Stem cell therapy for elbow dysplasia in dogs

Can stem cell therapy provide a more efficacious treatment option for dogs suffering elbow dysplasia and related conditions?

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Elbow dysplasia (ED) is one of the most common causes of thoracic limb lameness in Labradors and other large- and giant-breed dogs (Michelsen, 2013). ED is a term used to describe the presence of one or more developmental conditions that involve the elbow joint.

This collective term includes conditions such as medial coronoid disease (MCD), radio-ulnar incongruity, ununited anconeal process (UAP) and osteochondrosis (OCD) (Cook and Cook, 2009; Kirberger and Fourie, 1998; Michelsen, 2013; Samoy et al., 2006). These conditions develop in juvenile animals and clinical signs (pain and lameness) are often present at four to six months of age. However, many dogs do not present until much later, when their osteoarthritis (OA) is advanced and lameness is a constant feature.

Current treatment and management for elbow dysplasia

There have been many techniques for both medical and surgical management for ED described in the literature (Fitzpatrick et al., 2013, 2015; Fitzpatrick and Yeadon, 2009; Gutbrod and Guerrero, 2012; McConkey et al., 2016; Michelsen, 2013; Quinn and Preston, 2014; Samoy et al., 2013):

  • Arthroscopic treatment
  • Ulnar osteotomies
  • Proximal ulnar osteotomy
  • Distal ulnar osteotomy
  • Biceps ulnar release procedure
  • Proximal abducting ulnar osteotomy
  • Sliding humeral osteotomy
  • Canine uni-compartment elbow replacement
  • Full elbow replacement
  • Elbow arthrodesis

However, irrespective of which medical or surgical intervention is performed, ED leads to cartilage damage and degenerative OA with time (Burton et al., 2011; Dempsey et al., 2019). The only exception to this would be full elbow replacement, but this procedure is not currently recommended due to the high complication rate.

OA leads to a progressive degenerative state in the joint that inevitably leads to chronic pain and loss of limb function. The number of surgical procedures described in the literature shows that no one technique is 100 percent effective, and the multifactorial causes of ED provide challenges to effective surgical treatment.

 Irrespective of which medical or surgical intervention is performed, elbow dysplasia leads to cartilage damage and degenerative osteoarthritis with time 

In cases of ED, arthroscopy is commonly performed to aid diagnosis, perform fragmented coronoid process (FCP) removal and remove diseased cartilage. This leads to potential short-term benefits in improved function and pain reduction; however, the long-term prognosis has been shown to be no different to conservative management (Burton et al., 2011; Dempsey et al., 2019).

Conservative management involves analgesic medications, exercise restriction, environmental adaptation and maintaining an ideal body condition score. In addition, physical therapies can form part of a conservative approach through modalities such as physiotherapy and hydrotherapy. However, conservatively managed patients will also go on to develop OA eventually, and these cases can be difficult to manage effectively.

More recently, a variety of intra-articular treatments have been trialled and have shown some promise in managing ED conditions using a multimodal approach. Hyaluronic acid and other joint lubricants have been used to help smooth joint articulation in OA, but medium- to long-term effects appear to be limited.

Innovations in treatment for elbow dysplasia

The lack of efficacious treatments for ED has resulted in trials of biological therapies such as stem cell therapy and platelet-rich plasma (PRP) (Huňáková et al., 2020; Kim et al., 2019; Kriston-Pál et al., 2017, 2020; Olsen et al., 2019). These therapies, used under a new branch of medicine termed “regenerative medicine” (RM), show great promise in better treating the disease. Furthermore, they have a disease-modifying effect rather than just treating the symptoms such as pain.

Stem cell therapy to treat elbow dysplasia

Greenside Veterinary Practice has been using stem cell therapy, along with PRP, to treat ED for a number of years and has modified its protocols with experience to develop a minimally invasive, highly effective treatment option. Using RM, Greenside is able to stop the degenerative process, reverse some signs of OA and restore joint health.

 Although regenerative medicine cannot reverse the disease process [...] Greenside has shown it to be highly effective in managing the condition 

Although RM cannot reverse the disease process (the dysplasia or abnormal development of the elbow joint) which results in the formation of OA, Greenside has shown it to be highly effective in managing the condition with outcomes and longevity of effects that outperform many surgical interventions and conservative management (Armitage et al., 2018; Armitage and Reid, 2019).

This treatment allows Greenside to resolve lameness, reduce pain and improve function for extended periods of time. Positive treatment responses commonly last for 18 months to 2 years before a top-up injection is required. However, because RM cannot reverse the underlying ED, with time the joint will start to degenerate again. At this point, further treatment can be provided to regain control and arrest the degenerative process.

Once stem cells have been harvested from the patient by a small surgical procedure under general anaesthetic, the stem cells are cultured to provide the required numbers needed for effective treatment. The stem cells can be stored in liquid nitrogen in a process called cryopreservation, which means practices can have a supply of stem cells usually for the lifetime of the patient. When further treatment is required, practitioners can simply “wake the cells up” at a lab and culture more without having to harvest more adipose tissue (fat) from the patient.

 Stem cells can be stored in liquid nitrogen in a process called cryopreservation, which means practices can have a supply of stem cells usually for the lifetime of the patient 

Culturing the stem cells has many advantages, such as knowing the exact concentration and viability of cells to provide a reliable “dose” specific to the condition being treated. The sterility, morphology and purity of the resultant cultured stem cells are checked before shipment from the lab to ensure patient safety and ensure the best possible cells are used.

What has Greenside discovered about elbow dysplasia?

Complications from arthroscopic intervention

From the extensive experience of treating ED, Greenside has found that dogs that have undergone arthroscopic intervention before treatment with RM tend to do less well than dogs that have not undergone the procedure.

Practitioners at Greenside believe that this is due to the invasive nature of arthroscopy and the potential to cause further instability and more severe OA changes following FCP removal and curetting of the cartilage. For this reason, they do not advocate the use of arthroscopy to manage ED. Patients that have had arthroscopy need to be treated with RM more aggressively, requiring two treatments 12 weeks apart and the addition of hyaluronic acid into the treatment plan. Greenside has improved its outcomes in these patients, but repeat treatments are more commonly required on an annual basis.

Correlated issues in the shoulders

In patients presenting with ED and OA, the team at Greenside commonly find other problems associated with the disease process in the shoulders. Patients with ED have altered gait and loading patterns due to pain in the medial compartment of the elbow. This results in changes to the directional forces in the shoulder support structures and the tendons involved in shoulder and elbow movement. For this reason, the team always evaluates a patient’s shoulder soft tissue structures with musculoskeletal ultrasound when they present with ED. In the experience of the Greenside team, 95 percent of dogs with ED have concurrent shoulder tendon problems, which can result in another significant source of pain and loss of function.

In addition to the mechanical effects of altered gait, elbows that have advanced OA changes commonly have a significant reduction in range of motion (ROM). This is due to new arthritic bone formation throughout the joint and thickening and fibrosis of the joint capsule, physically obstructing joint flexion and extension. This, in turn, has secondary consequences that result in shoulder tendon degeneration. Disease or degeneration in other parts of the body or other limbs can also play a role due to compensatory adaptations to lameness and pain.

 Regenerative medicine is highly effective if used with specific bespoke protocols in treating osteoarthritis and other degenerative conditions such as tendon degeneration 

Fortunately, RM is highly effective if used with specific bespoke protocols in treating OA and other degenerative conditions such as tendon degeneration. Not all stem cell treatments and PRP therapies are the same and many have not been validated in dogs which can result in suboptimal treatment outcomes.

Final thoughts

At Greenside, the team has investigated and trialled many different products and believe they have found and validated the best possible products to ensure successful and consistent positive treatment outcomes.

RM is a targeted treatment that requires a holistic approach to treat all causes of pain and degeneration in the body simultaneously to get the best treatment responses. Greenside, therefore, perform a thorough physical examination and further diagnostic tests (X-rays and musculoskeletal ultrasound) to diagnose concurrent orthopaedic musculoskeletal conditions. All musculoskeletal diseases are amenable for treatment using RM if correctly diagnosed and specifically targeted – this includes many spinal conditions. Bloods are also taken to look at the patient’s general health profile and check thyroid levels, as other non-orthopaedic disease processes can affect treatment outcomes if not identified.

Greenside Regenerative Therapies and Rehabilitation was the first specialist referral centre in the UK to provide treatments using stem cell therapy and rehabilitation. It uses objective data to ensure patients are improving and to modify treatments using an evidence-based approach rather than only subjective assessment. After treatment, Greenside monitors patients and provides further support, including home exercise plans and rehabilitative therapies, and offers regular reassessments and remote support as required.

There is no cure for canine elbow dysplasia, but Greenside has developed a more efficacious treatment option providing reduced pain, increased function and a better quality of life for dogs with elbow dysplasia and related issues.

To find out more about the pioneering regenerative medicine treatment being carried out at Greenside, visit www.stemcellsscotland.co.uk.
References (click to expand)
Armitage, A. and Reid, J. 2019 Measuring the impact of regenerative medicine (RM) on chronic degenerative conditions in dogs, using a validated owner-reported outcome measure (VetMetrica) which provides scores in 4 domains of health-related quality of life (HRQL). In: BSAVA Congress Proceedings 2019, British Small Animal Veterinary Association, pp. 515-516
Armitage, A., Miller, J., Frost, L. and Standen, C. 2018 Clinical efficacy of intra-articular injections of autologous mesenchymal stem cells in moderate to severe osteoarthritis (OA): a case series of 19 dogs evaluated using both LOAD and CBPI owner questionnaires. In: BSAVA Congress Proceedings 2018, British Small Animal Veterinary Association, pp. 474-474
Burton, N. J., Owen, M. R., Kirk, L. S., Toscano, M. J. and Colborne, G. R. 2011 Conservative versus arthroscopic management for medial coronoid process disease in dogs: a prospective gait evaluation. Veterinary Surgery, 40, 972-980
Cook, C. R. and Cook, J. L. 2009 Diagnostic imaging of canine elbow dysplasia: a review. Veterinary Surgery, 38, 144-153
Dempsey, L. M., Maddox, T. W., Comerford, E. J., Pettitt, R. A. and Tomlinson, A. W. 2019 A comparison of owner-assessed long-term outcome of arthroscopic intervention versus conservative management of dogs with medial coronoid process disease. Veterinary and Comparative Orthopaedics and Traumatology, 32, 1-9
Dragoo, J. L. and Meadows, M. C. 2019 The use of biologics for the elbow: a critical analysis review. Journal of Shoulder and Elbow Surgery, 28, 2053-2060
Fitzpatrick, N. and Yeadon, R. 2009 Working algorithm for treatment decision making for developmental disease of the medial compartment of the elbow in dogs. Veterinary Surgery, 38, 285-300
Fitzpatrick, N., Bertran, J. and Solano, M. A. 2015 Sliding humeral osteotomy: medium‐term objective outcome measures and reduction of complications with a modified technique. Veterinary Surgery, 44, 137-149
Fitzpatrick, N., Caron, A. and Solano, M. A. 2013 Bi‐oblique dynamic proximal ulnar osteotomy in dogs: reconstructed computed tomographic assessment of radioulnar congruence over 12 weeks. Veterinary Surgery, 42, 727-738
Gutbrod, A. and Guerrero, T. G. 2012 Effect of external rotational humeral osteotomy on the contact mechanics of the canine elbow joint. Veterinary Surgery, 41, 845-852
Huňáková, K., Hluchý, M., Špaková, T., Matejová, J., Mudroňová, D., Kuricová, M., Rosocha, J. and Ledecký, V. 2020 Study of bilateral elbow joint osteoarthritis treatment using conditioned medium from allogeneic adipose tissue-derived MSCs in Labrador Retrievers. Research in Veterinary Science, 132, 513-520
Kim, S. E., Pozzi, A., Yeh, J. C., Lopez-Velazquez, M., Au Yong, J. A., Townsend, S., Dunlap, A. E., Christopher, S. A., Lewis, D. D., Johnson, M. D. and Petrucci, K. 2019 Intra-articular umbilical cord derived mesenchymal stem cell therapy for chronic elbow osteoarthritis in dogs: a double-blinded, placebo-controlled clinical trial. Frontiers in Veterinary Science, 6, 474
Kirberger, R. M. and Fourie, S. L. 1998 Elbow dysplasia in the dog: pathophysiology, diagnosis and control. Journal of the South African Veterinary Association, 69, 43-54
Kriston-Pál, É., Czibula, Á., Gyuris, Z., Balka, G., Seregi, A., Sükösd, F., Süth, M., Kiss-Tóth, E., Haracska, L., Uher, F. and Monostori, É. 2017 Characterization and therapeutic application of canine adipose mesenchymal stem cells to treat elbow osteoarthritis. Canadian Journal of Veterinary Research, 81, 73-78
Kriston-Pál, É., Haracska, L., Cooper, P., Kiss-Tóth, E., Szukacsov, V. and Monostori, É. 2020 A regenerative approach to canine osteoarthritis using allogeneic, adipose-derived mesenchymal stem cells. Safety results of a long-term follow-up. Frontiers in Veterinary Science, 13, 510
McConkey, M. J., Valenzano, D. M., Wei, A., Li, T., Thompson, M. S., Mohammed, H. O., Van der Meulen, M. C. and Krotscheck, U. 2016 Effect of the proximal abducting ulnar osteotomy on intra‐articular pressure distribution and contact mechanics of congruent and incongruent canine elbows ex vivo. Veterinary Surgery, 45, 347-355
Michelsen, J. 2013 Canine elbow dysplasia: aetiopathogenesis and current treatment recommendations. The Veterinary Journal, 196, 12-19
Olsen, A., Johnson, V., Webb, T., Santangelo, K. S., Dow, S. and Duerr, F. M. 2019 Evaluation of intravenously delivered allogeneic mesenchymal stem cells for treatment of elbow osteoarthritis in dogs: a pilot study. Veterinary and Comparative Orthopaedics and Traumatology, 32, 173-181
Quinn, R. and Preston, C. 2014 Arthroscopic assessment of osteochondrosis of the medial humeral condyle treated with debridement and sliding humeral osteotomy. Veterinary Surgery, 43, 814-818
Samoy, Y. C., de Bakker, E., Van Vynckt, D., Coppieters, E., van Bree, H. and Van Ryssen, B. 2013 Arthroscopic treatment of fragmented coronoid process with severe elbow incongruity. Veterinary and Comparative Orthopaedics and Traumatology, 26, 27-33
Samoy, Y., Van Ryssen, B., Gielen, I., Walschot, N. and Van Bree, H. 2006 Review of the literature: elbow incongruity in the dog. Veterinary and Comparative Orthopaedics and Traumatology, 19, 1-8