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The Role of Platelet-Rich Plasma in Inducing Musculoskeletal Tissue Healing
Brian C. Halpern, Salma Chaudhury and Scott A. Rodeo HSS Journal; DOI: 10.1007/s11420-011-9239-7
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Background
Platelet-rich plasma [PRP] has received increasing interest across many musculoskeletal disciplines and has been widely applied clinically to stimulate tissue healing in numerous anatomical regions. The known actions of platelet-derived factors suggest that PRP may have significant potential in the treatment of pathological conditions of cartilage, tendon, ligament, and muscle.
Purpose
The aim of this manuscript is to review current literature regarding the biology of PRP and the efficacy of using PRP to augment healing of tendon ligament and muscle injuries, as well as early osteoarthritis.
Methods
A comprehensive literature review of musculoskeletal applications of PRP was performed, including basic science and clinical studies such as randomized controlled trials, case controlled series, and case series.
Results
The most compelling evidence to support the efficacy of PRP is for its application to tendon damage associated with lateral and medial epicondylitis. Although some promising studies have been reported supporting the use of PRP in osteoarthritis and ligament and muscle injuries, it currently remains unknown whether PRP effectively alters the progression of osteoarthritis or aids the healing of ligament and muscle tissues.
Conclusion
The rationale for the use of PRP to improve tissue healing is strong, but the efficacy for many musculoskeletal applications remains unproven. PRP has been shown to be a safe treatment. A number of questions regarding PRP remain unanswered, including the optimal concentration of platelets, what cell types should be present, the ideal frequency of application, or the optimal rehabilitation regimen for tissue repair and return to full function.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
Efficacy of Autologous Platelet-Rich Plasma Use for Orthopaedic Indications: A Meta-Analysis
Ujash Sheth, BHSc; Nicole Simunovic, MSc; Guy Klein, DO; Freddie Fu, MD; Thomas A. Einhorn, MD; Emil Schemitsch, MD; Olufemi R. Ayeni, MD; Mohit Bhandari, MD, PhD The Journal of Bone & Joint Surgery. 2012; 94:298-307 doi:10.2106/JBJS.K.00154
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Background:
The recent emergence of autologous blood concentrates, such as platelet-rich plasma, as a treatment option for patients with orthopaedic injuries has led to an extensive debate about their clinical benefit. We conducted a systematic review and meta-analysis to determine the efficacy of autologous blood concentrates in decreasing pain and improving healing and function in patients with orthopaedic bone and soft-tissue injuries.
Methods:
We searched MEDLINE and Embase for randomized controlled trials or prospective cohort studies that compared autologous blood concentrates with a control therapy in patients with an orthopaedic injury. We identified additional studies by searching through the bibliographies of eligible studies as well as the archives of orthopaedic conferences and meetings.
Results:
Twenty-three randomized trials and ten prospective cohort studies were identified. There was a lack of consistency in outcome measures across all studies. In six randomized controlled trials (n = 358) and three prospective cohort studies (n = 88), the authors reported visual analog scale (VAS) scores when comparing platelet-rich plasma with a control therapy across injuries to the acromion, rotator cuff, lateral humeral epicondyle, anterior cruciate ligament, patella, tibia, and spine. The use of platelet-rich plasma provided no significant benefit up to (and including) twenty-four months across the randomized trials (standardized mean difference, −0.34; 95% confidence interval [CI], −0.75 to 0.06) or the prospective cohort studies (standardized mean difference, −0.20; 95% CI, −0.64 to 0.23). Both point estimates suggested a small trend favoring platelet-rich plasma, but the associated wide confidence intervals were consistent with nonsignificant effects.
Conclusions:
The current literature is complicated by a lack of standardization of study protocols, platelet-separation techniques, and outcome measures. As a result, there is uncertainty about the evidence to support the increasing clinical use of platelet-rich plasma and autologous blood concentrates as a treatment modality for orthopaedic bone and soft-tissue injuries.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
Platelet-Rich Plasma Differs According to Preparation Method and Human Variability Augustus D. Mazzocca, MS, MD; Mary Beth R. McCarthy, BS; David M. Chowaniec, BS; Mark P. Cote, DPT; Anthony A. Romeo, MD; James P. Bradley, MD; Robert A. Arciero, MD; Knut Beitzel, MD The Journal of Bone & Joint Surgery. 2012; 94:308-316 doi:10.2106/JBJS.K.00430
Quote:
Background:
Varying concentrations of blood components in platelet-rich plasma preparations may contribute to the variable results seen in recently published clinical studies. The purposes of this investigation were (1) to quantify the level of platelets, growth factors, red blood cells, and white blood cells in so-called one-step (clinically used commercial devices) and two-step separation systems and (2) to determine the influence of three separate blood draws on the resulting components of platelet-rich plasma.
Methods:
Three different platelet-rich plasma (PRP) separation methods (on blood samples from eight subjects with a mean age [and standard deviation] of 31.6 ± 10.9 years) were used: two single-spin processes (PRPLP and PRPHP) and a double-spin process (PRPDS) were evaluated for concentrations of platelets, red and white blood cells, and growth factors. Additionally, the effect of three repetitive blood draws on platelet-rich plasma components was evaluated.
Results:
The content and concentrations of platelets, white blood cells, and growth factors for each method of separation differed significantly. All separation techniques resulted in a significant increase in platelet concentration compared with native blood. Platelet and white blood-cell concentrations of the PRPHP procedure were significantly higher than platelet and white blood-cell concentrations produced by the so-called single-step PRPLP and the so-called two-step PRPDS procedures, although significant differences between PRPLP and PRPDS were not observed. Comparing the results of the three blood draws with regard to the reliability of platelet number and cell counts, wide variations of intra-individual numbers were observed.
Conclusions:
Single-step procedures are capable of producing sufficient amounts of platelets for clinical usage. Within the evaluated procedures, platelet numbers and numbers of white blood cells differ significantly. The intra-individual results of platelet-rich plasma separations showed wide variations in platelet and cell numbers as well as levels of growth factors regardless of separation method.
Clinical Relevance:
The variability of components and its effects on dosage should be considered in single or consecutive treatments of platelet-rich plasma. Significant differences in components were observed in different separation methods and may have specific results on treated tissue.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
The National Institute for Health and Clinical Excellence (NICE) issued full guidance to the NHS in England, Wales, Scotland and Northern Ireland on Autologous blood injection for tendinopathy today.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
Patellar Tendon Healing With Platelet-Rich Plasma: A Prospective Randomized Controlled Trial
Adriano Marques de Almeida et al
Am J Sports Med April 2, 2012
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Background: The patellar tendon has limited ability to heal after harvesting its central third. Platelet-rich plasma (PRP) could improve patellar tendon healing.
Hypothesis: Adding PRP to the patellar tendon harvest site would improve donor site healing and improve clinical outcome at 6 months after anterior cruciate ligament (ACL) reconstruction with a patellar tendon graft.
Study Design: Randomized controlled trial; Level of evidence, 1.
Methods: Twenty-seven patients were randomly divided to receive (n = 12) or not receive (n = 15) PRP in the patellar tendon harvest site during ACL reconstruction. The primary outcome was magnetic resonance imaging (MRI) assessment of patellar tendon healing (gap area) after 6 months. Secondary outcomes were questionnaires and isokinetic testing of ACL reconstruction with a patellar tendon graft comparing both groups.
Results: Patellar tendon gap area was significantly smaller in the PRP group (4.9 ± 5.3 mm2; 95% confidence interval [CI], 1.1-8.8) than in the control group (9.4 ± 4.4 mm2; 95% CI, 6.6-12.2; P = .046). Visual analog scale score for pain was lower in the PRP group immediately postoperatively (3.8 ± 1.0; 95% CI, 3.18-4.49) than in the control group (5.1 ± 1.4; 95% CI, 4.24-5.90; P = .02). There were no differences after 6 months in questionnaire and isokinetic testing results comparing both groups.
Conclusion: We showed that PRP had a positive effect on patellar tendon harvest site healing on MRI after 6 months and also reduced pain in the immediate postoperative period. Questionnaire and isokinetic testing results were not different between the groups at 6 months.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
Platelet-Rich Plasma Update: Clinical Use in Musculoskeletal Care
The therapy has seen increased demand from the general patient population
CHRISTOPHER ALLAN WEBB, J Musculoskel Med. 2012;29:96-101
ABSTRACT:
Quote:
Platelet-rich plasma (PRP) therapy has been evaluated for its effect on acute and chronic tendinopathies, ligament rupture, acute fracture healing, bone nonunions, muscle injuries, and degenerative joint disease, as well as surgical outcomes. The concept of using PRP to enhance local tissue healing is based on several growth factors. Once the platelet-rich graft has been prepared, it is administered directly to the injury site. The associated risks mimic those of any traditional percutaneous injection. The most common patient complaint is pain at the treatment site. PRP therapy offers great promise in musculoskeletal medicine, but an abundance of level 1 data to support its efficacy is still lacking. PRP therapy seems to show its greatest potential in chronic tendinopathy conditions.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
Press Release: Platelet-rich plasma therapy a safe option for cartilage damage, new study finds
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When it comes to treating cartilage tears in athletes, Platelet Rich Plasma (PRP) therapy is a safe and effective method of treatment, according to research presented today at the American Orthopaedic Society for Sports Medicine's (AOSSM) Annual Meeting in Baltimore.
"Using PRP therapy to repair cartilage is still relatively experimental, but studies like this show it's not only safe but also offers a significant improvement in function and quality of life for patients," said Elizaveta Kon, MD, lead author for the study and Director of Nano-Biotecnology Laboratory at the Rizzoli Orthopaedic Institute in Bologna, Italy. "None of the patients treated experienced complications like infection, deep vein thrombosis or fever."
During the study, 180 patients were treated for chronic pain or swelling of the knee with either PRP therapy or viscosupplementation, a more common hyaluronic acid-based treatment for cartilage damage. A total of 109 patients, with an average age of 56, reached a final evaluation. Both treatment groups demonstrated significant improvement based on higher post-treatment IKDC scores, which measure pain and basic function in follow-up interviews.
"As athletic participation has grown," Kon noted, "new problems like cartilage lesions, or tears, continue to emerge. Finding the right approach to treatment is difficult, but PRP has emerged as a viable option according to our research."
Kon also noted that long-term follow-ups for PRP treatments are needed to further evaluate the overall effectiveness of the therapy for future patients.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
The Positive Effects of Different Platelet-Rich Plasma Methods on Human Muscle, Bone, and Tendon Cells
Augustus D. Mazzocca, Am J Sports Med July 16, 2012
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Background: Clinical application of platelet-rich plasma (PRP) in the realm of orthopaedic sports medicine has yielded variable results. Differences in separation methods and variability of the individual may contribute to these variable results.
Purpose: To compare the effects of different PRP separation methods on human bone, muscle, and tendon cells in an in vitro model.
Study Design: Controlled laboratory study.
Methods: Blood collected from 8 participants (mean ± SD age 31.6 ± 10.9 years) was used to obtain PRP preparations. Three different PRP separation methods were used: a single-spin process yielding a lower platelet concentration (PRPLP), a single-spin process yielding high platelet and white blood cell concentrations (PRPHP), and a double-spin that produces a higher platelet concentration and lower white blood cell concentration (PRPDS). Human bone, muscle, and tendon cells obtained from discarded tissue samples during shoulder surgery were placed into culture and treated with the 3 PRP preparations, control media (2% fetal bovine serum [FBS] and 10% FBS), and native blood. Radioactive thymidine assays were obtained to examine cell proliferation, and testing with enzyme-linked immunosorbent assay was used to determine growth factor concentrations.
Results: Addition of PRPLP to osteocytes, myocytes, and tenocytes significantly increased cell proliferation (P ≤ .05) compared with the controls. Adding PRPDS to osteoblasts and tenocytes increased cell proliferation significantly (P ≤ .05), but no significance was shown for its addition to myocytes. The addition of PRPHP significantly increased cell proliferation compared with the controls only when added to tenocytes (P ≤ .05). Osteoblasts: Proliferation was significantly increased by addition of PRPLP compared with all controls (2% FBS, 10% FBS, native blood) (P ≤ .05). Addition of PRPDS led to significantly increased proliferation compared with all controls, native blood, and PRPHP (P ≤ .05). Proliferation was significantly less when PRPHP was added compared with PRPDS (P ≤ .05). Myocytes: Proliferation was significantly increased by addition of PRPLP compared with native blood (P ≤ .05). Adding PRPHP or PRPDS to myocytes showed no significant increase in proliferation compared with the controls or the other separations. Tenocytes: Proliferation was significantly increased by addition of PRPLP compared with all controls (2% FBS, 10% FBS, native blood) (P ≤ .05). Addition of PRPDS showed a significant increase compared with the controls and native blood. For tenocytes, there was a significant increase (P ≤ .05) seen when PRPHP was added compared with the controls and native blood but not compared with the other separations.
Conclusion: The primary findings of this study suggest the application of different PRP separations may result in a potential beneficial effect on the clinically relevant target cells in vitro. However, it is unclear which platelet concentration or PRP preparation may be optimal for the treatment of various cell types. In addition, a “more is better” theory for the use of higher platelet concentrations cannot be supported. This study was not intended to prove efficacy but to provide a platform for future research to be built upon.
Clinical Relevance: The utilization of different PRP separations may result in a potentially beneficial effect on the clinically relevant target cells in vitro, but it is unclear which platelet concentration or PRP preparation may be optimal for the treatment of various cell types.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
The Biomechanical and Histologic Effects of Platelet-Rich Plasma on Rat Rotator Cuff Repairs
Jennifer Beck et al
Am J Sports Med July 19, 2012
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Background: Rotator cuff tears are common injuries that are often treated with surgical repair. Because of the high concentration of growth factors within platelets, platelet-rich plasma (PRP) has the potential to enhance healing in rotator cuff repairs.
Hypothesis: Platelet-rich plasma would alter the biomechanical and histologic properties of rotator cuff repair during an acute injury response.
Study Design: Controlled laboratory study.
Methods: Platelet-rich plasma was produced from inbred donor rats. A tendon-from-bone supraspinatus tear was created surgically and an immediate transosseous repair performed. The control group underwent repair only. The PRP group underwent a repair with PRP augmentation. Rats in each group were sacrificed at 7, 14, and 21 days. The surgically repaired tendons underwent biomechanical testing, including failure load, stiffness, failure strain, and stress relaxation characteristics. Histological analysis evaluated the cellular characteristics of the repair tissue.
Results: At 7- and 21-day periods, augmentation with PRP showed statistically significant effects on the biomechanical properties of the repaired rat supraspinatus tear, but failure load was not increased at the 7-, 14-, or 21-day periods (P = .688, .209, and .477, respectively). The control group had significantly higher stiffness at 21 days (P = .006). The control group had higher failure strain at 7 days (P = .02), whereas the PRP group had higher failure strain at 21 days (P = .008). Histologically, the PRP group showed increased fibroblastic response and vascular proliferation at each time point. At 21 days, the collagen fibers in the PRP group were oriented in a more linear fashion toward the tendon footprint.
Conclusion: In this controlled, rat model study, PRP altered the tissue properties of the supraspinatus tendon without affecting the construct’s failure load.
Clinical Relevance: The decreased tendon tissue stiffness acutely and failure to enhance tendon-to-bone healing of repairs should be considered before augmenting rotator cuff repairs with PRP. Further studies will be necessary to determine the role of PRP in clinical practice.
Tendinopathy and osteoarthritis are common chronic musculoskeletal conditions that are associated with frequent pain and reduced function. With the advent of autologous platelet-rich plasma (PRP), new opportunities are available to elucidate potential healing mechanisms and elaborate safe injection therapies. PRP therapy involves the use of autologous activated platelets retained in fibrin matrices as a source of growth factors and cytokines that are active in healing mechanisms, such as inflammation, angiogenesis, cell migration and proliferation. Here we provide an overview of the main components of PRP products relevant to the mechanism of action in tendinopathy and osteoarthritis, and emphasize the importance of identifying and exploiting principal molecular components in PRP for therapeutic benefit. We review the clinical applications of PRP in osteoarthritis and tendinopathy and discuss the current existing challenges.
INTRODUCTION
The etiology, pathogenesis, and pain generators in chronic tendinopathy remain to be elucidated. Biologic therapies, such autologous blood (AB) and platelet rich plasma (PRP) injections, aimed at stimulating healing of degenerative tendons, have shown promise but clinical research is limited.
METHODS
The purpose of this study was to prospectively investigate the clinical effect of treatment with AB or PRP injection in patients with chronic tendinopathy. Patients over 18 years old were eligible for the study if they had more than 3 months of symptoms and had failed typical conservative treatment such as physical therapy, corticosteroid injections, massage, acupuncture, and/or chiropractic. All tendons were evaluated with musculoskeletal ultrasound and patients received treatment with either AB, leukocyte-rich PRP (LR-PRP), or leukocyte-poor PRP (LP-PRP), injected under ultrasound guidance into the tendinopathic areas. Patients were followed using visual analogue pain scales (VAS), site specific validated outcome scores, and a Likert post-treatment scale at six weeks, twelve weeks, six months and a year. A decrease in VAS of 20 was considered a clinically significant improvement. Likert post-treatment ratings of much or completely resolved were also considered clinically significant.
RESULTS
99 tendons were treated with average age 48.5 years (range 19-82). 44% were female and 56% were male. Patients had symptoms for an average of 34.4 months prior to treatment. Conditions treated included lateral epicondylosis (17), proximal hamstring tendinosis (22), Achilles tendinosis (11), patellar tendinosis (10), plantar fasciosis (9) and other tendinopathies (30).
Of patients with at least 12 weeks follow-up, 10 had AB, 77 LR-PRP, and 12 LP-PRP injections. For AB injection the average duration of symptoms was 12.3 months and average follow-up was 22.2 weeks. 70% of ABI patients had some improvement, although only 40% improved at least 20 points on VAS. Average decrease in VAS was 15.2. Of those patients that improved, the average decrease in VAS was 23.1. 60% of those with AB injections considered themselves mostly or completely improved. For LR-PRP the average duration of symptoms was 35.8 months and average follow-up was 33.4 weeks. 78% of patients improved at all with 62% having at least a 20 point decrease in VAS. The average decrease in VAS was 21.8, but for those that improved, it was a 30.9 decrease. 54% of LR-PRP patients rated themselves as mostly or completely improved. For LP-PRP the average duration of symptoms was 37.6 weeks prior to treatment and average follow-up was 39.3 weeks. 92% of patients improved at all with 83% decreasing VAS by at least 20. The average decrease in VAS was 25 and for those who improved it was 29.1. 50% of LP-PRP patients rated themselves as mostly or completely improved.
CONCLUSION
Biologic therapies such as AB and PRP injection were moderately effective for treatment of recalcitrant tendinopathy, and PRP appears to be more effective than AB. Further studies comparing these treatments to each other, to other treatment options, and to placebo should be undertaken to better define their clinical utility and indications in the treatment of chronic tendinopathy.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
The Systemic Effects of Platelet-Rich Plasma Injection
Amy S. Wasterlain, Hillary J. Braun, Alex H.S. Harris, Hyeon-Joo Kim and Jason L. Dragoo Am J Sports Med December 4, 2012
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Background: Platelet-rich plasma (PRP) is an autologous blood product used to treat acute and chronic tendon, ligament, and muscle injuries in over 86,000 athletes in the United States annually. The World Anti-Doping Agency (WADA) banned intramuscular PRP injections in competitive athletes in 2010 because of concerns that it may increase performance-enhancing growth factors. The ban on PRP was removed in 2011 because of limited evidence for a systemic ergogenic effect of PRP, but the growth factors within PRP remain prohibited.
Purpose: To quantify the effect of PRP injection on systemic growth factors with performance-enhancing effects and to identify molecular markers to detect treated athletes.
Study Design: Descriptive laboratory study.
Methods: Six ergogenic growth factors monitored by WADA—human growth hormone (hGH), insulin-like growth factor–1 (IGF-1), insulin-like growth factor binding protein–3 (IGFBP-3), basic fibroblast growth factor (bFGF or FGF-2), vascular endothelial growth factor (VEGF), and platelet-derived growth factor–BB (PDGF-BB)—were measured in 25 patients before (baseline) and at 0.25, 3, 24, 48, 72, and 96 hours after intratendinous leukocyte-rich PRP injection. Eating and exercise were prohibited for 3 hours before testing. Growth factors were quantified by enzyme-linked immunosorbent assay, and the change relative to each patient’s baseline was calculated.
Results: Relative to serum, PRP contained significantly more bFGF (226 vs 5 pg/mL), VEGF (1426 vs 236 pg/mL), and PDGF-BB (26,285 vs 392 pg/mL), but IGF-1 and hGH were not elevated. Serum levels increased significantly for IGF-1 at 24 and 48 hours, for bFGF at 72 and 96 hours, and for VEGF at 3, 24, 48, 72, and 96 hours after PRP injection. Additionally, VEGF was increased in all 25 patients after PRP treatment.
Conclusion: Serum IGF-1, VEGF, and bFGF levels are significantly elevated after PRP injection, supporting a possible ergogenic effect of PRP. An indirect marker for hGH doping, the product of IGFBP-3 × IGF-1, also significantly increased after PRP. Platelet-rich plasma appears to trigger an increase in circulating growth factors through activating biological pathways rather than by serving as a vehicle for the direct delivery of presynthesized growth factors. Elevated VEGF was observed in all patients after PRP, and ≥88% of patients had elevated VEGF at each time point from 3 to 96 hours after PRP, suggesting that VEGF may be a sensitive molecular marker to detect athletes recently treated with PRP.
Clinical Relevance: This is the first and only adequately powered study of the systemic effects of PRP. We present evidence that PRP contains and may trigger systemic increases in substances currently banned in competitive athletes. Finally, we provide evidence that VEGF could serve as a useful molecular marker to detect athletes treated with PRP.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
Press release: Platelet-rich plasma treatment shows potential for knee osteoarthritis
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A study by researchers from Hospital for Special Surgery has shown that platelet-rich plasma (PRP) holds great promise for treating patients with knee osteoarthritis. The treatment improved pain and function, and in up to 73% of patients, appeared to delay the progression of osteoarthritis, which is a progressive disease. The study appears online, ahead of print, in the Clinical Journal of Sports Medicine.
"This is a very positive study," said Brian Halpern, M.D., chief of the Primary Care Sports Medicine Service at Hospital for Special Surgery, New York City, and lead author of the study.
Several treatments for osteoarthritis exist, including exercise, weight control, bracing, nonsteroidal anti-inflammatories, Tylenol, cortisone shots and viscosupplementation, a procedure that involves injecting a gel-like substance into the knee to supplement the natural lubricant in the joint. A new treatment that is being studied by a small number of doctors is PRP injections. PRP, which is produced from a patient's own blood, delivers a high concentration of growth factors to arthritic cartilage that can potentially enhance healing.
"You take a person's blood, you spin it down, you concentrate the platelets, and you inject a person's knee with their own platelets in a concentrated form," said Dr. Halpern. "This then activates growth factors and stem cells to help repair the tissue, if possible, calm osteoarthritic symptoms and decrease inflammation."
In the new study, researchers at Hospital for Special Surgery enrolled patients with early osteoarthritis, gave them each an injection of PRP (6-mL), and then monitored them for one year. Fifteen patients underwent clinical assessments at baseline, one week, and one, three, six, and 12 months. At these time points, clinicians used validated tools to assess overall knee pain, stiffness and function, as well as a patient's ability to perform various activities of daily living. At baseline and then one year after the PRP injection, physicians also evaluated the knee cartilage with magnetic resonance imaging (MRI), something that has not previously been done by researchers in other PRP studies. The radiologists reading the MRIs did not know whether the examination was performed before or after the PRP treatment.
"The problem with a lot of the PRP studies is that most people have just used subjective outcome instruments, such as pain and function scores," said Hollis Potter, M.D., chief of the Division of Magnetic Resonance Imaging at Hospital for Special Surgery, another author of the study. "But even when patients are blinded, they know there has been some treatment, so there is often some bias interjected into those types of studies. When you add MRI assessment, it shows you the status of the disease at that time, regardless of whether the patient is symptomatic or asymptomatic or they have good or poor function in the knee. You find out what the cartilage actually looks like. We can noninvasively assess the matrix or the building blocks of cartilage."
While previous studies have shown that patients with osteoarthritis can lose roughly five percent of knee cartilage per year, the HSS investigators found that a large majority of patients in their study had no further cartilage loss. "The knee can be divided into three compartments, the medial compartment, the lateral compartment and the patellofemoral compartment," said Dr. Halpern. "If we look at these compartments individually, which we did, in at least 73% of these cases, there was no progression of arthritis per compartment at one year. That is very significant, because longitudinal studies suggest a four to six percent progression of arthritis at one year."
Treatment with PRP was also useful in improving pain, stiffness and function. The investigators found that pain, measured by a standard test called the Western Ontario and McMaster Universities Arthritis Index, significantly improved with a reduction of 41.7% at six months and 55.9% at one year. On a pain scale commonly used by clinicians called the Visual Analog Scale, pain was reduced by 56.2% at six months and 58.9% at one year. Functional scores improved by 24.3% at one year. Activity of Daily Living Scores also showed a significant increase at both six months (46.8%) and one year (55.7%).
"We are entering into an era of biologic treatment, which is incredibly ideal, where you can use your own cells to try to help repair your other cells, rather than using a substance that is artificial," Dr. Halpern said. "The downside is next to zero and the upside is huge." Dr. Halpern pointed out, however, that the study is a small case series and PRP needs to be pitted against a traditionally treated group in a randomized, controlled trial.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
Platelet-rich plasma application to treat chronic tendinopathies: A review
Kaux, Jean-François and Crielaard, Jean-Michel Acta Orthopaedica Belgica Feb-2013
Quote:
Platelet-rich plasma (PRP) may represent a new therapeutic option for chronic tendinopathies. Platelets release various cytokines and growth factors which promote angiogenesis, tissue remodeling, and wound healing. We made an exhaustive review of the use of PRP in chronic tendinopathies: epicondylitis, rotator cuff, patellar and calcaneal tendinopathies, and plantar fasciitis.
Medline, Embase and Google Scholar were used (until July 31, 2012). Clinical studies about PRP and tendinopathies (in English and French language peer-reviewed journals) were included. Articles with a high level of evidence were considered preferentially.
Despite the proven efficacy of PRP on tissue regeneration in experimental studies, there is currently scanty tangible clinical evidence with respect to chronic tendon disorders. The few studies that have been performed appear unlikely to be comparable.
Randomized controlled studies with appropriate placebo groups are needed to determine the real effectiveness of PRP for treating chronic musculoskeletal injuries.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
The role of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in orthopaedic bone repair and regeneration.
Friedlaender GE, Lin S, Solchaga LA, Snel LB, Lynch SE. Curr Pharm Des. 2013 Feb 11.
Quote:
Recombinant human PDGF BB homodimer (rhPDGF-BB) is a potent recruiter of, and strong mitogenic factor for, cells crucial to musculoskeletal tissue repair, including mesenchymal stem cells (MSCs), osteogenic cells and tenocytes. rhPDGF-BB also up-regulates angiogenesis. These properties allow rhPDGF-BB to trigger the cascade of bone and adjoining soft tissue repair and regeneration. This mechanism of action has been established in numerous preclinical and clinical studies. Demonstration of the safety and efficacy of rhPDGF-BB in the healing of chronic foot ulcers in diabetic patients and regeneration of alveolar (jaw) bone lost due to chronic infection from periodontal disease has resulted in two FDA-approved products based on this molecule. A third product is in late stages of clinical development, with pilot and pivotal clinical studies of rhPDGF-BB mixed with an osteoconductive bone matrix (Augment® Bone Graft) in foot and ankle fusions demonstrating that this product is at least as effective as bone autograft, and has an improved safety profile. Additional combinations of rhPDGF-BB with tissue-specific matrices are also being studied clinically in additional musculoskeletal indications.
Platelet-rich plasma (PRP) may represent a new therapeutic option for chronic tendinopathies. Platelets release various cytokines and growth factors which promote angiogenesis, tissue remodeling, and wound healing. We made an extended literature review of the use of PRP in chronic tendinopathies: epicondylitis, rotator cuff, patellar and calcaneal tendinopathies, and plantar fasciitis. Medline, Embase and Google Scholar were used (until July 31, 2012). Clinical studies on PRP and tendinopathies published in English and French language peer-reviewed journals were included. Articles with a high level of evidence were given special consideration. Despite the proven efficacy of PRP on tissue regeneration in experimental studies, there is currently scanty tangible clinical evidence with respect to its efficacy in chronic tendon disorders. The few studies that have been performed appear unlikely to be comparable. Randomized controlled studies with appropriate placebo groups are needed to determine the real effectiveness of PRP for treating chronic musculoskeletal injuries.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
Outcomes and Quality of Life after Platelet-rich Plasma Therapy in Patients with Recalcitrant Hindfoot and Ankle Diseases: A Preliminary Report of 12 Patients
Chayanin Angthong, MD, Anuwat Khadsongkram, MD, Wirana Angthong, MD Journal of Foot and Ankle Surgery; Article in Press
Quote:
The present study aimed to determine the outcomes and quality of life after platelet-rich plasma therapy in patients with chronic recalcitrant diseases of the hindfoot and ankle and to identify the crucial clinical variables. The records of 12 adult patients with diseases of the hindfoot and ankle were included in the present study. These patients had been treated with platelet-rich plasma from September 2010 to April 2011 after 3 to 6 months or more of conservative treatment had been unsuccessful. They had attended the follow-up visits, were consecutively enrolled, and retrospectively studied. A total of 3 mL of autologous platelet-rich plasma was injected under fluoroscopic or ultrasound guidance into the affected areas. All patients had been evaluated using visual analog scale foot and ankle scoring before treatment and at set intervals after treatment. According to their scores at the final follow-up visit (mean 16 months), the patients were allocated to the satisfactory (score ≥ 80; n = 8) and unsatisfactory (score < 80; n = 4) groups. The health-related quality of life was assessed using the Medical Outcomes Study short-form, 36-item survey at the final follow-up visit, because the study was retrospective, and the information was not available before treatment. The mean visual analog score at the final follow-up visit (79.71 ± 17.81) was significantly greater than the mean pretreatment score (57.89 ± 20.77; p = .002). Four patients (33%) had unsatisfactory results. The mean short-form, 36-item score for the satisfactory group (85.23 ± 11.30) was significantly greater than that (57.33 ± 12.91) of the unsatisfactory group (p = .003). No definitive factors influencing the outcome of this treatment were found. The substantial number of patients with an unsatisfactory outcome indicates that platelet-rich plasma injection might be an option but might not be a mainstay of nonoperative treatment of problematic conditions of the hindfoot and ankle. The actual benefit of this treatment, including the factors influencing its outcome, are still inconclusive.
Re: Platelet Rich Plasma for Musculoskeletal Conditions
I had a letter from an orthopod who referred a patient to me regarding plantar heel pain yesterday and unusually he cited "There is no level 1 evidence for the indication and use of PRP therapy in this patient". The only thought that went through my head was "Since when has that ever stopped you before...." I must be getting old and cynical in my old age!
Be aware - orthopods are now actually reading research!
Re: Platelet Rich Plasma for Musculoskeletal Conditions
Exercise and the platelet activator calcium chloride both influence the growth factor content of platelet-rich plasma (PRP): overlooked biochemical factors that could influence PRP treatment
Bruce Hamilton, Johannes L Tol, Wade Knez, Hakim Chalabi Br J Sports Med doi:10.1136/bjsports-2012-091916
Quote:
Background There is strong evidence that exercise affects platelet haemostasis factors, but this potential effect on growth factor concentrations in platelet-rich plasma (PRP) has never been studied. In addition, there is a paucity of studies focusing on the effects of activating agents used in conjunction with PRP. The first aim of this study was to evaluate the effect of exercise on platelet and platelet-derived growth factors (PDGF)-AB, hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) concentrations in PRP. The second aim was to study the effect of the activating agent calcium chloride (CaCl2) on growth factor concentration in relation to different exercise states.
Methods Controlled laboratory study. Ten healthy participants performed 1 h of submaximal exercise with blood being withdrawn immediately pre, post and 18 h following. PRP was prepared in each condition in both an activated CaCl2 and non-activated form. Concentrations of PDGF-AB, HGF, IGF-1 and VEGF were evaluated using standard ELISA systems.
Results Exercise had no significant effect on platelet concentration, but significantly suppressed both VEGF and PDGF-AB concentrations. Exercise state had no significant effect on IGF-1 or HGF concentration. Activation with CaCl2 resulted in a significant increase in PDGF-AB and IGF-1 concentrations, unchanged VEGF and significantly reduced HGF concentrations.
Conclusions Exercise significantly impacts on PDGFs in PRP with significantly reduced concentrations of VEGF and PDFG-AB. Furthermore, the activation of PRP with CaCl2 results in a differentiated GF release from platelets. These relevant factors can potentially influence outcome in daily clinical practice and are recommended to be accounted for in future study design.
Platelet Rich Plasma for Musculoskeletal Conditions
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