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

Abstract

Importance: Approximately 3.4% of adults have ankle (tibiotalar) osteoarthritis and, among younger patients, ankle osteoarthritis is more common than knee and hip osteoarthritis. Few effective nonsurgical interventions exist, but platelet-rich plasma (PRP) injections are widely used, with some evidence of efficacy in knee osteoarthritis.

Objective: To determine the effect of PRP injections on symptoms and function in patients with ankle osteoarthritis.

Design, setting, and participants: A multicenter, block-randomized, double-blinded, placebo-controlled clinical trial performed at 6 sites in the Netherlands that included 100 patients with pain greater than 40 on a visual analog scale (range, 0-100) and tibiotalar joint space narrowing. Enrollment began on August 24, 2018, and follow-up was completed on December 3, 2020.

Interventions: Patients were randomly assigned (1:1) to receive 2 ultrasonography-guided intra-articular injections of either PRP (n = 48) or placebo (saline; n = 52).

Main outcomes and measures: The primary outcome was the validated American Orthopaedic Foot and Ankle Society score (range, 0-100; higher scores indicate less pain and better function; minimal clinically important difference, 12 points) over 26 weeks.

Results: Among 100 randomized patients (mean age, 56 years; 45 [45%] women), no patients were lost to follow-up for the primary outcome. Compared with baseline values, the mean American Orthopaedic Foot and Ankle Society score improved by 10 points in the PRP group (from 63 to 73 points [95% CI, 6-14]; P < .001) and 11 points in the placebo group (from 64 to 75 points [95% CI, 7-15]; P < .001). The adjusted between-group difference over 26 weeks was -1 ([95% CI, -6 to 3]; P = .56). One serious adverse event was reported in the placebo group, which was unrelated to the intervention; there were 13 other adverse events in the PRP group and 8 in the placebo group.

Conclusions and relevance: 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.

Trial registration: Netherlands Trial Register: NTR7261.

Figure 1.. Patient Flow in a Study of the Effect of Platelet-Rich Plasma Injections vs Placebo on Ankle Symptoms and Function in Patients With Ankle Osteoarthritis

^avan Dijk classification: 0 indicates normal joint or subchondral sclerosis; 1, osteophytes without joint space narrowing; 2, joint space narrowing with or without osteophytes; 3, (sub)total disappearance or deformation of the joint space. ^bVisual analog scale (VAS) score ranges from 0 to 100, higher scores indicate more severe pain. ^cPrior to each consult the questionnaires were checked for completeness. A reminder was then sent by email in the event of incompleteness. Two patients did not complete the secondary outcome questionnaires at 26 weeks because they felt it was too time consuming.

Figure 2.. Changes in the American Orthopaedic Foot and Ankle Society (AOFAS) Score in a Study of the Effect of Platelet-Rich Plasma (PRP) Injections vs Placebo on Ankle Symptoms and Function in Patients With Ankle Osteoarthritis

See Table 1 footnotes for scale definitions. The mean difference between the PRP and the placebo group over 26 weeks was −1 (95% CI, −6 to 3). The boxes show the median and IQR, with the bottom and top indicating the 25th and 75th percentiles, respectively. The upper whisker extends from the top of the box to the largest value no further than 1.5 times the IQR. The bottom whiskers extend from the bottom of the boxes to the smallest value no further than 1.5 times the IQR. Dots indicate outliers outside the whisker range.

Figure 3.. Change in American Orthopaedic Foot and Ankle Society (AOFAS) Scores for Each Participant in a Study of the Effect of Platelet-Rich Plasma (PRP) Injections vs Placebo on Ankle Symptoms and Function in Patients With Ankle Osteoarthritis

See Table 1 footnotes for scale definitions. Changes from baseline or from 6 weeks to 26 weeks or 6 weeks are represented by the vertical lines. Upward and downward lines indicate improvement and deterioration, respectively. The horizontal lines in the boxplots from bottom to top show the 25th, 50th (median), and 75th percentiles. The dot in the boxplot indicates the mean. The whiskers indicate the highest and lowest values.

Figure 4.. Secondary Outcome Measures in a Study of the Effect of Platelet-Rich Plasma (PRP) Injections vs Placebo on Ankle Symptoms and Function in Patients With Ankle Osteoarthritis

See Table 2 footnotes for scale definitions. The other secondary outcome measures can be found in Supplement 2 (eTables 4-13 and eFigures 1-3). The boxes show the median and IQR of the data, with the bottom and top indicating the 25th and 75th percentiles, respectively. The upper whisker extends from the top of the box to the largest value no further than 1.5 times the IQR. The bottom whiskers extend from the bottom of the boxes to the smallest value no further than 1.5 times the IQR. Dots indicate outliers outside the whisker range.