Evidence Based PRP

[PMR2008]

Just wanted to share some resources that could help start a healthy discussion. I am attaching one of my favorite PRP related review article.
"Applications of Platelet-Rich Plasma in Musculoskeletal and Sports Medicine: An
Evidence-Based Approach"

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Treatment of lateral epicondylitis with platelet-rich plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial.
Krogh TP, Fredberg U, Stengaard-Pedersen K, Christensen R, Jensen P, Ellingsen T.
Am J Sports Med. 2013 Mar;41(3):625-35.

PURPOSE: To examine whether a single injection of platelet-rich plasma (PRP) is more effective than placebo (saline) or glucocorticoid in reducing pain in adults with LE after 3 months.

STUDY DESIGN: Randomized controlled trial; Level of evidence, 1.

METHODS: A total of 60 patients with chronic LE were randomized (1:1:1) to receive either a blinded injection of PRP, saline, or glucocorticoid. The primary end point was a change in pain using the Patient-Rated Tennis Elbow Evaluation (PRTEE) questionnaire at 3 months. Secondary outcomes were ultrasonographic changes in tendon thickness and color Doppler activity.

RESULTS: Pain reduction at 3 months (primary end point) was observed in all 3 groups, with no statistically significant difference between the groups; mean differences were the following: glucocorticoid versus saline: -3.8 (95% CI, -9.9 to 2.4); PRP versus saline: -2.7 (95% CI, -8.8 to 3.5); and glucocorticoid versus PRP: -1.1 (95% CI, -7.2 to 5.0). At 1 month, however, glucocorticoid reduced pain more effectively than did both saline and PRP; mean differences were the following: glucocorticoid versus saline: -8.1 (95% CI, -14.3 to -1.9); and glucocorticoid versus PRP: -9.3 (95% CI, -15.4 to -3.2). Among the secondary outcomes, at 3 months, glucocorticoid was more effective than PRP and saline in reducing color Doppler activity and tendon thickness. For color Doppler activity, mean differences were the following: glucocorticoid versus PRP: -2.6 (95% CI, -3.1 to -2.2); and glucocorticoid versus saline: -2.0 (95% CI, -2.5 to -1.6). For tendon thickness, mean differences were the following: glucocorticoid versus PRP: -0.5 (95% CI, -0.8 to -0.2); and glucocorticoid versus saline: -0.8 (95% CI, -1.2 to -0.5).

CONCLUSION: Neither injection of PRP nor glucocorticoid was superior to saline with regard to pain reduction in LE at the primary end point at 3 months. However, injection of glucocorticoid had a short-term pain-reducing effect at 1 month in contrast to the other therapies. Injection of glucocorticoid in LE reduces both color Doppler activity and tendon thickness compared with PRP and saline.

 

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Efficacy of autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis.
Sheth U, Simunovic N, Klein G, Fu F, Einhorn TA, Schemitsch E, Ayeni OR, Bhandari M.
Source
J Bone Joint Surg Am. 2012 Feb 15;94(4):298-307.

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.

 

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Commentary and Perspective
Platelet-Rich Plasma: The Next Big Thing?: Commentary on an article by Ujash Sheth, BHSc, et al.: "Efficacy of Autologous Platelet-Rich Plasma Use for Orthopaedic Indications: A Meta-Analysis"
Matthew J. Matava, MD
The Journal of Bone & Joint Surgery, Volume 94, Issue 4

Autologous blood concentrates, one of which is platelet-rich plasma, have been becoming more popular as a result of the increasing attention that these products have received in the mainstream media following their use by high-profile athletes. Platelet-rich plasma has been utilized for a number of musculoskeletal conditions despite a relative lack of rigorous supportive data. Thus, there is a growing debate regarding the clinical efficacy of this treatment regimen. Several uncontrolled studies have shown beneficial effects for a variety of indications. However, the results of controlled trials comparing platelet-rich plasma with standard therapies have not been as definitive. Despite this relative lack of robust evidence, the market for platelet-rich plasma is expected to be worth $126 million by 2016.

It is against this backdrop that Sheth et al. provided a timely meta-analysis and systematic review of twenty-three randomized controlled trials and ten prospective cohort studies to assess the clinical results of autologous blood concentrates compared with those of control therapy, such as a placebo, corticosteroid injection, or physical therapy, in the treatment of orthopaedic injuries. Of the 895 eligible studies, thirty-three met the authors' inclusion criteria, with the investigators in those studies using a variety of primary functional and imaging outcome measures.

The authors found significant heterogeneity in these clinical series as the duration of follow-up ranged from as little as five days to up to two years, and the final volume of platelet product used in each study ranged from just 2 mL to 70 mL. The authors found twenty studies to be of high methodological quality and thirteen studies to be of moderate quality. Nevertheless, there was a lack of consistency in outcome measures across the studies. Of the thirty-three trials, nine showed a significant functional benefit for platelet-rich plasma, twenty-one showed no difference between platelet-rich plasma and the control, and two studies actually revealed a significant functional benefit for the control. (Functional outcomes were not evaluated in the remaining study.) Overall, the authors found no significant benefit for platelet-rich plasma, up to and including twenty-four months, across both the randomized trials and the prospective cohort studies. According to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria, a classification scheme based on the strength of clinical recommendations and quality of evidence, the overall quality of evidence was very low because of serious methodological limitations, variability in platelet separation techniques, lack of standardization in outcome measures, and uncertainty surrounding the precision of the results.

In summary, the authors of this well-written, comprehensive study found a significant lack of 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. Strengths of this study include its rigid inclusion and exclusion criteria, application of a comprehensive search strategy, and use of a quantitative analysis designed to assess the methodological quality of the studies. Interestingly, the published data have shown that platelet-rich plasma, when used alone in various case series, is often effective in terms of decreasing symptoms in a variety of musculoskeletal conditions. Yet, the results of platelet-rich plasma therapy have not been as robust when compared with a standard control. This finding supports the implementation of Level-I randomized controlled trials as the "gold standard" for evidence-based clinical research. My own experience with platelet-rich plasma has been mixed at best, with approximately a 50% improvement in symptom relief noted by patients compared with what would be expected from typical treatment regimens for muscle strains and partial tendon tears.

Despite basic-science data that have demonstrated that platelet-rich plasma use in animal and in vitro studies has a positive effect on healing, there are several issues that remain unanswered regarding the use of this treatment in the care of patients. Questions regarding the timing of platelet-rich plasma administration, optimal platelet concentration and platelet separation technique, ideal volume of the platelet concentrate, number of applications, and duration of the treatment benefit should be addressed in future studies because of the heterogeneous nature of the previously published studies. The authors of future clinical trials should also use validated, disease-specific, and patient-relevant outcomes that can be consistently applied for a variety of similar indications. Until these important issues are adequately addressed, clinicians should temper their enthusiasm for the use of autologous blood products for the treatment of musculoskeletal conditions.

 

[Vinny121]

PRP is standard practice in prolotherapy for regenerating cartilage in patients with osteoarthritis. Standard primary care for any type of pain management is pain meds like naproxen.

Prolotherapy, mesotherapy are considered effective ways to treat chronic and acute pain, but very few MDs use this kind of therapy.

 

[PMR2008]

Treatment of lateral epicondylitis with platelet-rich plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial.
Krogh TP, Fredberg U, Stengaard-Pedersen K, Christensen R, Jensen P, Ellingsen T.
Am J Sports Med. 2013 Mar;41(3):625-35.

PURPOSE: To examine whether a single injection of platelet-rich plasma (PRP) is more effective than placebo (saline) or glucocorticoid in reducing pain in adults with LE after 3 months.

STUDY DESIGN: Randomized controlled trial; Level of evidence, 1.

METHODS: A total of 60 patients with chronic LE were randomized (1:1:1) to receive either a blinded injection of PRP, saline, or glucocorticoid. The primary end point was a change in pain using the Patient-Rated Tennis Elbow Evaluation (PRTEE) questionnaire at 3 months. Secondary outcomes were ultrasonographic changes in tendon thickness and color Doppler activity.

RESULTS: Pain reduction at 3 months (primary end point) was observed in all 3 groups, with no statistically significant difference between the groups; mean differences were the following: glucocorticoid versus saline: -3.8 (95% CI, -9.9 to 2.4); PRP versus saline: -2.7 (95% CI, -8.8 to 3.5); and glucocorticoid versus PRP: -1.1 (95% CI, -7.2 to 5.0). At 1 month, however, glucocorticoid reduced pain more effectively than did both saline and PRP; mean differences were the following: glucocorticoid versus saline: -8.1 (95% CI, -14.3 to -1.9); and glucocorticoid versus PRP: -9.3 (95% CI, -15.4 to -3.2). Among the secondary outcomes, at 3 months, glucocorticoid was more effective than PRP and saline in reducing color Doppler activity and tendon thickness. For color Doppler activity, mean differences were the following: glucocorticoid versus PRP: -2.6 (95% CI, -3.1 to -2.2); and glucocorticoid versus saline: -2.0 (95% CI, -2.5 to -1.6). For tendon thickness, mean differences were the following: glucocorticoid versus PRP: -0.5 (95% CI, -0.8 to -0.2); and glucocorticoid versus saline: -0.8 (95% CI, -1.2 to -0.5).

CONCLUSION: Neither injection of PRP nor glucocorticoid was superior to saline with regard to pain reduction in LE at the primary end point at 3 months. However, injection of glucocorticoid had a short-term pain-reducing effect at 1 month in contrast to the other therapies. Injection of glucocorticoid in LE reduces both color Doppler activity and tendon thickness compared with PRP and saline.

'The original goal of the study was to collect data at 6 and 12 months as well, but there was a large drop-out rate that did not allow this'. Most studies that I have gone through have shown better outcomes short term for steroids and long term for PRP which in opinion is the ideal outcome.

 

[PMR2008]

'Questions regarding the timing of platelet-rich plasma administration, optimal platelet concentration and platelet separation technique, ideal volume of the platelet concentrate, number of applications, and duration of the treatment benefit should be addressed in future studies because of the heterogeneous nature of the previously published studies'
I would strongly agree with this. Currently there is really no standard at all regarding the type of conditions PRP should be used for, the timing, concentration, activated vs non activated, injection technique, volume, post injection rehab. These are all questions that need to be answered. This field is certainly in its infancy.

 

[101N]

PLoS One. 2013 Jul 12;8(7):e69731. doi: 10.1371/journal.pone.0069731. Print 2013.
Are platelet-rich products necessary during the arthroscopic repair of full-thickness rotator cuff tears: a meta-analysis.
Zhang Q, Ge H, Zhou J, Cheng B.
Source
Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
Abstract
BACKGROUND:
Platelet-rich products (PRP) are widely used for rotator cuff tears. However, whether platelet-rich products produce superior clinical or radiological outcomes is controversial. This study aims to use meta-analysis to compare clinical and radiological outcomes between groups with or without platelet-rich products.
METHODS:
The Pubmed, Embase, and Cochrane library databases were searched for relevant studies published before April 20, 2013. Studies were selected that clearly reported a comparison between the use or not of platelet-rich products. The Constant, ASES, UCLA, and SST scale systems and the rotator cuff retear rate were evaluated. The weighted mean differences and relative risks were calculated using a fixed-effects model.
RESULTS:
Seven studies were enrolled in this meta-analysis. No significant differences were found for the Constant scale (0.73, 95% CI, -1.82 to 3.27, P=0.58), ASES scale (-2.89, 95% CI, -6.31 to 0.53, P=0.1), UCLA scale (-0.79, 95% CI, -2.20 to 0.63, P=0.28), SST scale (0.34, 95% CI, -0.01 to 0.69, P=0.05), and the overall rotator cuff retear rate (0.71, 95% CI, 0.48 to 1.05, P=0.08). Subgroup analysis according to the initial tear size showed a lower retear rate in small- and medium-sized tears (0.33, 95% CI, 0.12 to 0.91, P=0.03) after platelet-rich product application but no difference for large- and massive-sized tears (0.86, 95% CI, 0.60 to 1.23, P=0.42).
CONCLUSION:
In conclusion, the meta-analysis suggests that the platelet-rich products have no benefits on the overall clinical outcomes and retear rate for the arthroscopic repair of full-thickness rotator cuff tears. However, a decrease occurred in the rate of retears among patients treated with PRP for small- and medium-sized rotator cuff tears but not for large- and massive-sized tears.

 

[101N]

Am J Sports Med. 2013 Jul 26. [Epub ahead of print]
Platelet-Rich Plasma Injections in the Treatment of Chronic Rotator Cuff Tendinopathy: A Randomized Controlled Trial With 1-Year Follow-up.
Kesikburun S, Tan AK, Yilmaz B, Yasar E, Yazicioglu K.
Source
Department of Physical Medicine and Rehabilitation, Turkish Armed Forces Rehabilitation Center, Gülhane Military Medical Academy, Ankara, Turkey.
Abstract
BACKGROUND:Rotator cuff tendinopathy (RCT) is a significant source of disability and loss of work. Platelet-rich plasma (PRP) has been suggested to be beneficial in the treatment of RCT. PURPOSE:To investigate the effect of PRP injections on pain and shoulder functions in patients with chronic RCT. STUDY DESIGN:Randomized controlled trial; Level of evidence, 1. METHODS:A total of 40 patients, 18 to 70 years of age, with (1) a history of shoulder pain for >3 months during overhead-throwing activities, (2) MRI findings of RCT or partial tendon ruptures, and (3) a minimum 50% reduction in shoulder pain with subacromial injections of an anesthetic were included in this placebo-controlled, double-blind randomized clinical trial. Patients were randomized into a PRP group (n = 20) or placebo group (n = 20). Patients received an ultrasound-guided injection into the subacromial space that contained either 5 mL of PRP prepared from autologous venous blood or 5 mL of saline solution. All patients underwent a 6-week standard exercise program. Outcome measures (Western Ontario Rotator Cuff Index [WORC], Shoulder Pain and Disability Index [SPADI], 100-mm visual analog scale [VAS] of shoulder pain with the Neer test, and shoulder range of motion) were assessed at baseline and at 3, 6, 12, and 24 weeks and 1 year after injection. RESULTS:Comparison of the patients revealed no significant difference between the groups in WORC, SPADI, and VAS scores at 1-year follow-up (P = .174, P = .314, and P = .904, respectively). Similar results were found at other assessment points. Within each group, the WORC, SPADI, and VAS scores showed significant improvements compared with baseline at all time points (P < .001). In the range of motion measures, there were no significant group × time interactions. CONCLUSION:At 1-year follow-up, a PRP injection was found to be no more effective in improving quality of life, pain, disability, and shoulder range of motion than placebo in patients with chronic RCT who were treated with an exercise program.

 

[Vinny121]

You have to do PRP together with prolotherapy for its full effectiveness.

 

[ampaphb]

You have to do PRP together with prolotherapy for its full effectiveness.

Got a paper of similar quality to those below that documents that? Or is that just in your experience?

 

[RUOkie]

You have to do PRP together with prolotherapy for its full effectiveness.

how about showing a single study other than the one in Pediatrics recently that shows effectiveness of ANY prolotherapy.

 

[PMR2008]

how about showing a single study other than the one in Pediatrics recently that shows effectiveness of ANY prolotherapy.

I am not advocating PRP with Prolo but since you asked
http://www.annfammed.org/content/11/3/229.full

Dextrose Prolotherapy for Knee Osteoarthritis: A Randomized Controlled Trial
David Rabago, MD1&#8657;, Jeffrey J. Patterson, DO1, Marlon Mundt, PhD1, Richard Kijowski, MD2, Jessica Grettie, BS1, Neil A. Segal, MD, MS3 and Aleksandra Zgierska, MD, PhD1

Abstract

PURPOSE Knee osteoarthritis is a common, debilitating chronic disease. Prolotherapy is an injection therapy for chronic musculoskeletal pain. We conducted a 3-arm, blinded (injector, assessor, injection group participants), randomized controlled trial to assess the efficacy of prolotherapy for knee osteoarthritis.

METHODS Ninety adults with at least 3 months of painful knee osteoarthritis were randomized to blinded injection (dextrose prolotherapy or saline) or at-home exercise. Extra- and intra-articular injections were done at 1, 5, and 9 weeks with as-needed additional treatments at weeks 13 and 17. Exercise participants received an exercise manual and in-person instruction. Outcome measures included a composite score on the Western Ontario McMaster University Osteoarthritis Index (WOMAC; 100 points); knee pain scale (KPS; individual knee), post-procedure opioid medication use, and participant satisfaction. Intention-to-treat analysis using analysis of variance was used.

RESULTS No baseline differences existed between groups. All groups reported improved composite WOMAC scores compared with baseline status (P <.01) at 52 weeks. Adjusted for sex, age, and body mass index, WOMAC scores for patients receiving dextrose prolotherapy improved more (P <.05) at 52 weeks than did scores for patients receiving saline and exercise (score change: 15.3 ± 3.5 vs 7.6 ± 3.4, and 8.2 ± 3.3 points, respectively) and exceeded the WOMAC-based minimal clinically important difference. Individual knee pain scores also improved more in the prolotherapy group (P = .05). Use of prescribed postprocedure opioid medication resulted in rapid diminution of injection-related pain. Satisfaction with prolotherapy was high. There were no adverse events.

CONCLUSIONS Prolotherapy resulted in clinically meaningful sustained improvement of pain, function, and stiffness scores for knee osteoarthritis compared with blinded saline injections and at-home exercises.