Abstract
Objectives:
Platelet-rich plasma (PRP) injections have recently become commercially available and are marketed directly to consumers for the treatment of knee osteoarthritis (OA). Anabolic effects from cytokines concentrated in Leukocyte-Poor configurations of PRP (LP-PRP) are hypothesized to inhibit the native catabolic environment of the cartilage degeneration process. Multiple Level I trials comparing LP- PRP to hyaluronic acid and placebo injections have shown LP-PRP to improve patient symptoms from early knee OA for up to 1 year. However, it is unknown if changes to patient symptoms from LP-PRP treatment are due to analgesic effects or if clinical improvements are due to biologic alteration of the natural course of cartilage degeneration and prevention of OA progression. Quantitative magnetic resonance imaging (QMRI) sequences such as T1rho have been reliable for detection and mapping of early cartilage degeneration in the knee with T1rho values increasing with the degree of cartilage degeneration. The purpose of this study is 1) to utilize T1rho to delineate the effects of LP-PRP on the natural course of cartilage degeneration in the setting of mild to moderate knee OA and 2) determine if changes in patient symptoms are correlated with changes in cartilage health after treatment with LP- PRP. We hypothesize that LP-PRP injections will lead to improved T1rho relaxation times at 6 months after treatment compared to before treatment. Additionally, we hypothesize that improvement in patient-reported symptoms at 6- and 12-months after treatment will be correlated with improvement in T1rho relaxation times.
Methods:
Ten subjects [age: 52.9 years (range, 42 – 68 years); 9 female; BMI: 23.2 ± 1.9 kg/m2; Kellgren- Lawrence (KL): Grade 1, n = 1; Grade 2, n = 9] with symptomatic unilateral knee osteoarthritis were enrolled. Two patients were lost to follow-up at 12-months. Exclusion criteria included BMI > 30 kg/m2, prior knee surgery on affected side, prior knee injections on affected side (corticosteroid, hyaluronic acid, PRP, or stem cells), end-stage osteoarthritis (KL Grade 3 or 4) in any compartment of the knee, symptomatic meniscus tear (flap, bucket handle, root tear), and inflammatory arthropathy. The Regenkit BCT was used to make a standardized preparation of LP-PRP that was injected into the symptomatic knee. Patient-reported outcome measures [Knee Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) score] were administered before injection and at 3-, 6-, and 12-months after injection. Sagittal T1rho maps (TR/TE = 9.3/3.7 ms, time of recovery = 1500 ms, FOV = 36 cm, matrix = 256 x 256, slice thickness = 4 mm, time of spin-lock = 0, 10, 40, 80 ms, FSL = 500 Hz) of the symptomatic and contralateral knee were obtained at baseline and 6-months after treatment using a 3T MRI scanner. Cartilage lesions were graded using the Whole Organ Magnetic Resonance Imaging Score (WORMS). Articular cartilage was semi-automatically segmented into 6 regions: lateral femur, lateral tibia, medial femur, medial tibia, patella, and trochlea. T1rho values of regions with and without cartilage lesions were averaged for each subject. Minimal clinical important difference (MCID) was calculated using distribution based methods as 0.5 x standard deviation of change. Kruskal-Wallis signed-rank test and Spearman correlations were performed. Significance was set at p < 0.05.
Results:
KOOS in all subscales and IKDC scores improved significantly from baseline to 3-month follow- up (all p < 0.05) and improvements were sustained at 12-months except for KOOS sport subscale (p = 0.051) (Figure 1). 75%, 87.5%, 87.5%, 62.5%, 100%, and 87.5% of patients exceeded the MCID for KOOS (pain, symptoms, ADL, sports, QOL) and IKDC, respectively. At baseline, the symptomatic knee had higher WORMS cartilage lesion scores in the patellofemoral and total joint (PF: 9.5 ± 6.4 vs 7.0 ± 6.5, p = 0.074; total: 15.9 ± 15.3 vs 11.9 ± 15.4, p = 0.074) compared to that of the contralateral knee. There was no progression in WORMS cartilage lesion scores from baseline to 6-months in either knee. In the PRP- injected knee, T1rho values in regions with cartilage lesions significantly decreased from 46.5 ± 3.5 ms at baseline to 43.7 ± 3.5 ms at 6-months (p = 0.036) (Figure 2). In the non-injected knee, there was no significant change in T1rho values in regions with cartilage lesions from baseline to 6 months. The change in the cartilage T1rho values from baseline to 6-months was not associated with the improvement in KOOS or IKDC at 6-months or 12-months.
Conclusions:
This is the first study to determine the effects of LP-PRP injection on the cartilage health in knee osteoarthritis using QMRI. At 6-month post-injection, T1rho values significantly decreased in the regions of the knee with cartilage lesions. As T1rho indirectly measures proteoglycan content of cartilage, this may suggest that there may be some cartilage healing. Interestingly, the improvement in cartilage health was not associated with improvement in patient-reported symptoms. Longer-term studies with larger sample sizes are needed to further evaluate these relationships.
