State of the art treatment of osteoarthritis (Proceedings)

Current treatment options for osteoarthritis are extensive and can be categorized into medical/ conservative or surgical therapies. Medical therapies may consist of weight control, exercise modification, rehabilitation therapy, pain management medications, oral joint protective compounds, and intra-articular treatments. Surgical options may include arthroscopic treatments, osteochondral autologous transplantation, osteotomies, regenerative stem cell therapy, or joint replacement. A multimodal management plan is a more progressive approach to the treatment of osteoarthritis and includes a combination of medical and potentially surgical options.

Oral Joint Modifying Agents

Joint protective compounds (JPCs) are commonly used in small animals. JPCs include both oral agents, specifically glucosamine, chondroitin sulfate, and avocado/soybean unsaponifiables (ASU), and injectable compounds, such as polysulfated glycosaminoglycan and hyaluronic acid.

The administration of JPCs is indicated in a wide range of cases. JPCs may be used in animals with osteoarthritis or in healthy animals to help slow or protect against damage to the joint cartilage and synovium and to support the health of the tendons and ligaments. JPCs are often administered to working and performance dogs and should be considered in large breeds in general as well as in obese dogs due to the extra stress being placed on the joints. JPCs are also indicated when bone fractures involve the articulating surfaces or peri-operatively with surgical procedures involving the joint.

Glucosamine and chondroitin sulfate have been used in small animals since the mid 1990's. In vivo and in vitro research has demonstrated the compounds' efficacy. A rabbit instability model showed that a specific glucosamine hydrochloride and low molecular weight (LMW) chondroitin sulfate combination (Cosequin® , Nutramax Laboratories, Inc., Edgewood, MD) had a disease-modifying effect as administration slowed progression of cartilage degradation. In vitro the combination inhibited degradative enzymes. Results also demonstrated in vitro that the glucosamine and low molecular weight chondroitin sulfate synergistically stimulated proteoglycan production.

In a double-blind, placebo-controlled study in dogs, scintigraphic evaluation showed that pre-treatment with the specific glucosamine hydrochloride and LMW chondroitin sulfate combination protected against chymopapain-induced synovitis and the associated bone remodeling; treated dogs were also judged to be less lame. Dogs administered the same combination in a double-blind, placebo-controlled study using a cranial cruciate ligament transection model had less severe cartilage degradation and a return to a more normal physiologic state in the operated joint.

ASU has also been shown effective at supporting joint health. Recent international work in dogs indicates that this ingredient may have a positive effect on cartilage repair. While U.S. clinical trials in dogs and cats are in progress evaluating the use of an ASU/glucosamine hydrochloride/LMW chondroitin sulfate combination product (Dasuquin™, Nutramax Laboratories, Inc., Edgewood, MD), in vitro work strongly suggests that the three agents combined will produce excellent results. In IL-1β -stimulated canine chondrocytes, ASU, glucosamine hydrochloride, and LMW chondroitin sulfate reduced PGE2 levels by 80% versus activated controls. In feline chondrocytes, the combination also caused a significant reduction in PGE2 levels. Notably, the three agents together were shown more effective than just glucosamine and chondroitin sulfate at reducing expression of multiple inflammatory mediators in THP-1 cells, equine chondrocytes, and human chondrocytes.

Though JPCs may be used as part of a multimodal approach (with NSAIDs, weight reduction, exercise/rehabilitation therapy, and/or acupuncture), JPCs are often used alone especially for protection or in mild to moderate cases of OA, etc. In healthy animals for protection, an oral product may be given every other day with the dosage then adjusted as needed.

Polysulfated glycosaminoglycan

Polysulfated glycosaminoglycan (Adequan® Canine, Luitpold Pharmaceuticals, Inc., Shirley, NY) is primarily a chondroitin sulfate which can be administered intra-muscularly twice a week for up to 4 weeks. Adequan has been shown to decrease the amount of degradative enzymes which stimulate inflammation and cartilage erosion as well as promote repair and regeneration of cartilage. Clinical studies of Adequan have shown significant improvement in patients by the second or third injection with maximum benefit after the eight treatment. Clinical studies have also shown that 78.5 % of dogs that responded to Adequan® Canine were still improved six months later.

Hyaluronic Acid

Hyaluronic Acid (sodium hyaluronate, hyaluronan, HA) is a fluid that exists in every single living organism. Intra-articular HA is a form of viscosupplementation which restores the physical properties of joint fluid to aid in the lubricataion of the joint, decrease inflammation and degradation and help in cartilage repair. Intra-articular HA has been widely used in the treatment of OA in large animals and humans. Several clinical studies in humans have demonstrated relief of joint pain associated with OA following intra-articular injections of HA. Information regarding the effects of intra-articular HA on naturally occurring OA in dogs is not available; however, several experimental studies using intra-articular HA in dogs have been reported. Results from these studies have demonstrated decreases in pain, lameness, and cartilage degradation. There are several forms of hylauronic acid available for intra-articular injection however, Hylartin®V (Pfizer) which is approved for use in horses and used off-label in dogs, is preferred by this author due to its a high molecular weight which mimics the form of HA naturally occurring in the body.

Studies evaluating the effects of intra-articular HA in dogs have used doses ranging from 10-20 mg and treatment periods ranging from 3 to 5 weekly injections. The intra-articular dose used by the author is one 10 mg (10 mg/ml) injection weekly for 3 treatments. The injections must be given under sterile conditions and may be performed unsedated, sedated or under general anesthesia depending on the patient. Complications from these injections may include temporary increased pain and lameness and septic arthritis. Reportably, over 70% of dogs respond well to HA and improvement can be noted for over 6 months following administration. The author's clinical impression is that HA used alone is useful for mild to moderate elbow OA, but in the treatment of severe elbow OA intra-articular corticosteroid or stem cell therapy is recommended.

Corticosteroids

In humans intra-articular corticosteroids are recommended in several guidelines for the treatment of patients with OA. The benefits of corticosteroids are reduction in inflammation and improved comfort. Methylprednisolone Acetate (Depo-Medrol® ) and triamcinolone acetonide (Vetalog® ) are most commonly used. The intra-articular dose of Depo-Medrol used by the author is one 20 mg (20 mg/ml) injection followed by a second dose in 3 weeks; or one 3 mg (2mg/ml injection) injection of Vetalog. Intra-articular administration of corticosteroids is performed under sterile conditions with the patient unsedated, sedated or under general anesthesia depending on the patient. Side effects are minimal; however, some dogs show signs of discomfort for the first 12 hours following injection. Administration of Depo-Medrol or Vetalog typically results in pain relief in 24 hours and can last for weeks to months. In humans up to 3-4 injections can be given during a year period. Studies evaluating the safety and efficacy of long-term treatment in dogs are not well reported.

Regenerative Stem Cell Therapy (SCT)

Regenerative stem cell therapy (SCT) can also be used in the management of persistent clinical elbow osteoarthritis. Adult regenerative stem cells are multipotent cells located in bone marrow, joint capsule and fat tissue and are capable of maturing into bone, cartilage, tendon or ligament cells and can be used to repair and regenerate damaged tissues such as the cartilage in osteoarthritis. This is performed by harvesting cells from the fat located behind the shoulder, between the back legs, or falciform. The fat is removed surgically and sent to Vet Stem, a company in southern California, where it is purified into regenerative stem cells. Two days after tissue harvest, the regenerative stem cells are returned in sterile syringes and under sedation, the cells are injected into the osteoarthritic joint(s).

Clinical improvement from SCT has been noted in dogs 2-4 weeks after injection and improvement has been seen lasting for up to 2 years. A recent report in Veterinary Therapeutics 2008 evaluated the effect of intra-articular stem cell therapy for the treatment of elbow OA in dogs. This study showed a significant improvement in lameness and range of motion as well as a significant difference in client evaluation (functional disability scores) in patients treated with intra-articular SCT.

Surgical Treatments

Some dogs have discomfort refractory to the various medical modalities. A change in quality of life related to osteoarthritis may warrant more aggressive intervention. Surgical intervention may include arthroscopic treatments, OATS (osteochondral autologous transplantation), SHO (sliding humeral osteotomy), or joint replacement (hip, knee, elbow). It is important to note that animals undergoing surgical intervention, may also require continued medical management for optimal recovery.

Arthroscopy is an excellent modality for diagnosing and staging osteoarthritis as well as a minimally invasive means of treatment. Arthroscopic removal of the fragments (fragmented medial coronoid processes, osteochondral flaps, ununited anconeal processes, meniscal tears, etc.) is recommended to not only remove the inciting cause of lameness but to also help prevent/slow the progression of osteoarthritis. Arthroscopic treatment may include a combination of techniques such as fragment removal, debridement of diseased tissues, creation of vascular access by abrasion arthroplasty, forage, microfracture, and subtotal coronoid ostectomy depending on the progression and severity of disease. Arthroscopy is not only a great diagnostic modality, allowing for superior visualization of structures within the joint, but also has less soft tissue trauma, shorter surgery and hospitalization times, decreased infection and shorter recovery times compared to traditional arthrotomies.

The osteochondral autologous transplantation (OATS) method takes a graft of normal cartilage and underlying bone from an area of the joint not involved in weight bearing and transplants this graft to an area of cartilage loss. This graft of healthy tissue provides a means for cartilage healing and regeneration resulting in a more comfortable and functional joint.

Sliding Humeral Osteotomy (SHO)

Where extensive erosion of the cartilage surface of the medial compartment of the elbow is evident and is producing significant pain and lameness, a SHO may be performed. This procedure is based on similar procedures that are performed in humans suffering OA of the knee. The procedure realigns the limb to shift the forces off the area of cartilage damage and onto healthy cartilage thereby relieving the pain of grinding of bone and gives the damaged area the opportunity to heal. A horizontal cut through the midshaft of the humerus is made and slinding the bottom portion of the humerus toward the inside of the leg, the weight bearing portion of the leg distributes weight-bearing toward the healthy lateral portion of the elbow joint, lessening the load to the arthritic medial aspect of the joint thereby decreasing pain associated with the arthritis. After the cut in the humerus is made, a special plate is applied to the bone, holding it in this new position during healing. As with a traumatic fracture, the bone takes approximately 8 to 12 weeks to heal. Early and long-term clinical follow up have shown favorable response and second look arthroscopy has revealed in-growth of cartilage into the eroded areas of the medial compartment as proof of principle unloading

Total Joint Replacement

Total joint replacement is the gold standard for animals with osteoarthritis that have discomfort refractory to the above modalities. After recovery from surgery, a joint replacement results in near normal joint function and use. At this time, total joint replacements are available for the elbow, stifle and hips. For all joints, the diseased portion is removed and a prosthesis is cemented into place. A new addition to the cemented hip system allows total hip replacements in cats and dogs as small as 5 pounds. A non-cemented hip system also exists which is press-fitted into place. There are beads surrounding the implant which provide for bone in-growth into the prosthesis. This allows for a longer implant life span and joint replacements to be performed in dogs as young as 6 months.

Total Elbow Replacement (TER) is an option in dogs with severe OA that have discomfort refractory to any of the above modalities and for dogs in which the lateral compartment is affected eliminating use of the SHO procedure. The first TER system was described in 1996 and used a cemented, fully constrained (implant components are linked together) hinged design. High complication rates were encountered with this initial design. Further development of TER systems was investigated. The first commercially available TER became available 2005 and consisted of a cemented, semi-constrained design. While this design was superior to the initial system, severe complication rates were still greater than 20%.

In 2007, a radically novel TER system, the TATE Elbow™ was developed by Acker and Van Der Meulen. Ten years in development, the impetus for the TATE Elbow™ was Acker's own yellow Labrador retriever, Tate. Tate developed severe elbow dysplasia and while Acker tried the common treatments of injections, arthroscopic surgery, acupuncture and pain medication, the outcome was unsuccessful. Ultimately, the TATE Elbow™ System became the eventual result.

Implementation of the TATE Elbow™ was first performed in July 2007. Since then many dogs affected with intractable elbow arthritis have been successfully treated with this new prosthesis. The TATE Elbow™ is also a semi-constrained design, however, several fundamental differences are present is this system as compared to the previous systems. Specifically, this system does not rely on stemmed and cemented implants instead, it is pressed fit. Long term stability relies on bone ingrowth into the porous structure of the implants (osteointegration). Cementless prostheses have potential advantages over cemented models, including reduced risk of infection and reduced rate of implant wear, both of which are regarding as leading causes of post-operative failure. Because the components of this system are impacted simultaneously as a pre-assembled cartridge, reduced trauma to the patient is achieved and accurate alignment and tracking of the prosthetic components throughout range of motion is guaranteed. Today, the surgery can be completed in two hours with an 8-12 week restorative period for the patient's full functional recovery

Due to space limitations references will be available upon request