Ross Hauser, MD; Danielle Matias, PA-C; Demi Foster, APRN

In this article, we will explore recent findings in the comparison of injection treatments for ankle osteoarthritis. There is really not much by way of evidence to suggest one type of injection works better than another. Many times, clinical and empirical observation, confirmed by self-reported patient outcomes is the main tool to assess the success or failure of injections for ankle osteoarthritis.

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.

Traditional diagnosis will often include the collection of one’s medical history; a physical examination; a discussion of the frequency, intensity, and duration of the pain; identification of the location of the pain, and a history of a 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.

I am bone on bone 

Of the more interesting emails, we get is the person who describes themselves as being bone-on-bone and has a recommendation to an ankle fusion or replacement based on how much range of motion that they have in their ankle. They are on anti-inflammatories such as Diclofenac that are working well for them as long as they or “respectful” of their ankle and do not overdo it. Some of these people will report that they can still run or still walk many miles a day. What makes these emails interesting is the imminent recommendation for fusion or replacement surgery. Generally speaking in these types of people, surgery can be avoided.

In an attempt to treat ankle osteoarthritis, people will travel a familiar trail of treatment starting with conservative care options that include pain relievers that are stronger than the ones you can purchase over-the-counter and anti-inflammatories that are 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.

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.

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 ankles.

Doctors from The University of Melbourne and the University of South Hampton published a study in March 2019 in the journal Drugs and Aging (1). 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 are no diagnostic criteria for 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 ankles.

Let’s get back to the study:

• “Clinical guidelines based on the 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 are so clearly misunderstood, that doctors are using hip and knee guidelines to treat the ankle patient and that these treatment guidelines are NOT successful.

There is not enough evidence in the research to support the use of one injection treatment over another.

Let’s now get to the published research, we will start with a February 2021 study published in the journal International Orthopaedics (1). The authors of this paper tried to offer evidence supporting the safety and effectiveness of intra-articular injective treatments for ankle lesions ranging from osteochondral lesions (ultimately a  “bone-on-bone” situation) of the talus to full degenerative ankle osteoarthritis. They explored previously published research on:

• Hyaluronic acid (HA) injections.
• Platelet-rich plasma (PRP).
• Saline injections.
• Methylprednisolone (steroid).
• Botulinum toxin type A (BoNT-A).
• Mesenchymal stem cells (MSCs – stem cell therapy) and
• Prolotherapy.

In all the injection research there were no severe adverse events were reported.

• For osteochondral lesions of the talus, a comparison was possible between Hyaluronic acid (HA) injections and PRP showing no significant difference.
• For ankle osteoarthritis, a significant difference favoring Hyaluronic acid (HA) injections versus saline was documented at six months. The GRADE level of evidence was very low.

Conclusion: This meta-analysis supports the safety of intra-articular treatment for ankle osteoarthritis and osteochondral lesions of the talus, while only very low evidence supports the efficacy of Hyaluronic acid (HA) injections in terms of better results versus placebo for the treatment of ankle osteoarthritis, and other conclusions are hindered by the scarcity of the available literature.

In other words, there is not enough evidence in the research to support the use of one injection treatment over another.

A September 2023 paper in the Clinical Orthopaedics and Related Research (2)  also confirmed conflicting evidence for Hyaluronic acid (HA) injections, PRP injections, and Botulinum toxin type A (BoNT-A) injections. The researchers suggest: “No clinically relevant differences were found among Hyaluronic acid (HA) injections, PRP injections, and Botulinum toxin type A (BoNT-A) and their control groups in the treatment of ankle osteoarthritis. After using the GRADE tool (to examine the strength of evidence), the level of evidence was very low for Hyaluronic acid (HA) injections, moderate for PRP, and very low for Botulinum toxin type A (BoNT-A). No studies reported any serious adverse events in any treatment group. There is currently insufficient evidence to justify the use of any type of intra-articular injection in ankle osteoarthritis treatment.

The relative efficacy of all injectable therapies is far from definitive and warrants further high-quality comparative trials.

This study built upon the same theme of earlier research, for example, an October 2018 (3) study on whether Intra-articular injections commonly used to treat knee arthritis pain are any good at helping people with ankle arthritis.

In examining

• Hyaluronic acid (HA) injections,
• Platelet-rich plasma (PRP),
• Corticosteroid injection, and
• Mesenchymal stem cells (MSCs – stem cell therapy)

The researchers found evidence from small trials favors:

• Hyaluronic acid (HA) injections and PRP injections for the treatment of pain associated with ankle osteoarthritis. However, the relative efficacy of all injectable therapies is far from definitive and warrants further high-quality comparative trials.

The above research is considered current research as there are, as we will see below, limited studies on ankle osteoarthritis injections. Most studies focus on the knee, and as we see above, it is speculated that good results in the knee would transmit to equal results in the ankle. But do they?

Hyaluronic acid for ankle osteoarthritis

An October 2020 study published in The Journal of Foot and Ankle Surgery (6) examined the benefits and effectiveness of hyaluronic acid injections in treating ankle osteoarthritis.

The idea behind hyaluronic acid injections is to protect the ankle by reintroducing lost or diminished hyaluronic acid in the ankle’s synovial fluid. The synovial fluid is a thick gel-like liquid that helps cushion the ankle and acts to absorb the daily impact of walking and running. The treatment of Hyaluronic Acid Injections is also called Viscosupplementation – supplementing the “viscosity” or the thick, sticky, gel-like properties of the synovial fluid.

We have seen many patients who have tried hyaluronic acid injections. These injections have worked for these people in the short term. These patients are now in our office because the short-term has not transpired to the long-term and now a different treatment approach needs to be undertaken.

Here are the summary learning points of the above research:

• The effectiveness of hyaluronic acid injections in the ankle joint is uncertain. In this study, a single intra-articular injection of Cingal or MonoVisc was administered.
• Two different groups, those with grade I-II osteoarthritis and grade III-IV osteoarthritis showed no statistically significant changes for the better even though patients with grade III-IV arthrosis seemed to benefit more from the treatment.
• The results indicate that a single injection of hyaluronic acid is insufficient to produce a clinically relevant response after 6 months.

This was a small-scale study of 15 patients. The researchers did suggest a larger-scale study may provide more conclusive results.

An April 2022 paper in The Journal of Foot and Ankle Surgery (7) evaluated the efficacy and complications of hyaluronate injection using various clinical scoring systems. This study included 37 patients with unilateral ankle osteoarthritis (grade 2 or 3) who did not respond to previous pharmacological treatment. Three weekly hyaluronate injections were administered. The efficacy of intra-articular hyaluronate injection was evaluated on the basis of patient-reported foot and ankle clinical assessment at a mean follow-up of 14 months. Ankle Osteoarthritis Scale scores for pain and disability, American Orthopedic Foot and Ankle Society ankle-hindfoot scores, and visual analog scale for pain significantly improved at the final follow-up compared to that before intra-articular hyaluronate injection. This study suggests that 3 weekly intra-articular hyaluronate injections can be performed safely to reduce pain and improve function without serious complications in patients with early or intermediate-grade ankle osteoarthritis when patients inadequately respond to medication.

Combining cortisone and hyaluronic acid

A February 2023 paper in The Journal of Foot and Ankle Surgery (8) investigated the potential of combined hyaluronic acid/corticosteroid injections to improve pain and function for the treatment of post-traumatic subtalar osteoarthritis, in comparison with isolated intra-articular corticosteroid.

• Twenty-five symptomatic participants with a minimum follow-up of 1 year after surgery for calcaneus fractures were enrolled.
• Participants were randomly assigned into two groups:
  • isolated corticosteroid intra-articular subtalar injection (12 patients) or a combination of hyaluronic acid plus corticosteroid injections (12 patients).
  • All participants underwent three repeated injections at intervals of 1 week.
  • Pain and function scores using the visual analog scale of pain (VAS) and the American Orthopedic Foot and Ankle Score (pain and function) scores before treatment, 4 weeks, 12 weeks, and 24 weeks following the last injection.
• The hyaluronic acid plus corticosteroid injections group showed improved visual analog scale of pain (VAS) at the 12th and 24th weeks and greater AOFAS score improvement at the 4th, 12th, and 24th weeks, in comparison to the Corticosteroid Group.
• The combination of exogenous hyaluronic acid and corticosteroid showed greater and longer analgesic effects and function improvement in comparison with isolated intra-articular corticosteroids.

Botulinum toxin type A injections for ankle osteoarthritis

A paper published in the Journal of Foot and Ankle Research (9) compared the efficacy of intraarticular Botulinum toxin type A against intraarticular hyaluronate plus rehabilitation exercise in patients with ankle osteoarthritis.

• Seventy-five patients with symptomatic ankle osteoarthritis were randomized to receive either a single Botulinum toxin type A injection into the target ankle or a single hyaluronate (hyaluronic acid) injection plus 12 sessions of rehabilitation exercise (30 minutes/day, 3 times/week for 4 weeks).
• The primary outcome measure was the Ankle Osteoarthritis Scale (The patient is asked to self-assess their disability, pain, and function). Other scores and scales included pain, function, and medication usage.

Conclusions: Treatment with intraarticular Botulinum toxin type A or hyaluronate injection plus rehabilitation exercise was associated with improvements in pain, physical function, and balance in patients with ankle osteoarthritis. These effects were rapid at 2 weeks and might last for at least 6 months. There was no difference in effectiveness between the two interventions.

Prolotherapy injections

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 with 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 to the body that healing is needed.

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 the 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.

PRP injections for ankle osteoarthritis | When it works and when it does not

The use of PRP and bone marrow-derived stem cells in ankle osteoarthritis patients

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 hollow (interior) of bones. It is primarily a fatty tissue that houses stem cells that 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 Prolotherapy and PRP Procedures. We use stem cell therapy when joint degeneration calls for it.

Research on these treatments

There is not a lot of evidence to show that bone marrow concentrate injections work or do not work. In December 2016 researchers (10) cautioned:

“. . . there exists an overwhelming paucity of long-term data and high-level evidence supporting bone marrow aspirate concentrations for the treatment of chondral defects. Nonetheless, the evidence available showed varying degrees of beneficial results of bone marrow aspirate concentrations for the treatment of ankle cartilage defects. The limited literature presented in this review demonstrates the need for more advanced, comparative studies to further investigate the efficacy, safety, and techniques for bone marrow aspirate concentrations  in the treatment of osteochondral defects.”

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.”(11)

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 cell transplantation (BMDCT) for osteochondral lesions of the talus, the doctors applied this procedure for 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. (12)

A July 2024 study published in the Journal of sport rehabilitation, (48) asked: “Does the injection of PRP relieve pain faster and improve function compared with no injection or placebo in patients with a lateral ankle sprain?” In reviewing data from three previously published studies, the researchers found: “PRP injection reduces pain and increases function after lateral ankle sprain five to eight weeks after intervention.” Further, “The use of PRP after lateral ankle sprain to decrease pain and increase function is supported with moderate evidence.”

We hope you found this article informative and that it helped answer many of the questions you may have surrounding your ankle problems.  If you would like to get more information specific to your challenges please email us: Get help and information from our Caring Medical staff

 

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References:

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