Quantitative MRI T2 mapping techniques have been used as a non-invasive biomarker of early degenerative changes in knee OA [11, 12, 20]. MRI relaxation times are translated into quantitative values of tissues [21] in order to show subtle changes in cartilage composition in the early stages [9, 10]. In this randomized, double-blind, placebo-controlled study T2 mapping was used specifically to detect any changes in the cartilage tissue after intraarticular treatment with PRP and HA in patients with knee OA. Specially designed software and methodology was utilized in order to generate T2 relaxation times in the region of interest (ROI) [19]. Since research in this field has mainly focused on the clinical outcome by monitoring various subjective questionnaires and clinical measurements [7, 8, 22] the T2 mapping represents a novelty in this research field.
The most important finding in the present study was a substantial focal decrease in T2 relaxation time after HA applications (p = 0.002, power = 56%) and a statistically significant decrease after PRP applications in patients with knee OA. The focal change in T2 relaxation times within each group was observed at the articular side of the cartilage (ROI 2), whereas there were no differences observed in the subchondral cartilage layer (ROI 1). These results indirectly suggest that the target location of intraarticular application is mainly on the articular side of the cartilage. On the contrary, T2 relaxation times in placebo group substantially increased (p = 0.029, power = 72%). There were no differences in cartilage thickness at follow-up in the placebo group, whereas the thickness of articular cartilage substantially increased in PRP group (p = 0.033, power = 55%) and significantly increased in HA group. This may in turn indicate a modification in the cartilage microstructure, collagen orientation, and water content after intraarticular PRP and HA applications (5,6), possibly to prevent further deterioration of OA by restoring cartilage tissue [9, 10, 18]. Furthermore, T2 relaxation times were significantly lower in both ROI 1 and 2 after PRP and HA applications compared to the placebo group at follow-up. Therefore, PRP and HA applications might provide some sort of protective effect even in the deeper cartilage layer.
On the other hand, the differences in T2 relaxation times might be due to the altered loading of articular cartilage as a consequence of intraarticular applications [13]. Different volumes of intraarticular applications (5 ml in PRP and 2 ml in HA) and extraarticular (subcutaneous) administration of saline solution in placebo group might have influenced the results of T2 relaxation times. A similar impact on T2 relaxation times were demonstrated in surgical treatments of cartilage lesions, especially in matrix autologous chondrocyte implantation (MACI) [16, 17]. Since this is the first study using T2 mapping to evaluate a potential cartilage repair after intraarticular administration of PRP or HA, there is a lack of evidence regarding the interpretation of the T2 relaxation time of potentially “recovered” cartilage. Nevertheless, several parameters clearly indicate that there were some favourable changes in articular cartilage after intraarticular applications of HA and PRP compared to the placebo group at follow-up. Other factors that may affect T2 relaxation times, such as gender and age [12, 23, 24], BMI and daily activity [25], and time after loading [13, 26] were excluded by providing homogenous groups and using the pre-loading protocol.
The other objective of this study was to evaluate the effect of intraarticular applications of PRP and HA on knee function, pain, and quality of life by using WOMAC questionnaires and clinical examination. The positive effect of intraarticular applications in treatment of symptomatic knee OA was well documented in the literature [7, 8, 22]. The results of this study showed significant decrease in WOMAC pain score and overall WOMAC score in the PRP group at follow-ups, which is consistent with the literature [27, 28]. This, in combination with the results of T2 mapping, seems to be in favour of improving cartilage properties (5,6). On the other hand, the results in the placebo group are surprising as the significant decrease in WOMAC scores was similar to the PRP group despite the deterioration of cartilage characteristics based on T2 mapping [9, 10, 18]. The opposite proved to be the case for the HA group since a significant decrease in WOMAC pain score was observed only at the first follow-up at 2 months, whereas no difference was observed at the second follow-up at 6 months. Similarly, mixed clinical outcomes were demonstrated in randomized controlled trials when the effect of intraarticular HA administration was compared to PRP in knee OA treatment [2, 29, 30].
Finally, the results of T2 mapping seem to match the clinical findings and patients’ satisfaction only in the PRP group, whereas this was not observed in the HA or placebo group. Namely, patients in the placebo group showed the same level of satisfaction (according to WOMAC score) compared to the PRP group, while in the HA group the level of satisfaction no longer improved over time. Thus, the actual significance of the observed changes in cartilage T2 mapping is questionable since it does not match the clinical findings. Although the results of T2 mapping indicated improving cartilage properties after receiving PRP or HA, there was no overall superior clinical improvement compared to the placebo group. Therefore, further research needs to be conducted in order to successfully validate the actual relevance of T2 mapping after administration of intraarticular therapy, possibly with concurrent histological analysis and clinical data. In addition, the long-lasting effect of T2 changes and overall cost benefit ratio of intraarticular therapy in knee OA should also be re-evaluated.
In conclusion, T2 mapping of cartilage tissue may aid in monitoring cartilage improvement or deterioration after the administration of intraarticular therapy in knee OA. However, clinical data seem not to match the results of T2 mapping in all cases. Therefore, the actual significance of T2 mapping in this clinical setting should be further investigated. Intraarticular therapy did not demonstrate any superior effect on patient’s satisfaction and level of pain compared to placebo group. Thus, the effectiveness of intraarticular therapy with PRP or HA in knee OA needs to be reassessed in placebo-controlled trials.