Osteoarthritis (OA) is a disabling degenerative joint disease that affects more adults globally than any other rheumatic disease, leading to joint pain, stiffness and loss of function predominantly in the knees, hips, hands, spine and other weight-bearing joints. An estimated 27 million adults in the US have OA, which is associated with considerable healthcare costs. OA is incurable and at present most treatments, which include physiotherapy, life-style modifications, pharmacotherapy and surgery, aim to provide symptomatic relief rather than targeting the disease processes themselves.
As our understanding of the pathogenesis of this disease, at the molecular and cellular level, increases it is hoped that disease-modifying rather than just symptom-modifying therapies will become a reality for this devastating condition. This Focus issue on OA comprises a series of Reviews from leading researchers in the field looking at disease pathogenesis in terms of cytokines, subchondral bone, cartilage matrix, and muscle strength and proprioception, with the hope of clarifying what the key processes are; in addition, Reviews focusing on the prospects for disease-modifying therapies for OA, and on the genetic epidemiology of this disease are included.
An NPG library of relevant Reviews, Perspectives, News and Views, Research Highlights and Original Research papers is also provided.
REVIEWS
Pharmacologic therapy for osteoarthritis—the era of disease modification
David J. Hunter
doi:10.1038/nrrheum.2010.178
Nature Reviews Rheumatology 7, 13-22 (2011)
Current therapeutic strategies for osteoarthritis (OA) are mostly palliative; modifying the structural progression of OA has, therefore, become a focus of drug development. This Review discusses the challenges involved in the discovery and development of disease-modifying OA drugs, and describes specific agents that have shown promise in phase II and III trials.
Genetic epidemiology of hip and knee osteoarthritis
Ana M. Valdes & Tim D. Spector
doi:10.1038/nrrheum.2010.191
Nature Reviews Rheumatology 7, 23-32 (2011)
Severe OA is the main cause of an increasing need for joint replacements and is, therefore, a large burden on both patients and the health-care sector. This Review discusses the genetic contribution to hip and knee OA and the authors suggest that identifying individuals at a high risk of OA with a combination of genetic markers might aid preventive and disease-management strategies.
Role of proinflammatory cytokines in the pathophysiology of osteoarthritis
Mohit Kapoor, Johanne Martel-Pelletier, Daniel Lajeunesse, Jean-Pierre Pelletier & Hassan Fahmi
doi:10.1038/nrrheum.2010.196
Nature Reviews Rheumatology 7, 33-42 (2011)
Proinflammatory cytokines are known to be critically implicated in the etiology and pathogenesis of OA. In this Review, the authors discuss the current knowledge regarding the role of proinflammatory cytokines, particularly interleukin (IL) 1β, tumor necrosis factor and IL 6 in the pathophysiology of OA, and give an overview of efforts to develop adequate and specific anticytokine therapies.
The bone–cartilage unit in osteoarthritis
Rik J. Lories & Frank P. Luyten
doi:10.1038/nrrheum.2010.197
Nature Reviews Rheumatology 7, 43-49 (2011)
OA is a disease of the whole joint, at the centre of which lies the interface between cartilage and bone. Altered transfer of mechanical stress across this boundary is thought to result from, and to exacerbate, OA. Until recently molecular crosstalk was presumed to be minimal but, as explored in this Review, accumulating data challenge this assumption.
The role of the cartilage matrix in osteoarthritis
Dick Heinegård & Tore Saxne
doi:10.1038/nrrheum.2010.198
Nature Reviews Rheumatology 7, 50-56 (2011)
The factors that trigger OA have been difficult to identify, as the earliest molecular changes substantially precede clinical presentation of symptoms. Nevertheless, we are beginning to piece together the processes that occur in articular cartilage, both before and after substantial loss of the tissue occurs, and new tools promise to expedite completion of the puzzle.
Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis
Ewa M. Roos, Walter Herzog, Joel A. Block & Kim L. Bennell
doi:10.1038/nrrheum.2010.195
Nature Reviews Rheumatology 7, 57-63 (2011)
Research into the effects of lower-extremity muscle weakness on OA onset and progression has increased over the past decade, owing to its potential for modification using exercise training interventions. Similarly, afferent sensory dysfunction has been suggested as an important yet modifiable risk factor for OA progression. In this Review, the authors provide an overview of these risk factors, and discuss the effectiveness of preventive or therapeutic neuromuscular and exercise training interventions.
PERSPECTIVES
Obesity punches above its weight in osteoarthritis
Richard M. Aspden
doi:10.1038/nrrheum.2010.123
Nature Reviews Rheumatology 7, 65-68 (2011)
The mechanical effect of excess weight is commonly thought to be the direct cause of OA. In this Perspectives article, the author questions whether the evidence actually supports this prevalent view, and instead proposes that the increase in adipose tissue associated with obesity might drive the development of widespread OA.
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