The evidence for treating ankle osteoarthritis pain and loss of function without surgery

Ross A. Hauser, MD. Caring Medical Florida
Danielle R. Steilen-Matias, MMS, PA-C. Caring Medical Florida

The evidence for Non-surgical treatments for Ankle Osteoarthritis

In this article, we will make the connection from ankle ligament instability to ankle osteoarthritis, to the need for ankle fusion or ankle replacement surgery. We will also present research on regenerative medicine injections as an alternative to this predicament.

In our office’s 27+ years of service, we have seen countless people with ankle osteoarthritis. Many are very active people, heavily into sports. Many have a physically challenging job, many come to us after suffering an injury or accident that was very damaging. They all have a story of “non-healing.”

This is what we typically hear in our examination rooms:

  • I have had ankle sprains since I was a teenager more than 30 years ago. As I get older, the ankle sprains get worse. The last one was really bad. It is why I am here. I stopped working out my legs and running for 3 months. When I tried to run again, the pain was back. I went to a specialist and he told me my running days were over. The more running I do the more damage I am doing. I do not want to give up running.
  • I am here because I do not know what to do, I have been doing physical therapy “forever,” and it does not help. I am trying to exercise, mostly walking and doing some stretching. The doctor keeps telling me the same thing over and over Rest, Ice, Compression, Elevate – mostly Ice. Sometimes Anti-inflammatories and some pain medications. When I complain that these treatments are not helping, my doctor tells me, “we can consider surgery.” I do not want surgery.

What almost all these people have in common is that:

  • An x-ray has revealed that there is some type of cartilage loss,
  • there is some type of reduced range of motion,
  • after a day on their feet or extended walking, they can barely stand,
  • their diet now consists of large helpings of Advil and Motrin,
  • they are still trying to carry on,
  • surgery seems to be the only way, but many do not want it.

Let’s get to some answers and some understanding.

This article will focus heavily on understanding that weak, damaged, compromised ankle ligaments are a primary cause of your ankle problems. The problems with your ligaments have likely not been addressed. We will also cover how this problem can be healed with regenerative injections called H3 Prolotherapy.

Understanding what is happening in your ankle. Here is the progression of ankle instability caused by chronic ankle sprains leading to disabling full-blown osteoarthritis. This is what stops you from running.

If you are an athlete, a runner, someone on their feet all day, someone with a physically demanding job, and you have had chronic ankle sprains, the more you try the conservative treatments of Ice and medications and ankle braces, the more you seem destined to ultimately requiring surgery. The simple fact of the matter is, you are not getting better, you are getting worse. Your treatment plan now is more about slowing the degenerative condition of your ankle than regenerating and repairing the weakened elements in your ankle/heel.

Even your doctors believe that you are on a one-way path to surgery:

  • In December 2016, the Journal of British Sports Medicine published the Executive Committee of the International Ankle Consortium position paper on the progression of ankle instability caused by chronic ankle sprains to disabling full-blown osteoarthritis and the need for ankle surgery or fusion.

Some doctors, however, think that they can alter your path to surgery and heal your ankle by regenerating the damaged ligaments and supporting structures with simple injections.

  • In 2010, we published our Caring Medical research position paper on the progression of ankle instability caused by chronic ankle sprains to disabling full-blown osteoarthritis and the need for ankle surgery or fusion. We found that many people could avoid surgery if their ligaments were repaired and strengthened. That updated research is discussed below.

Can you really avoid surgery? The surgeons say patients must address ankle instability early to stop the degenerative progression.

Hopefully, you are at a stage where the damage to your ankle is not irreversible. If you have chronic instability but a good range of motion in your ankle, we believe we can help you avoid future surgery and strengthen your ankle. The key is fixing the instability before the instability creates significant bone damage.

In December 2016, the Journal of British Sports Medicine (1published the Executive Committee of the International Ankle Consortium position paper on the progression of ankle instability caused by chronic ankle sprains to disabling full-blown osteoarthritis and the need for ankle surgery or fusion. These are the treatment guidelines doctors follow today.

That position paper which was compiled by researchers from the University of Kentucky, University College Dublin, UK National Centre for Sport and Exercise Medicine, the University of Delaware, University of North Carolina, among many other medical universities stated:

  • “this 2016 position paper with recommendations for information implementation and continued research based on the paradigm that lateral ankle sprain and the development of chronic ankle instability, serve as a conduit to a significant global healthcare burden.
  • We intend our recommendations to serve as a mechanism to promote efforts to improve prevention and early management of lateral ankle sprain.
  • We believe this will reduce the prevalence of chronic ankle instability and associated sequelae that have led to the broader public health burdens of decreased physical activity and early onset ankle joint post-traumatic osteoarthritis. Ultimately, this can contribute to healthier lifestyles and the promotion of physical activity.”

Simply: People are at high risk of developing ankle osteoarthritis. It is a big problem.

Ligament treatment is the key to stopping the progression of ankle osteoarthritis

For many people, it is easy to understand that they have a loose ankle or an ankle that feels like it is giving way. They have problems walking, their ankle makes a lot of crunching, cracking and popping noises, some have chronic, never goes away swelling, and their ankle hurts all the time. What is not always as easily understood when all they hear at the doctor’s office is “cartilage, cartilage, cartilage,” is that they have damaged, weakened ankle ligaments. “Cartilage, cartilage, cartilage,” is a problem of damaged ligaments.

A June 2019 study (2) from Army-Baylor University, which used the above 2016 study as one of their references offered these guidelines:

  • “Individuals who sustain an acute lateral ankle sprain may not receive timely formal rehabilitation and are at an increased risk to have subsequent sprains which can lead to chronic pain and instability. Attention to essential factors for ligament protection and healing while preserving ankle movement, may result in a more stable yet mobile ankle offering improved outcomes.

The recommendations above are for the early management of lateral ankle sprain as the best way to avoid surgery. Recently, doctors from Rutgers University in New Jersey published their findings in the Journal of Orthopaedic Research (3) that listed the top five common athletic injuries as high-risk factors for developing osteoarthritis, among the top 5 HIGH-RISK injuries?

  • Chronic Ankle Instability.

In summary, ankle sprains cause ankle osteoarthritis by creating an environment of joint instability caused by weakened ligaments. Treat the unstable ligaments – prevent a worsening of factors that lead to advancing ankle osteoarthritis.

In 2010, our Caring Medical research team published this abstract in the medical journal Practical Pain Management:(4)

Here are some of our learning points:

  • Chronic ankle sprains or recurrence rate for lateral ankle sprains has been reported to be as high as 80%.
  • Up to 40% of individuals have residual ankle symptoms due to chronic instability. This means even after the sprain has “healed,” the ankle is “not the same,”
  • Studies suggested 70% to 80% of patients with chronic ankle instability end up with arthritic ankles.
  • Long-term residual symptoms from ankle sprains that do not heal can result in ongoing problems including pain, stiffness, limited range of motion and the inability to exercise or walk long distances and osteoarthritis.

These were the reasons we gave for suggesting another way of treatment to prevent and repair degenerative ankle disease.  Our other way is Prolotherapy injections.

Untreated damage to ankle ligaments = ankle osteoarthritis

Picture demonstrating chronic ankle instability from ligament injury. Describing symptoms of popping, loss of motion, foot and toe pain, numbness in toes, cracking and crunching sounds.

This illustration demonstrates ankle instability caused by ankle ligament damage. Ankle ligament damage can be seen in symptoms of ankle popping, loss of motion, pain, arch cramping, foot and toe pain, cracking and crepitation, loss of muscle strength, numbness in toes.

The ankle consists of an intricate structure of bones, ligaments, tendons, and muscles. This complexity provides stability but also exposes the ankle to damage and instability through chronic ankle sprains. That these injuries commonly lead to osteoarthritis so we should not be surprised by research that confirms this.

Damage to ankle ligaments, including the talofibular ligament, can bring about ligament laxity. This allows the ankle bones to rub together abnormally, having a degenerative effect on the joint often demonstrated by ankle popping and dislocations.

As a person continues to walk and bear weight on the unstable ankle joint, the bones abnormally wear and tear on the cartilage. In this situation, the body will attempt to stabilize the joint. Because ligaments have less of a blood supply compared to other tissues, such as muscle, they are less likely to heal on their own. The joint will typically inflame, in an attempt to bring healing cells to the joint. An overgrowth of bone is also likely to occur in an attempt to stabilize the joint.

Lateral ankle instability: Damage to the anterior talofibular ligament, the calcaneofibular ligament, and the posterior talofibular ligament and the progression of osteoarthritis

In the updated 2020 medical publication Stat Pearls (5), the problems of lateral ankle instability and the progression to ankle osteoarthritis is observed this way:

“Lateral ankle instability is a complex condition that can, at times, prove difficult to evaluate and treat for general practitioners. The difficulty in evaluation and treatment is due in part to the ankle complex is composed of three joints: talocrural, subtalar, and tibiofibular syndesmosis. All three joints function in conjunction to allow complex motions of the ankle joint. The main contributors to the stability of the ankle joint are the articular surfaces, the ligamentous complex and the musculature – which allows for the dynamic stabilization of the joints.”

The ligamentous complex – the ligament function

  • The anterior talofibular ligament’s (ATFL), primary function is to resist inversion in plantar flexion (your foot bends too far forward or downward will twisting to the inside) and to prevent the talus from moving forward or away from the mortise and contributing to problems of “widening of the ankle mortise.”
  • The primary functions of the calcaneofibular ligament (CFL)  are to resist inversion in neutral and dorsiflexed position (prevents your foot from bending too far back) and also restrains subtalar inversion (your ankle from rolling over to the outside), which limits talar tilt (the outward roll of the ankle)within the mortise.
  • The posterior talofibular ligament is seen as a secondary ligament to support the function of the anterior talofibular ligament and calcaneofibular ligament.

It is easy to see why then when you walk, your foot turns inwards causing pain, there is pain when walking up and down steps, when driving, if it is your right ankle, you have dull throbbing pain when stepping on gas or brakes. Your weakened ligaments are allowing for your talus to bang against the mortise causing loss of cartilage, pain, and the development of bone spurs.

Diagnosis and treatment of ankle arthritis

Traditional diagnosis will often include the collection of one’s medical history; a physical examination; discussion of the frequency, intensity and duration of the pain; identification of the location of the pain and a history treatment since the onset of the pain. Sometimes a physician may analyze how the patient walks, known as gait analysis, to determine how the bones in the leg and foot align while walking. X-rays will usually show the spacing between bones and the level of cartilage degeneration. To see the joint in motion and perform stress maneuvers to determine the level of joint stability, musculoskeletal ultrasound is utilized. In addition, the providers should perform a physical examination to check the range of motion and ligament laxity/joint instability.

Your familiar trail of treatment started with conservative care options that included pain relievers that were stronger than the ones you can purchase over-the-counter and anti-inflammatories that were stronger than the ones you can purchase over-the-counter to reduce pain and swelling. Steroid injections such as cortisone are often prescribed in order to bring temporary pain relief. Arch supports in the shoes may be recommended to compensate for the change in one’s gait and to cushion the act of walking.

Research: the ankle osteoarthritis anti-inflammatory path of treatment is NOT good.

Doctors from The University of Melbourne and the University of Southampton published a study in March 2019 in the journal Drugs and Aging (6). The title of the paper is “Clinical Assessment and Management of Foot and Ankle Osteoarthritis: A Review of Current Evidence and Focus on Pharmacological Treatment.”

Let’s see if the path the doctors describe in their study sounds like the path you took to get to significant ankle osteoarthritis. Let’s listen to the research:

  • “Despite the high prevalence and disabling nature of foot and ankle osteoarthritis, the condition has been neglected by clinical researchers, and there are very few trials investigating non-surgical foot or ankle osteoarthritis treatment options.”
  • “There are no accepted clinical diagnostic criteria for foot or ankle osteoarthritis so imaging remains common.”

The MRI is sending you to a surgery that you may not need

This is a March 2019 study from leading physicians. They are telling you that non-surgical options are neglected when it comes to treating ankle osteoarthritis and that since there is no diagnostic criteria ankle osteoarthritis, you will get an MRI or a scan to help decide the treatment options. We have seen so many patients over the years who were sent to surgery for an MRI abnormality and not treated for what was really happening in their ankle.

Let’s get back to the study:

  • “Clinical guidelines based on knee and hip osteoarthritis research recommend education, exercise, and weight loss in the first instance.
  • Topical non-steroidal anti-inflammatory drugs (NSAIDs) or capsaicin may be used as an adjunct. Failing these approaches, acetaminophen (paracetamol) should be recommended; however, if there is inadequate symptomatic relief, then clinicians should try an oral NSAID or a cyclo-oxygenase-2 inhibitor.
  • Given that adverse events and co-morbidities are common in the elderly, older patients should be closely monitored when taking these medications.
  • Some studies have investigated intra-articular injections for foot and ankle osteoarthritis, and there is some evidence to suggest hyaluronic acid may be effective in the short term for ankle osteoarthritis. With the lack of research on foot or ankle osteoarthritis treatments, however, robust clinical trials are urgently needed.”

What is all this saying?

The problems of ankle instability and osteoarthritis is so clearly misunderstood, that doctors are using hip and knee guidelines to treat the ankle patient and that these treatment guidelines are NOT successful.

Ankle Fusion and Ankle Replacement

For a much more detailed discussion ankle surgery please see our article on Ankle Fusion and Ankle Replacement.

Typically, when an MRI shows an abnormality, and the problem of the ankle is not well understood, there is the surgical recommendation. With the surgical recommendation comes a pain management plan. Usually increased doses of medications until surgery day.

Arthrodesis is a surgical pain-relieving procedure that fuses the bones of the joint making it one continuous bone. The surgeon uses pins or screws and rods to hold the bones in the proper position while the joints fuse. This also dramatically reduces mobility and range of motion.

Doctors at the Department of Orthopaedic Surgery, College of Medicine, Chungbuk National University in Korea writing in the journal Foot and Ankle International (7) found:

“Ankle fusion combined with calcaneal sliding osteotomy (surgeons break your heel bone to restructure the joint complex) can be an effective operative option for ball and socket ankle deformity with advanced arthritis. In spite of increased complication rate, reliable pain relief, and restoration of gait ability through correcting hindfoot malalignment could improve the quality of life.”

In other words, you need to gamble reliable pain relief against increased complication rate and the chance for greater pain and immobility.

As far as ankle replacement goes, this is addressed in a November 2016 paper from Canadian University researchers who also published in the journal Foot and Ankle International.(8)

“Repeated surgery can be a measure of failure of the primary surgery. Future reoperations might be avoided if the cause is recognized and procedures or devices modified accordingly. Reoperations result in costs to both patient and the health care system. This paper proposes a new classification system for reoperations in end-stage ankle arthritis, and analyzes reoperation rates for ankle joint replacement and arthrodesis surgeries.”

These doctors looked at data with a 25% re-operation rate in patients.

Addressing the underlying cause of ankle arthritis – joint instability – in order to avoid ankle surgery

Dextrose injection, Prolotherapy offers a non-surgical option that corrects the underlying ligament damage and ankle joint instability which led to arthritis in the first place. It is a regenerative injection procedure in which a dextrose-based proliferant solution is injected into the joint, and along the ligaments of the ankle.

Prolotherapy injections create a mild inflammatory reaction in the area of damaged tissue. This dramatically increases the blood supply to an area where the blood supply is usually weak. This signals the body that healing is needed.

In this video Danielle R. Steilen-Matias, MMS, PA-C demonstrates treatment to the lateral ankle

The treatment begins immediately in the video

This is comprehensive Prolotherapy, meaning there are a lot of injections. The patient getting the injections in this video is comfortable and tolerates the treatment well. The patient in this video is having the lateral or outer ankle treated.

  • The injections are given at the ligament attachment to the bone. This helps stimulate healing and strengthening of the ankle ligaments.
  • At 0:48 the importance of treating the lateral ligaments of the ankle, the anterior talo-fibular ligament (ATFL), the calcaneo-fibular ligament (CFL) and the posterior talo-fibular ligament.
  • The patient is not sedated in anyway, once treatment begins patients are surprised that it is not as painful as it looks. We do offer various pre-treatment medications to help the patient including IV sedation. Especially those with a fear of needles.
  • This patient came to see us for an old ankle sprain injury causing chronic ankle instability and pain with running and lower body activities.
  • On his first physical exam he had some ligament laxity, a lot of tenderness and instability in his ankle. At that visit we treated the lateral side. This is a follow up treatment.
  • Depending on the severity of the ankle sprain, it could take 3 to 8 treatments to affect a repair.

Published research from our Caring Medical doctors, that appeared in Clinical Medicine Insights Arthritis and Musculoskeletal Disorders, we discussed this patient case:

  • A 59-year-old female patient presented with a history of three years of right ankle pain following a lateral sprain. The patient was unable to walk more than 30 feet without severe ankle pain and had ceased all weight-bearing recreational activities.
  • Cortisone therapy had been unsuccessful and ankle fusion had been recommended.
  • Based on X-ray and MRI findings, the patient was diagnosed with osteoarthritis, avascular necrosis of the talus, and synovitis. Serologic tests were suggestive of scleroderma (rheumatic disease).
  • The patient received four stem cell/Prolotherapy treatments over a period of eight months.
  • At the second treatment, the patient reported the ability to stand for long periods and walk for half a mile without pain.
  • At the third treatment, she reported an improved range of motion, less frequent pain, and ability to take two-mile walks on hilly, uneven ground, although steep climbs still induced pain.
  • These gains were maintained throughout the treatment period.

Hauser RA, Orlofsky A. Regenerative Injection Therapy with Whole Bone Marrow Aspirate for Degenerative Joint Disease: A Case Series. Clinical Medicine Insights Arthritis and Musculoskeletal Disorders. 2013;6:65-72. doi:10.4137/CMAMD.S10951.

Other research that supports the use of PRP and stem cells in ankle osteoarthritis patients includes:

Let’s start with a brief explanation of treatments:

  • Prolotherapy as mentioned is the injection of a simple dextrose solution that causes ligament repair by initiating the body’s natural healing response
  • PRP is Platelet Rich Plasma Therapy – it is demonstrated in the video below.
    • PRP treatment re-introduces your own concentrated blood platelets into the ankle area.
    • Your blood platelets contain growth and healing factors. When concentrated through simple centrifuging, your blood plasma becomes “rich” in healing factors, thus the name Platelet RICH plasma.
  • Stem cell therapy in our office is the use of bone marrow aspirate. Bone Marrow is the liquid spongy-type tissue found in the hallow (interior) of bones. It is primarily a fatty tissue that houses stem cells which are responsible for the formation of other cells. These mesenchymal stem cells (MSC), also called marrow stromal cells, can differentiate (change) into a variety of cell types including osteoblasts (bone cells)chondrocytes (cartilage cells), myocytes (muscle cells), fibroblasts (ligament and tendon cells) and others when reintroduced into the body by injection.
    • It is important to note that we do not treat every patient with stem cell therapy. We have found equal success in many patients with the simpler H3 Prolotherapy and PRP Procedures. We use stem cell therapy when the joint degeneration calls for it.

A demonstration of how we offer PRP and Prolotherapy.

  • In this video, the treatment begins with an ultrasound examination to help guide some of the injections during the treatment.
  • Before the treatment begins the patient receives some numbing solutions in the form of injections, while the ultrasound examination continues. Not all patients request the numbing solutions. It is an option that we do offer. Typically while the patients receive many injections, the treatment is tolerated quite well with or without being numbed.
  • At 0:45 we see the PRP / Prolotherapy treatment begin. Our PRP treatments are more than “one shot.” In our opinion to best treat ankle pain, injections are given into the joint as well as the outer and surrounding ligaments and the muscle/tendon attachments to the bone.
  • At 1:00 we see the Prolotherapy injections into the medial and lateral ankle, the inside and outside.
  • In this particular patient, he had suffered an ankle fracture 30 years prior and had a repair surgery. His range of motion had decreased significantly becoming harder for him to perform his job.
  • In total, this patient received 6 treatments over 6 months. The difference between surgery and our treatments was that he was able to continue to work during the treatment phase while his ankle pain and stability improved.

Research on these treatments

In a well cited and noted study, doctors in Iran found that stem cell injections into the ankle in patients with ankle osteoarthritis were safe, effective, and clinically beneficial long-term. This 2015 study however, also stated: “further studies are needed with larger sample sizes and longer follow-up periods to confirm these findings.”(10)

Some of those studies include research from doctors from Rizzoli Orthopedic Institute, University of Bologna, Bologna, Italy who examined bone marrow-derived stem cells and their impact on osteochondral lesions of the talus in ankle osteoarthritis. Here is a summary of their research:

  • Ankle osteoarthritis is a challenging pathology, often requiring surgical treatments. In young patients, joint-sparing, biologic procedures would be desirable.
  • Recently, a few reports have described the efficacy of bone marrow stem cells in osteoarthritis. Considering the good outcomes of one-step bone marrow-derived cells transplantation (BMDCT) for osteochondral lesions of the talus, the doctors applied this procedure for in concomitant ankle osteoarthritis. (The surgical implantation of a “patch” scaffold from donor cartilage).
  • 56 patients, with an average age of 35.6 years (range 16-50), who suffered from osteochondral lesions of the talus and ankle osteoarthritis, were treated using BMDCT.
  • The whole clinical outcome had a remarkable improvement at 12 months, a further amelioration at 24 months and a lowering trend at 36 months. Early osteoarthritis had better outcomes. 16 patients required another treatment and they were considered failures. (11)

In April 2017, researchers in Japan reported on the safety and effectiveness of an intra-articular injection of PRP in ankle osteoarthritis patients during a 24-week treatment period. They found that PRP resulted in no serious adverse effects and significantly reduced pain in the patients with ankle osteoarthritis.(12)

In July 2019, doctors at the Department of Orthopedics Surgery at Tokat State Hospital in Turkey published these findings comparing Prolotherapy to Platelet Rich Plasma injections, in the journal Medical science monitor (13). In brief summary, the comparison showed both treatments worked very well in helping patients with Osteochondral lesions of the Talus.

Here are the research highlights:

  • 49 patients with Osteochondral lesions of the Talus symptoms of more than 6 months who had been refractory (not responding to more traditional, conservative treatments) for the previous 3 months.
  • The patients were divided into 2 groups:
    • 27 patients received Prolotherapy
    • 22 patients received PRP injections
    • The patients were given 3 injections

RESULTS Both PRP and Prolotherapy treatments resulted in greater improvement in pain and ankle functions at follow-up periods extending to 1 year and there was no difference between the groups for the outcomes at follow-up periods .

  • Excellent or good outcomes were reported by 88.8% of the patients in Prolotherapy group and 90.9% of the patients in PRP group.

A demonstration of Stem Cell Therapy and Prolotherapy

In our clinics, stem cell therapy, which are cells taken from the patient, NOT donated “stem cells,” are used in only the most advanced cases. This is not our “go to,” treatment. In the same way the joint degeneration does not occur overnight, one cannot expect the repair to be achieved overnight. In more advanced cases it can take more than 1 treatment to achieve treatment goals.

The treatment begins at 1:06 of the video

  • When someone has very advanced osteoarthritis of a joint, like an ankle joint, we may use platelet rich plasma combined with lipoaspirate (fat-derived stem cells).  Very advanced osteoarthritis have a deficiency of cells in the joint, or better understood as deficiency of building material.
  • In this video, fat-derived stem cells are drawn in the liposuction procedure from the buttocks of this patient.
  • This procedure begins at 1:42 of the video. A very dilute anesthetic is injected into the area to numb the pain. The collected fat is then combined with Platelet Rich Plasma. and injected into the ankle.
  • The ankle injections begin at 2:29. This patient is having numbing solutions to make the treatment more comfortable.
  • The procedure is done very quickly.
  • At 3:30 the stem cell/PRP combination is injected.
  • Advanced degeneration is usually seen every few weeks for up to 4 to 6 visits.

Summary

Prolotherapy can permanently strengthen the ligaments of the ankle, eliminating chronic ankle sprains, subluxations, and instability. Because H3 Prolotherapy stimulates the repair of the soft tissue injuries and instability that are associated with bunions, heel spurs, plantar fasciitis, ankle sprains, fallen arches, and Achilles tendinopathy, chronic pain from these conditions is eliminated. For advanced degenerative conditions, Cellular Prolotherapy (PRP or Stem cell Prolotherapy) is often utilized for accelerated recovery.

Cortisone injections, NSAIDs, and surgery work against a patient’s best long-term interest because they are degenerative by nature.  Patients with chronic ankle and foot pain need regenerative options to stop the degenerative process. This is also true for athletes with acute foot and ankle problems, as well as anyone who wishes to stay active without taking extended time off for surgical recovery.

Would you like to ask a question about Ankle Osteoarthritis?
Get help and information from our Caring Medical staff.

1 Gribble PA, Bleakley CM, Caulfield BM, Docherty CL, Fourchet F, Fong DT, Hertel J, Hiller CE, Kaminski TW, McKeon PO, Refshauge KM. 2016 consensus statement of the International Ankle Consortium: prevalence, impact and long-term consequences of lateral ankle sprains. Br J Sports Med. 2016 Jun 3:bjsports-2016. [Google Scholar]
2 Wells B, Allen C, Deyle G, Croy T. Management of acute grade II lateral ankle sprains with an emphasis on ligament protection: a descriptive case series. International journal of sports physical therapy. 2019 Jun;14(3):445. [Google Scholar]
3 Carbone A, Rodeo S. A review of current understanding of post-traumatic osteoarthritis resulting from sports injuries. J Orthop Res. 2016 Jun 16. [Google Scholar]
4 Hauser R, Hauser M, Cukla J. Dextrose prolotherapy injection for chronic ankle pain. Pract Pain Manag. 2010;10(1):70-6. [Google Scholar]
5 Gibboney MD, Dreyer MA. Lateral Ankle Instability. InStatPearls [Internet] 2019 Apr 7. StatPearls Publishing. [Google Scholar]
6 Paterson KL, Gates L. Clinical Assessment and Management of Foot and Ankle Osteoarthritis: A Review of Current Evidence and Focus on Pharmacological Treatment. Drugs & aging. 2019 Jan 25:1-9. [Google Scholar]
7. Cho BK, Park KJ, Choi SM, Kang SW, Lee HK. Ankle Fusion Combined With Calcaneal Sliding Osteotomy for Severe Arthritic Ball and Socket Ankle Deformity. Foot Ankle Int. 2016 Dec;37(12):1310-1316. [Google Scholar]
8 Younger AS, Glazebrook M, Veljkovic A, et al A Coding System for Reoperations Following Total Ankle Replacement and Ankle Arthrodesis. Foot Ankle Int. 2016 Nov;37(11):1157-1164. Epub 2016 Aug 16.  [Google Scholar]
9 Hauser RA, Orlofsky A. Regenerative Injection Therapy with Whole Bone Marrow Aspirate for Degenerative Joint Disease: A Case Series. Clinical Medicine Insights Arthritis and Musculoskeletal Disorders. 2013;6:65-72. doi:10.4137/CMAMD.S10951. [Google Scholar]
10 Emadedin M, GHORBANI LM, Fazeli R, Mohseni F, Moghadasali R, Mardpour S, Hosseini SE, Niknejadi M, Moeininia F, AGHAHOSSEIN FA, BAGHABAN EM. Long-term follow-up of intra-articular injection of autologous mesenchymal stem cells in patients with knee, ankle, or hip osteoarthritis. [Google Scholar]
11. Buda R, Castagnini F, Cavallo M, Ramponi L, Vannini F, Giannini S. “One-step” bone marrow-derived cells transplantation and joint debridement for osteochondral lesions of the talus in ankle osteoarthritis: clinical and radiological outcomes at 36 months. Archives of orthopaedic and trauma surgery. 2016 Jan 1;136(1):107-16. [Google Scholar]
12. Fukawa T, Yamaguchi S, Akatsu Y, Yamamoto Y, Akagi R, Sasho T. Safety and Efficacy of Intra-articular Injection of Platelet-Rich Plasma in Patients With Ankle Osteoarthritis. Foot Ankle Int. 2017 Apr 1:1071100717700377. [Google Scholar]
13 Akpancar S, Gül D. Comparison of Platelet Rich Plasma and Prolotherapy in the Management of Osteochondral Lesions of the Talus: A Retrospective Cohort Study. Medical Science Monitor. 2019 Jul 30;25:5640-7.  [Google Scholar]

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