Elbow epicondylar tendinosis is a common problem for patients whose activities require strong gripping or repeti- tive wrist movements. Histologic specimens from chronic cases confirm that tendinosis is not an acute inflammatory condition but rather a failure of the normal tendon repair mechanism associated with angiofibroblastic degeneration.8 The cause of elbow tendinosis is most likely a combination of mechanical overloading21 and abnormal microvascular responses.19 Further research into the precise cause of tendinosis is, however, still needed. Numerous methods have been advocated for treating elbow tendinosis, including rest, nonsteroidal anti-inflamma- tory medication, bracing, physical therapy, iontophoresis,15 extracorporeal shock wave therapy, and botulism toxin.9 Injections of corticosteroids or whole blood,3 and various types of surgical procedures have also been recommended. The utility of several of these treatments has recently come into question. For example, one recent report noted that there is no difference between using corticosteroid or local anesthetic when treating elbow tendinosis with an injection.1 In this study, we evaluated the use of platelet-rich plasma (PRP) as a treatment for chronic severe epicondylar tendi- nosis. Platelet-rich plasma contains a more concentrated amount of platelets than does whole blood. Within platelets are powerful growth factors, including platelet-derived growth factor, transforming growth factor beta, and epider- mal growth factor. Slater et al17 reported that the addition of platelets to a culture medium stimulated the proliferation Treatment of Chronic Elbow Tendinosis With Buffered Platelet-Rich Plasma Allan Mishra,* MD, and Terri Pavelko, PAC, PT From the Department of Orthopedic Surgery, Menlo Medical Clinic, Stanford University Medical Center, Menlo Park, California Background: Elbow epicondylar tendinosis is a common problem that usually resolves with nonoperative treatments. When these measures fail, however, patients are interested in an alternative to surgical intervention. Hypothesis: Treatment of chronic severe elbow tendinosis with buffered platelet-rich plasma will reduce pain and increase func- tion in patients considering surgery for their problem. Study Design: Cohort study Level of evidence, 2. Methods: One hundred forty patients with elbow epicondylar pain were evaluated in this study. All these patients were initially given a standardized physical therapy protocol and a variety of other nonoperative treatments. Twenty of these patients had sig- nificant persistent pain for a mean of 15 months (mean, 82 of 100 range, 60-100 of 100 on a visual analog pain scale), despite these interventions. All patients were considering surgery. This cohort of patients who had failed nonoperative treatment was then given either a single percutaneous injection of platelet-rich plasma (active group, n = 15) or bupivacaine (control group, n = 5). Results: Eight weeks after the treatment, the platelet-rich plasma patients noted 60% improvement in their visual analog pain scores versus 16% improvement in control patients (P = .001). Sixty percent (3 of 5) of the control subjects withdrew or sought other treatments after the 8-week period, preventing further direct analysis. Therefore, only the patients treated with platelet-rich plasma were available for continued evaluation. At 6 months, the patients treated with platelet-rich plasma noted 81% improve- ment in their visual analog pain scores (P = .0001). At final follow-up (mean, 25.6 months range, 12-38 months), the platelet-rich plasma patients reported 93% reduction in pain compared with before the treatment (P .0001). Conclusion: Treatment of patients with chronic elbow tendinosis with buffered platelet-rich plasma reduced pain significantly in this pilot investigation. Further evaluation of this novel treatment is warranted. Finally, platelet-rich plasma should be considered before surgical intervention. Keywords: platelet-rich plasma (PRP) tennis elbow lateral epicondylitis tendonitis tendinosis 1 *Address correspondence to Allan Mishra, MD, Menlo Medical Clinic, Stanford University Medical Center, Department of Orthopedic Surgery, 1300 Crane Street, Menlo Park, CA 94025 (e-mail: allan_mishra@yahoo.com). One or more of the authors have declared a potential conflict of inter- est. Part of this research was funded by Cell Factor Technologies, and Dr Allan Mishra is a consultant for this company. He has also received reimbursement for attending a symposium. The American Journal of Sports Medicine, Vol. X, No. X DOI: 10.1177/0363546506288850 �� 2006 American Orthopaedic Society for Sports Medicine AJSM PreView, published on May 30, 2006 as doi:10.1177/0363546506288850 Copyright 2006 by the American Orthopaedic Society for Sports Medicine.

2 Mishra and Pavelko The American Journal of Sports Medicine of human osteoblast-like cells. They further proposed that exogenous platelet growth factors may play a significant role in fracture repair.17 A recent review of common growth factors suggested PRP may be useful for tendon and ligament healing in vivo.11 The specific goal of this investigation was to meas- ure the efficacy of buffered PRP as a potential new treat- ment for chronic severe elbow tendinosis. MATERIALS AND METHODS The study design and protocol were evaluated and approved by the authors��� investigational review board. This board refused to allow the drawing and discarding of 55 mL blood that would be required to blind the patients to their treatment. All patients signed a detailed informed consent form. Before starting the formal study, 2 healthy volunteers were treated with the PRP formulation and the protocol. No adverse effects were noted in these patients at 1 month, 3 months, 6 months, or 1 year after the procedure. Patient Data One hundred forty patients were evaluated in this study. Criteria for participation included elbow epicondylar pain for longer than 3 months of at least 60 of 100 on a visual analog score (0, no pain 100, maximum pain possible), in spite of completing a standardized stretching and strengthening pro- tocol. All patients had the same physical therapist instruct them in the same set of exercises. This specific protocol was posted on a Web site (www.emedx.com) for patients to follow. Patients also had failure with some combination of non- steroidal medication, bracing, or corticosteroid injections. Elbow epicondylar tendinosis was defined as pain over the lateral or medial epicondyle,with direct palpation and pain at the elbow with resisted wrist extension (for lateral tendinosis) and resisted wrist flexion (for medial tendinosis). Exclusion criteria included pregnancy,history of carpal tunnel syndrome, cervical radiculopathy, and systemic disorders such as dia- betes, rheumatoid arthritis, and hepatitis. Twenty (15%) of the 140 patients evaluated met these strict inclusion-exclu- sion criteria and were enrolled in the study. There was a total of 15 PRP-treated and 5 control patients included in this study.The PRP-treated patients (15 patients: 14 lateral tendinosis, 1 medial tendinosis) received an injec- tion of PRP that had been buffered to physiologic pH. The duration of symptoms in this group was 15.3 months, and the mean patient age was 48.1 years. The control patients (5 patients: 5 lateral tendinosis) received an injection of bupi- vacaine with epinephrine.The mean duration of symptoms in this group was 11.8 months,and the mean age was 42.2 years. Ten of the patients included in this report were part of a con- secutive series, and 10 were part of a randomized trial. The randomization of the second group was done with an envelope randomization protocol. Both groups of patients were told that needling of the tendon by itself may produce improve- ment in symptoms. All patients were evaluated and treated during the same time frame (2002-2004). Platelet-Rich Plasma Preparation Fifty-five milliliters whole blood was collected from the uninvolved arm into a 60-mL syringe that contained 5 mL sodium citrate. A peripheral complete blood count was also collected at the time of the initial blood draw. The blood was then prepared according to the GPS System instructions (Cell Factor Technologies, Warsaw, Ind). This device is a desktop-size centrifuge with disposable cylinders for the blood. All the procedures were performed in the same office setting. Approximately 5 mL PRP was obtained for each patient.The PRP was then buffered to physiologic pH using 8.4% sodium bicarbonate. No activating agent was used. Two milliliters of this PRP was then sent to the laboratory for analysis of platelet concentration, whereas the remain- ing 2 to 3 mL was used to inject into the patient. On aver- age, 3.31 million platelets were given to each PRP-treated patient via this injection. The total number of platelets per milliliter in the PRP represented a mean increase of 539% compared with whole blood values in the active patient group. The total time from blood draw to injection in the patients was about 30 minutes. No specialized equipment, other than the GPS machine, was required. The cost of the machine and the kit with all the materials to perform the procedure has not been determined because they are not yet commercially available. Injection Technique Initially, bupivacaine with epinephrine was infiltrated into the skin and subcutaneous tissue of both groups as a local field block. Approximately 0.5 mL was also injected directly into the area of maximum tenderness. Then, either 2 to 3 mL PRP or 2 to 3 mL bupivacaine with epinephrine was injected using a 22-g needle into the common extensor or flexor tendon using a peppering technique. This tech- nique involved a single skin portal and then 5 penetrations of the tendon (Figure 1). Postprocedure Protocol Immediately after the injection, the patient was kept in a supine position without moving the arm for 15 minutes. Patients were sent home with instructions to limit their use of the arm for approximately 24 hours and use hydrocodone or acetaminophen for pain. The use of nonsteroidal medication was prohibited. After 24 hours, patients were given a stan- dardized stretching protocol to follow for 2 weeks. A formal strengthening program was initiated after this stretching. At 4 weeks after the procedure, patients were allowed to proceed with normal sporting or recreational activities as tolerated. A 100-mm visual analog pain score (0, no pain 100, worst pain possible) and a modified Mayo elbow score (best score, 100) were used as outcome measures. The patients were examined at 4 weeks, 8 weeks, and 6 months after the index procedure.A final follow-up overall evaluation was also done. Paired and unpaired t tests were used to statistically com- pare the 2 groups of patients. Initially, the visual analog pain