"Arthrix® Plus HA is a great tasting supplement intended for the the long term maintenance of canine joint health. It is designed to help aging or seriously injured dogs that clearly show joint discomfort, have trouble getting up, and/or walking. Arthrix® Plus HA stands out from other joint health products because it contains nearly all branded, pharmaceutical-grade ingredients. The “HA” represents our addition of Hyaluronic Acid to complete to trio with Regenasure®-brand plant-sourced glucosamine HCl and the bioactive, low-molecular-weight ChondroPure™ chondroitin. This formula also contains OptiMSM®-brand MSM, Ester-C®-brand Vitamin C, the highly concentrated Myristin®-brand cetyl myristoleate complex (a modified Omega-5 fatty acid with powerful anti-inflammatory effects), combined with OmniMin™-brand elements & trace minerals and the AstraGin™-brand herbal preparation, which both ensure maximum nutrient uptake and effectiveness."

What Causes Arthritis?

Prostaglandins and Leukotrienes

The following information gives some background information on what causes arthritis at the cellular level. Prostaglandins are a group of hormone-like substances present in many tissues and body fluids. They act as regulatory substances and messengers. Prostaglandins are not hormones as they are not produced by glands. They are metabolized on site and used very quickly. Their effects are strictly local, and modulate the tissues in which they are formed. Prostaglandins are vital regulators - they control every cell and organ in the body. Their functions include the regulation of platelet aggregation, the lowering of blood pressure, the regulation of body temperature, the function of nerve transmission, the action of certain hormones and the control of inflammation and vascular permeability. So, it is easy to see how something that regulates these prostaglandins would be of great benefit to our pets.

Most prostaglandins are biosynthesized during the metabolism of arachidonic acid (arachidonic acid, AA, is an essential fatty acid). Other prostaglandins are formed during the breakdown of omega 3 and omega 6 fatty acids (see Figure below). Not all prostaglandins are beneficial. PG1 prostaglandins and EIC3 prostaglandins are important examples of good prostaglandins; while prostaglandins formed by the cyclooxygenase pathway (COX 2) of arachidonic acid metabolism (PG2) have potent inflammation-supporting properties. Bad prostaglandins are capable of attracting large numbers of leukocytes (white blood cells) to the site of inflammation, causing pain and tissue damage.

Beneficial prostaglandins (PG1 and EIC3) play an important role in reducing inflammation by improvingcellpermeability and blood flow, thereby reducing pain, tenderness and stiffness. Long-term daily intake of Essential Fatty Acids will regulate the arachidonic acid metabolism, supporting the formation of good prostaglandins and inhibiting the formation of bad prostaglandins.

Leukotrienes are products of the lipooxygenase pathway of arachidonic acid metabolism and play an important role in the inflammatory process. Like prostaglandins, they are short-lived, locally-active hormone like substances. Leukotriene LT4 and its metabolites LTC4, LTD4 and LTE4 have important inflammation-supporting properties. Leukotriene LT4 and its metabolites are potent chemotactic agents. What this means, is that they falsely attract white blood cells whose normal function is to destroy unwanted bacteria, protozoa, cells and cellular debris, to the site of injury. Once there, these otherwise useful cellsstartto attack healthy tissues. This inability to differentiate beneficial cell tissue from unwanted foreign substances is know as a auto-immune disorder, and lead to arthritis and a host of other inflammatory diseases.

Canine Hip Dysplasia¹

 It is important to distinguish between Canine Hip Dysplasia (CHD) and Degenerative Joint Disease (DJD). Hip Dysplasia is the abnormal development of the hips which results in an increased amount of looseness in the hip joint. Degenerative Joint Disease (arthritis) is the changes within the joint which occur as a result of this increased looseness. Pain can result from either of these problems. Young dogs with hip dysplasia can be in pain without having degenerative joint disease, and dogs with chronic DJD do not always have hip dysplasia.

Young Dogs With Hip Dysplasia

Pain relief associated with conservative treatment are derived from strengthening the joint capsule and preventing further capsuler sprain. Initially, painful dogs should be treated for acute sprain. Complete rest is mandatory for two weeks. Physical therapy during this time can be performed to maintain good range of motion. However, resuming normal activity early can predispose to further injury, pain, and prolonged recovery. According to one source, approximately 60% of young dogs treated conservatively return to acceptable clinical function with maturity.

Mature Animals With Chronic DJD

Medical therapies for chronic degenerative joint disease can be subdivided into 3 areas - weight control, proper exercise, and anti-inflammatory substances.

Weight Control: Regardless of whether or not a dog has hip dysplasia, they will be at higher risk for joint disease if they are over weight. The further they are from their ideal weight, the more likely they will be to have orthopedic problems such as arthritis, intervertebral disk disease and cruciate ligament disease. Dogs who have hip dysplasia and are over weight are at extremely high risk for chronic arthritis in the hips. Proper weight control should be obtained through proper exercise and dietary management. If your pet is over weight, please consider proper weight control to minimize these risks.

Proper Exercise: If your dog has hip dysplasia you should limit him or her to moderate exercise such as swimming and long walks. High-intensity activity should be of short duration and should only be allowed after an adequate warm-up period.

Anti-inflammatory substances: There are many nonsteroidal anti-inflammatory medications (NSAIDs) available for use in dogs. However, all of these medications must be used with caution, as the pharmacokinetics are largely unknown and over dosage may result in severe gastrointestinal ulceration (the Senior Dogs Project's web site gives many examples of side effects caused by the popular drug Rimadyl.) NSAIDs should never be given without the specific recommendation of a veterinarian. Most NSAIDs interfere with glycosaminoglycan synthesis in the joint fluid and therefore should not be used for extended periods of time. In general, NSAIDs should be reserved for acute flare-ups of pain, but should not be used for long term management due to the potential for gastrointestinal side effects and continued joint breakdown.

¹Most of the information contained on this page was obtained from the chapter "Management of Joint Disease" in Small Animal Surgery by Theresa Fossum, et al, copyright 1997 and "Handbook of Small Animal Orthopedics and Fracture Treatment" by Brinker, Piermattei, and Flo.

Feline Hip Dysplasia

Hip dysplasia is an inherited trait involving multiple gene pairs - it is not congenital (meaning an animal is not born with it). The condition develops over time from instability in the hip joint which results from an improper fit of the femoral head (ball-like structure) into the acetabulum (hip socket). This instability, called hip joint laxity, results in abnormal weight bearing within the hip joint. From this, secondary changes and remodeling occur in an effort to stabilize the joint or avoid bone-on-bone contact. When cartilage disintegrates, from abnormal wear, the femoral head and acetabulum rub together with every step causing pain and eventual osteoarthritis.

What are the symptoms of feline hip dysplasia?

It has been suggested that cats with feline hip dysplasia (FHD) are not in pain. Well, unless you can talk directly to your cat, and he can ANSWER you, how can you know for sure? Cats are rather stoic creatures and it is speculated that they hide or mask their pain well. Out in the wilds if a cat showed pain by limping or moving slowly, he would appear vulnerable and be an immediate target for predators. Our domestic cats are still driven by natural instincts that tell them NOT to limp or not to move too slowly. There may be a gradual decrease in certain movements or particular activities that cause pain. For example, a cat in pain may not jump as high as usual, or it may move more and more slowly over time. These may be symptoms that most people simply would not notice or would attribute to other things. The gradual lack of movement may go undetected until one day - perhaps years from the onset of pain - the disease has progressed so that it becomes quite obvious with limping, not climbing, not jumping or the inability to go up stairs. Even then, because onset has been so gradual and there was not a drastic change in behavior from one day to the next some people may still not realize there is a problem.

Other symptoms that may indicate hip dysplasia include: continued dislike of being picked up, carried or being stretched as done at shows, yowling or grumbling when lifted or handled, a lack of motivation to move, stiffness, lameness, sensitivity to touch in the hindquarters, or even a popping sound coming from the back legs with each step. Also seen as possibly associated with dysplastic felines: early rapid growth and weight gain and hips that are noticeably narrower than the shoulders (lean, narrow bodies as opposed to broad, sturdy bodies). In addition, an association between medial patella luxation and hip dysplasia has been found. (See FHDA Library, abstract by Gail Smith, VMD, et.al.) Further information on Dr. Smith's findings can be found in in an article published in the Journal of the American Veterinary Medical Association, Vol 213, No.10, November 15, 1998 called "Relationship between degenerative joint disease and hip joint laxity by use of distraction index and Norberg angle measurement in a group of cats".

These signs and symptoms don't always mean hip dysplasia, but if one or more are observed over time, consult your veterinarian. X-rays may be indicated. Since feline hip dysplasia is still relatively new to the veterinary community, be sure to mention FHD to your vet. Some vets appreciate seeing information on new animal research so you might consider giving your vet the FHDA web site address.

NOTE: X-rays sent to OFA are evaluated by board-certified veterinary radiologists; you may wish to request that your vet go ahead and send the film to OFA for further evaluation.

Arthritis in Dogs and Cats

It is estimated that one in five of the 80 million adult dogs and cats in the United States suffer from arthritis to some degree, according to James Roush, doctor of veterinary medicine at Kansas State University. There are some signs owners should look for to tell when your pet experiences pain from arthritis.

"First, you will see some sort of lameness or reluctance to get up or move around," Roush said. "Owners will often note that he or she doesn't jump on or off the bed as often. The other things you may see are swelling in the joints, and heat or pain when you touch the joints. Dogs also won't like their legs moved."

There are two common reasons animals develop arthritis. The most common reason for skeletal or joint diseases are congenital, which means the diseased joints form because the dog or cat inherits imperfect physical traits, Roush said.

Hip and elbow displasia, degenerative joint diseases, are examples of common congenital diseases in large-breed dogs. Large dogs have big skeletal frames and grow faster than normal, which can cause stress on the joints, leading to arthritis.

The second most common cause of arthritis in dogs or cats is damage to joints from accidents. Damage to ligaments in knees and shoulders are common joint injuries received from accidents. In time, this can lead to inflamed joints and arthritic symptoms.

Your pet may not be able to tell you if he or she is in pain: dogs and cats don't moan and complain about their aching joints! This slowly progressive disease starts with almost undetectable discomfort, and may progress to the point that the animal refuses to stand, go outside when nature calls, or even eat. Similar to an aging person, the joints of our four-legged friends undergo aging changes as well. The joint fluid is not produced in enough quantity and the bones and ligaments begin to degenerate and become inflamed. The range of motion of these joints diminishes. The incidence of arthritis is most common in larger breed dogs but can affect small dogs and cats as well.

Hyaluronic Acid Clinical Studies

Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin.
J Eur Acad Dermatol Venereol. 2005 May;19(3):308-18.

Hyaluronic acid is a naturally occurring polyanionic, polysaccharide that consists of N-acetyl-d-glucosamine and beta-glucoronic acid. It is present in the intercellular matrix of most vertebrate connective tissues especially skin where it has a protective, structure stabilizing and shock-absorbing role. The unique viscoelastic nature of Hyaluronic acid along with its biocompatibility and non-immunogenicity has led to its use in a number of clinical applications, which include: the supplementation of joint fluid in arthritis; as a surgical aid in eye surgery; and to facilitate the healing and regeneration of surgical wounds. More recently, Hyaluronic acid has been investigated as a drug delivery agent for various routes of administration, including ophtalmic, nasal, pulmonary, parenteral and topical. In fact, regulatory approval in the USA, Canada and Europe was granted recently for 3% diclofenac in 2.5% Hyaluronic acid gel, Solaraze(R), for the topical treatment of actinic keratoses, which is the third most common skin complaint in the USA. The gel is well tolerated, safe and efficacious and provides an attractive, cost-effective alternative to cryoablation, curettage or dermabrasion, or treatment with 5-fluorouracil. The purpose of this review is to describe briefly the physical, chemical and biological properties of Hyaluronic acid together with some details of its medical and pharmaceutical uses with emphasis on this more recent topical application.

Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis.
CMAJ. 2005 Apr 12;172(8):1039-43.

Osteoarthritis of the knee affects up to 10% of the elderly population. The condition is frequently treated by intra-articular injection of hyaluronic acid. We performed a systematic review and meta-analysis of randomized controlled trials to assess the effectiveness of this treatment. We searched MEDLINE, EMBASE, CINAHL, BIOSIS and the Cochrane Controlled Trial Register from inception until April 2004 using a combination of search terms for knee osteoarthritis and hyaluronic acid and a filter for randomized controlled trials. We extracted data on pain at rest, pain during or immediately after movement, joint function and adverse events. Twenty-two trials that reported usable quantitative information on any of the predefined end points were identified and included in the systematic review. Even though pain at rest may be improved by hyaluronic acid, the data available from these studies did not allow an appropriate assessment of this end point. According to the currently available evidence, intra-articular hyaluronic acid has not been proven clinically effective and may be associated with a greater risk of adverse events. Large trials with clinically relevant and uniform end points are necessary to clarify the benefit-risk ratio.

Hyaluronic acid for the treatment of knee osteoarthritis: long-term outcomes from a naturalistic primary care experience.
Am J Phys Med Rehabil. 2005 Apr;84(4):278-83; quiz 284, 293. Petrella RJ. Department of Family Medicine, University of Western Ontario, Ontario, Canada.

Intraarticular hyaluronic acid is indicated for patients with osteoarthritis of the knee. However, clinical experience, especially efficacy and adverse events, with repeated injection series in the long term are limited. DESIGN: Patients were referred to a large primary care center for management of osteoarthritis of the knee. All were naive to intraarticular hyaluronic acid therapy and met our entry criteria, including resting visual analog scale pain of > 45 mm, radiographic confirmation of unilateral knee grade 1-3 osteoarthritis, and willingness to receive intra articular therapy. Patients received a three-intraarticular injection series with Suplasyn (10 mg/ml, 2-ml injection) over 3 wks. CONCLUSIONS: Intraarticular hyaluronic acid injections were highly effective in improving resting and walking pain in patients with osteoarthritis of the knee on a first and a second treatment series. Duration of symptom control was about 6 mos, and the therapy was highly satisfactory to patients and was associated with very few local adverse events and limited use of concomitant therapeutic modalities. These data support the potential role of intraarticular hyaluronic acid as an effective long-term therapeutic option for patients with osteoarthritis of the knee.

A double blind, randomized, multicenter, parallel group study of the effectiveness and tolerance of intraarticular hyaluronan in osteoarthritis of the knee.
J Rheumatol. 2004 Apr;31(4):775-82.

To investigate the efficacy and tolerability of a course of 5 injections of hyaluronan ( HA or hyaluronic acid ) given at intervals of one week in patients with symptomatic, mild to moderate osteoarthritis (OA) of the knee. A double blind, randomized, parallel group, multicenter (17 centers), saline vehicle-controlled study was conducted over 18 weeks. Patients received either 25 mg (2.5 ml) hyaluronic acid in a phosphate buffered solution or 2.5 ml vehicle containing only the buffer by intraarticular injection. Five injections were given at one week intervals and the patients were followed for a further 13 weeks. Of 240 patients randomized for inclusion in the study, 223 were evaluable for the modified intention to treat analysis. The hyaluronic acid treatment and control groups were comparable for demographic details, OA history, and previous treatments. Scores for the pain and stiffness were modestly but significantly lower in the hyaluronic acid -treated group overall and the statistically significant difference from the control was not apparent until after the series of injections was complete. The physical function subscale did not reach statistical significance. Tolerability of the procedure was good and there were no serious adverse events that were considered to have a possible causal relationship with hyaluronic acid. CONCLUSION: Intraarticular hyaluronic acid treatment was significantly more effective than saline vehicle in mild to moderate OA of the knee for the 13 week postinjection period of the study.
 

Intra-articular hyaluranic acid compared with progressive knee exercises in osteoarthritis of the knee: a prospective randomized trial with long-term follow-up.
Rheumatol Int. 2005 Mar 18;

The goal of this study was to determine whether hyaluronic acid or progressive knee exercises (PE) can improve functional parameters in patients with osteoarthritis (OA) of the knee. In a prospective clinical trial 200 knees (105 patients) with radiographic Kellgren Lawrence grade III OA were randomized and received either three intra-articular injections of hyaluronic acid (Hylan G-F 20) at one-week intervals or PE for 6 weeks. Patients were evaluated by use of the Hospital for Special Surgery (HSS) Knee Score and followed-up for 18 months. Total HSS score for hyaluronic acid and PE patients improved from 62.6+/-13.8 to 88.8+/-11.1 and from 65.4+/-12.3 to 88.3+/-9.1, respectively, at the end of the trial (P<0.01). There were no statistically significant differences between the groups. Twenty-one patients of the hyaluronic acid group were excluded from the study because they had received another form of therapy. All patients in the PE group completed the trial. The patients who dropped out had also significant improvement. This prospective randomized trial confirmed that both hyaluronic acid injections and PE result in functional improvement. Hyaluronic acid injections also increase the levels of satisfaction of the OA patients.
 

A one-year, randomised, placebo (saline) controlled clinical trial of 500-730 kDa sodium hyaluronate (Hyalgan, Hyaluronic acid) on the radiological change in osteoarthritis of the knee.
Int J Clin Pract. 2003 Jul-Aug;57(6):467-74.

The primary objective of this study was to investigate structural changes, as measured by joint space narrowing (JSN), within the knee joint during treatment with intra-articular sodium hyaluronate ( Hyaluronic acid ) of molecular weight 500-730 kDa in patients with osteoarthritis (OA) of the knee. Patients received a weekly intra-articular injection of either 20 mg2/ml Hyaluronic acid or a 2 ml vehicle placebo (saline) for three weeks. This course was repeated twice more at four-monthly intervals. Concomitant treatment with analgesics or NSAIDs was allowed. The primary efficacy measure was the reduction in mean joint space width (JSW) of the medial compartment at 52 weeks. A total of 408 patients were randomised and 319 completed the one-year study (Hyaluronic acid: n=160, placebo: n=159); 273 of the 319 were included in the primary analysis. Analysis of variance on these 273 patients did not show a statistically significant difference between the two treatment groups. However, there was a significant difference in response to treatment in terms of the baseline JSW (p=0.01), indicating that outcome of treatment may depend on-baseline JSW. Therefore, a subgroup analysis by baseline JSW was conducted. This compared patients with a JSW >4.6 mm with those with a JSW <4.6 mm. In those with radiologically milder disease at baseline and receiving Hyaluronic acid, the JSN was significantly reduced compared with placebo (p=0.02). In patients with radiologically more severe disease there was no difference in JSN between the two treatments. Although, in this one-year study, no overall treatment effect was seen, those with radiologically milder disease at baseline had less progression of joint space narrowing when treated with Hyaluronic acid.
 

Treatment of gingivitis with hyaluronan ( hyaluronic acid ).
J Clin Periodontol. 2003 Feb;30(2):159-64.

Hyaluronic acid (hyaluronan) is a glycosaminoglycan with anti-inflammatory and antiedematous properties. It was evaluated in a gel formulation for its effect in the treatment of plaque-induced gingivitis. METHOD: In a randomised double-blind study, 50 male subjects with plaque-induced gingivitis were divided into two groups and used a verum or placebo gel twice daily additionally to oral hygiene for a 3-week treatment period. Clinical indices (API, Turesky index, PBI) and crevicular fluid variables (peroxidase, lysozyme) were determined at baseline and after 4, 7, 14 and 21 days, respectively. Significant improvements could be found for all clinical variables in both groups. The Hyaluronic acid group showed significant improvement in the study area for the plaque indices beginning with day 4 and the PBI beginning with day 7in comparison with the placebo group. The crevicular fluid variables were significantly improved in the centre of the studied inflammation area in the Hyaluronic acid group. Here all studied sites had significant decreases in peroxidase and lysozyme activities after 7, 14 and 21 days, whereas in the placebo group only one site showed a significant decrease for lysozyme after 7 and 21 days. These data suggest that a Hyaluronic acid containing gel has a beneficial effect in the treatment of plaque-induced gingivitis.
 

Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis. A controlled, randomized, double-blind, parallel-design multicentre study.
Rheumatology (Oxford). 2002 Nov;41(11):1240-8.

To compare the efficacy and safety of intra-articular injections of two different hyaluronan ( hyaluronic acid ) preparations and placebo in patients with knee osteoarthritis. In a randomized, patient- and observer-blind, placebo-controlled and multicentre trial with parallel groups, 210 patients, aged 60 yr or above, with knee osteoarthritis were included in a per protocol analysis. The patients were treated with three injections, once weekly, of either native high-molecular-weight hyaluronan (Artzal((R))) or cross-linked hyaluronan (Synvisc) or with placebo and were followed for 52 weeks. The primary efficacy measures were weight-bearing pain during study weeks 0-26 and the duration of clinical benefit measured with Kaplan-Meier survival analysis for weeks 0-52. The secondary outcome measures were resting and maximum pain, Lequesne index, WOMAC (Western Ontario and McMaster University Osteoarthritis Index) and SF-36 (Medical Outcomes Study Short Form Health Survey) scores. RESULTS: The intra-articular injections produced a significant reduction in weight-bearing pain, resting pain, maximum pain and Lequesne and WOMAC scores after 26 weeks. There were no significant differences in outcome between any of the three study groups during the first 26 weeks. In direct comparison against placebo for weeks 0-52, neither hyaluronan treatment (Artzal or Synvisc) showed a significantly longer duration of clinical benefit than placebo. However, when data for the two hyaluronan-treated groups were pooled, treatment with hyaluronan had a significantly longer duration of benefit compared with placebo (P = 0.047). CONCLUSION: Patients with knee osteoarthritis who were treated by injection into the knee of either of two hyaluronan preparations or placebo showed clinical improvement during the first 26 weeks of treatment, though neither hyaluronan preparation gave a longer duration of clinical benefit than placebo. However, when data for the two hyaluronan treatments were pooled, there was a significantly longer duration of clinical benefit for hyaluronan treatment than for placebo.