Canine osteoarthritis therapies – a scientific review

Introduction

An article discussing the etiology, detection and diagnosis of canine osteoarthritis (OA) was published by the group in 2024, and this article concludes the review with a presentation of the options available to treat OA-related chronic pain management in dogs. Today’s veterinarian has an extensive choice of possible therapies – both pharmaceutical treatments and non-pharmacological alternatives. Many of these therapies have been drawn initially from human clinical studies, and this paper aims to evaluate the various treatment options in an objective manner via a wholesale literature review.

Pharmaceutical therapies 

When it comes to pharmaceutical options for OA management, it is important to know what the benefit:risk ratio is for the available therapies. Figure 1 offers a classification on the level of evidence for efficacy based on the quality of referenced studies in Table 1, i.e., if the experimental design employed favored a randomized, (placebo) controlled, blinded study using objective pain assessment, alongside statistical analysis. A placebo response is possible in any individual suffering from a condition, and with any assessment method – as is a nocebo (detrimental) response. However, a placebo effect on “group” is more common and is elevated with subjective (more sensitive to bias) measures, whereas placebo and nocebo responses measured in an objective outcome tend to neutralize for a group. Despite this recognized major weakness, there are still too many studies using subjective, non-validated assessments, and that lack a comparative control to draw any conclusion about efficacy of pain management.

 

Table 1. Literature search: pharmaceutical OA management options.

Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAID efficacy in canine OA has been reported in at least 40 scientific publications in the last 30 years, but several contained significant shortcomings that call into question the reliability of the results obtained. For instance, only 13/40 studies used objective assessment measures such as podobarometric gait analysis (PGA) or actimetry, while the remainder relied on subjective outcomes to evaluate treatment efficacy. To our knowledge, 16/40 studies employed a (partially) validated subjective pain assessment method, most commonly (14/16) the Canine Brief Pain Inventory (CBPI). Moreover, only 42.5% of the studies incorporated a placebo control; of these, only 8 included a placebo group as well as an objective assessment, allowing for valid conclusions to be drawn regarding the efficacy of the tested NSAID.

One study demonstrated a significant improvement in peak vertical force (PVF) values at day 60 in OA dogs receiving carprofen or meloxicam (1). Similar PVF results were subsequently obtained with carprofen dosed either short-term (≤ 14 days) (2-4) or over 6 weeks (5). Both drugs appear to decrease night-time activity, potentially suggesting better sleep quality (6,7).

Previous studies used oral administration, but a recent study found that intra-articular (IA) injection of celecoxib significantly decreased local PGE2 concentrations and improved PGA over a 2-month follow-up (8), and although the study is a proof of concept, this new route of administration is promising.

Carprofen seems to be effective in reducing biomechanical OA pain (18/40 publications, 45%), as does meloxicam (8/40, 20%). Coxibs and piprants, being more recent drugs, were mostly tested using subjective evaluation (15/19 studies) compared to a positive or placebo control (12/19), but only 7 utilized a validated clinical metrology instrument, 4 included PGA, 6 a placebo control, and only one with both PGA and placebo control.

Considering the scarcity of studies using validated objective-based results, the effectiveness of NSAIDs in OA dogs cannot be undoubtedly confirmed for all products, particularly with regards to:

1. The remaining lack of evidence-based dosage recommendations, which may vary with OA severity, the different administration regimes (continuous or “as-needed”), and inclusion of other multimodal products, which could impact synergic and safe use. 
2. The well-known low compliance with NSAID treatment.

This is worrying, because NSAIDs are the principle pharmacological class used to manage OA, even more so when considering the known and observed side effects. The true incidence of adverse events is currently unknown, and in most randomized, placebo-controlled, blinded studies it was not statistically different between treated and control dogs. The most common adverse events were gastrointestinal events (nausea, vomiting, diarrhea, and anorexia), although hepatotoxicity and nephrotoxicity are also possible. Signs were observed in 36/46 trials, with a global incidence of 8.1% from 4,398 treated dogs. 

Finally, it is important to note that most of the studies were funded by pharmaceutical companies seeking to validate the effectiveness of their product, as reflected by a 81% rate of “conflict of interest” when reported transparently.

Monoclonal antibodies

Excessive nerve growth factor (NGF), which has been demonstrated to be implied in OA pain and sensitization, has become a pharmacological target of choice within the last decade. Four published articles (three with a placebo group) report on the potential benefits of caninized anti-NGF monoclonal antibodies, mainly involving subjective methods of assessment, with the CBPI used as the primary outcome. One study also included an objective assessment method (actimetry), and found that day-time activity increased over a 28 day period with one injection of ranevetmab (not available commercially), when compared to placebo (9); bedinvetmab also showed effective analgesia from days 28-84 when compared to placebo (10). As defined by CBPI, higher responder rate (around 53-58%) occurred two weeks after the second monthly injection and plateaued after this, the placebo rate reaching up to 42%. Due to the ubiquitous role of NGF in many bodily functions, long-term adverse effects are possible, but these appear to be infrequent (1-10 cases for 10,000 administered doses in pharmacovigilance data) and have not yet been studied specifically to identify true causality. Guidelines on case indication (mild, moderate or severe OA) and on potential safe and efficient drug combination are missing for the moment.

Tramadol

Only three recent articles have focused on the opioid tramadol for its effects in canine OA pain. Two included a placebo group and one a healthy group as control, and two studies used objective assessments (i.e., actimetry and/or PGA). Toxicity was reported in two articles (but with contradictory results), and one article was associated with some conflict of interest. No effect was reported for the tramadol (4 or 5 mg/kg TID PO) treated group (for only 14 or 10 days) compared to placebo group with PGA (4,6), but CBPI subjective score improved for the treated group (6). With such a short treatment duration, objective assessment confirmed that tramadol does not induce an opioid effect in dogs, but long-term (1 month) administration of slow-release tramadol (5 mg/kg SID PO) was associated with a synergistic analgesic effect, allowing reduced dosage (0.25 mg/kg SID PO) of the NSAID ketoprofen, suggesting an inhibition of serotonin and norepinephrine reuptake, the central monoamine neuromediators that accentuate endogenous inhibitory pain control (11).

Disease-modifying OA drugs (DMOADs)

As an alternative to NSAIDs, which target chronic inflammation, DMOADs aim to stop or limit structural joint alterations, with the intention that reduced catabolism will no longer fuel the inflammation-driven neurosensitization. DMOADs include:

• pentosan and doxycycline, which target mediators of cartilage tissue renewal,
• bisphosphonates such as tiludronate, which affect bone renewal,
• hyaluronic acid and radioisotopes, which combat synovial inflammation and provide viscosupplementation.

Twenty-five research articles were published between 1985-2022 on various DMOADs for canine OA pain management; 15/25 used objective assessments (such as PGA, histology, and serologic analysis), 9/25 used an experimental canine OA model, and only 48% included a placebo group. This is a major limitation, as studies employing an induced OA model would require confirmation using natural canine OA with a randomized, controlled and blinded clinical trial. Furthermore, 40% of studies did not mention their conflict of interest.

Experimental models were usually supportive of promising structural effects, but translation in clinical canine OA was often disappointing, at the best non-conclusive: an injectable commercial fatty acid co-polymer was studied only once (in 1985) and showed 64% functional improvement in treated dogs, but several factors (no placebo group, no objective evaluation, and a 41% loss at follow-up) meant no efficacy conclusion could be drawn (12). For pentosan polysulfate, two multicentric randomized trials using 3 mg/kg SC q7D for 4 injections failed to show any significant analgesic effect, and these were deemed to be poor quality studies using non-validated subjective scales. Corticosteroids in the form of prednisone (0.25 mg/kg SID PO) or triamcinolone (5 mg, q4week IA) appeared to reduce the size of osteophytes and cartilage lesions in a canine OA model (13), but in general subsequent convincing clinical trials are missing. In summary, effectiveness of DMOADs remains dubious, and most studies did not report potential toxicity despite the use of repeated injections, and although the use of IA injections in canine OA management remains promising, various factors contribute to its current limited use.

Amantadine

The potential complementary analgesic effect of amantadine, an antiviral drug, was explored in a single study alongside meloxicam (14), but methodological weaknesses, including subjective assessments without validation, cast doubt on its efficacy. Overall, there is no evidence to support the use of amantadine as an analgesic treatment for OA canine pain, compounded by its restricted availability since the COVID pandemic.

Gabapentin

Gabapentin is increasingly being used in veterinary prescriptions to relieve the pain of canine OA, but there are currently no scientific publications to support this practice. A conference abstract reported that dogs were treated with a combination of carprofen and gabapentin (8-12 mg/kg TID PO) or tramadol (3-5 mg/kg TID PO) for a total of 4 weeks, but no information regarding the NSAID was provided. Although a similar improvement in PGA was reported with both central analgesics, there was no placebo group, so this improvement cannot be attributed reliably to the treatment. In addition, side effects were reported in up to 70% of treated dogs, but these were not detailed, and (to the author’s knowledge) no article has been published following this abstract. There is a need for qualified studies using gabapentin alone or in association with a parallel placebo group, alongside objective evaluations.

Non-pharmaceutical options

The animal health market is brimming with non-pharmacological options for managing canine OA (Table 2), but are they effective and are they safe? While some require consultation with a veterinarian, others are administered by para-professionals or even used autonomously by owners, and there is a growing inclination among owners to utilize more natural products to care for their pets (15). A review of various options is given below, with a diagrammatic representation of their proven efficacies shown in Figure 2. 

 

Table 2. Literature search: non-pharmaceutical OA management options.

Adjunctive musculoskeletal treatments

Joint (IA) injections with biological adjunctive musculoskeletal treatments (AMT), with or without a combination of other options, seem to offer promise. AMTs target cartilage regeneration and reduces synovial inflammation, improving the animal’s functional abilities. Among AMTs for canine OA, there are two categories of injectable biological products: 

1. Mesenchymal stromal cells (MSC) or stromal vascular fraction (SVF) of autologous, allogeneic or xenogeneic origins. 
2. Platelet-rich plasma (PRP), plasma rich in growth factors (PRGF) and autologous protein solution (APS), including activated conditioned serum (ACS) or autologous platelet concentrate (APC).

Several reports on MSC/SVF injections for canine OA (n=36) found efficacy and safety, either alone (n=26) or combined with NSAID (n=1), PRP (n=4) or hyaluronic acid (n=5) (16). Owners reported a 50% subjective improvement (which is considerable) post-injection in lameness, Range of Motion (ROM), activity and OA pain, especially for severe cases (16). However, these improvements were not corroborated by veterinarians and objective assessments. Placebo-controlled studies (n=6) showed subjective improvement ranging from 16.4-40.8% (n=4) and objective improvement from 0-37.5% (n=2) for the treated group vs. the placebo group. The size (or clinical) effect of such AMT interventions is small (20-50% difference). Study design and methodological limitations, such as lack of a placebo group and standardization in MSC preparation, hinder drawing conclusions from these findings (16).

Limited evidence exists for PRP, PRGF, and APS/ACS/APC injections (n=19), either used alone (n=10) or combined with MSC (n=4) or physical therapy (n=5) (16,17). A multispecies systematic review (n=7 articles in dogs) indicated clinical benefits and disease-modifying effects of PRP injections (one or multiple) in 1,251 animals (17). Subjective outcomes improved by 30-50% at 30 days post-injection, but tended to regress by 120-180 days. Only 6/19 were placebo-controlled, all showing no significant difference between treatment and placebo groups (17).

In summary, biologic AMTs show promise in treating canine OA safely, even with long-term repeated injections (16,17). Safety concerns are mostly related to the preparation and injection process, warranting further investigations. Combined biologics AMT, or AMT with physiotherapeutic modalities, showed better long-term effectiveness (90-180 days) in both clinical/subjective and objective outcomes, but most studies emphasized the lack of scientific rigor and weakness in experimental design, with limited objective pain assessments and methodological shortcomings highlighted (16,17), so IA biologics cannot be currently recommended.

Physiotherapy modalities

There have been a few studies looking at options that include pulsed electromagnetic field therapy, photobiomodulation (laser) therapy, extracorporeal shockwave treatment, and nuclear magnetic resonance therapy, but with variable results. A recent exhaustive narrative review (18) highlighted that transcutaneous electrical nerve stimulation and ultrasound therapies were beneficial for OA pain management in humans, but could not achieve the same conclusion for canine OA due to the lack of scientific evidence. Overall, the efficacy of physiotherapeutic modalities in managing canine OA remains uncertain due to limitations in existing research, such as subjective assessments, lack of placebo control, unblinded interventions, heterogeneity in treatment protocols and patient populations.

Other therapies 

Acupuncture studies (n=10) have shown conflicting results, with discrepancies observed between owner-reported improvements and assessments conducted by veterinary professionals. Several investigations – including hydrotherapy, aquatic exercise, and manual therapy for canine OA – have shown mixed outcomes; for example, while hydrotherapy demonstrated promise in improving parameters related to hip dysplasia, aquatic exercise yielded unconvincing results. Manual therapy studies encounter design difficulties: one uncontrolled study showed passive stretching to significantly increase joint ROM in OA dogs, while another report highlighted conflicting effects of walking on different terrains, emphasizing the importance of tailoring exercises in rehabilitation programs. 

One systematic review has examined the use of homeopathy in OA dogs (n=2) (19), and only one study, conducted on 44 dogs, yielded conclusive results. It suggested that the mobility, PVF, and pain of treated dogs changed significantly vs. placebo, when the analysis was restricted to positive responders. The second study presented a high risk of bias, and was not considered.

It appears that no study has examined the effects of olfactory or auditory stimulation in the management of canine OA, although such stimulation has been studied in relation to other conditions. A study in 55 shelter dogs suggested that lavender oil seemed to induce activities evocative of relaxation. Another study with 60 shelter dogs demonstrated a reduction in arousal-related behaviors when exposed to music and pheromones for three hours each day, and, to a lesser extent, if exposed to lavender for the same period. However, according to a systematic review, the use of pheromones for the treatment of undesirable canine behavior lacks sufficient evidence of efficacy (n=7) (20).

 

Box 1. A list of the acronyms most frequently used in the article.

 

Lifestyle and diet

Food restriction and weight loss

Only three clinical studies have examined the effects of a weight management diet and OA, and how weight control can impact on overweight or obese OA dogs. Subjective and objective measures, when performed, showed that weight loss improved lameness in OA dogs, but the studies had small sample sizes, no control group, and were not blinded (21). One longitudinal review that started at 8 weeks of age in Labradors investigated if dietary restriction would reduce OA incidence and severity; half the dogs were fed a control diet and the other half a 25% calorie-restricted ration (21). The incidence of OA lesions in the control vs. the restricted diet were respectively 61.1% vs. 14.2% for hip, 86.3% vs. 57.1% for shoulder, and 36.3% vs. 19.0% for elbow. The prevalence of OA affecting multiple joints was higher in the control group, as was the severity of hip, elbow and shoulder injuries. Moreover, dogs on the restricted diet showed a delayed initiation for OA treatment, and those that required euthanasia due to OA were considerably older than dogs fed the control diet. Interestingly, a PGA study in privately-owned OA lame dogs demonstrated that a gain in bodyweight exacerbated lameness, with more alteration in PVF than dogs with a stable bodyweight (22). 

In summary, large breed dogs maintained at a body condition score of around 5/9 for life may present with: 

• A reduced incidence of hip dysplasia. 
• A reduced incidence and severity of OA. 
• A delayed need for treatment of OA (and of other chronic diseases). 
• A delayed need for euthanasia due to chronic disease (OA-associated altered animal welfare was a leading cause of euthanasia); and 
• A delayed natural death due to disease other than OA (to be tested in the future).

Therapeutic diets and nutraceuticals

A systematic review (n=54) discussed the effectiveness of therapeutic diets and nutraceuticals in managing canine OA (23). Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) of marine source (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) appeared to be the most studied (n=15) and effective either as supplements or in therapeutic diets (only 10% had a non-effect), without side effects. Nutraceuticals based on collagen (n=8; 18.2% non-effect) and cannabinoids (n=5; 14.3% non-effect) presented lower efficacy and lower size effects. Chondroitin-glucosamine nutraceuticals (n=8, 88.9% non-effect) were clearly ineffective and should not be recommended for canine OA management. The studies associated with collagen- and chondroitin-glucosamine-based nutraceuticals were of mediocre methodological quality, unlike those on ω-3 PUFAs and cannabinoids (23).

It is to be recommended that ω-3 PUFAs should be marine in origin (rich in EPA/DHA) and not sourced from plants. The latter (such as flaxseed, soy or nut oils) are rich in alpha-linolenic acid (ALA)) which is poorly (if at all) metabolized into EPA/DHA by animals. Unlike drugs, dietary supplementations are not controlled, and there is the risk of potential content variability, therefore efficacy, quality and safety are not guaranteed. Further research is needed to document recommended doses, formulations and combinations for each product. Veterinarians should review their current recommendations, making dog owners aware of these subtleties, and practice more evidence-based-medicine (23), as well as encouraging owners to invest in actions that can make a difference in their dog’s health.

Environmental modifications and exercise

It is recommended that OA dogs engage in daily low-impact exercises to avoid exacerbating the condition, which could lead to supplemental cartilage and bone damage and the development of scar tissue and articular fibrosis. Limited proof of the effectiveness of daily exercise in canine OA exists: the author’s group have reported that 54 minutes of daily activity led to a clinically significant increase in PVF. However, owners should receive training and regular veterinary follow-up to adjust the recommendations correctly (24). Even a moderate exercise level can lead to a deterioration of gait in OA-afflicted dogs compared to control dogs.

Recommendations for environmental modifications are based primarily on the experience and judgement of veterinarians and owners, but as far as is known there are no studies that measure their effectiveness in the management of canine OA pain. These changes are likely beneficial for an optimal owner-dog cohabitation in their daily interactions, but poses the question – is it possible they will lessen or increase the caregiver burden?

Conclusion

The management options for canine osteoarthritis (OA) are extensive, drawing upon human studies to propose both pharmaceutical treatments and non-pharmacological alternatives. It is expected that combination therapy will demonstrate superior outcomes compared to individual treatments alone, due to additive or synergistic effects. Good scientific evidence for individual therapies can be scarce, and almost non-existent for multimodal approaches. Primum non nocere must be the frontispiece for OA therapy, and should take into account many patient-related factors, such as OA severity, duration and evolution, alongside any comorbidities, with treatment choice based on the diagnosed (or suspected) OA pain mechanisms. Ideally a better framework for canine OA management will emerge in the future, making it easier to correspond adapted and efficient treatment to the dog’s needs.

 

 

 

References

1. Moreau M, Dupuis J, Bonneau NH, et al. Clinical evaluation of a nutraceutical, carprofen and meloxicam for the treatment of dogs with osteoarthritis. Vet. Rec. 2003;152(11):323-329.
2. Vasseur PB, Johnson AL, Budsberg SC, et al. Randomized, controlled trial of the efficacy of carprofen, a nonsteroidal anti-inflammatory drug, in the treatment of osteoarthritis in dogs. J. Am. Vet. Med. Assoc. 1995;206(6):807-811.
3. Brown DC, Boston RC, Farrar JT Comparison of force plate gait analysis and owner assessment of pain using the Canine Brief Pain Inventory in dogs with osteoarthritis. J. Vet. Intern. Med. 2013;27(1):22-30.
4. Budsberg S, Torres B, Kleine S, et al. Lack of effectiveness of tramadol hydrochloride for the treatment of pain and joint dysfunction in dogs with chronic osteoarthritis. J. Am. Vet. Med. Assoc. 2018;252:427-432.
5. Kampa N, Kaenkangploo D, Jitpean S, et al. Study of the effectiveness of glucosamine and chondroitin sulfate, marine based fatty acid compounds (PCSO-524 and EAB-277), and carprofen for the treatment of dogs with hip osteoarthritis: A prospective, block-randomized, double-blinded, placebo-controlled clinical trial. Front. Vet. Sci. 2023;10:1033188.
6. Malek S, Sample SJ, Schwartz Z, et al. Effect of analgesic therapy on clinical outcome measures in a randomized controlled trial using client-owned dogs with hip osteoarthritis. BMC Vet. Res. 2012;8:185-202.
7. Gruen ME, Samson DR, Lascelles BDX. Functional linear modeling of activity data shows analgesic-mediated improved sleep in dogs with spontaneous osteoarthritis pain. Sci. Rep. 2019;9(1):14192.
8. Tellegen AR, Rudnik-Jansen I, Utomo L, et al. Sustained release of locally delivered celecoxib provides pain relief for osteoarthritis: a proof of concept in dog patients. Osteo. Cart. 2023;31(3):351-362.
9. Lascelles BD, Knazovicky D, Case B, et al. A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain. BMC Vet. Res. 2015;11:101.
10. Corral MJ, Moyaert H, Fernandes T, et al. A prospective, randomized, blinded, placebo-controlled multisite clinical study of bedinvetmab, a canine monoclonal antibody targeting nerve growth factor, in dogs with osteoarthritis. Vet. Anaesth. Analg. 2021;48(6):943-955.
11. Monteiro BP, Lambert C, Bianchi E, et al. Safety and efficacy of reduced dosage ketoprofen with or without tramadol for long-term treatment of osteoarthritis in dogs: a randomized clinical trial. BMC Vet. Res. 2019;15(1):213.
12. Genevois JP, Autefage A, Fayolle P, et al. Traitement de l'arthrose chez le chien avec un polymère d'acide gras. Le Point Vétérinaire. 1985;17(89):2.
13. Pelletier JP, Martel-Pelletier J. Protective effects of corticosteroids on cartilage lesions and osteophyte formation in the Pond-Nuki dog model of osteoarthritis. Arthritis Rheum. 1989;32(2):181-193.
14. Lascelles BD, Gaynor JS, Smith ES, et al. Amantadine in a multimodal analgesic regimen for alleviation of refractory osteoarthritis pain in dogs. J. Vet. Intern. Med. 2008;22(1):53-59.
15. Mosley C, Edwards T, Romano L, et al. Proposed Canadian Consensus Guidelines on Osteoarthritis Treatment based on OA-COAST Stages 1-4. Front. Vet. Sci. 2022;9:23.
16. Ivanovska A, Wang M, Arshaghi TE, et al. Manufacturing mesenchymal stromal cells for the treatment of osteoarthritis in canine patients: challenges and recommendations. Front. Vet. Sci. 2022;9:897150.
17. Boffa A, Salerno M, Merli G, et al. Platelet-rich plasma injections induce disease-modifying effects in the treatment of osteoarthritis in animal models. Knee Surg. Sports Traumatol. Arthrosc. 2021;29(12):4100-4121.
18. Pye C, Clark N, Bruniges N, et al. Current evidence for non-pharmaceutical, non-surgical treatments of canine osteoarthritis. J. Small Anim. Pract. 2024;65(1):3-23.
19. Bergh A, Lund I, Boström A, et al. A systematic review of complementary and alternative veterinary medicine: “miscellaneous therapies”. Animals (Basel). 2021;11(12):27.
20. Frank D, Beauchamp G, Palestrini C. Systematic review of the use of pheromones for treatment of undesirable behavior in cats and dogs. J. Am. Vet. Med. Assoc. 2010;236(12):1308-1316.
21. Marshall WG, Bockstahler BA, Hulse DA, et al. A review of osteoarthritis and obesity: current understanding of the relationship and benefit of obesity treatment and prevention in the dog. Vet. Comp. Orthop. Traumatol. 2009;22(05):339-345.
22. Moreau M, Troncy E, Bichot S, et al. Influence of changes in bodyweight on peak vertical force in osteoarthritic dogs: a possible bias in study outcome. Vet. Surg. 2010;39(1):43-47.
23. Barbeau-Grégoire M, Otis C, Cournoyer A, et al. A 2022 Systematic Review and Meta-analysis of enriched therapeutic diets and nutraceuticals in canine and feline osteoarthritis. Int. J. Mol. Sci. 2022;23(18):23.
24. Mille MA, McClement J, Lauer S. Physiotherapeutic strategies and their current evidence for canine osteoarthritis. Vet. Sci. 2022;10(1);23.