SLR - January 2022 - Stefany Carvalho

Effect of Platelet-Rich Plasma Injections vs Placebo on Ankle Symptoms and Function in Patients with Ankle Osteoarthritis: A Randomized Clinical Trial

Reference: Paget LDA, Reurink,G, Jan de Vos,R, Weir, A, Moen MH, Bierma-Zeinstra SMA, Stufkens SAS, Kerkhoffs GMMJ, Tol JL. Effect of Platelet-Rich Plasma Injections vs Placebo on Ankle Symptoms and Function in Patients with Ankle Osteoarthritis: A Randomized Clinical Trial. JAMA. 2021 Oct 26;326(16):1595-1605.

Level of Evidence: 1

Scientific Literature Review

Reviewed By: Stefany Carvalho, DPM
Residency Program: University Hospital – Newark, NJ

Podiatric Relevance: Joint pain and loss of ankle motion in osteoarthritis can be significantly debilitating, subsequently impacting quality of life. The current goal of conservative and surgical therapies is to improve function and control pain. Therapeutic options in the literature often provide poor clinical benefit and unpredictable results. Numerous conservative and surgical therapies are available, but research regarding platelet-rich plasma injections for the management of ankle osteoarthritis is limited.

Methods: A total of 100 patients with at least a van Dijk classification grade 2 tibiotalar osteoarthritis and pain rated greater than 40 out of 100 on the visual analog scale (VAS) were included. Subjects participated in a multicenter, block randomized, double-blinded, placebo-controlled trial where 2 intra-articular injections of either platelet rich plasma (PRP) or placebo (saline) was administered. Outcomes were evaluated at six, 12 and 26 weeks by using American Orthopaedic Foot and Ankle Score (AOFAS), VAS,  and Short Form-36 score (SF-36) among additional questionnaires.

Results: When comparing pre-injection scores to the 26 week follow up, the AOFAS score improved by 10 points in the PRP group compared to 11 points in the placebo group. However, once adjusted for duration of ankle osteoarthritis symptoms and radiological talar tilt, AOFAS improvement over 26 weeks was -1 point between groups which was not significant. No statistical significance was identified between groups for secondary outcomes at six, 12 or 26 weeks either.

Conclusions: In contrast to data supporting the use of PRP injections in knee osteoarthritis, the use of PRP injections in the ankle does not demonstrate comparable clinical benefits. Deviation in success of PRP injections between ankle and knee osteoarthritis may correspond to inherent differences in cellular composition and biomechanics. Previous studies demonstrated ankle cartilage is significantly more cellular and synthesizes more proteoglycans and collagen than knee chondrocytes. Increased proteoglycans in the ankle allows for greater stiffness and lower permeability than the knee joint protecting the ankle cartilage from continuous microtrauma. Additionally, ankle chondrocytes have decreased response to catabolic factors, IL-1 and fibronectin, suggesting greater capacity for repair and resistance to progressive degeneration in comparison to the knee.

Although previous studies assessing the benefit of PRP in ankle osteoarthritis have shown clinical improvement, these studies possessed study design limitations. The present study holds greater weight in comparison to its counterparts in its double-blinded and placebo-controlled design adjusted for constraining variables. However, groups were not controlled for physical therapy, which is a beneficial conservative treatment option for osteoarthritis. Conversely, the generalizability of these results is limited since there are varying compositions of PRP and protocols of dosing, timing and number of injections.

Considering the goal of conservative treatments is often to postpone surgical intervention, future studies could investigate the success of modalities such as PRP injections in delaying surgical treatment, including more definitive joint sacrificing methods. 

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