Identification of important interactions between subchondral bone ...
Identification of important interactions between subchondral bone ...
Identification of important interactions between subchondral bone ...
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CHAPTER 2<br />
Introduction<br />
CHAPTER 2: Introduction<br />
This Introduction aims to introduce the knowledge that forms the basis for my thesis work. The<br />
scope <strong>of</strong> the introduction is: i) to provide an overview <strong>of</strong> the development and biology <strong>of</strong> the<br />
joint, ii) the degeneration <strong>of</strong> the joint, with emphasis on osteoarthritis (OA), iii) and to introduce<br />
the current knowledge on the mode <strong>of</strong> action <strong>of</strong> glucocorticoids.<br />
2.1 Epidemiology and etiology <strong>of</strong> osteoarthritis<br />
There are more than 100 different types <strong>of</strong> arthritis 1 . The most common type is OA, also known<br />
as degenerative joint disease or degenerative arthritis. It is a condition that affects more than 46<br />
million people in the USA, and it is expected to affect 67 million people by the year 2030 1 .<br />
According to Gigtforeningen (The Danish Arthritis Society), more than 210.000 people in Denmark<br />
are diagnosed with OA, but experts estimate that the actual number is much higher. Although the<br />
disease occurs in people <strong>of</strong> all ages, it is most common in the older population; 50% <strong>of</strong> people<br />
over the age <strong>of</strong> 40 years and 100% <strong>of</strong> people over the age <strong>of</strong> 60 years have OA in one or more<br />
joints 2 . Epidemiologic studies further suggest that there are clear sex-specific differences 3 . Before<br />
50 years <strong>of</strong> age, the prevalence <strong>of</strong> OA in most joints is higher in men than in women. After the<br />
age <strong>of</strong> 50 years, women are more <strong>of</strong>ten affected with hand-, foot-, and knee OA than men 4 .<br />
The etiology <strong>of</strong> OA is unknown. The general perception <strong>of</strong> OA is that it is a<br />
cartilage disease. However, OA is not only affecting the articular cartilage, but the entire joint,<br />
including the <strong>subchondral</strong> <strong>bone</strong>, ligaments, joint capsule, synovial membrane and periarticular<br />
muscles. However, loss <strong>of</strong> cartilage is the obvious central hallmark <strong>of</strong> OA 5 . An increasing line <strong>of</strong><br />
evidence suggests that both <strong>bone</strong> and cartilage contribute to the onset <strong>of</strong> the disease. One <strong>of</strong> the<br />
first indications came from clinical observations suggesting that osteopenic women generally do<br />
not develop severe OA 6 . Likewise, subjects with OA <strong>of</strong> the hip have greater <strong>bone</strong> mass than<br />
normal subjects or subjects with osteoporosis 7 , suggesting that OA could initially be a disease <strong>of</strong><br />
the <strong>bone</strong> 8 . To date, the majority <strong>of</strong> clinical studies support the idea that OA is associated with<br />
increased <strong>bone</strong> density, but the subject remains controversial 9 .<br />
OA commonly affects hands, feet, spine, and large weight-bearing joints, such as<br />
the hip and knees. In most cases, the mechanisms underlying the development <strong>of</strong> OA are<br />
unknown. These cases are classified as primary OA and are mostly related to aging or heredity.<br />
When the cause <strong>of</strong> OA is known, as after an injury, trauma, anatomic abnormalities or obesity,<br />
the condition is referred to as secondary OA 5,10,11 . OA is characterized by gradual loss <strong>of</strong> articular<br />
cartilage, alterations <strong>of</strong> the <strong>subchondral</strong> <strong>bone</strong>, and development <strong>of</strong> osteophytes. These alterations<br />
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