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

This article will explore research on the effectiveness of PRP injections for ankle osteoarthritis. Research is often mixed because of the variants present in studies. As you will see below, some research examines one shot one time and other research suggests better results with more frequent applications. In general PRP can be effective in the right patient population and a more aggressive treatment. Let’s look at the research.

PRP is short for Platelet Rich Plasma; A sample of your blood is drawn, similar to a routine blood test. Plasma is separated out by spinning in a centrifuge  concentrating platelets and growth factors. The concentrated PRP is then injected into the ankle joint.

The research into PRP has been ongoing.

In April 2017, (1) researchers in Japan reported on the safety and effectiveness of intra-articular injection of PRP in ankle osteoarthritis patients during a 24-week treatment period. Publishing in the journal Foot and ankle international, this study of twenty ankles belonging to 20 patients diagnosed with varus-type ankle osteoarthritis who underwent intra-articular injections of platelet-rich plasma (PRP) were assessed for improvements. In this study patients received three separate injections of 2 mL of PRP were delivered to the ankle at two-week intervals, guided by ultrasound. Adverse events and treatment efficacy were evaluated at 4, 12, and 24 weeks following the final injection. Clinical outcomes were measured using the visual analog scale (VAS) for pain, the Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot scale, and the Self-Administered Foot Evaluation Questionnaire (SAFE-Q).  At follow ups the scores on the VAS and JSSF scales showed a substantial decrease (improvement in pain and function) from baseline to 4, 12, and 24 weeks post-treatment. The average score in the pain-related subscale of the SAFE-Q demonstrated a notable improvement from baseline to 12 weeks following treatment. In general, the greatest reduction in pain was observed at 12 weeks after the final injection, with a decrease in effect noted at 24 weeks. Patients suffering from late-stage OA exhibited poorer scores across all outcomes compared to those with early-stage OA.

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 (2). 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 the Prolotherapy group and 90.9% of the patients in the PRP group.

One shot of Platelet Rich Plasma -research says it can work

We constantly want to remind our patients and readers that one shot of PRP usually will not provide the pain relief or functional improvement that they are seeking. That is our realistic assessment based on twenty-eight years of experience with regenerative medicine. We also do not want people to have an over-expectation of what these treatments can do. One-shot PRP treatments are usually not as effective as a more comprehensive PRP treatment plan.

The success of one injection of PRP into the ankle for ankle osteoarthritis was demonstrated in a February 2021 study published in The Journal of Foot and Ankle Surgery (3)

The learning and summary points of this research:

• The aim of this study was to evaluate the effectiveness and safety of a single intraarticular injection of platelet-rich plasma (PRP) for patients with ankle osteoarthritis.
• In this study, 44 patients with ankle osteoarthritis were offered a single PRP injection.
• Patients received a single injection of PRP (3 mL) into symptomatic ankles.

What the researchers were looking for was:

• Changes in ankle pain measured by standard pain scales.
• Changes in ankle function measured by standard functional assessment scales.
• Changes in medications, specifically reduction in pain medication usage (Acetaminophen – Tylenol).

The researchers reported significant improvement in pain, function and a drop in medication usage, and no serious side effects from the PRP injection. They concluded: “(Our) study showed promise for a single intraarticular injection of PRP in the treatment of ankle osteoarthritis.”

PRP injections for ankle osteoarthritis vs Placebo

In October 2021, a paper in JAMA the Journal of the American Association (4) wrote: “Among patients with ankle osteoarthritis, intra-articular PRP injections, compared with placebo injections, did not significantly improve ankle symptoms and function over 26 weeks. The results of this study do not support the use of PRP injections for ankle osteoarthritis.” A number of questions about these findings were also published in JAMA.

One commentary wrote: “After review of the recent clinical trial examining platelet-rich plasma (PRP) injections for ankle osteoarthritis, we think there are several methodological concerns that make its concluding statement of “not supporting the use of PRP injections for ankle osteoarthritis,” without qualifiers, appear to be an overstatement.” (5) Another commentary suggested findings were more appropriate “in the context of acute ankle fracture rather than ankle osteoarthritis.” (6)

Another commentary suggested “Compared with patients in the placebo group, those in the PRP group had a higher body mass index, which is significantly associated with ankle osteoarthritis and worsening ankle symptoms. Second, a higher proportion of patients in the PRP group had more advanced stages of ankle osteoarthritis using several different radiological classification systems. Third, because ankle osteoarthritis leads to poorer mental and physical quality of life, it is understandable that patients in the PRP group with higher body mass index and more advanced stages of ankle osteoarthritis had lower frequency of playing sports than those in the placebo group.” (7)

The research authors did share with colleagues some of the limitations of the study (8) including “an “optimal” PRP preparation protocol has not yet been established (therefore) analyzing the PRP content would not alter the outcome or conclusion of our trial. . . patients with polyarticular osteoarthritis might mask a possible intervention effect on the outcome measures. For instance, a potential benefit of PRP on ankle function may be masked by limitations that knee osteoarthritis poses on a patient’s function in daily activities and walking distance.” (I alluded to the impact of other joints on ankle osteoarthritis above.) In this article we describe the challenges of one injection versus multiple injections. As all the researchers point out, it is difficult to determine the true effectiveness of PRP for ankle osteoarthritis because of the many variables of treatment. A study that does not suggest its use can be equally scientifically sound as a study that suggests the great benefit of the use of PRP.

In August 2023 the same research group published expanded findings (9) on the the long-term effect of PRP in patients with ankle osteoarthritis. Two injections, six months apart were given and the patients were followed for a year. Again, these researchers did not find intra-articular PRP injections, compared with saline placebo injections,  significantly improved any of the outcome measures. They found the likelihood of a clinically relevant benefit is very small.

A May 2023 study published in the Journal of Orthopaedic Surgery and Research (10) 0reviewed previously reported patient outcome data to answer the question, as best as possible, does PP injections work for osteoarthritis?” Here is what the authors found:

“Treatments of ankle osteoarthritis with various PRP preparations seemed to be effective, in terms of pain and function, when compared with before treatment. With very low-quality shreds of evidence, high costs, and diverging (differing opinions on how the treatment should be administered) settings, PRP is weakly recommended for ankle osteoarthritis as an alternative or adjunct therapy after failed conservative treatment. Its benefits would be attained approximately 12 weeks after injection with acceptable minor complications.” Further the authors suggest that “the best available evidence of pooling different PRPs for ankle osteoarthritis demonstrated only short-term, before–after pain, and functional improvement. Its benefit was similar to placebo effects. . . “

An August 2023 study (11) in the journal International Orthopaedics assessed the data of 127 patient outcomes from four previously published studies on the effectiveness of PRP for ankle osteoarthritis.

• In short-term follow-ups of less than six months, patient-reported outcomes results suggested significant improvement of the American Orthopaedic Foot and Ankle Society (AOFAS) score (0 – 100 scoring in pain, function, and disability) in the PRP injection group compared to the control group.
• Equally, there was a statistical difference in the pain, function, and disability patient-reported outcome scores between PRP injection and control groups in the final follow-up (more than 6 months).
• Conclusion: “This meta-analysis supports the safety of PRP intra-articular injection for ankle osteoarthritis.” The authors did note a concern that improvements in the outcomes scores in the PRP group at short-term follow-up do not exceed the minimal clinically important difference (MCID) to be clinically significant and it should be noted that PRP injection provides significant improvement more than six months follow-up.”

A December 2024 study in the Journal of orthopaedic surgery and research (12) processed patient data from 10 studies and found that PRP injections did not demonstrate over all improvements in various diseases of the ankle. However, a subgroup analysis revealed a more pronounced effect in patients suffering from talar cartilage injuries. Furthermore, the treatment effect of PRP remained effective during long-term follow-up. PRP alleviated patients’ pain, demonstrating a more substantial benefit in those with talar cartilage injuries.

In other words, PRP is a long-term treatment, results may be best seen in long-term follow-up.

Related articles

Avascular Necrosis Case Report of Direct Bone Marrow Injections and Prolotherapy Treatment

Chronic Ankle Instability Surgery
In the patients we see, they have at some point considered surgical intervention for their chronic ankle instability because they are basically done with treatments that are not effective. The reason they have not jumped right into surgery is because of its risks and the possibility that it will not help. But clearly, surgery does address ligament and tendon problems. These problems can also be addressed in a non-surgical manner.

Our published research

Avascular Necrosis Case Report of Direct Bone Marrow Injections and Prolotherapy Treatment

References

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