Hypothesis 2 :  Osteoarthritis

The signs we are seeing in Bonnie could be caused by osteoarthritis.  This disease 
causes degenerative joint changes.  The disease is characterized by several clinical signs 
including variable degrees of inflammation within the joint, which can lead to joint 
effusion causing swelling, crepitation, and pain on palpation.  BonnieÕs clinical signs are 
consistent with these findings.  A dogÕs normal joint is made up of hyaline cartilage which 
is composed of collagen and proteoglycans. These substrates which are made by 
chondrocytes and give the cartilage compressive stiffness and tensile strength .  
Chondrocytes have anabolic and catabolic functions.  Their anabolic functions are to 
produce the components that make up the hyaline cartilage.  Their catabolic functions are 
to produce degradative enzymes called metalloproteinases which break down the collagen 
and proteoglycans.  The purpose of the anabolic and catabolic functions is to keep the 
periarticular environment in an appropriate balance under the events of stress. Normally 
the balance between cartilage production and degradation happens slowly. It is a very 
delicate process which can be interrupted.  In osteoarthritis the catabolic functions 
eventually overcome the anabolic functions and the cartilage begins to break down faster 
than it can be replaced.  This leads to the degeneration of the joint. This balance can be 
disrupted by primary or secondary causes. 
 Osteoarthritis is almost always secondary to another event, which is usually 
trauma.  The trauma can either be from abnormal forces working on normal cartilage or 
normal forces working on abnormal cartilage.  In BonnieÕs case we can assume that the 
cause would be the former of the two due to her weight problem,  her history of sporadic 
exercise patterns, and her physical exam findings.  Both fractures and rupture of the 
cranial cruciate ligament are examples of abnormal forces acting on normal cartilage.  The 
degenerative changes within the joint are damaging due to the alteration of the properties 
of cartilage.  As mentioned cartilage is made of collagen and proteoglycans.  Proteoglycans 
are proteins which are attached to hyaluronan to form aggrecans.  Many aggrecans can 
combine to form what is known as an aggregan aggregate.  Proteoglycans are very 
hydophilic and can retain large amounts of water.  The matrix of the aggregates can 
contain this water which provides swelling pressure and turgidity.  Collagen is also a part 
of the cartilage configuration.  Collagen sets a boundary for the proteoglycan matrix.  
Without cartilage the proteoglycans would continue to soak up water and create unlimited 
amounts of swelling.  Collagen prevents this and limits the swelling by providing tensile 
strength to the tissue.  
In osteoarthritis there is breakdown of the collagen matrix which allows for the 
continual swelling within the joint which can be seen grossly. Cartilage normally serves to 
distribute the forces applied to the joint across the bone surface to lessen the shock to the 
area.  With osteoarthritis the cartilage loses its flexibility and its shear and compressive 
properties become altered.  These changes also cause increased water retention which is 
another cause for the swelling we are observing in BonnieÕs stifle joint.  The changes in 
the cartilage causes increased stiffness in the subchondral bone.  The subchondral bone 
normally acts as a cushion to lessen the force of weight applied to the joint.  This 
stiffening of the bone decreases its ability to absorb the force and causes more 
degeneration within the joint. Ultimately, the result of osteoarthritis is inflammation 
within the joint. The swelling, and eventually inflammation, is also due to the release of 
cytokines from the overactive chondrocytes.  It is important, however that we do not 
think of this disease as an inflammatory disease. As osteoarthritis continues the 
subchondral bone undergoes more stress and responds to this stress by thickening. This 
thickening leads to the sclerosis of tissue which eventually leads to remodeling of the 
bone.  These changes are self perpetuating due to the continual degeneration of the 
cartilage.  This causes more damage to occur on the remaining cartilage leading to increased 
thickening.  The changes eventually become irreversible and the animal must adapt to a 
decreased ability to use the affected joint.  
The joint capsule plays a role in osteoarthritis in addition to the cartilage.  The 
synoviocytes release inflammatory mediators (i.e. cytokines) in response to the 
breakdown of the cartilage matrix.  This inflammatory reaction causes thickening of the 
synovial lining layer and results in an increase in permeability of the vessels in this area.  
This allows more fluid to leak into the space adding to the increased swelling and 
decreased range of motion.  In addition to the gross changes within the joint a common 
sequelae to the disease is pain.  Pain can be the predominant sign with this disease.  It is 
caused by the loss of lubrication within the joint.  Nociceptors are abundant within the 
joint capsule. Sensitivity to these nociceptors is increased due to the presence of 
inflammatory mediators such as prostaglandins. The pain tends to be dull and aching and 
can be induced with mechanical stimulation.  Bonnie is showing pain upon palpation 
within her stifle joint.