315 TH E JO U R NA L O F B O N E & JO I N T SU RG E RY J B J S . O RG V O L U M E 98-A N U M B E R 4 F E B R UA R Y 17, 2 016 d
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E V I D E N C E -B A S E D O R T H O PA E D I C S
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Evidence-Based Orthopaedics
Platelet-Rich Plasma Injections Were Not Better Than Hyaluronic Acid Injections for Knee Joint Degeneration Filardo G, Di Matteo B, Di Martino A, Merli ML, Cenacchi A, Fornasari P, Marcacci M, Kon E. Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial. Am J Sports Med. 2015 Jul;43(7):1575-82. Question: In patients with knee joint degeneration, how do injections of platelet-rich plasma (PRP) compare with those of hyaluronic acid (HA)? Design: Randomized (unclear allocation concealment), blinded (patients and outcome assessors), controlled trial with 12 months of follow-up. Setting: A specialized referral center for orthopaedics in Bologna, Italy. Patients: 192 patients with chronic knee pain lasting £4 months or swelling and imaging findings of cartilage degeneration indicating chondropathy or osteoarthritis. Exclusion criteria were an age ,80 years, Kellgren-Lawrence score .3, major axial deviation, focal chondral or osteochondral lesion, concomitant knee lesion causing pain or swelling, inflammatory arthropathy, hematological or severe cardiovascular diseases, infection, immunodepression, treatment with anticoagulants or nonsteroidal anti-inflammatory drugs, or decreased hemoglobin or platelet counts. 183 patients (mean age, 55 years; 61% men) completed follow-up.
Intervention: Patients were allocated to 3 weekly intra-articular injections of PRP (n = 96) or HA (n = 96). PRP preparation involved harvesting 150 mL of peripheral venous blood from each patient. 2 centrifugations were performed to separate erythrocytes and platelets to provide 20 mL of PRP, divided into 4 5-mL units, with 1 unit sent to the laboratory for quality testing. Before each injection, the PRP was activated by adding 10% calcium chloride. Patients in both groups were instructed to restrict use of the leg for £24 hours after each injection and to apply ice or other cold therapy to relieve pain. Main outcome measures: The primary outcome measure was the International Knee Documentation Committee (IKDC) subjective score (range, 0 to 100, with higher scores indicating better outcomes). Patients were also assessed with the Knee injury and Osteoarthritis Outcome Score, EuroQol visual analog scale, and Tegner score. Range of motion and the transpatellar circumference of the knee were also measured.
Main results: The study was powered to detect a minimum clinically significant difference of 6.7 points on the IKDC score. The PRP and HA groups both demonstrated improvement in terms of the IKDC score and did not differ at any follow-up time point. The baseline scores were 52.4 and 49.6 and the 12-month scores were 66.2 and 64.2 in the PRP and HA groups, respectively. PRP was associated with more post-injection swelling and pain, but the effects lasted only a few days and required no medical intervention. The PRP and HA groups did not differ in terms of any secondary outcome measures. Conclusion: In patients with knee joint degeneration, injections of PRP did not provide more benefit than injections of HA. Source of funding: RICERCA FINALIZZATA 2009; Italian Health Ministry; PRRU (Emilia-Romagna/ University of Bologna Project). For correspondence: Dr. B. Di Matteo, Orthopaedic and Traumatologic Clinic—Biomechanics and Technology Innovation Laboratory, Rizzoli Orthopaedic Institute, 1/10 Via Di Barbiano, Bologna, 40136, Italy. E-mail address: [email protected]
Commentary In this well-constructed trial, Filardo and colleagues compared the effect of PRP injections with that of HA injections for the treatment of symptomatic chondropathy of the knee. This is the largest study of its kind and was adequately powered for the primary outcome measure (IKDC score). The size of the study, combined with the rigorous methodology, gives the findings weight: there was no difference between the two groups, and the improvement in both groups was, at best, modest. Given the enthusiasm with which PRP injections have been used, practitioners should take note of this study. The authors provide a comprehensive review of the available literature and place their study in context. In seeking explanations for the disparity between their findings and those of studies that have demonstrated findings in favor of PRP injections, they highlight two issues. One is that their study cohort was older and thus the effect of age cannot be excluded. The other is that the PRP preparation in the current study contained leukocytes. Preparations of PRP vary widely in terms of the presence of leukocytes, activation of the platelets, and platelet concentra-
tions. Arguments based on in vitro studies can be made for and against the inclusion of leukocytes. Nonetheless, the authors acknowledge that leukocyte inclusion may be a reason for the absence of a favorable outcome for PRP over HA. The authors make no mention of physical therapy. It is unclear whether the patients had physical therapy before or after the injections. The inclusion criteria include pain or swelling. One could question the inclusion of patients with painless swelling, although it is unclear how many of the participants were in this category. Given the lack of difference between PRP and HA injections and the modest clinical improvement following both, there is a place for appropriately sized and similarly well-constructed studies comparing each with a placebo.
Julian Feller, MBBS OrthoSport, Richmond, Victoria, Australia
Disclosure: The author indicated that no external funding was received for any aspect of this work. The Disclosure of Potential Conflicts of Interest form is provided with the online version of the article.
J Bone Joint Surg Am. 2016;98:315
d
http://dx.doi.org/10.2106/JBJS.15.01441
d
E V I D E N C E -B A S E D O R T H O PA E D I C S
d
Evidence-Based Orthopaedics
Platelet-Rich Plasma Injections Were Not Better Than Hyaluronic Acid Injections for Knee Joint Degeneration Filardo G, Di Matteo B, Di Martino A, Merli ML, Cenacchi A, Fornasari P, Marcacci M, Kon E. Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial. Am J Sports Med. 2015 Jul;43(7):1575-82. Question: In patients with knee joint degeneration, how do injections of platelet-rich plasma (PRP) compare with those of hyaluronic acid (HA)? Design: Randomized (unclear allocation concealment), blinded (patients and outcome assessors), controlled trial with 12 months of follow-up. Setting: A specialized referral center for orthopaedics in Bologna, Italy. Patients: 192 patients with chronic knee pain lasting £4 months or swelling and imaging findings of cartilage degeneration indicating chondropathy or osteoarthritis. Exclusion criteria were an age ,80 years, Kellgren-Lawrence score .3, major axial deviation, focal chondral or osteochondral lesion, concomitant knee lesion causing pain or swelling, inflammatory arthropathy, hematological or severe cardiovascular diseases, infection, immunodepression, treatment with anticoagulants or nonsteroidal anti-inflammatory drugs, or decreased hemoglobin or platelet counts. 183 patients (mean age, 55 years; 61% men) completed follow-up.
Intervention: Patients were allocated to 3 weekly intra-articular injections of PRP (n = 96) or HA (n = 96). PRP preparation involved harvesting 150 mL of peripheral venous blood from each patient. 2 centrifugations were performed to separate erythrocytes and platelets to provide 20 mL of PRP, divided into 4 5-mL units, with 1 unit sent to the laboratory for quality testing. Before each injection, the PRP was activated by adding 10% calcium chloride. Patients in both groups were instructed to restrict use of the leg for £24 hours after each injection and to apply ice or other cold therapy to relieve pain. Main outcome measures: The primary outcome measure was the International Knee Documentation Committee (IKDC) subjective score (range, 0 to 100, with higher scores indicating better outcomes). Patients were also assessed with the Knee injury and Osteoarthritis Outcome Score, EuroQol visual analog scale, and Tegner score. Range of motion and the transpatellar circumference of the knee were also measured.
Main results: The study was powered to detect a minimum clinically significant difference of 6.7 points on the IKDC score. The PRP and HA groups both demonstrated improvement in terms of the IKDC score and did not differ at any follow-up time point. The baseline scores were 52.4 and 49.6 and the 12-month scores were 66.2 and 64.2 in the PRP and HA groups, respectively. PRP was associated with more post-injection swelling and pain, but the effects lasted only a few days and required no medical intervention. The PRP and HA groups did not differ in terms of any secondary outcome measures. Conclusion: In patients with knee joint degeneration, injections of PRP did not provide more benefit than injections of HA. Source of funding: RICERCA FINALIZZATA 2009; Italian Health Ministry; PRRU (Emilia-Romagna/ University of Bologna Project). For correspondence: Dr. B. Di Matteo, Orthopaedic and Traumatologic Clinic—Biomechanics and Technology Innovation Laboratory, Rizzoli Orthopaedic Institute, 1/10 Via Di Barbiano, Bologna, 40136, Italy. E-mail address: [email protected]
Commentary In this well-constructed trial, Filardo and colleagues compared the effect of PRP injections with that of HA injections for the treatment of symptomatic chondropathy of the knee. This is the largest study of its kind and was adequately powered for the primary outcome measure (IKDC score). The size of the study, combined with the rigorous methodology, gives the findings weight: there was no difference between the two groups, and the improvement in both groups was, at best, modest. Given the enthusiasm with which PRP injections have been used, practitioners should take note of this study. The authors provide a comprehensive review of the available literature and place their study in context. In seeking explanations for the disparity between their findings and those of studies that have demonstrated findings in favor of PRP injections, they highlight two issues. One is that their study cohort was older and thus the effect of age cannot be excluded. The other is that the PRP preparation in the current study contained leukocytes. Preparations of PRP vary widely in terms of the presence of leukocytes, activation of the platelets, and platelet concentra-
tions. Arguments based on in vitro studies can be made for and against the inclusion of leukocytes. Nonetheless, the authors acknowledge that leukocyte inclusion may be a reason for the absence of a favorable outcome for PRP over HA. The authors make no mention of physical therapy. It is unclear whether the patients had physical therapy before or after the injections. The inclusion criteria include pain or swelling. One could question the inclusion of patients with painless swelling, although it is unclear how many of the participants were in this category. Given the lack of difference between PRP and HA injections and the modest clinical improvement following both, there is a place for appropriately sized and similarly well-constructed studies comparing each with a placebo.
Julian Feller, MBBS OrthoSport, Richmond, Victoria, Australia
Disclosure: The author indicated that no external funding was received for any aspect of this work. The Disclosure of Potential Conflicts of Interest form is provided with the online version of the article.
J Bone Joint Surg Am. 2016;98:315
d
http://dx.doi.org/10.2106/JBJS.15.01441
