Sample Topic

Feline | Canine

Osteoarthritis

Summary

  • Osteoarthritis (OA) is a chronic, progressive disease characterized by deterioration of synovial joint cartilage, proliferative bony changes involving articular surfaces, and disruption of normal cartilage repair; often leads to pain and reduced joint function
  • OA is the most common joint disease affecting dogs and cats; affects an estimated 20% of dogs > 1 year old, and 90% of cats > 12 years old
  • Pets of any age can be affected; however, prevalence tends to increase with age
  • Secondary OA (arising from an underlying condition that damages normal joint cartilage), is most common; primary OA (resulting from abnormal cartilage production and maintenance) is less common
  • Clinical signs include lameness, stiffness, exercise intolerance, aggression/irritability, and refusal to perform certain tasks (e.g., jumping onto furniture or using stairs); cats may also have difficulty grooming and climbing into the litterbox
  • Physical exam findings include joint swelling, pain, instability, crepitus, and reduced range of motion
  • Diagnosis is generally based on history, physical exam findings, and radiographic changes; however, radiographs may not reveal early OA changes (despite historical evidence of significant pain)
  • More advanced diagnostic modalities include computed tomography, magnetic resonance imaging, nuclear scintigraphy, and arthroscopy
  • Medical management of OA is best accomplished through a multimodal approach individualized to the needs of each patient; NSAIDs, weight loss/weight management, joint supplements, therapeutic diets, and physical therapy are among the available options
  • Surgical correction of underlying problems (e.g., cruciate repair) should be considered, if possible, to avoid further joint degeneration
  • Owner expectations must be managed carefully, as life-long treatment is required for most affected pets
  • With appropriate intervention, prognosis for return to function and good quality of life is good; however, OA is incurable, so treatment re-assessments and periodic modifications are necessary as the disease progresses
  • Preventive options are limited, but include maintaining an optimal weight and preventing breeding in dogs with hip dysplasia or other inherited disease that predispose to OA

Causes and Risk Factors

Causes

  • Cause is not always determined, but osteoarthritis can be further categorized as primary or secondary:
    • Primary osteoarthritis
      • Uncommon
      • Arises from abnormalities in the normal process of cartilage destruction and repair, leading to abnormal cartilage that is prone to injury when subjected to normal stresses
    • Secondary osteoarthritis
      • Most common form of the disease
      • Arises from an underlying problem that subjects normal cartilage to abnormal stresses
    • Over time, cartilage degradation and other factors contribute to fibrosis, osteophytes and proliferative changes, reduced range of motion, poor joint functionality, and chronic pain

Risk Factors

  • Genetics is seemingly the most influential risk factor
  • Risk factors include predisposition to an underlying disease that leads to secondary osteoarthritis, including:
    • Hip dysplasia
    • Elbow dysplasia
    • Osteochondrosis dissecans
    • Osteochondrodysplasia
    • Patellar luxation
    • Cruciate ligament injury
  • Mechanical stress (e.g., athletic dogs or working dogs)
  • Obesity (places increased stress on joints; fat may also secrete inflammatory cytokines)
  • Traumatic injury (e.g., fractures or luxations)
  • Abnormal joint conformation
  • Joint instability
  • Medical conditions that affect collagen metabolism (e.g., diabetes mellitus, hyperadrenocorticism, hypothyroidism)

Signalment

  • Prevalence increases with age; however, very young animals may be affected if a congenital predisposing factor is present (e.g., hip dysplasia, elbow dysplasia)
  • Osteoarthritis (OA) due to trauma can affect pets of any age
  • Can affect any breed; large and giant breed dogs are predisposed to joint problems (e.g., hip or elbow dysplasia) which are risk factors for OA
  • Working/athletic dogs are more prone to joint trauma that may initiate OA
  • There is no apparent gender predilection
  • One study (Level 1) suggested neutered dogs are more likely to have joint disease

Differential Diagnosis

Diagnosis and Screening

General Points

  • Diagnosis is generally based on history, physical exam findings, and radiographic changes; however, radiographs may not reveal early osteoarthritis (OA) changes (despite historical evidence of significant pain)
  • Subtle abnormalities may go unnoticed by pet owners, so presentation may appear to be acute, or wax and wane; radiographic changes may be advanced at time of diagnosis
  • Because OA may present in elderly pets, some disease signs may be mistaken for normal signs of aging

Signs and History

  • Clinical signs may include:
    • Lameness (acute, chronic, or intermittent)
    • Exercise intolerance
    • Stiffness (especially after a period of rest)
    • Aggression (especially if touched near a painful area)
    • Reluctance to move
    • Reluctance to perform certain activities, such as using the stairs, or jumping onto furniture
  • In cats, signs of lameness may go unnoticed, but additional signs may include:
    • Difficulty grooming or reluctance to groom; coat may become matted and unkempt
    • Reduced activity
    • Reduced appetite
    • Reluctance to jump
    • Unwillingness to use the litterbox
    • Generalized irritability
    • Resisting petting or handling
    • Hair loss over affected joints
  • Clinical signs may be worse in overweight animals, or larger breed dogs
  • Signs may worsen after exercise or after periods of inactivity
  • Signs may worsen during damp, cold weather

Physical Exam

  • Physical exam findings may include:
    • Joint swelling and/or pain
    • Lameness (not as common in cats)
    • Crepitus
    • Joint instability
    • Reduced range of motion in affected joints
    • Gait alterations (e.g., "bunny hopping" with rear legs, in patients with hip osteoarthritis)

Laboratory Tests

  • Routine laboratory tests
    • Complete blood count, biochemistry panel, and urinalysis
      • Likely unremarkable, but may help rule out differential diagnoses and identify comorbidities

  • Arthrocentesis and synovial fluid analysis
    • Should be considered to identify infectious or immune-mediated joint disease
    • Cytologic examination of synovial fluid may reveal:
      • Reduced numbers of leukocytes
      • High protein levels
      • Mononuclear cells may predominate
    • Bacterial culture and sensitivity testing is indicated if an infectious process is suspected

  • Tick-borne disease testing
    • Should be considered for patients in endemic areas where an obvious underlying cause for osteoarthritis has not been identified
    • Screening with an in-house ELISA antibody test for borreliosis, ehrlichiosis, and anaplasmosis should be considered; positive results should be investigated further

  • Histopathology
    • Biopsy of synovial tissue may help rule out neoplasia or immune-mediated disease

Imaging

  • Radiography
    • Radiographic changes may include:
      • Soft tissue swelling around the affected joints
      • Distension of the joint capsule
      • Joint effusion
      • Narrowed joint spaces
      • Osteophytes
      • Subchondral bone thickening
      • Erosion of subchondral bone
    • If subchondral bone has not yet become involved in the disease process, radiographs may be unremarkable
    • Severity of radiographic changes does not always correlate with severity of clinical signs

  • Computed tomography (CT), magnetic resonance imaging (MRI), and nuclear scintigraphy
    • Advanced imaging may be useful in identifying early osteoarthritis changes before radiographic evidence is appreciable
    • May be helpful for evaluating articular and periarticular soft tissue structures

Other Diagnostic Tests

  • Arthroscopy
    • Can be considered for joint exploration and to characterize the severity of cartilage damage
    • May have therapeutic applications as well:
      • Remove osteophytes and cartilage fragments
      • Joint irrigation to flush inflammatory mediators from the articular space

Screening Recommendations

  • Young dogs or dogs that will be used as part of a breeding program should be screened for heritable conditions (e.g., hip dysplasia) that can increase the risk for osteoarthritis

Prevention

General Points

  • Dogs with inherited diseases (e.g., hip dysplasia) should not be bred
  • Some early interventions (e.g., weight management) may help delay or slow the progression of osteoarthritis

Surgical Interventions

  • For young dogs with hip dysplasia, early surgical intervention may prevent or limit development of further disease

Other Therapies

  • In two studies of Labrador retrievers (Level 2), controlling caloric intake and preventing obesity throughout life reduced the prevalence of osteoarthritis and delayed the onset of disease

Treatment

General Points

  • Effective client education is important, as treatment for osteoarthritis (OA) is likely life-long, and may involve combining multiple modalities
  • Conservative management focuses on relieving pain, reducing inflammation, and improving mobility
  • Surgical options are available to address some causes of OA (e.g. hip dysplasia, patellar luxation)
  • Direct comparison of various treatment options is limited in part by inconsistent outcome measures among studies
  • A 2020 “Best-Bets-for-Vets” review evaluated the addition of CBD oil alongside nonsteroidal anti-inflammatory drug treatment for pain in dogs with osteoarthritis
    • No changes were detected in veterinarian-assessed pain; the authors suggested better quality evidence is required for a definitive answer
  • Robust efficacy data on cannabinoids in cats are not yet available; dose-response studies and dosage regimens for cats are lacking

Medications

  • Multimodal management of osteoarthritis is commonly recommended to create an individualized treatment plan for each patient
  • Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
    • NSAIDs remain the mainstay of therapy for management of pain and inflammation
    • Routine laboratory tests are recommended before initiating treatment with NSAIDs to ensure appropriate renal and hepatic function
    • NSAIDs should not be combined and should not be used in conjunction with glucocorticoids
    • Tapering to the lowest effective dose, and using medication for the shortest duration necessary, should be considered where appropriate
    • Concurrent administration of proton pump inhibitors or other gastroprotectants may have benefit in preventing stomach irritation

    • Dogs:
      • Carprofen 4.4 mg/kg PO every 24 hours, or divided every 12 hours
      • Deracoxib 1 to 2 mg/kg PO every 24 hours
      • Meloxicam
        • Transmucosal oral spray: 0.1 mg/kg PO every 24 hours
        • Oral suspension: 0.2 mg/kg PO on the first day, then 0.1 mg/kg PO every 24 hours thereafter
      • Firocoxib (Previcox®) 5 mg/kg PO every 24 hours
      • Robenacoxib (Onsior®) 1 to 2 mg/kg PO every 24 hours

    • Cats:
      • Meloxicam 0.05 to 0.1 mg/kg PO once, then 0.01 to 0.03 mg/kg PO every 24 hours or 0.05 mg/kg every 48 to 72 hours
        • FDA warning label: repeated use of meloxicam in cats has been associated with acute renal failure and death
      • Robenacoxib (Onsior®) 1 to 2.4 mg/kg PO every 24 hours

  • Chondroprotective Agents
    • Polysulfated glycosaminoglycan (PSGAG)
      • May stimulate collagen synthesis and slow collagen breakdown
      • Dogs: 4.4 mg/kg IM twice weekly, for up to 4 weeks
      • Cats: 2 mg/kg IM every 3 to 5 days for 4 treatments; alternatively, can be given at 5 mg/kg SC twice weekly for 4 weeks, then once weekly for 4 weeks, then once monthly
        • Efficacy is unclear

  • Other Medications
    • Tramadol:
      • Limited data are available
        • In one study (Level 2) dogs with arthritis had improved mobility (based on owner questionnaires) after receiving tramadol for 2 weeks
        • In another study (Level 2), 10 days of treatment with tramadol provided no clinical benefit for dogs with osteoarthritis of the elbow or stifle joint
        • A third study (Level 2) reported a beneficial effect of twice-daily oral administration of tramadol (2 mg/kg) in geriatric cats with osteoarthritis
      • Dogs: 4 to 10 mg/kg PO every 8 hours
      • Cats: 1 to 4 mg/kg PO every 8 to 12 hours
    • Amantadine:
      • May be considered as adjunctive therapy for patients that are refractory to NSAIDs
      • Dogs: 2 to 5 mg/kg PO every 12 to 24 hours
      • Cats: 2 to 5 mg/kg PO every 24 hours
    • Gabapentin:
      • Anticonvulsant with some analgesic properties; particularly for chronic pain with a neuropathic component
      • Studies in dogs are limited; however, one study (Level 2) reported that gabapentin treatment was associated with improvement in owner-identified impaired activities of osteoarthritic cats and another feline study (Level 3) showed improvement of musculoskeletal pain
        • Dogs: 5 to 20 mg/kg PO every 8 to 12 hours
        • Cats: 3 to 10 mg/kg PO every 12 hours

Surgical Interventions

  • For some osteoarthritis-associated conditions, surgical correction may result in better long-term outcomes compared with medical management; however, early intervention is recommended
  • Consultation with a veterinary surgeon is recommended

  • Arthrotomy
    • Can be used to correct underlying or aggravating causes, such as fragmented coronoid process, or ununited anconeal process
    • Facilitates joint exploration and removal of osteochondral flaps/fragmented cartilage
    • Facilitates correction of anatomical abnormalities (e.g., patellar luxation)

  • Specific Surgical Procedures
    • Tibial-plateau-leveling osteotomy (TPLO) for cranial cruciate ligament injury
    • Total joint replacement (e.g., hip or knee replacement)
    • Salvage procedures (e.g., femoral head and neck ostectomy, arthrodesis)

  • Arthroscopy
    • Minimally invasive method for exploring affected joints, removing fragmented cartilage/osteophytes
    • Facilitates joint irrigation

Other Therapies

  • Dietary Supplements and Nutraceuticals
    • Some available products have limited scientific evidence demonstrating positive effects
    • For many dietary supplements, optimal dosing recommendations have not been standardized, contributing to potential variation in therapeutic response
      • Glucosamine and chondroitin sulfate
        • Dogs/cats: 15 to 30 mg/kg (of the chondroitin component) PO daily
        • Frequently formulated together in combination products
        • Multiple in-vitro studies suggest a positive effect on joint disease; in 2 studies (Level 2), dogs with osteoarthritis demonstrated improvement in pain and weight-bearing after receiving glucosamine and chondroitin
      • Fatty acid supplements
        • No consensus on efficacy
        • In one study (Level 2), arthritic dogs that received a diet supplemented with omega-3 fatty acids were able to tolerate reduction in their NSAID dose
        • Another study (Level 2) showed no difference between dogs that received fish oil and dogs that received placebo

  • Therapeutic Diets
    • Therapeutic diets supplemented with fatty acids, glucosamine/chondroitin, green-lipped mussel, and other enhancements have been associated with improvement in some arthritic animals
      • In one study of cats (Level 2), a therapeutic diet supplemented with fatty acids, green-lipped mussel, and glucosamine/chondroitin was associated with improved mobility, based on owner assessments

  • Weight management
    • Obesity contributes to the progression of OA, so effective weight management can have a positive influence on disease progression
      • In one study (Level 3), modest weight loss of 6.1% to 8.9% improved signs of OA in affected dogs that were obese
    • Therapeutic weight loss diets supplemented with omega-3 fatty acids have shown benefit in dogs and cats

  • Rehabilitative medicine
    • A variety of modalities can be considered which may improve strength and mobility; these include:
      • Physical therapy
      • Massage therapy
      • Passive range-of-motion exercises
      • Hydrotherapy/swimming
      • Under-water treadmill
      • Cold and/or heat therapy

  • Controlled exercise
    • In moderation, may improve strength, flexibility, and mobility
    • Excessive exercise can contribute to pain; monitoring and effective analgesia are essential

  • Environmental Modifications
    • May include:
      • Ramps
      • Non-skid mats or rugs
      • Shallow litterboxes
      • Portable stairs (for accessing furniture)

  • Acupuncture
    • Commonly considered as an alternative therapeutic option, but supporting evidence is equivocal
    • Used in conjunction with other modalities

Follow-up

General Points

  • Due to the progressive nature of osteoarthritis, periodic re-evaluation is recommended to assess goals (e.g., weight loss, improved mobility) and determine if the treatment plan requires modification

Diagnostic Follow-up

  • Repeat radiography may have a role post-operatively or if disease signs worsen acutely; however, because clinical signs do not necessarily correlate with radiographic changes, the utility of repeat radiographs is limited
  • Validated pet owner questionnaires may help monitor disease progression, by continually re-assessing at-home behaviors that indicate changes in mobility, comfort level, and overall well-being

Therapeutic Follow-up

  • NSAIDs may cause stomach irritation in some patients; concurrent administration of proton pump inhibitors or other gastroprotectants may have benefit
    • Clients should be instructed to watch for signs of melena and report any signs of gastrointestinal disease right away
  • For patients receiving NSAID therapy, a serum chemistry panel should be re-evaluated 2 weeks after initiating therapy and again every 3 to 6 months, to monitor for changes in renal or hepatic function

Prognosis

  • Osteoarthritis is incurable; however, effective management resulting in good quality of life is possible in many cases

Evidence

Guidelines and Consensus Statements

  • Epstein M, Rodan I, Griffenhagen G, et al. 2015 AAHA/AAFP Pain Management Guidelines for Dogs and Cats. J Am Anim Hosp Assoc. 2015 Mar-Apr. 51(2):67-84. Level B Abstract
  • Mathews K, Kronen PW, Lascelles D, et al. Guidelines for recognition, assessment and treatment of pain: WSAVA Global Pain Council. J Small Anim Pract. 2014 Jun;55(6):E10-68. Level B (IND) Article

Systematic Reviews/Meta-analyses

  • Anderson KL, Zulch H, O'Neill DG, et al. Risk factors for canine osteoarthritis and its predisposing arthropathies: A systematic review. Front Vet Sci. 2020;7:220. Level 1 Article

  • Morrow L, Belshaw Z. Does the addition of cannabidiol alongside current drug treatments reduce pain in dogs with osteoarthritis? Vet Rec. 2020;186(15):493-4. Level 2 Abstract
  • Belshaw Z, Asher L, Dean RS. Systematic review of outcome measures reported in clinical canine osteoarthritis research. Vet Surg. 2016 May;45(4):480-7. Level 2 (IND) Article
  • Vandeweerd J-M, Coisnon C, Clegg P, et al. Systematic review of efficacy of nutraceuticals to alleviate clinical signs of osteoarthritis. J Vet Intern Med. 2012 May-Jun;26(3):448-56. Level 2 Article
  • Innes JF, Clayton J, Lascelles BDX. Review of the safety and efficacy of long-term NSAID use in the treatment of canine osteoarthritis. Vet Rec. 2010 Feb 20;166(8):226-30. Level 2 Abstract

Randomized, Controlled Trials (RCTs)

  • Guedes AGP, Meadows JM, Pypendop BH, et al. Assessment of the effects of gabapentin on activity levels and owner-perceived mobility impairment and quality of life in osteoarthritic geriatric cats. J Am Vet Med Assoc. 2018 Sept 1;253(5):579-85. Level 2 Abstract
  • Guedes AGP, Meadows JM, Pypendop BH, et al. Evaluation of tramadol for treatment of osteoarthritis in geriatric cats. J Am Vet Med Assoc. 2018 Mar 1;252(5):565-71. Level 2 Abstract
  • Budsberg SC, Torres BT, Kleine SA, 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 Feb 15;252(4):427-32. Level 2 Abstract
  • Hielm-Bjorkman A, Roine J, Elo K, et al. An un-commissioned randomized, placebo-controlled double-blind study to test the effect of deep sea fish oil as a pain reliever for dogs suffering from canine OA. BMC Vet Res. 2012 Sep 6;8:157. Level 2 (IND) Article
  • Lascelles BD, DePuy V, Thomson A, et al. Evaluation of a therapeutic diet for feline degenerative joint disease. J Vet Intern Med. 2010 May-Jun;24(3):487-95. Level 2 (IND) Article
  • Fritsch DA, Allen TA, Dodd CE, et al. A multicenter study of the effect of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. J Am Vet Med Assoc. 2010 Mar 1;236(5):535-9. Level 2 (IND) Abstract
  • 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 Jan-Feb;22(1):53-9. Level 2 Article
  • McCarthy G, O'Donovan J, Jones B, et al. Randomized double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis. Vet J. 2007 Jul;174(1):54-61. Level 2 Abstract
  • Smith GK, Paster ER, Powers MY, et al. Lifelong diet restriction and radiographic evidence of osteoarthritis of the hip joint in dogs. J Am Vet Med Assoc. 2006 Sep 1;229(5):690-3. Level 2 (IND) Abstract
  • Kealy RD, Lawler DF, Ballam JM, et al. Evaluation of the effect of limited food consumption on radiographic evidence of osteoarthritis in dogs. J Am Vet Med Assoc. 2000 Dec 1;217(11):1678-80. Level 2 (IND) Abstract

Other Studies or Reviews

  • Monteiro BP. Feline chronic pain and osteoarthritis. Vet Clin North Am Small Anim Pract. 2020 July;50(4):769-88. Level 3
  • Plumb’s Veterinary Drugs (online database), Tulsa, OK: Brief Media; 2020. Accessed June 17, 2020. Level 3
  • Johnson KA, Lee AH, Swanson KS. Nutrition and nutraceuticals in the changing management of osteoarthritis for dogs and cats. J Am Vet Med Assoc. 2020;256(12):1335-41. Level 3
  • Papich MG. Saunders Handbook of Veterinary Drugs: Small and Large Animal, 4th Edition. St Louis, MO: Elsevier; 2016. Level 3
  • Comblain F, Serisier S, Barthelemy N, et al. Review of dietary supplements for the management of osteoarthritis in dogs in studies from 2004 to 2014. J Vet Pharmacol Therap. 2016 Feb;39(1):1-15. Level 3 (IND)
  • Renberg WC. Arthritis (Osteoarthritis). In: Tilley LP, Smith, Jr FWK, ed.'s. Blackwell's Five-Minute Veterinary Consult: Canine and Feline. 6th ed. Ames: John Wiley & Sons, Inc; 2016:113-14. Level 3
  • MacFarlane PD, Tute AS, Alderson B. Therapeutic options for the treatment of chronic pain in dogs. J Sm Anim Pract. 2014 Mar;55(3):127-34. Level 3
  • Lorenz ND, Comerford EJ, Iff I. Long-term use of gabapentin for musculoskeletal disease and trauma in three cats. J Fel Med Surg. 2013 Jun;15(6):507-12. Level 3
  • Railland P, Bichot S, Lussier B, et al. Effect of a diet enriched with green-lipped mussel on pain behavior and functioning in dogs with clinical osteoarthritis. Can J Vet Res. 2013 Jan;77(1):66-74. Level 3
  • Harasen GLG, Little SE. Musculoskeletal Diseases: Arthridites (Degenerative Joint Disease). In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders;2012:709-10. Level 3
  • 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 Oct 4;8:185-202. Level 3
  • Anderson A. Treatment of hip dysplasia. J Small Anim Pract. 2011 Apr:52(4):182-9. Level 3
  • Franklin SP, Cook JL. What is the evidence? J Am Vet Med Assoc. 2011 Feb 15;238(4):440-2. Level 3
  • Bennett D. Canine and Feline Osteoarthritis. In: Ettinger SJ, Feldman EC, ed.'s. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. 7th ed. St. Louis: Saunders Elsevier;2010:750-61. Level 3
  • McKenzie BA. What is the evidence? J Am Vet Med Assoc. 2010 Dec 15;237(12):1382-3. Level 3
  • Fritsch D, Allen TA, Dodd CE, et al. Dose-titration effects of fish oil in osteoarthritic dogs. J Vet Intern Med 2010 Sep-Oct;24(5):1020-6. Level 3 (IND)
  • Lascelles BD, Henry JB 3rd, Brown J, et al. Cross-sectional study of the prevalence of radiographic degenerative joint disease in domesticated cats. Vet Surg. 2010 Jul 39(5):535-44. Level 3
  • Marshall WG, Hazewinkel HA, Mullen D, et al. The effect of weight loss on lameness in obese dogs with osteoarthritis. Vet Res Commun. 2010 Mar;34(3):241-53. Level 3
  • D'Altillio M, Pearl A, Alvey M, et al. Therapeutic efficacy and safety of undenatured type II collagen singly or in combination with glucosamine and chondroitin in arthritic dogs. Toxicol Mech Methods. 2007;17(4):189-96. Level 3

Additional Reading

  • Pavarotti GS, Hivernaud V, Brincin M, et al. Evaluation of a single intra-articular injection of autologous adipose tissue for the treatment of osteoarthritis: A prospective clinical study in dogs [published online ahead of print, 2020 Apr 21]. Vet Comp Orthop Traumatol. 2020;10.1055/s-0040-1708524. (IND)
  • Kim SE, Pozzi A, Yeh JC, et al. Intra-articular umbilical cord derived mesenchymal stem cell therapy for chronic elbow osteoarthritis in dogs: A double-blinded, placebo-controlled clinical trial. Front Vet Sci. 2019;6:474. (IND)
  • Lee MI, Kim JH, Kwak HH, et al. A placebo-controlled study comparing the efficacy of intra-articular injections of hyaluronic acid and a novel hyaluronic acid-platelet-rich plasma conjugate in a canine model of osteoarthritis. J Orthop Surg Res. 2019;14(1):314. (IND)
  • Souza ANA, Ferreira MP, Hagen SCF, et al. Radial shock wave therapy in dogs with hip osteoarthritis. Vet Comp Orthop Traumatol. 2016:29(2):108-14.
  • Kapatkin AS, Nordquist B, Garcia TC, et al. Effect of single dose radiation therapy on weight-bearing lameness in dogs with elbow osteoarthritis. Vet Comp Orthop Traumatol. 2016 Jul 18;29(4):338-43.
  • Rausch-Derra L, Huebner M, Wolford J, et al. A prospective, randomized, masked, placebo-controlled multisite clinical study of grapiprant, an EP4 prostaglandin receptor antagonist (PRA), in dogs with osteoarthritis. J Vet Intern Med. 2016 May-Jun 30(3):756-63.
  • Vilar JM, Rubio M, Spinella G, et al. Serum collagen type II cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring of dogs with hip osteoarthritis. PLoS One. 2016 Feb 17;11(2):e0149472.
  • Lascelles BDX, 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 Apr 30;11:101.
  • Moreau M, Lussier B, Pelletier J-P, et al. A medicinal herb-based natural health product improves the condition of a canine natural osteoarthritis model: a randomized placebo-controlled trial. Res Vet Sci. 2014 Dec;97(3):574-81.
  • Whitworth DJ, Banks TA. Stem cell therapies for treating osteoarthritis: prescient or premature? Vet J. 2014 Dec;202(3):416-24.
  • Cuervo B, Rubio M, Sopena J, et al. Hip osteoarthritis in dogs: a randomized study using mesenchymal stem cells from adipose tissue and plasma rich in growth factors. Int J Mol Sci. 2014 Jul 31;15(8):13437-60.
  • Vilar JM, Batista M, Morales M, et al. Assessment of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells in osteoarthritic dogs using a double blinded force platform analysis. BMC Vet Res 2014 Jul 1;10:143.
  • Fahie MA, Ortolano GA, Guercio V, et al. A randomized controlled trail of the efficacy of autologous platelet therapy for the treatment of osteoarthritis in dogs. J Am Vet Med Assoc. 2013 Nov 1;243(9):1291-7.
  • Vilar JM, Morales M, Santana A, et al. Controlled, blinded force platform analysis of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells associated to PRGF-Endoret in osteoarthritic dogs. BMC Vet Res. 2013 Jul 2;9:131.
  • Sullivan MO, Gordon-Evans WJ, Knap KE, et al. Randomized, controlled clinical trial evaluating the efficacy of pulsed signal therapy in dogs with osteoarthritis. Vet Surg. 2013 Apr;42(3):250-4.
  • Bennett D, Eckersall PD, Waterston M, et al. The effect of robenacoxib on the concentration of C-reactive protein in synovial fluid from dogs with osteoarthritis. BMC Vet Res. 2013 Mar 1;9:42.