Canine Osteoarthritis and Cartilage Repair
James L. Cook, DVM, PhD
Diplomate ACVS & ACVSMR
Comparative Orthopaedic Laboratory, University of Missouri, Columbia, MO, USA
Osteoarthritis (OA) is a painful and debilitating problem affecting millions of dogs in the
United States. Understanding how and why OA occurs in small animals is critical for
optimal diagnosis and treatment of patients and comprehensive communication with
owners. OA, arthritis, degenerative joint disease, and osteoarthrosis are often used
interchangeably to describe the progressive degeneration of diarthrodial joints. Although
loss of functional articular cartilage is considered the hallmark of this disease process,
all of the tissues in and around the joint are involved in the clinical signs and pathology
and therefore must be considered in a comprehensive management strategy.
The two broad classes of OA are primary (idiopathic) and secondary. Primary OA is
often referred to as “wear-and-tear” joint disease. It has an insidious onset, and is
thought to be caused by chronic use combined with aging and senility. In addition, it
may involve a genetic predisposition to cartilage degradation. This class of OA is not as
commonly recognized in veterinary medicine, in contrast to human medicine.
Secondary OA, identified most commonly in small animal patients, results from an
initiating cause, such as soft-tissue laxity, joint instability, joint immobilization, trauma,
osteochondritis dissecans, dysplasias, or joint incongruity. Although secondary OA still
constitutes an incurable disorder, the inciting problem can be addressed in some cases,
which may help to retard the progression of the OA and provide improved function and
quality of life for the patient.
An extremely important concept to understand is that the joint is an organ. This means
that all diarthrodial joints are functional units composed of multiple tissue types. All
components of joint composition and function are vital for maintaining joint health, and
conversely, each must be addressed when trying to optimally manage joint diseases
such as OA.
Articular cartilage is a very specialized structure whose integrity is essential to normal
joint function. It is an aneural (not a direct source of pain) and avascular (receives
nutrition from synovial fluid) tissue. The basic components of articular cartilage are cells
(chondrocytes) and extracellular matrix. The chondrocytes produce and maintain the
matrix, which is in a continual and dynamic state of synthesis and degradation. The
matrix is primarily composed of water, collagen (primarily type II collagen), and
proteoglycans (primarily aggrecan, composed of specific glycosaminoglycans [GAGs]).
Any damage to (biomechanical insult) or imbalance in (biological insult) the process of
matrix integrity, synthesis, and/or degradation can result in severe abnormalities
affecting the entire joint
The joint capsule is composed of two basic components: (1) the outer fibrous layer
(primarily collagen), which is responsible for the biomechanical function of the capsule
and contains the nerve fibers responsible for pain perception and proprioception, and
(2) the inner synovial membrane layer composed of synoviocytes and vascular areolar
tissue. This inner layer is responsible for hyaluronic acid production, filtration of synovial
fluid, and cellular responses to changes in joint homeostasis
Synovial fluid is a dialysate of blood. Blood is filtered by the capillary plexus and
interstitium of the synovial membrane. A fluid similar to serum is produced and
hyaluronic acid is added by the synoviocytes as it is filtered into the joint. Normally,
there are very few cells in the synovial fluid. It is important to remember that synovial
fluid is essential for lubrication of soft tissues in the joint, as well as the cartilage.
Cartilage-on-cartilage lubrication also occurs by weeping lubrication of water from the
cartilage matrix. Synovial fluid is the sole source of nutrition for articular cartilage and
the “primary means of communication” for all intra-articular tissues, in that growth
factors, cytokines, chemokines, and other mediators are conveyed in synovial fluid to
have their effects on the tissues in the joint organ.
The subchondral bone is another important player in health and disease of the “joint
organ.” Subchondral bone provides the foundation for the weight-bearing function of
articular cartilage and needs to maintain normal structure and integration with articular
cartilage (tidemark) for joint health. Subchondral bone is another primary source of pain
receptors in the joint and can also produce mediators of inflammation and degradation
in OA
Any condition that directly or indirectly affects the normal homeostasis of the joint organ
may result in OA, depending on the severity and duration of the insult. Abnormal
biomechanics, abnormal nutrition, or abnormal cell function leads to an imbalance of
anabolism versus catabolism in the tissues, which starts the vicious cycle of
inflammation, degradation, and dysfunction via the production of cytokines and other
mediators. On a cellular level, chondrocytes and synoviocytes are the primary players.
Both of these cell types become involved in their own demise by producing mediators of
inflammation and degradation. The major mediators of OA that we currently know about
include proinflammatory cytokines (interleukin-1 [IL-1] and tumor necrosis factor-alpha
[TNF-), inflammatory mediators (cyclooxygenases, lipoxygenases, prostaglandin E 2,
nitric oxide, leptins, and substance P), and degradative enzymes (matrix
metalloproteinases and a disintegrin and metalloproteinase with thrombospondin motifs
(ADAMTS)). Once stimulated by the initiation of joint insult to levels above that which
the joint can counterbalance, these mediators work together to drive the cycle of
inflammation, synovial fluid alterations, cartilage destruction, bone remodeling,
degeneration, and pain that result in joint pathology and signs that we recognize
clinically.
Although many different conditions initiate OA, the ultimate joint organ response is
consistent, encompassing synovitis, synovial effusion, synovial hypertrophy,
osteophytosis, fibrillation with subsequent degradation and erosion of the articular
cartilage, and peri-articular fibrosis. Subchondral bone and bone marrow changes
cause and perpetuate pain, stiffness, and dysfunction. Although changes in the synovial
membrane and synovial fluid may be reversible, cartilage damage is inevitably
irreversible and self-perpetuating.
It should be noted that destruction of articular cartilage is a necessary criterion for
designation as OA. Normal articular cartilage is white, translucent, and smooth. In OA,
the cartilage becomes yellowish, opaque, and roughened (fibrillated). Fibrillation of
cartilage exposes the collagen and proteoglycan framework of extracellular matrix.
Because the balance between synthesis and degradation has shifted toward
catabolism, the extracellular matrix loses its structural and functional integrity. This
matrix loss results in initial softening of the cartilage (chondromalacia) due to loss of
proteoglycans and retention of water, followed by stiffening of the cartilage with
continued deterioration. Both of these processes result in articular cartilage having
inferior biomechanical properties, leading to dysfunction and progression of the OA
processes. Erosion of the cartilage progresses until subchondral bone is exposed. This
exposed subchondral bone becomes sclerotic and eburnated.
Periarticular osteophytes can be seen as early as 2 weeks after the onset of OA.
Osteophytes are cartilage-capped bony exostoses typically developing at sites of joint
capsule attachment. Enthesiophytes are another manifestation of OA in that the
exostoses extend from and into tendon, ligament, and regional soft-tissue attachments.
Osteophytes represent an attempt by the body to compensate for increased tension on
joint tissue attachments due to chronic synovial effusion, concomitant joint capsule
distention, and persistent joint instability. They can provide some stability to the joint
and do produce growth factors that could have potential benefits to the osteoarthritic
joint. However, osteophytes can also produce inflammatory and degradative mediators,
may participate in loss of joint range of motion (ROM), can be a direct mechanical
irritant to other joint tissues, and may break loose to become free bodies (“joint mice”).
So, osteophytes can be both “good” and “bad” in the process of OA.
In OA, the synovial fluid increases in volume concurrent with loss of viscosity due to
decreases in the quantity and quality of hyaluronic acid content. Synovial fluid cell
counts are slightly higher than normal, with mostly a mononuclear response, including
histiocytes, lymphocytes, and desquamated joint lining cells (clasmatocytes). Few, if
any, neutrophils will be seen. Erythrocytes should also be few in number unless
associated with hemorrhage. The background typically has an amorphous granularity.
Occasionally, cartilaginous debris can be seen in the synovial fluid of OA patients.
Cartilage injuries occur frequently in humans, horses, and dogs. They can result from
sports, work, and trauma, and can be exacerbated by aging and/or genetic factors.
While the knee and ankle are most often diagnosed with cartilage injuries in people, any
of the major weightbearing joints in veterinary patients are at risk. The location, extent,
and severity of cartilage injuries vary widely among patients and it is important to
understand this spectrum with respect to etiology, biology, biomechanics, healing
potential, progression, and prognosis. Similarly, it is critical for us to remember that “the
joint is an organ.” As such, cartilage injuries cannot be treated in isolation. The status of
the synovium, subchondral bone, and associated ligaments, tendons, meniscus, and
musculature must be accounted for in a comprehensive management plan for
addressing cartilage injuries.
Some of the physical features that are important to determine and address with respect
to cartilage injuries include the size of the lesion, the depth of the lesion, whether it is
shouldered/contained or not, and the status of the perilesional cartilage. Each of these
factors has major influences on treatment options and prognosis, and when taken
together, they can be “make it or break it” variables with respect to outcomes.
In terms of the biology of cartilage injuries, the key facets to understand and assess
include the viability of chondrocytes in the injured area, associated subchondral and
trabecular bone pathology (i.e., bone marrow lesions), production and release of
inflammatory and degradative mediators, and the resultant effects on the rest of the
organ. With respect to the biomechanics of cartilage injuries, both micro and macro
mechanical factors should be included. The micromechanics include the material
properties of the cartilage that are dependent on its biochemical composition in relation
to the structural architecture of the components, as well as the interface to subchondral
bone. The macromechanics involve the types and degree of loads placed on the
injured tissue, joint congruity and stability, and limb alignment.
Diagnosis of cartilage injury in veterinary medicine can be very difficult based on the
cause and nature of the injuries and the time frame of presentation after injury. The
most important part of diagnosis of cartilage injury in veterinary medicine is to look for it.
This may sound obvious and simplistic, but it is neither. Many cartilage injuries are
overlooked in veterinary patients because of a simple lack of considering the possibility
of their presence and/or a careful pursuit of finding them. Arthroscopy and MRI are the
two primary modalities for determining the presence and extent of cartilage injuries,
however, other diagnostic tools may also be helpful.
The indications for treatment of cartilage injuries in veterinary medicine include pain and
or dysfunction attributable to the lesion or its sequelae. Other factors that will influence
treatment include the intended function of the patient and the goals of the client, the size
of the defect, concurrent orthopaedic problems, and financial considerations.
Treatments for cartilage injury range from non-surgical to minimally invasive surgical to
total joint arthroplasty. General algorithms for treatment decision making are available
and will be discussed, however, optimal treatment plans must be considered on a caseby-case basis. The principles, limitations, and outcomes associated with current
therapies will be reviewed.
Animal models provide a mechanism by which we can translate diagnostic, therapeutic,
and pathophysiologic findings to clinical application with safety and efficacy. Animal
model studies are required for most biologics and devices to receive FDA approval for
clinical trials.
Cartilage defects resulting from OA, fractures, osteochondrosis, and athletic injuries are
common clinical conditions in dogs. While the knee and ankle are most often diagnosed
with cartilage injuries in people, any of the major weightbearing joints in veterinary
patients are at risk. The location, extent, and severity of cartilage injuries vary widely
among patients and it is important to understand this spectrum with respect to etiology,
biology, biomechanics, healing potential, progression, and prognosis. Similarly, it is
critical for us to remember that “the joint is an organ.” As such, cartilage injuries cannot
be treated in isolation. The status of the synovium, subchondral bone, and associated
ligaments, tendons, meniscus, and musculature must be accounted for in a
comprehensive management plan for addressing cartilage injuries.
Some of the physical features that are important to determine and address with respect
to cartilage injuries include the size of the lesion, the depth of the lesion, whether it is
shouldered/contained or not, and the status of the perilesional cartilage. Each of these
factors has major influences on treatment options and prognosis, and when taken
together, they can be “make it or break it” variables with respect to outcomes.
In terms of the biology of cartilage injuries, the key facets to understand and assess
include the viability of chondrocytes in the injured area, associated subchondral and
trabecular bone pathology (i.e., bone marrow lesions), production and release of
inflammatory and degradative mediators, and the resultant effects on the rest of the
organ. With respect to the biomechanics of cartilage injuries, both micro and macro
mechanical factors should be included. The micromechanics include the material
properties of the cartilage that are dependent on its biochemical composition in relation
to the structural architecture of the components, as well as the interface to subchondral
bone. The macromechanics involve the types and degree of loads placed on the
injured tissue, joint congruity and stability, and limb alignment.
Diagnosis of cartilage injury in veterinary medicine can be very difficult based on the
cause and nature of the injuries and the time frame of presentation after injury. The
most important part of diagnosis of cartilage injury in veterinary medicine is to look for it.
This may sound obvious and simplistic, but it is neither. Many cartilage injuries are
overlooked in veterinary patients because of a simple lack of considering the possibility
of their presence and/or a careful pursuit of finding them. Arthroscopy and MRI are the
two primary modalities for determining the presence and extent of cartilage injuries,
however, other diagnostic tools may also be helpful.
The indications for treatment of cartilage injuries in veterinary medicine include pain and
or dysfunction attributable to the lesion or its sequelae. Other factors that will influence
treatment include the intended function of the patient and the goals of the client, the size
of the defect, concurrent orthopaedic problems, and financial considerations.
Treatments for cartilage injury range from non-surgical to minimally invasive surgical to
total joint arthroplasty. General algorithms for treatment decision making are available
and will be discussed, however, optimal treatment plans must be considered on a caseby-case basis.
Biologic resurfacing of articular cartilage is the Holy Grail of joint surgery. While no
current resurfacing treatment option consistently results in re-creation of fully integrated
and functional hyaline cartilage and subchondral bone long term and the available
options are more limited in veterinary medicine compared to human medicine, there are
still some viable biologic treatment options that can result in very good outcomes in our
patients. We will discuss marrow stimulation, osteochondral autografts, osteochondral
allografts, and synthetic resurfacing as realistic clinical options, and cell-based and
tissue engineering strategies as potential future modalities.
Marrow stimulation is the simplest and most common method for surgical repair of
cartilage defects. This is typically accomplished using specifically designed picks or
awls, but can also be accomplished with drilling techniques using Kirschner wires or drill
bits. These techniques are only effective for contained defects, and at best, result in
formation of reparative fibrocartilage tissue in the defect.
Osteochondral autograft treatment has been reported to improve outcomes in human
patients when compared to other treatment modalities. Based on the human success,
we adapted the concept and the OATS (Arthrex) technique to veterinary surgery for use
in dogs and horses. We performed a body of research using cadavers, research dogs,
and finally, clinical cases. We have reported the results of that work in the peerreviewed literature. We have found the OATS procedure can be successfully performed
in the stifle of dogs for treatment of OCD. Clinical results have been excellent with
respect to graft viability and integration, and improved clinical function. Others have
reported their work on the technical aspects of this technique in dogs and use of OATS
in other joints including the elbow and shoulder. Further work is needed to determine
appropriate indications and long-term results.
Again, based on the research and clinical use in people, we implemented osteochondral
allografts (OCA) for treatment of severe articular defects in canine patients. Dogs
presenting for lameness associated with major articular defects of the elbow, stifle, or
hock were included when owners consented to OCA and allowing data to be collected,
analyzed, and reported. After full diagnostic work-up, discussion of treatment options,
costs, and prognosis, and consent to treatment, the affected joint was treated with OCA
via open arthrotomy. OCA grafts were harvested aseptically in an OR from dogs
euthanatized for unrelated reasons and immediately cultured in sterile chondrogenic
media using a protocol developed in our laboratory. Pre-operative, intra-operative, and
postoperative treatments varied among patients. Outcomes measures included
complications, radiographic assessment, and clinical function. Six patients were
included: 10-month-old Husky with humeral condyle dysgenesis of the humeral condyle;
4-year-old Labrador with a patellar malunion; 20-month-old Mastiff with stifle OCD; 3year-old mixed-breed dog with stifle OCD; 14-month-old St. Bernard with hock OCD; 7year-old Pointer with severe stifle OA. Appropriately sized OCA grafts were cultured
with no evidence of contamination or infection and successfully implanted in all 6
patients using various methods of fixation. No evidence of frank rejection, infection, or
fixation failure was noted. Clinical follow-up was performed 8-10 weeks after surgery
and at variable time points (range 8 weeks - 29 months). Radiographic assessments
indicated graft incorporation in all cases, however, OA progressed for all patients and
implant migration requiring K-wire removal occurred in 2 cases. Four of six cases
returned to full athletic function. The hock OCA was improved, but did not achieve
intended athletic function by 14 months. The Pointer with femoral condylar and tibial
plateau OCAs returned to work and competition. These data suggest that OCA can be
successfully performed in select dogs with major articular defects in the elbow, stifle, or
hock and result in acceptable functional outcomes.
Synthetic grafts for treatment of focal cartilage defects are available from Arthrex and
have been successfully used in the elbow, shoulder, and stifle of clinical canine patients.
This technique is in its infancy of clinical use and a further work is needed before we can
make definitive recommendations regarding indications and efficacy. To date, the
technique has proven to be safe.
We have also developed a system for synthetic resurfacing of the medial compartment
of the canine elbow for treatment of medial compartment disease. Medial Compartment
Disease (MCD) refers to pathology of the medial aspect of the humeral condyle and
medial coronoid process. The surgical treatment we have developed for MCD is the
Canine Unicompartmental Elbow (CUE) arthroplasty. To date, we have performed all of
the pre-clinical testing and have treated 26 clinical cases for which we have at least 6month follow-up on. Examinations at 6-8 weeks and ~6 months postoperatively were
performed and included assessment of lameness, pain, range of motion, and
radiographs. At the time of writing, the overall success rate for return to intended
function is 80% with a 24% major/catastrophic complication rate. These data provide
initial evidence for safety and efficacy of the Arthrex Canine Unicompartmental Elbow
arthroplasty system and justify further clinical study, which is ongoing.
Cell-based and tissue engineering strategies for articular cartilage regeneration are
being researched intensively all over the world. Some of these strategies, including
autologous chondrocyte implantation (ACI), MACI, CAIS, DeNOVO, and others, have
made it to clinical use. None of these current techniques has reached the Holy Grail of
complete regeneration of large articular cartilage surfaces such that full function is
consistently seen long term, but these and others do have promise for providing biologic
solutions for articular cartilage problems in dogs, horses, and humans.