Joint health supplementation at different life stages

This content is sponsored by Nutramax

Osteoarthritis (OA), with hallmark features of inflammation and cartilage breakdown, is best described as a disease resulting from many potential causes.^1-3 Veterinarians can alleviate patient pain and work to slow the cartilage breakdown in this chronic, progressive condition. Inflammation occurs before cartilage breakdown, so multimodal management approaches aim to reduce inflammatory mediators. In a multimodal approach to joint health, various modalities are available to individualize patient care, including pharmaceuticals targeted at inflammatory mediators and pain relief, weight management, physical therapy, alternative options, and joint health supplementation, providing an additional tool for joint health support.

Pathogenesis

Both the synovial lining and articular cartilage are instrumental in OA pathogenesis. Synovial lining cells produce joint fluid, whereas other synovial cells provide immune function and can produce inflammatory cytokines. The synovial lining contains many nerve endings, some of which carry pain signals. The cartilage surface of the joint consists of cartilage cells and the extracellular matrix made by those cells. The matrix is comprised of collagen and large molecules called aggrecan. The tensile strength of the matrix comes from the collagen network; the compressive stiffness and elasticity come from the aggrecan, which holds water.

Healthy cartilage matrix is constantly manufactured. When there is an imbalance between removal of old matrix and synthesis of new matrix in OA, with an overabundance of breakdown enzymes being produced, there is loss of healthy matrix. This results in water loss from the matrix and loss of strength from the collagen, making everyday weight-bearing loads uncomfortable at the joint level. As the cartilage surface roughens, the underlying bone is eventually exposed, which is more painful. Because of joint pain, activity is limited; then tissues tighten and stiffness occurs.

Synovial mediation of inflammation is seen very early in OA and may precede cartilage degeneration. Management approaches target inflammatory cytokines produced by cells in the synovium and by chondrocytes. These cytokines cause 2 main adverse effects: directly decreasing matrix synthesis and inducing the expression and secretion of matrix-degrading protease enzymes.

Joint health supplementation as part of a multimodal approach

Supplementation to support joint health has been practiced in veterinary medicine for decades. Supplements are not regulated in the US by the FDA, so not all supplements will have bioavailable ingredients or have confirmed amounts of label claims.⁴ This review is not exhaustive but instead gives guidelines on indications for supplementation.

Essential omega-3 fatty acids

Long-chain omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) should be the mainstay of supplementation and have good evidence of improving gait and comfort in dogs with OA, with reduction in both systemic and joint inflammatory mediators.⁵ There is also evidence of a positive effect on OA in cats. EPA and DHA have anti-inflammatory properties, and when consumed in high enough amounts, replace part of the pro-inflammatory molecule arachidonic acid in cell membranes.⁶

Both EPA and DHA are found in high concentrations in fish oil and in oil collected from Perna canaliculus (green-lipped mussel), also from plant-based sources like algae. Algal oil has been shown to have good bioavailability in cats.⁷ The recommended intake of EPA and DHA is approximately 69 mg/kg body weight per day for dogs to achieve systemic modulation of inflammatory mediators.⁶ It is important to consider the caloric intake when supplementing omega-3s. Concentrated sources of omega-3s or a restricted-calorie diet high in omega-3s are recommended to aid weight loss for many obese patients with OA, and to reduce the chance of weight gain in our sedentary OA patients of normal weight.

Glucosamine hydrochloride and chondroitin sulfate

Glucosamine and chondroitin are both components of articular cartilage and have been used in humans and pets for joint health support. Glucosamine is a building block of glycosaminoglycans, which help bind water to give cartilage its resistance to compression. Chondroitin also has a role in resistance to cartilage compression. Evidence for oral glucosamine and chondroitin sulfate is equivocal in dogs and cats; however, chondroitin sulfate has been demonstrated in other species and in vitro to support joint health at the synovial membrane and impact inflammatory mediator release. A recent review on the use of glucosamine and chondroitin in humans found that more than 90% of efficacy studies demonstrated positive outcomes, and most safety studies found minimal to no adverse effects.⁸ Glucosamine is also active in both cellular and molecular aspects of the inflammatory reaction. In vivo studies in dogs show that glucosamine and chondroitin sulfate can ameliorate chemically induced synovitis, stimulate cartilage metabolism, and inhibit cartilage degradation.^9,10 There is no evidence of a positive impact on pain and lameness. The purpose of supplementation is to modify the joint environment over the long term and is only part of a multimodal management plan.

Avocado/soybean unsaponifiable

Avocado/soybean unsaponifiables (ASUs) are slow-acting inflammatory modulating agents due to effects from phytosterols.¹¹ Studies in humans have shown a reduction in pain with oral ASUs.¹² The substances have been shown in vitro to promote the synthesis of collagen and aggrecan by chondrocytes and to reduce production of proinflammatory cytokines.¹³ This is also found when used in combination with chondroitin sulfate.¹⁴ Subchondral bone is metabolically active and involved early in OA; in a rat model of OA, ASUs have been shown to inhibit subchondral bone resorption.^15,16 Feeding ASUs to dogs resulted in an increase in levels of TGF-β in joint fluid; TGF-β is a cytokine important in synthesizing matrix components by chondrocytes.¹⁷ ASUs can be considered in combination with other ingredients as part of multimodal management.

Undenatured type II collagen

Undenatured type II collagen (UC-II) is present in cartilage, sealed under the surface of matrix. In OA, this matrix is broken down, exposing the collagen. The body’s innate inflammatory cells react to this collagen as if it were foreign or a sign of an injury. UC-II supplements work through oral tolerance, an immune process the body uses to distinguish between innocuous compounds (eg, dietary proteins, intestinal bacteria) and potentially harmful foreign invaders.¹⁸ A study in dogs with OA administered UC-II alone or in combination with glucosamine, and chondroitin showed that dogs moved better and had lower pain scores in a nonblinded study.¹⁹ In a different nonblinded study comparing with the nonsteroidal antiinflammatory drug robenacoxib, pain scores and mobility were similarly improved in the UC-II and the robenacoxib groups.²⁰ A review of 14 articles about UC-II showed it had a positive effect on OA in dogs, decreasing clinical signs and improving mobility.²¹

Eggshell membrane

Eggshell membrane (ESM) is the thin layer between the calcified shell and albumin in chicken eggs and contains collagen, glycosaminoglycans, and elastin. One study in dogs evaluated the supplementation of ESM over 6 weeks in dogs with altered joint function and found that supplementation helped support a quick response in joint comfort and function, along with reduced serum levels of CTX-II, a cartilage degradation biomarker.²² Another study in dogs looked at an eggshell membrane based supplement that also contained the antioxidant astaxanthin, omega-3 fats, and Boswellia serrata extract (Boswellia), which found a small change in pain scores and serum inflammatory markers.²³

Unfortunately, this does not separate the effects of eggshell membrane from the already proven effect of omega-3 fats, nor does it exclude any potential positive contribution from astaxanthin or Boswellia. Like eggshell membrane, Boswellia has been mostly studied in combination supplements; therefore, the effects of Boswellia alone are difficult to interpret.^21,23-25 Synergistic effects have been shown with the combination of glucosamine, chondroitin, ASUs, and Boswellia serrata in Nutramax studies.²⁶

Life stage considerations

Dogs near or at skeletal maturity At this stage, joint supplementation can be added to a multimodal management plan, but is primarily advised in clinical cases secondary to dysplasia or trauma, with early screening for dysplasia recommended. In one study, 20% of dogs between 9 and 18 months had radiographic evidence of OA, though only 16% of those dogs with OA on radiograph were reported to be painful.²⁷

In the author’s experience, examinations on young prospective sporting dogs often elicit pain on joint compression if they have dysplasia, even though they are not limping.

Young adults (2-4 years old)

Predisposing factors for OA in this age range are similar to those in the prior age group; traumatic injury and dysplasia, although obesity can be more of a predisposing factor by this age.²⁸ In the US, close to 50% of dogs and cats are overweight or obese.²⁹

Clinical presentation of joint pain from dysplasia can often be delayed, and diagnosis occurs in this age period when joint changes from dysplasia have already progressed.³⁰ When evaluating radiographic evidence of OA, 47% of dogs from 2.3 to 3.1 years and 57% of dogs 3 to 4 years were affected, and of that, only 1 in 5 had palpable joint pain.²⁷ In clinical rehabilitation practice, functional testing is used (leg lifts, range of motion measurements), along with questionnaires about daily activities at home, which helps to identify likely or high-risk patients, necessitating screening radiographs.

As part of a multimodal approach, supplementation with glucosamine and chondroitin sulfate is safe in this age group and is advised if a patient has predisposing factors. If screening radiographs show joint changes, then omega-3s and ASU should be added in addition to disease-modifying OA pharmaceuticals (polysulfated glycosaminoglycan; PSGAGs).

When it comes to working and sporting dogs, there are no specific reports of the prevalence of OA in these dogs, and so it is not scientifically known whether there is a higher incidence in this population. This is also compounded by breeds often used for work (Labrador retrievers, German shepherds) having a higher incidence of dysplasia.^31,32 Clinical experience, however, tells us that trauma is highly likely in this population, which predisposes them to OA. As a sports medicine specialist, the author recommends supplementation with glucosamine and chondroitin in any sporting dog over 5 years old, and in any with a history of trauma at any age beyond young puppyhood, with the additional recommendation of adding omega-3s and ASU in these dogs.

Mature adults (aged 4-7 years)

Most dogs with dysplasia will present with clinical signs before the age of 4. The most likely predisposing factor for OA in mature adults is obesity. The lifetime study on Labrador retrievers showed that even slightly overweight dogs had a greater incidence of OA.³³ These studies show that keeping dogs lean via dietary restriction can be preventive for OA, and that once dogs are overweight, they are about 1.5 times more likely to have OA.³³ Obese and overweight adult dogs should be carefully screened and, in addition to dietary counseling and caloric restriction, omega-3s should be fed during weight loss. If a mature adult gains a few pounds, the primary focus should be on weight loss. For every 1 lb of excess body weight, approximately 4 lb of shear force is applied to the joints.³⁴

Senior adults (aged 8-11 years)

As dogs age, they are more prone to weight gain as they become more sedentary.³⁵ Muscle size also begins to diminish, even with unchanged activity.³⁶ This can mean less stamina and less muscle action to cushion joints from impact, further diminishing activity and increasing discomfort in dogs with OA. OA incidence in dogs over 8 years is reported to be 40%.³⁷ A diet rich in omega-3s is recommended for most aging dogs, with calorie restriction as indicated. In addition to pain management and PSGAGs, supplementation for dogs with OA in this age group should include ASU with glucosamine and chondroitin sulfate, and, ideally, UC-II.

Geriatric adults (12 years and older)

As patients become very elderly, muscle size is very small, and frailty syndrome occurs.³⁸ Food intake can be minimal, with caloric intake and adequate dietary protein taking precedence. Medications can suppress appetite, as can supplements. Practitioners should prioritize food and medications over adding supplements if a patient is at end of life and won’t eat supplements.

References

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