This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.
There are many suggested applications for platelet-rich plasma (PRP), including tendon repair, osteoarthritis, and other musculoskeletal conditions. However there is considerable controversy in the absence of convincing evidence about the optimal mix and concentration of white blood cells and platelets in PRP, and the most clinically effective nature and quantity of constituent cytokines or other biochemical agents in PRP.
Despite these lingering questions, PRP is commonly used to treat lateral epicondylitis (LE), commonly called “tennis elbow.” As with its other applications, the clinical use of PRP for painful tendons has received much attention, but its efficacy remains controversial.
To continue investigating the clinical effects of PRP and its individual components, researchers recruited 156 patients with LE and randomly divided them into those treated with a single injection of 2-mL autologous PRP and those who received only physical therapy without injection.1 Both groups used a tennis elbow strap and performed stretching and strengthening exercises for 24 weeks, at which point pain and functional improvements were assessed using the visual analog scale (VAS), Modified Mayo Clinic Performance Index for the elbow, and MRI. Levels of platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, transforming growth factor-β (TGF-β), vascular endothelial growth factor, epithelial growth factor, and interleukin-1 β in the PRP were measured for statistical correlation with clinical scores.
At 24 weeks, all pain and functional variables—including VAS score, Mayo Clinic performance scores, and MRI grade—improved significantly in the PRP group, relative to the noninjection group (p < 0.05). The TGF-β level in the PRP significantly correlated with Mayo Clinic performance score and MRI grade improvement.
The PRP level of TGF-β appears to be important in tendon healing, but future studies will be required to determine the best relative concentrations of white blood cells and platelets that deliver specific cytokines such as TGF-β. However, these results help identify a viable protocol for measuring PRP efficacy in tendinopathies.
- Lim W, Park SH, Kim B, Kang SW, Lee JW, Moon YL. Relationship of cytokine levels and clinical effect on platelet-rich plasma-treated lateral epicondylitis. J Orthop Res. 2018 Mar;36(3):913-920. doi: 10.1002/jor.23714. Epub 2017 Sep 20. PMID: 28851099
Lateral epicondylar tendinopathy (“tennis elbow”) that is refractory to the usual interventions of physical therapy/home-directed exercise, ice therapy, corticosteroid injections, and rest is a relatively common but very difficult clinical situation. Patients often become frustrated by the lack of improvement and want something to alleviate the pain and disability. However, the orthopaedic community has been reluctant to recommend surgical intervention except for the most severe cases because the outcomes of this surgery are not as predictable as we would like.
It is within this context that Creuzé et al., in the May 16, 2018 issue of The Journal, present results from a double-blind randomized trial elucidating the impact of low-dose Botulinum toxin injection on this chronic condition. Just over half of the patients treated with the Botulinum toxin injection (n = 29) had a >50% reduction in their initial pain intensity at day 90, and almost 20% felt completely cured. Those results were significantly better than those experienced by the group treated with placebo injections (n = 28).
Kudos to the industry sponsor of this study for supporting the double-blind design, because it removed a significant potential bias that might have otherwise tainted the results. The only fault I can find in the trial is a lack of reporting on the patients’ hand dominance and the magnitude of functional demand on their affected limbs. Before and after treatment, a patient who uses power tools with a dominant and affected limb during a physically demanding job may well have more severe symptoms than a person who works at a computer and whose dominant and affected limb is the “non-mouse” extremity.
It is rare indeed to find a study that blinds the administrator of an orthopaedic intervention, as injections and oral medications are not the most prominent tools in our predominantly surgical armamentarium. The inclusion criteria in the Creuzé et al. study reflected a realistic but difficult patient-enrollment scenario—a minimum of 6 months of symptoms (a mean of almost 19 months) despite previous attempts at all other well-known interventions. The fact that nearly all subjects in both groups had a previous steroid injection into the extensor carpi radialis brevis (ECRB) muscle and continued to experience symptoms confirms the difficulty of these cases and represents what many patients go through in search of an effective treatment.
Furthermore, the fact that only 50% of patients in the intervention group achieved significant pain relief reflects the refractory nature of this condition in many patients. These findings seem to indicate that surgical intervention will remain a necessary component of care for patients with lateral epicondylitis who are not cured by Botulinum toxin injection or other, more common treatment modalities—and that we should pay attention to improving surgical outcomes.
Marc Swiontkowski, MD
Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Here is a summary of selected findings from Level I and II studies cited in the October 21, 2015 Specialty Update on shoulder and elbow surgery:
–A prospective evaluation of 224 subjects with asymptomatic rotator cuff tears followed annually for an average of five years found that the risk of tear enlargement and muscle degeneration was greater in full-thickness tears, and that pain and supraspinatus muscle degeneration were associated with tear enlargement.
–The authors of a randomized trial comparing physical therapy and primary surgical repair for initial management of degenerative rotator cuff tears concluded that the effects of surgery were not profound enough to justify surgical management for patients who present initially with painful degenerative cuff tears.
–A randomized trial comparing clinical outcomes in 58 patients with a rotator cuff tear and symptomatic acromioclavicular joint arthritis found no differences in function or pain scores between those who underwent cuff repair + distal clavicle resection and those who underwent cuff repair alone.1
–After two years of follow-up, no differences in functional outcomes or rate or quality of postoperative tendon healing were found in a randomized trial comparing patients who received platelet-rich plasma following surgical cuff repair and those who did not.2
–In a three-way randomized trial comparing physical therapy, acromioplasty + physical therapy, and cuff repair + acromioplasty + physical therapy for treating symptomatic, nontraumatic supraspinatus tendon tears in patients older than 55, there were no between-group differences in the mean Constant score one year after treatment.3
–A randomized trial comparing treatments for calcific tendinitis found that ultrasound-guided needling plus a subacromial corticosteroid injection resulted in better functional scores and larger decreases in calcium-deposit size than extracorporeal shock wave therapy.4
–A randomized trial of 196 patients with recurrent traumatic anterior shoulder instability found no significant differences in WOSI and ASES scores or range of motion between groups that underwent open or arthroscopic stabilization procedures.
–A randomized study comparing the effectiveness of immobilization in abduction (15°) and external rotation (10°) versus adduction and internal rotation after primary anterior shoulder dislocation found that after two years, only 3.9% of patients in the abduction/external-rotation group had repeat instability, compared to 33.3% in the adduction/internal-rotation group.5 A separate randomized trial found no significant difference in instability recurrence after one year between a group immobilized in internal rotation (sling) and a group immobilized in adduction and external rotation (brace).6
–A randomized trial of 250 patients (mean age of 65 years) with displaced surgical neck fractures of the proximal humerus compared surgical treatment (internal fixation or hemiarthroplasty) with conservative treatment. Finding no statistically or clinically significant difference in outcomes, the authors concluded that these results do not support the recent trend toward surgical management for proximal humeral fractures.7
–A randomized trial comparing reverse shoulder arthroplasty with hemiarthroplasty for acute proximal humeral fractures found that after two years of follow-up, reverse arthroplasty yielded better functional scores, better active elevation, and fewer complications than hemiarthroplasty.8
–A randomized trial comparing the use of concentric and eccentric glenospheres in reverse shoulder arthroplasty revealed no differences in scapular notching rates or clinical outcomes at a minimum follow-up of two years.
–A systematic review comparing radiographic and clinical survivorship of all-polyethylene versus metal-backed glenoid components used in total shoulder arthroplasty found that all-poly glenoids had a higher rate of radiolucencies and radiographic loosening but a much lower rate of revision after a mean follow-up of 5.8 years.
–A retrospective review found that arthroscopic biopsy was much more accurate than fluoroscopically guided fluid aspiration in diagnosing periprosthetic shoulder infections caused by Propionibacterium acnes.
–In a randomized trial of 76 workers’-comp patients with a displaced midshaft clavicular fracture, those receiving surgical management had faster time to union and return to work and better Constant scores than those managed conservatively.9
–Two studies compared plate fixation with intramedullary fixation for stabilizing clavicular fractures. One that randomized 59 patients found no differences in functional outcomes or time to healing. The other, which randomized 120 patients, found no between-group differences in DASH or Constant-Murley scores, but shoulder function improved more quickly in the plate-fixation group.
–A study that compared standard arthroscopic capsular release with capsular release extending to the posterior capsule for treating frozen shoulder found no difference in postoperative clinical or range-of-motion outcomes between the two groups.10
–A randomized trial comparing regional analgesia to local anesthetic injections in patients undergoing elbow arthroscopy found no differences in pain, oral analgesic use, or patient satisfaction within 48 hours after surgery.11
–A randomized trial comparing eccentric and concentric resistance exercises for the treatment of chronic lateral epicondylitis found that the eccentric-exercise group had faster pain regression, lower pain scores at 12 months, and greater strength increases.12
- Park YB, Koh KH, Shon MS, Park YE, Yoo JC. Arthroscopic distal clavicle resection in symptomatic acromioclavicular joint arthritis combined with rotator cuff tear: a prospective randomized trial. Am J Sports Med. 2015 Apr;43(4):985-90.Epub 2015 Jan 12.
- Malavolta EA, Gracitelli ME, Ferreira Neto AA, Assunção JH, Bordalo-RodriguesM, de Camargo OP. Platelet-rich plasma in rotator cuff repair: a prospective randomized study. Am J Sports Med. 2014 Oct;42(10):2446-54. Epub 2014 Aug 1.
- Kukkonen J, Joukainen A, Lehtinen J, Mattila KT, Tuominen EK, Kauko T, Aärimaa V.Treatment of non-traumatic rotator cuff tears: a randomised controlled trial with one-year clinical results. Bone Joint J. 2014 Jan;96-B(1):75-81.
- Kim YS, Lee HJ, Kim YV, Kong CG. Which method is more effective in treatment of calcific tendinitis in the shoulder? Prospective randomized comparison between ultrasound-guided needling and extracorporeal shock wave therapy. J Shoulder Elbow Surg. 2014 Nov;23(11):1640-6. Epub 2014 Sep 12.
- Heidari K, Asadollahi S, Vafaee R, Barfehei A, Kamalifar H, Chaboksavar ZA,Sabbaghi M. Immobilization in external rotation combined with abduction reduces the risk of recurrence after primary anterior shoulder dislocation. J Shoulder Elbow Surg. 2014 Jun;23(6):759-66. Epub 2014 Apr 13.
- Whelan DB, Litchfield R, Wambolt E, Dainty KN; Joint Orthopaedic Initiative for National Trials of the Shoulder (JOINTS).External rotation immobilization for primary shoulder dislocation: a randomized controlled trial. Clin Orthop Relat Res. 2014 Aug;472(8):2380-6.
- Rangan A, Handoll H, Brealey S, Jefferson L, Keding A, Martin BC, Goodchild L,Chuang LH, Hewitt C, Torgerson D; PROFHER Trial Collaborators. Surgical vs nonsurgical treatment of adults with displaced fractures of the proximal humerus: the PROFHER randomized clinical trial. JAMA. 2015 Mar 10;313(10):1037-47.
- Sebastiá-Forcada E, Cebrián-Gómez R, Lizaur-Utrilla A, Gil-Guillén V. Reverse shoulder arthroplasty versus hemiarthroplasty for acute proximal humeral fractures. A blinded, randomized, controlled, prospective study. J Shoulder Elbow Surg. 2014Oct;23(10):1419-26. Epub 2014 Jul 30
- Melean PA, Zuniga A, Marsalli M, Fritis NA, Cook ER, Zilleruelo M, Alvarez C.Surgical treatment of displaced middle-third clavicular fractures: a prospective, randomized trial in a working compensation population. J Shoulder Elbow Surg.2015 Apr;24(4):587-92. Epub 2015 Jan 22.
- Kim YS, Lee HJ, Park IJ. Clinical outcomes do not support arthroscopic posterior capsular release in addition to anterior release for shoulder stiffness: a randomized controlled study. Am J Sports Med. 2014 May;42(5):1143-9. Epub 2014 Feb 28.
- Wada T, Yamauchi M, Oki G, Sonoda T, Yamakage M, Yamashita T. Efficacy of axillary nerve block in elbow arthroscopic surgery: a randomized trial. J Shoulder Elbow Surg. 2014 Mar;23(3):291-6. Epub 2014 Jan 15.
- Peterson M, Butler S, Eriksson M, Svärdsudd K.A randomized controlled trial of eccentric vs. concentric graded exercise in chronic tennis elbow (lateral elbow tendinopathy). Clin Rehabil. 2014 Sep;28(9):862-72. Epub 2014 Mar 14.