Marc Darrow MD,JD

Someone who has a medical history including numerous ankle arthroscopic procedures will usually contact out office looking for options to their next surgery which would be an ankle fusion or a total ankle replacement. Usually, someone being told they need one more surgery will lead these people to more exhaustively research alternatives. This includes the various types of ankle injections.

A July 2020 paper (1) compared various injection treatments for ankle pain caused by osteochondral lesions (loss of cartilage leading to a bone on bone situation) and osteoarthritis. The injection treatments included were hyaluronic acid, Platelet-rich plasma (PRP), saline, methylprednisolone (steroid), botulinum toxin type A, mesenchymal stem cells (MSCs), and prolotherapy.

This was a review study where researchers combined studies and the study data to form an opinion on which of these treatments would work best. The problem with the results of this study? There were not enough studies of good evidence in direct comparisons of ALL the treatments for the researchers to review to give any opinion. While we then cannot offer a direct comparison of the treatments, we can review the research in this article where there is a direct comparison and give a broad over view of these treatments for ankle pain.

Botox vs hyaluronic acid

While Botox and hyaluronic acid may be effective in cosmetics, we do not use these treatments in our orthopedic work. The reason is that in our 23 years of clinical experience we have found other injections to be superior in our clinical outcomes.

In a study published in the Journal of foot and ankle research (2) investigators compared the effectiveness of intraarticular Botulinum toxin type A and intraarticular hyaluronate plus rehabilitation exercise in patients with ankle osteoarthritis over a 6 month period.

  • Seventy-five patients with symptomatic ankle osteoarthritis grade 2 were randomized to receive either a single 100-unit Botulinum toxin type A injection into the target ankle or a single hyaluronate injection plus 12 sessions of rehabilitation exercise (30 minutes/day, 3 times/week for 4 weeks).
  • There were no significant between-group differences in pain, disability and functional scores.
  • 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.

There are many studies which favor the Botox injections in cases of Cerebral Palsy, post-stroke when there is neurological deficit, or in helping patients who had severe burns to their legs. The Botox helps with movement. At our practice, we do not treat these conditions.

Hyaluronic acid vs ankle osteoarthritis

I often tell patients who come in with a lot of effusion (swelling) in a joint, that their effusion, that large amount of joint fluid, is hyaluronic acid. So why would you put in more hyaluronic acid with an injection of it? It’s already causing pain. In the early part of my practice I use to give hyaluronic acid injections. I did not get very good results.

A September 2020 study (3) also examined the effectiveness of hyaluronic acid injections in varying stages of ankle osteoarthritis. Here is what the paper said:

“Nonoperative measures are often used as first line treatment in ankle osteoarthritis. One of these measures consists of hyaluronic acid injections in the affected ankle joint, but efficiency of this treatment is uncertain. The purpose of the study was to evaluate the effect on Self-reported Foot and Ankle Score, visual analog (pain) scale score at rest, and visual analog (pain) scale score at activity 6 months after a single dose of hyaluronic acid in patients with ankle osteoarthritis.

Fifteen 15 patients were included for analysis. Median Self-reported Foot and Ankle Score remained unchanged (no improvement), whereas visual analog score at activity went from and visual analog score at rest showed small improvement. Subgroup analysis on arthrosis grade (grade I-II and III-IV) showed no statistically significant changes for all variables even though patients with grade III-IV degenerative arthritis seemed to benefit more from the treatment.

The results indicate that a single injection of hyaluronic acid is insufficient to produce at clinically relevant response after 6 months.”


Remarkably there is very little research on the effectiveness of cortisone for ankle pain. A study from October 2018 (4) recorded these observations:

  • “Intra-articular injections are commonly used to treat knee arthritis pain; however, whether their efficacy generalizes to ankle arthritis remains debatable.”

When these researchers compared cortisone to hyaluronic acid, PRP, and stem cell injections, they found the effects of cortisone may only be short term and the evidence. They wrote: “Evidence from small trials favors hyaluronic acid and PRP injections for the treatment of pain associated with ankle osteoarthritis.” At the time of this study, the researchers could not find enough research on stem cell therapy to make a recommendation. I cover this below.

Platelet Rich Plasma Injections

A February 2021 study (5) tested how effective and safe a single intraarticular injection of platelet-rich plasma was for patients with ankle osteoarthritis.

  • Thirty-nine patients with symptomatic ankle osteoarthritis were assessed.
  • These patients had ankle osteoarthritis for at least six months
  • The patients received a single injection of PRP (3 mL) into symptomatic ankles.

The goal of the study was to see how these patients did at six months after the single injection.

  • Results: Significantly improvement in the pain and function scores were noted at 1-, 3-, and 6-month follow-ups.
  • Acetaminophen consumption dropped significantly and no serious adverse events occurred.
  • The study showed promise for a single intraarticular injection of PRP in the treatment of ankle ankle osteoarthritis.

Comparing PRP and Prolotherapy in treating ankle osteoarthritis

In 1997 I began practicing regenerative medicine for musculoskeletal problems by offering Prolotherapy. Prolotherapy is the injection of a simple sugar (dextrose). I found the newer, far more effective techniques of Stem Cell Therapy and Platelet-Rich Plasma (PRP) Therapy are actually more advanced versions of Prolotherapy, which is short for “proliferation therapy” (the proliferation of new cells following the injection of a substance that will stimulate new tissue growth).

A little more than 10 years later I started to use PRP or platelet rich plasma therapy. PRP treatments involve collecting a small amount of your blood and spinning it in a centrifuge to separate the platelets from the red cells. The platelets contain healing agents, or “growth factors.”  The collected platelets are then injected back into the injured area to stimulate healing and regeneration. The platelets contain healing agents, or “growth factors.” Even though I found both these treatments effective and used both treatments on myself, I began to favor using PRP because of the clinical evidence we were seeing of its superior healing power.

A July 2019 study (6) compared PRP and Prolotherapy. Here is what the study reported:

“Osteochondral lesions of talus are among the most common ankle problems. Platelet-rich plasma (PRP) and prolotherapy are 2 successful injection-based techniques for treatment of chronic musculoskeletal problems. The aim of the present study was to compare PRP and prolotherapy injections for the management of osteochondral lesions of talus.”

This was a retrospective cohort study of 49 patients with osteochondral lesions of talus symptoms of more than 6 months who had been refractory (not responsive) to 3 months of treatment using (other) conservative methods.

The patients were divided into 2 groups:

Prolotherapy injections – 27 patients and PRP injections- 22 patients.

The patients were given 3 injections of 4 mL solution into periarticular and intra-articular ankle joint spaces.

After treatment, patients were evaluated via Visual Analogue Scale (VAS), American Orthopedic Foot and Ankle Society Score (AOFAS), and Ankle Osteoarthritis Scale (AOS) at baseline and 21 days, 90 days, 180 days, and 360-day follow-up periods.

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.

In our office we evaluate every patient to offer a recommendation as to which treatment would be most beneficial to them.

Stem Cell Therapy for ankle osteoarthritis

I have a more comprehensive article on this site Stem Cell therapy and alternatives to ankle fusion and ankle replacement surgery.

Here is a summary of that article:

December 2016 research in the Journal of experimental orthopaedics from doctors at the Steadman Philippon Research Institute (7) reviewed the research in the treatment of ankle osteoarthritis with bone marrow derived stem cells.

  • The goal of this study was to review outcomes of bone marrow aspirate concentrate (bone marrow derived stem cells) for the treatment of chondral (cartilage) defects and osteoarthritis of the talus of the ankle. The researchers noted that there is not much research (at the time of this paper’s writing). . . Nonetheless, the evidence available showed varying degrees of beneficial results of bone marrow derived stem cell therapy for the treatment of ankle cartilage defects. The researchers hypothesized that bone marrow aspirate concentrate may be useful in regeneration of tissue, enhancing the quality of cartilage repair. As a result, BMAC promotes a potentially healthy environment for hyaline cartilage growth and repair.

Research cited:

  • A 2009 study published in Clinical Orthopaedics and Related Research, reported that 94 % of patients returned to low impact sports activity at an average 4.4 months after bone marrow aspirate transplantation and 77 % of patients returned to high impact sports activity at an average 11.3 months. (8)
  • The same researchers in 2013 reported that 73 % of the 36 patients playing sports before surgery were able to return to sports. They also reported that 22 % of these 36 patients were able to return to sport, but at a lower level than before surgery. (9)
  • A 2011 study reported that 95 % of patients who had undergone bone marrow concentrate treatments returned to their pre-symptom level of sporting activity at an average 13 weeks.(10)

A heavily cited and received 2015 study showed that stem cell treatments were able to regrow cartilage in ankles significant enough to improve function and pain levels in selected patients. Walking distances were shown to dramatically improve in the patient group.(11)

In a post-surgical study from December 2018, (12) researchers found the injection of bone marrow mesenchymal stem cells could improve the repair process of the osteonecrosis.

Ask Dr. Darrow

We do see many patients with a history of ankle problems and I stated above, if you have a good range of motion, even through pain, you may be able to avoid surgery. At our practice we use Platelet Rich Plasma and Stem Cell Therapy injections.

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A leading provider of stem cell therapy, platelet rich plasma and prolotherapy

PHONE: (800) 300-9300 or 310-231-7000

Stem cell and PRP injections for musculoskeletal conditions are not FDA approved. We do not treat disease. We do not offer IV treatments. There are no guarantees that this treatment will help you. Prior to our treatment, seek advice from your medical physician. Neither Dr. Darrow, nor any associate, offer medical advice from this transmission. This information is offered for educational purposes only. The transmission of this information does not create a physician-patient relationship between you and Dr. Darrow or any associate. We do not guarantee the accuracy, completeness, usefulness or adequacy of any resource, information, product, or process available from this transmission. We cannot be responsible for the receipt of your email since spam filters and servers often block their receipt. If you have a medical issue, please call our office. If you have a medical emergency, please call 911.

Citations for this article:

1 Boffa A, Previtali D, Frattura GD, Vannini F, Candrian C, Filardo G. Evidence on ankle injections for osteochondral lesions and osteoarthritis: a systematic review and meta-analysis. International Orthopaedics. 2020 Jul 9:1-5.
2 Sun SF, Hsu CW, Lin HS, Chou YJ, Chen JY, Wang JL. Efficacy of intraarticular botulinum toxin A and intraarticular hyaluronate plus rehabilitation exercise in patients with unilateral ankle osteoarthritis: a randomized controlled trial. Journal of foot and ankle research. 2014 Dec 1;7(1):9.
3 Jantzen C, Ebskov LB, Andersen KH, Benyahia M, Rasmussen PB, Johansen JK. The Effect of a Single Hyaluronic Acid Injection in Ankle Arthritis-A Prospective Cohort Study. The Journal of Foot and Ankle Surgery. 2020 May 29.
4 Vannabouathong C, Del Fabbro G, Sales B, Smith C, Li CS, Yardley D, Bhandari M, Petrisor BA. Intra-articular injections in the treatment of symptoms from ankle arthritis: a systematic review. Foot & ankle international. 2018 Oct;39(10):1141-50.
5 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: international medical journal of experimental and clinical research. 2019;25:5640.
6 Chahla J, Cinque ME, Schon JM, et al. Bone marrow aspirate concentrate for the treatment of osteochondral lesions of the talus: a systematic review of outcomesJournal of Experimental Orthopaedics. 2016;3:33. doi:10.1186/s40634-016-0069-x.
7 Giannini S, Buda R, Vannini F, Cavallo M, Grigolo B. One-step Bone Marrow-derived Cell Transplantation in Talar Osteochondral Lesions. Clinical Orthopaedics and Related Research. 2009;467(12):3307-3320. doi:10.1007/s11999-009-0885-8.
8 Giannini S, Buda R, Battaglia M, Cavallo M, Ruffilli A, Ramponi L, Pagliazzi G, Vannini F. One-step repair in talar osteochondral lesions: 4-year clinical results and t2-mapping capability in outcome prediction. The American journal of sports medicine. 2013 Mar;41(3):511-8.
9 Kennedy JG, Murawski CD. The Treatment of Osteochondral Lesions of the Talus with Autologous Osteochondral Transplantation and Bone Marrow Aspirate Concentrate: Surgical TechniqueCartilage. 2011 Oct;2(4):327-36. doi: 10.1177/1947603511400726. PMID: 26069591; PMCID: PMC4297142.
10 Emadedin M, Ghorbani Liastani M, Fazeli R, et al.Long-Term Follow-up of Intra-articular Injection of Autologous Mesenchymal Stem Cells in Patients with Knee, Ankle, or Hip Osteoarthritis. Arch Iran Med. 2015 Jun;18(6):336-44. doi: 015186/AIM.003.
11 Hernigou P, Dubory A, Lachaniette CH, Khaled I, Chevallier N, Rouard H. Stem cell therapy in early post-traumatic talus osteonecrosis. International orthopaedics. 2018 Dec 1;42(12):2949-56.1767–2139

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