PRP Dosing for Knee Osteoarthritis
For knee osteoarthritis, a series of 3 PRP injections administered 1-2 weeks apart is superior to a single injection and should be the preferred treatment protocol when PRP is used.
Evidence Supporting Multiple Injections
The most recent high-quality randomized controlled trial directly comparing single versus multiple PRP doses demonstrates clear superiority of three injections over one or two doses 1. In this 2021 study of 180 knees with early OA (Kellgren-Lawrence grades 1-2), all three dosing regimens showed comparable results through 6 months, but at 1-year follow-up, the three-dose group demonstrated statistically significant superiority across all outcome measures 1. Critically, while all groups improved initially, only the three-dose group maintained these gains with minimal deterioration after 6 months 1.
A 2015 randomized trial of 98 patients with grade 3 knee OA corroborates these findings, showing that two or three injections produced significantly better outcomes than a single injection across WOMAC pain, stiffness, and function scores 2. The mean differences between single injection versus both two-injection and three-injection groups were statistically significant 2.
Single Injection Evidence
A 2013 double-blind RCT found that single-dose PRP was as effective as two doses given 3 weeks apart for symptom relief in early knee OA, with both groups showing significant improvement over placebo through 6 months 3. However, this study noted that results deteriorated after 6 months in both PRP groups, suggesting the need for repeat dosing to maintain benefits 3.
Guideline Context and Limitations
While the American Academy of Orthopaedic Surgeons provides only "limited" strength recommendation for PRP use in knee OA, and the American College of Rheumatology/Arthritis Foundation recommends against its routine use due to preparation heterogeneity 4, 5, 6, when the clinical decision is made to use PRP, the evidence clearly favors multiple injections.
Important Caveats
- PRP should not be first-line treatment - patients should first trial physical therapy, weight management, NSAIDs, and potentially corticosteroid injections 5, 6
- Disease severity matters - PRP shows worse treatment response in severe knee OA (Kellgren-Lawrence grade 4) 4
- Platelet concentration influences outcomes - higher platelet concentrations correlate with better clinical results and lower failure rates (15.0% failure with low-platelet PRP versus 3.3% with high-platelet PRP) 7
- Preparation standardization is lacking - significant variability exists in PRP preparation methods, which limits generalizability of results 5, 8
Practical Protocol
When using PRP for mild-to-moderate knee OA after conservative measures have failed:
- Administer 3 intra-articular injections spaced 1-2 weeks apart 2, 1
- Use leukocyte-filtered PRP with platelet concentration at least 3 times baseline 3
- Expect maximal benefit at 3-6 months with sustained improvement at 1 year only with the three-dose protocol 1
- Counsel patients that mild complications (nausea, dizziness) occur in 22-44% of cases but are self-limited 3