Originally published to Purina Pro Club, Issue 82, 2014.
When an 8 1/2-year-old black male Labrador Retriever named “Weezer” hobbled into Dr. Jeffrey J. Schuett’s veterinary clinic in Pewaukee, Wis., it was a classic case of a torn cruciate ligament injury. During training, the Labrador yelped in pain while running to make a blind retrieve and then refused to put weight on his left rear leg.
The dog’s owner, Bob Johnson of Madison, Wis., took Weezer to Schuett, an upland game hunter and retriever enthusiast. Johnson not only wanted the injury repaired, he hoped his accomplished retriever could return to field trials.
“We discussed the options and decided that a TightRope procedure would work best for Weezer,” says Schuett. “Weezer stayed at my clinic for one and a half months postoperatively while undergoing hydrotherapy treadmill rehabilitation six days a week.”
A finalist in six National Retriever Championship Stakes before his injury, FC-AFC Weezer Retreezer went on to qualify for the 2010 National Open Stake after taking a year off for rehabilitation. In 2011, he qualified for the National Amateur Retriever Championship and won a double header at Vicksburg, Fla.
The cranial cruciate ligament (CCL) is a critical stabilizer of the stifle (knee) joint. It functions as a rope as it stabilizes the femur (thighbone) to the tibia (shinbone), preventing the stifle bones from shifting during activity. Without the normal CCL stabilization, a dog’s movement is compromised and painful osteoarthritis develops.
“In most dogs, CCL rupture occurs due to preexisting, progressive fatigue of the cranial cruciate ligament,” says Dominique J. Griffon, D.M.V., Ph.D., DECVS, DACVS, professor of small animal surgery at Western University of Health Sciences in Pomona, Calif. “Though trauma can cause the CCL to tear, it is more likely due to a complex, multifactorial condition that develops over time.”
The less-invasive TightRope stabilizing procedure, which Schuett performed on Weezer, and lateral suture are extracapsular surgeries that use a synthetic material to mimic the function of the CCL for long-term stability. Bone-cutting surgeries, such as the popular tibial plateau leveling osteotomy (TPLO) and tibial tuberosity advancement (TTA), alter the anatomy of the stifle to achieve stability.
No one surgical procedure is consistently successful for all dogs. In fact, the tibial osteotomies are associated with complications in 28 to 59 percent of dogs.1 Long-term success of the procedures used to manage CCL disease is shortchanged by the return of instability and degenerative joint disease, causing pain and decreased range of motion and functioning.2
Experts estimate that $2 billion is spent annually treating dogs for CCL disease. The most common orthopedic problem seen by veterinarians, the disorder has gradually increased over the past 40 years.2 The majority of dogs, even Weezer, end up having CCL disease in both stifles. The prevalence rate across all breeds is 2.55 percent. Large breeds are considered predisposed, with 8.90 percent of Newfoundlands affected, 8.29 percent of Rotttweilers and 5.79 percent of Labradors.3
Research funded by the AKC Canine Health Foundation is providing better understanding of CCL disease, a condition that 60 percent of parent clubs report as a health concern in their breeds. Here is a review of this research.
Identifying Dogs at Risk
After more than a decade performing surgery on dogs with CCL disease at the University of Illinois Veterinary Teaching Hospital, Griffon believed that some conformation factors affected the way dogs move, thus predisposing them to CCL disease. She began studying the conformation of the hindlimbs and the gait mechanics of Labradors with and without CCL disease.
The research led to the development of a conformation score system that helps to identify Labrador Retrievers at risk for CCL disease. The equation used to determine the conformation score came from a study of 20 Labradors. The researchers observed sound Labradors, classified as predisposed or low risk, trotting on the ground or running on a treadmill. They discovered that dogs at risk for CCL disease generated more energy around their stifle and tended to extend their hocks.
“When we evaluated the gait of sound Labradors at low risk for CCL disease, we found the difference in conformation between the groups was associated with a modification of gait that would lead to the overloading that occurs in CCL disease,” Griffon explains. “We also found some evidence that the gastrocnemius (calf) muscle plays a dominant role. It is the muscle that generates the cranial tibial thrust normally antagonized by the CCL.”
Griffon’s current research is testing how well the conformation score system works in a larger population of Labrador Retrievers. She and her team aim to evaluate 200 Labradors, a breed chosen based on its predisposition for CCL disease and popularity as the No. 1 breed registered in the U.S.
Adult purebred Labradors with CCL disease and sound Labradors over 6 years of age are eligible to participate. Radiographs taken of their pelvis and both hind limbs will help determine the validity of the conformation score equation. The study includes healthy dogs that are not lame, those that have had surgery for CCL disease, and those scheduled for CCL surgery.
“We believe these gait characteristics are due to the dogs’ conformation, hence our interest in identifying them before they develop CCL disease,” Griffon says.
Determining the Best Treatment
Knowing which surgical procedure is likely to have the best outcome for a dog with CCL disease is part of the challenge for veterinarians and owners. Gina Bertocci, Ph.D., the endowed chair of biomechanics at the University of Louisville, put her expertise to work trying to answer this question.
A 3-D computer model, developed by Bertocci and her research team, provides an insightful view of how anatomical characteristics may affect the likelihood of CCL deficiency and the biomechanical effectiveness of treatment options. “While no single procedure has proved to be superior, we can use our 3-D model to see how well these procedures return the stifle biomechanics to that of a healthy dog,” Bertocci says.
The 3-D modeling technique was developed from a computed tomography (CT) scan of the pelvic limb of a healthy Golden Retriever.4 “We reconstructed the CT image to create a 3-D model of each bone segment using specialized software,” explains Bertocci. “We joined the 3-D segments using elements to represent ligaments and muscles. We then conducted gait analysis, recording the same dog’s motion using cameras and a force platform to measure the force of his paws on the ground surface.”
The dog’s hind limb motion and ground force data, combined with data from the CT scan, allowed the researchers to create a model simulating the dog’s gait. The model will allow the researchers to gauge the biomechanical effectiveness of TPLO, TTA and extracapsular stifle stabilizing procedures for dogs with CCL disease.
The ability to assess the influence of various anatomical characteristics for a given surgical treatment option is promising. “We can compare a multitude of scenarios through a parametric sensitivity analysis,” Bertocci says. “By varying a specific parameter, such as the tibial plateau angle, and then running our model to simulate gait, we can determine the influence these changes have on a dog’s stifle biomechanics.”
Although the 3-D computer model is only practical for research, it may provide information that will one day benefit clinicians. “Computer modeling and parametric analysis should help improve the clinical decision-making process,” Griffon says.
The Future of Regenerative Therapy
Regenerative medicine, the process of replacing or regenerating cells, tissues or organs to restore or establish normal function, has taken hold in human medicine. Today, researchers are applying this concept to helping dogs with CCL disease.
Peter Muir, BVSc, Ph.D., DACVS, DECVS, professor of small animal orthopedics at the University of Wisconsin-Madison School of Veterinary Medicine, is investigating whether platelet-rich plasma (PRP) from a dog’s own blood can help heal cranial cruciate ligament damage. “This approach may offer a safe, effective therapy to prevent the progressive tearing of ligament fibers, enable healing and block progression of osteoarthritis over time,” he says. “It has potential to modify ligament damage, reduce joint inflammation and promote ligament healing.”
Muir has begun a two-year study evaluating PRP that will include 25 dogs undergoing treatment for CCL rupture at the University of Wisconsin Veterinary Care Teaching Hospital. Platelets from the dogs’ own blood, which are rich in growth factors, will be separated and concentrated by centrifugation. PRP treatment will be provided to the stable second stifle with early cruciate damage.
“Three scenarios are common in dogs with CCL rupture,” explains Muir, who has studied the condition for more than 10 years. “Bilateral rupture makes up about 10 to 15 percent of cases. The rest of the cases are a complete rupture in one stifle with severe lameness, or dogs that have clinically stable stifles usually with mild lameness. In dogs with a complete rupture in one stifle, there usually are signs of early disease in the second stifle joint. Over time, a second rupture is fairly predictable.”
If the PRP therapy for the second stifle with early cruciate damage proves successful, the researchers will begin using it routinely in dogs brought to the hospital. “Treatment for the unstable stifle is a great challenge,” Muir says. “With the current surgical management procedures, progression of arthritis over time is typical. If PRP therapy has a sparing effect in the second stable stifle in the trial, we plan to extend this work to regenerative medicine treatment for unstable stifles with complete CCL rupture.”
The potential use of stem cells to repair torn cranial cruciate ligaments is the focus of Mandi J. Lopez, D.V.M., Ph.D., DACVS, associate professor of veterinary surgery at Louisiana State University School of Veterinary Medicine. “The best way to restore CCL function is to recreate the native structure,” she says. “We found that infrapatellar adipose tissue in front of the cruciate ligament has the most progenitor cells that have the best ability to grow in culture and differentiate into diverse tissues. This finding is important for continued efforts to restore joint tissues like the CCL that have been lost to disease, age or trauma.”
Besides the infrapatellar adipose tissue, the researchers have isolated cells from the joint capsule, the lining inside the joint, and the CCL synovial covering, between the ligament and the joint, in considering the best source of stem cells.5 “There are several tissues in the stifle containing cells capable of dividing and maturing into different tissues that came from the same layer during embryonic development,” Lopez explains.
The use of stem cells to manage canine CCL disease is coming in the not-too-distant future, Lopez predicts. “Recent scientific advances make it feasible that stem cells isolated from individual patients may soon be used to direct stem cells in the body to regrow new tissues or generate new tissues in the laboratory,” she says.
The future of diagnosing, preventing and managing CCL disease will likely be shaped by this collection of research. The ability to return a dog to normal functioning is the goal. Despite suffering from CCL disease, even a cruciate rupture, most dogs cannot wait to get back to the things they enjoy most.
Weezer is an example. Now retired, the 11-year-old Labrador thrives on weekly visits to the retriever club. His desire, as strong as when he was winning field trials, is seen in the intensity of his focus as Johnson prepares to send him on a retrieve. After two TightRope procedures, Weezer is on top of his game.
- Griffon DJ. A Review of the Pathogenesis of Canine Cranial Cruciate Ligament Disease as a Basis for Future Preventive Strategies. Veterinary Surgery. 2010;39:399-409.
- Ragetly CA, Evans R, Mostafa AA, Griffon DJ. Multivariate Analysis of Morphometric Characteristics to Evaluate Risk Factors for Cranial Cruciate Ligament Deficiency in Labrador Retrievers. Veterinary Surgery. 2011;40:327-333.
- Witsberger TH, Villamil JA, Schultz LG, Hahn AW, Cook JL. Prevalence of and Risk Factors for Hip Dysplasia and CCL Deficiency in Dogs. Journal of the American Veterinary Medical Association. 2008;232(12):1818-1824.
- Brown N, Bertocci G, Marcellin-Little D. Development of a Canine Stifle Model for Evaluation of Cranial Cruciate Ligament Deficiency. Journal of Mechanics in Medicine and Biology. 2013:13(2);1350043-1350071.
- Zhang N, Dietrich MA, Lopez MJ. Canine Intra-Articular Multipotent Stromal Cells (MSC) from Adipose Tissue Have the Highest In Vitro Expansion Rates, Multipotentiality and MSC Immunophenotypes. Veterinary Surgery. 2013:42(2);137-146.
Foundation Funds CCL Research Portfolio
The AKC Canine Health Foundation is funding a portfolio of research aimed at learning more about cranial cruciate ligament (CCL) disease, the No. 1 cause of lameness in dogs. The research, featured in this article, includes a conformation score to determine risk, a 3-D computer model to evaluate the biomechanics of surgical procedures, and regenerative medicine as an alternative therapy.
“Research does not work in isolation,” says Shila Nordone, Ph.D., Chief Scientific Officer for the Foundation. “To create depth in areas of importance, we have to address health problems from multiple angles.”
Evaluating a Canine Brace to Support the Cruciate Ligament
The 3-D computer model that researchers at the University of Louisville are using to assess the best treatment option for a dog with cranial cruciate ligament (CCL) disease also is being used to evaluate the effectiveness of a canine stifle brace.
“The stifle brace provides a surgical alternative for dogs that are older, poor anesthesia candidates, suffer from other disorders and whose owners cannot afford surgical management,” says lead investigator Gina Bertocci, Ph.D. “The brace also can be used pre- and postoperatively to stabilize and protect the stifle joint.”
The 3-D model is helping Bertocci to evaluate the effect of the brace on a dog’s pelvic limb biomechanics in a CCL-deficient stifle and determine how well it returns a dog to normal stifle biomechanics. They are studying the brace design, including the type of material and the hinge joint.
“We want to minimize the loss of muscle mass and strength,” Bertocci says. “We also want to improve our understanding of how design factors influence stifle stabilization.”
Made by OrthoPets, a Denver-based custom orthotics provider for pets, the canine stifle brace is similar to what is used for humans with knee instability. The cost, which varies by the size of dog, ranges from $600 to $850. For information about the brace, contact Dr. Patrice Mich, the co-principle investigator, at OrthoPets at 303-953-2545.
Tips on Reducing the Risk of CCL Disease
Cranial cruciate ligament (CCL) disease occurs in all breeds of dog and is particularly common in large breeds. Researchers attribute CCL to many causes, including a dog’s genetics, conformation, environment, inflammation and compromised immune functioning. Here are tips from the experts to help prevent a CCL rupture.
- Keep excessive weight off your dog. An overweight dog has two times greater risk for developing CCL disease than healthy, fit dogs. Obesity increases the amount of force applied on the stifle joint at each step, causing repetitive loading that overuses and fatigues the CCL.
- Keep your dog active. Inactivity decreases the stimulation of the CCL, potentially causing atrophy and weakening of the ligament. An active lifestyle helps maintain muscle tone and joint health, as well as optimum weight, and may help reduce the risk of CCL rupture.