a
key joint tissue component, such as a ligament tear, it is often difficult to know
exactly which joint tissues are affected first. Plain radiographs underestimate the
joint tissue involvement in OA since they only visualize a component of the
condition including cartilage loss that results in joint space narrowing and bony
changes that result in subchondral sclerosis, cysts, and osteophyte formation.
Once these changes are apparent on radiographs, the condition has significantly
advanced. Magnetic resonance imaging (MRI) studies can detect early disease and
have provided evidence of matrix changes in cartilage, synovitis, bone marrow
lesions, and degenerative changes in soft-tissue structures beyond the cartilage
including ligaments and the knee menisci [4,5]. As OA progresses, it eventually
affects the entire joint, resulting in failure of the component parts. However, OA
does not progress to at a similar rate in all individuals and not everyone with early
disease will develop more severe OA. Predicting which patients will advance to the
end stages of the disease remains a challenge.
Risk factors — Multiple risk factors have been linked to the pathogenesis of OA.
Risk factors for OA include age, joint injury, obesity, genetics, anatomical factors
including joint shape and alignment, and gender [15].
Aging — OA is clearly related to aging, with both the incidence and prevalence of
OA increasing with age [31]. However, it is also clear that aging of joint tissues and
the development of OA are distinct processes. Rather than being one and the
same, aging changes most likely make the joint more susceptible to the
development of OA and promote progression. The aging changes within the joint
that contribute to OA can be divided into aging of the extracellular matrix and
cellular aging. Matrix changes include thinning of the articular cartilage with age,
reduced hydration, and an accumulation of proteins containing advanced glycation
end-products (AGEs) [32]. AGEs cause increased crosslinking of collagen,
resulting in altered biomechanical properties characterized by increased
"brittleness" [33]. AGEs are best known for their role in diabetes, where their
production is facilitated by chronic elevations in glucose (eg, hemoglobin A1c,
which is glycosylated hemoglobin). In cartilage, AGEs can form and accumulate
independent of blood glucose levels. The most likely explanation is the very long
half-life of matrix proteins in cartilage, particularly type II collagen, which has a half-
life calculated at over 100 years [34]. The low turnover rate in cartilage [7] allows
for a very slow accumulation of AGEs that are not removed as they would be in
tissues that have a higher turnover of their matrix such as bone.
There are a host of cellular changes that can link aging and OA. These include
mitochondrial dysfunction related to oxidative stress and mitochondrial DNA
damage, reduced responsiveness to anabolic growth factor stimulation including
insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-beta, cell
senescence that results in the senescence-associated secretory phenotype, and a
reduction in the process called autophagy which is a protective mechanism
responsible for the degradation and removal of damaged cellular constituents [32].
These cellular changes contribute to an imbalance between anabolic activity
mediated by growth factors that is necessary to produce and repair damaged
matrix and catabolic activity mediated by proinflammatory mediators and proteases
that promote joint tissue destruction. (See 'Inflammatory mediators' below and
'Proteases' below.)
SUMMARY
REFERENCES