Age-related changes in the musculoskeletal system and the development of osteoarthritis

Abstract

Osteoarthritis (OA) is the most common cause of chronic disability in older adults. Although classically considered a "wear and tear" degenerative condition of articular joints, recent studies have demonstrated an inflammatory component to OA that includes increased activity of several cytokines and chemokines in joint tissues that drive production of matrix-degrading enzymes. Rather than directly causing OA, aging changes in the musculoskeletal system contribute to the development of OA by making the joint more susceptible to the effects of other OA risk factors that include abnormal biomechanics, joint injury, genetics, and obesity. Age-related sarcopenia and increased bone turnover may also contribute to the development of OA. Understanding the basic mechanisms by which aging affects joint tissues should provide new targets for slowing or preventing the development of OA.

Figure 1. Pathology of osteoarthritis

The osteoarthritic joint is characterized by degradation and loss of the articular cartilage, thickening of the subchondral bone accompanied by formation of bone marrow lesions and cysts, osteophytes at the joint margins, variable degrees of synovitis with synovial hypertrophy, meniscal degeneration (knee), and thickening of the joint capsule.

Figure 2. Catabolic and anabolic factors that regulate chondrocyte function

A host of factors, produced locally by articular chondrocytes, regulate matrix synthesis and degradation in articular cartilage. As osteoarthritis develops, catabolic activators overwhelm anabolic factors resulting in an imbalance in matrix synthesis and degradation. Matrix degradation is mediated by MMPs, aggrecanase, and other proteases produced by the chondrocyte in response to the catabolic factors. A change in the chondrocyte phenotype to a hypertrophic phenotype also occurs, likely in response to one or more of the catabolic factors.

Figure 3. Relationship between osteoarthritis risk factors and aging changes that interact to promote the development of osteoarthritis

Osteoarthritis (OA) is a multifactorial condition that is not simply the direct result of aging. Rather aging changes increase the susceptibility to the development of OA when OA risk factors are also present. The OA factors are both local and systemic. Obesity can have local effects due to increased joint loading and systemic effects due to the production of adipokines and cytokines by adipose tissue that may contribute to the development of OA. The various aging and OA factors interact to influence the site and severity of the disease.