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Why is osteoarthritis an age-related disease?

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Although older age is the greatest risk factor for osteoarthritis (OA), OA is not an inevitable consequence of growing old. Radiographic changes of OA, particularly osteophytes, are common in the aged population, but symptoms of joint pain may be independent of radiographic severity in many older adults. Ageing changes in the musculoskeletal system increase the propensity to OA but the joints affected and the severity of disease are most closely related to other OA risk factors such as joint injury, obesity, genetics and anatomical factors that affect joint mechanics. The ageing changes in joint tissues that contribute to the development of OA include cell senescence that results in development of the senescent secretory phenotype and ageing changes in the matrix including formation of advanced glycation end-products that affect the mechanical properties of joint tissues. An improved mechanistic understanding of joint ageing will likely reveal new therapeutic targets to slow or halt disease progression. The ability to slow progression of OA in older adults will have enormous public health implications given the ageing of our population and the increase in other OA risk factors such as obesity.

Section snippets

Epidemiology of OA relevant to ageing

OA is the most common joint disorder in the world and one of the most common sources of pain and disability in the elderly [1], [2]. While there remains considerable heterogeneity in defining OA among epidemiological studies, the evidence is conclusive that age remains the single greatest risk factor for the development of OA in susceptible joints. Radiographic changes, in particular, osteophytosis, are very common in the ageing population and, when used alone, may provide an overestimation of

Knee

The knee is commonly affected by OA and is thought to account for most of disability from OA. The Framingham Osteoarthritis Study evaluated the prevalence of knee osteoarthritis in 1420 subjects aged 60 and older [11]. OA was defined as the presence of knee symptoms in a patient with ipsilateral (KL) grade 2 or greater radiographic changes. The prevalence of radiographic OA increased with each decade of life from 33% among those aged 60–70 to 43.7% among those over 80 years of age (Fig. 2). The

Risk factors for development of OA in the elderly

The common risk factors for OA such as obesity, joint injury, genetics and anatomical abnormalities are important in the elderly just as they are in younger adult populations. There is some evidence to suggest that after an acute joint injury, such as an anterior cruciate ligament tear, that older adults will develop OA faster than younger adults [25]. Some factors contributing to the development of OA, including degenerative changes in the meniscus and joint ligaments, increased bone turnover

Cell and tissue ageing and the development of OA

Most of the conditions associated with ageing, OA included, result from an age-related loss in the ability of cells and tissues in the body to maintain homeostasis, particularly when placed under stress [44]. In OA, excessive or abnormal mechanical stresses clearly play a key role in the development of the disease [45]. Under conditions where an anatomically normal joint is stressed, the joint tissues appear to be capable of adapting to stress without resulting in OA. As an example of

Chondrocyte senescence

Chondrocytes are very unique cells that may be particularly prone to the development of ageing-related changes. The chondrocytes present in the cartilage of an 80-year-old are likely to be the very same cells that were present at age 25 years. There is little to no cell division or cell death in normal adult articular cartilage [53], and there does not appear to be a ready supply of progenitor cells to replace chondrocytes if they do die. Although recent studies have challenged the notion that

The ageing cartilage matrix

In addition to age-related changes in chondrocytes, age-related changes that occur in the cartilage matrix have been described that could also contribute to the development of OA. MRI studies have shown that knee cartilage thins with ageing, particularly at the femoral side of the joint [82] and at the patella [83], suggesting a gradual loss of cartilage matrix with ageing. One of the best studied ageing-related matrix protein modification in cartilage is the formation of advanced glycation

Ageing, oxidative stress and OA

Oxidative damage from the chronic production of endogenous ROS or free radicals has been associated with ageing in various human tissues and in animal models [97] and has long been thought to play a central role in the ageing process [98]. Increased production of ROS leads to oxidative stress, a condition within cells where the amount of ROS exceeds the anti-oxidant capacity of the cell. Human articular chondrocytes can actively produce ROS including superoxide, hydroxyl radical, hydrogen

Acknowledgements

Dr. Loeser's work was supported by the National Institute on Aging (RO1 AG16697 and the Wake Forest University Claude D. Pepper Older Americans Independence Center P30 AG021332), the National Institute on Arthritis, Musculoskeletal and Skin Diseases (RO1 AR49003), the American Federation for Aging Research and the Dorothy Rhyne Kimbrell and Willard Duke Kimbrell Professorship.

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