Page 675 - Small Animal Clinical Nutrition 5th Edition

Osteoarthritis 699

dral bone, joint capsule and supporting ligaments and tendons. to compensate for this imbalance by producing increased quan-
VetBooks.ir The normal joint provides low friction motion and transfer of tities of proteoglycans and collagen. This may lead to an initial
thickening of the articular cartilage; however, the quantity and
body weight across the articular surface during movement.
quality of the proteoglycans and collagen produced are abnor-
Articular cartilage is made up of chondrocytes and extracellular
matrix. Chondrocytes are terminally differentiated cells that are mal (Renberg, 2005). Eventually aggrecanases destroy proteo-
highly metabolically active throughout life (Roush et al, 2002). glycans faster than new ones can be formed. This imbalance
Normal cartilage is dynamic and is replaced over a one- to two- escalates the deterioration of the extracellular matrix and carti-
year period by the balance of the catabolic action of degradative lage’s normal physiologic properties.
enzymes on the extracellular matrix with the anabolic synthesis Without a healthy extracellular matrix, cartilage is unable to
of matrix components by chondrocytes. withstand the compressive forces of weight bearing. The net
The extracellular matrix is composed of collagen, proteogly- result is cartilage with decreased load bearing capacity and
cans and water (Figure 34-3). Chondrocytes produce and main- localized areas of softening (Vaughan-Scott and Taylor, 1997).
tain the extracellular matrix. Collagen fibrils (primarily collagen Fibrillations and microfractures are early histopathologic
type II) provide structural support for the cartilage matrix. changes. With progression of osteoarthritis, gross evidence of
Proteoglycans are composed of glycosaminoglycan (GAG) damage to articular cartilage becomes obvious. The normally
chains attached to a central core protein. Chondroitin sulfate, smooth glistening surface becomes dull and rough. Fissures
keratin sulfate and dermatan sulfate are the most common become evident and ultimately areas of cartilage erosion devel-
GAGs in articular cartilage. Aggrecan is the shortened name for op (Figure 34-4) (Renberg, 2005). Osteoarthritis affects not
the large aggregating chondroitin sulfate proteoglycan. Aggrecan only the articular cartilage, but also the underlying bone and
is the most common and well-defined proteoglycan in articular adjacent joint structures. Stiffening of the subchondral bone
cartilage and is comprised of a core protein to which as many as occurs concurrently with changes in the articular cartilage
100 GAG chains are attached (Lepine and Hayek, 2001). matrix. Osteoblasts in the trabecular portion of underlying
Because GAGs are anionic and hydrophilic,they attract and hold bone begin to form new bone and the subchondral region is
water in a gel-like consistency. Aggrecans, with their hydrophilic often thickened and sclerotic. Although changes in subchon-
GAGs,are normally contained within the framework of collagen dral bone may not be necessary for the development of
fibrils, which limit their expansion when hydrated. osteoarthritis, these changes may play an important role in the
In the normal joint, cartilage must withstand both compres- progression of the disease (Johnston, 1997).
sive and shearing forces. The unique relationship between col- Osteophytes are commonly associated with osteoarthritis.
lagen and proteoglycans provides the biomechanical properties Generally, they develop at the periphery of the joint and are
necessary to withstand these forces. Collagen fibrils alone can- thought to form as a result of joint instability. Although they
not resist compressive forces without collapse but tolerate ten- normally form over weeks to months, experimental models
sile forces well, whereas hydrated aggrecan complexes weakly have demonstrated formation as early as three days after cre-
resist shear forces but withstand compressive forces (Johnston, ation of instability (Johnston, 1997). However, osteophytes
2005). When the normal distribution of collagen, proteogly- have been documented to develop in the presence of inflamma-
cans and water is disturbed, the function of articular cartilage is tion without instability, suggesting that synovial membrane
altered, leading to changes typically associated with inflammation may play a role (Johnston, 1997). Osteoarthritis
osteoarthritis. and the accompanying inflammation also cause changes in the
Normal cartilage metabolism is a highly regulated balance joint capsule.These changes may include thickening of the syn-
between synthesis and degradation of the various matrix com- ovium and increased vascularity. Conversely, synoviocytes con-
ponents. Osteoarthritis can be initiated by a variety of physical tribute to the progression of osteoarthritis by producing
stresses that damage chondrocytes such as trauma, obesity or cytokines and leukotrienes, which attract inflammatory cells
developmental orthopedic diseases. Despite the variety of initi- and the release of prostaglandins and other inflammatory
ating events, there seems to be common pathways that lead to mediators. This inflammation of the synovium contributes to
the destruction of articular cartilage (Johnston, 1997). Once decreased elasticity and viscosity of synovial fluid. Synovitis can
initiated, these molecular and cellular pathways interact to form either precede or follow observable cartilage changes and is
a self-perpetuating cycle. likely secondary to exposure of neoantigens on the cartilage or
The instigating event of this cycle is thought to be loss of release of inflammatory mediators by damaged synovium or
proteoglycans (aggrecans) (Caterson et al, 2000; Hegemann et chondrocytes (Renberg, 2005).
al, 2002). Damage to chondrocytes causes up-regulation of
catabolic enzymes, particularly aggrecanases (enzymes that Key Nutritional Factors
cleave aggrecans at specific peptide bonds).This shift from ana- Besides supplying age-appropriate nutrition, foods designed for
bolic to catabolic pathways is responsible for the loss of proteo- companion animals with osteoarthritis need to provide specific
glycans. Damaged chondrocytes also produce inflammatory nutrients that may help reduce inflammation and pain, enhance
mediators. Inflammatory cytokines contribute to the perpetua- cartilage repair, slow the degradative process, complement pre-
tion and progression of arthritis by sustaining catabolic process- scribed medications and provide tangible improvement in clin-
es (Curtis et al, 2002). Initially, damaged chondrocytes attempt ical signs. Because foods for osteoarthritis are fed in place of