Identification of important interactions between subchondral bone ...

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