December 2023 17 Leading Article improvements in scores for pain, weight-bearing and OA severity by day 70, and was non-inferior to carprofen at day 70. Contrastingly, Scott et al. (2017) found that dogs treated with oral glucosamine hydrochloride and chondroitin sulphate for 90 days did not display increased activity levels when compared with a placebo, although owner assessment scores increased, indicating a possible caregiver placebo effect. Further research (evidence level I or II) is required to determine the efficacy of using glucosamine and chondroitin in improving clinical outcomes in OA as their analgesic efficacy has not been well demonstrated (Moreau et al. 2003). Curcuminoids Curcuminoids are natural turmeric-derived polyphenols (Henrotin et al. 2010). Many in vitro studies have demonstrated the anti-oxidant and anti-inflammatory properties of these compounds (Henrotin et al. 2010, Comblain et al. 2017). However, the bioavailability of naturally occurring curcumin in dogs is uncertain. Innes et al. (2003) described a significant effect for dogs treated with Curcuminoid P54FP using objective assessments, although owners failed to notice a difference in their dogs’ mobility. In contrast, Comblain et al. (2017) found no changes in objective variables (PVF and OA biomarkers). A recent systematic review of 10 human studies demonstrated reduction in pain and improved function in patients with knee OA pain (Paultre et al. 2021). Curcumin has been shown to be an active iron chelator in vivo, although it is unclear how this would affect carnivores such as dogs (Jiao et al. 2009, Badria et al. 2015). There is a need for a large-scale clinical trial as most data is relying on experimental, in vivo studies. Currently, recommended doses include 50 to 250 mg curcumin three times daily (Fougère & Wynn 2007), although future trials also need to focus on the bioavailability of the available forms and thus accurate dosages before these can be recommended as a reliable treatment for canine OA. Elk velvet antler Elk velvet antler is a Chinese medicine used to treat various diseases and is derived from the inner antler core in the velvet stage of growth (Zhang et al. 1992). In vivo studies have shown antiinflammatory effects in a rodent model of inflammation (Cheng et al. 2022). Velvet antler also contains chondroitin sulphate (Moreau et al. 2003, Henrotin & Lambert 2013, Bhathal et al. 2017, Scott et al. 2017). Moreau et al. (2004) used quality elk velvet antler in dogs with OA, with the majority of dogs improving in daily activities and their weight-bearing abilities (based on gait analysis). Further research into how elk velvet antler can inhibit the degenerative process of OA would be useful, alongside its efficacy compared to commonly prescribed OA medication (e.g. NSAIDs). Vitamin E Several human studies have shown benefits of vitamin E on OA clinical signs over a short-term period, primarily by reducing free radicals and synthesis of pro-inflammatory cytokines (Farbstein et al. 2010, Rizvi et al. 2014, Chin & Ima-Nirwana 2018). In dogs with surgically induced OA, nitric oxide and prostaglandin E2 in synovial fluid were lower following treatment with vitamin E, and histological OA lesions were reduced in dogs fed a high dose of vitamin E (400 IU/day) (Rhouma et al. 2013). Lameness and pain [assessed by visual analogue scales (VAS), numerical rating scales (NRS) and electrodermal activity] were also reduced in the vitamin E-treated group (Rhouma et al. 2013). Vitamin E is thought to be well tolerated in dogs with no adverse effects reported (Musco et al. 2019). However, there is a requirement for studies in naturally occurring canine OA and a longitudinal study to assess the synergy between Vitamin E and other compounds used to treat canine OA to determine the overall effectiveness. Avocado/soybean unsaponifiables The use of avocado/soybean unsaponifiables (ASU) in vitro has been shown to reduce interleukin-1 beta, and increase collagen synthesis in chondrocytes (Mauviel et al. 1991). Oral treatment improved subchondral bone structure (Cake et al. 2000) and reduced early OA cartilage and subchondral bone lesions (Boileau et al. 2009). ASU acts by downregulating synthesis by chondrocytes and correcting the imbalance between catabolic and anabolic processes which contribute to the onset and development of cartilage lesions in OA (Henrotin et al. 2003). Some studies have demonstrated that the beneficial effects of ASU can persist after treatment has ended (Blotman et al. 1997, Maheu et al. 1998). One human study found ASU to be a slow-acting drug, with symptomatic efficacy only occurring from the second month (Maheu et al. 1998). Canine studies have a maximum duration of treatment of eight weeks (Boileau et al. 2009). Thus, a longer study is required to identify the use and efficacy of ASU in the management of canine OA when used alone and in conjunctionwith other medication. S-adenosyl l-methionine S-adenosyl l-methionine (SAMe) is a nutraceutical commonly used to treat canine liver diseases such as chronic hepatitis, hepatic lipidosis and cholangiohepatitis (Wallace et al. 2002, Center et al. 2005). Due to its anti-oxidant properties, some have suggested that SAMe may have a beneficial use in canine OA (Gutierrez et al. 1997, McCarty & Russell 1999). SAMe has been shown to maintain the biomechanical strength of articular cartilage (Gutierrez et al. 1997) and promote a functional articular matrix (Bradley et al. 1994). One study found that SAMe was not an effective standalone treatment for canine OA as both subjective and objective outcomes did not show improvement in reducing clinical signs within 6 weeks of treatment (Imhoff et al. 2011). Previous human research has shown that SAMe has a slower onset of action when compared with NSAIDs; patients noticed no difference in pain scores with SAMe and NSAIDs after 2 months (Najm et al. 2004). Imhoff et al. (2011) did not assess the equivalence between SAMe and NSAIDs, thus, further research would be interesting for comparison to human medicine. However, from current research, there is no evidence to show the use of SAMe would be beneficial in the treatment of canine OA. Nutraceuticals –conclusion In reviewing the available evidence, the use of omega-3 could provide some analgesic effect for dogs with OA. However, commonly used products such as chondroitin-glucosamine have not been shown to have an analgesic effect (Paultre et al. 2021). Despite this, it is important to note that OA is a progressive disease and the duration of the trial is a key factor when assessing response to treatment. Other nutraceuticals such as green-lipped mussel and elk velvet antler demonstrate promising results, yet evidence is minimal for these products and further clinical studies are required to fully assess their efficacy. ACUPUNCTURE Acupuncture originated as a treatment of pain for people in China around 3000 years ago (Hao & Mittelman 2014). Over the past few decades, a growing yet mixed body of evidence has emerged in
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