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FASXXX10.1177/1938640015599038Foot & Ankle Specialist MONTH XXXXvol. X no. X Foot & Ankle Specialist
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〈 Evolving Techniques 〉 Preliminary Treatment of Achilles Tendinopathy Using Low-Intensity Pulsed Ultrasound Abstract: Background. Achilles tendinopathy is a degenerative process of the tendon associated with diminished vascularity, microtrauma, and aging. Nonoperative treatments such as activity modification, immobilization, night splints, and physical therapy have good outcomes for the majority of patients. However, there are cohorts of patients that remain symptomatic despite use of all nonoperative measures that eventually require surgical intervention. The present study reports the preliminary short-term clinical outcomes of low-intensity pulsed ultrasound (LIPUS) for treatment for Achilles tendinopathy. Materials and Methods. Fourteen patients with clinically diagnosed Achilles tendinopathy who failed previous nonoperative treatments underwent LIPUS stimulation directly over the area of maximum tendon tenderness for 20 min/d for 8 weeks total. No other treatment modalities were used during the period of LIPUS stimulation. All patients had serial clinical exams and evaluations with an average follow-up of 12 months
Andrew R. Hsu, MD, and George B. Holmes, MD
(range, 6-50 months). Results. disadvantages, and cost-effectiveness Excellent clinical outcomes with of this alternative treatment for complete resolution of pain and other tendinopathy. symptoms were obtained in 7 patients Levels of Evidence: Therapeutic, (50%). Two patients (14%) had good Level IV: Case series outcomes with mild tendon irritation and stiffness not requiring further Keywords: Achilles tendon; intervention. Five patients (36%) tendinopathy; low-intensity pulsed had minimal benefit with continued ultrasound; LIPUS; ultrasound; bone pain, swelling, and tenderness over stimulator; Exogen the Achilles and functional deficits. No patients had The present case series shows early worsening pain promising results of low-intensity pulsed or progression of disability requiring ultrasound (LIPUS) for treatment of surgery. Conclusions. LIPUS is an additional Achilles tendinopathy with decreases in noninvasive treatment modality for chronic pain and improvements in function at Achilles tendinopathy that may potentially short-term follow-up.” help improve clinical symptoms and delay and/or prevent the need for surgical intervention. While chilles tendinopathy is a LIPUS is easy to use, well-tolerated, degenerative process of the and has promising early clinical tendon without inflammation that results, further research is needed is commonly associated with chronic to determine the long-term benefits, tendinitis, diminished vascularity,
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DOI: 10.1177/1938640015599038. From the OrthoCarolina Foot & Ankle Institute, Charlotte, North Carolina (ARH); and Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois (GBH). Address correspondence to: Andrew R. Hsu, MD, OrthoCarolina Foot & Ankle Institute, 2001 Vail Avenue, Suite 200B, Charlotte, NC 28207; e-mail:
[email protected]. For reprints and permissions queries, please visit SAGE’s Web site at http://www.sagepub.com/journalsPermissions.nav. Copyright © 2015 The Author(s)
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repetitive microtrauma, and aging.1,2 The tendon can be affected at its insertion or within the midsubstance, generally 2 to 6 cm from the insertion where there is an area of decreased blood flow.2 Achilles tendinopathy has significant functional morbidity, and associated risk factors include hypertension, diabetes, obesity, smoking history, steroid use, and estrogen exposure.2,3 The significance of these risk factors suggests that decreased local microvascularity may play a key role in the final development of tendon dysfunction.2 Symptoms typically include pain and swelling localized over an area of observable and palpable nodular thickening within the Achilles. Ankle range of motion is often limited with decreased ankle plantarflexion leading to difficulty with normal gait and push-off.4 Diagnosis is primarily clinical, but radiographs can show calcifications within the tendon with chronic disease.5 Ultrasound imaging and magnetic resonance imaging (MRI) may reveal tendon thickening, edema, and signal changes while also delineating the location and extent of diseased tendon.6,7 Initial conservative treatment can include activity modification, immobilization, night splints, ankle-foot orthoses (AFO), physical therapy with eccentric exercises, and local administration of iontophoresis and phonophoresis.8 Use of local corticosteroid injection for chronic tendinopathy is contraindicated due to the risk of causing frank tendon rupture.9 Nonsurgical management can be effective in the majority of patients (75%),8 but there are a multitude of factors influencing clinical outcomes such as patient age, duration of symptoms, and severity of tendon degeneration.10 Surgical management is indicated for patients who have failed conservative treatment and consists of debridement of tendon and fibrous tissue, decompression of insertional calcific spurs, and/or deep tendon transfer using the flexor hallucis longus (FHL) tendon.11 Tendon transfers using FHL, flexor digitorum longus, or peroneus brevis are generally indicated when more than 50%
of the tendon is unhealthy, particularly in patients older than 55 years.5,12,13 While significant improvements in clinical and functional outcomes have been found with FHL transfer, recovery can often take up to 1 to 2 years with the possibility of wound healing problems, scar pain, and deep vein thrombosis.13 Low-intensity pulsed ultrasound (LIPUS) is a promising treatment modality that has been shown to increase cellular growth factor expression and neovascularization in animal models.14 However, clinical results of LIPUS to treat patellar tendinopathy in humans have been inconclusive with minimal additional benefits over placebo.15,16 The purpose of the present study was to report the preliminary short-term clinical outcomes of LIPUS for treatment of Achilles tendinopathy.
Materials and Methods Research approval was obtained by a local institutional review board prior to study initiation. A retrospective review was performed for all cases of Achilles tendinopathy treated with LIPUS by the senior author between 2007 and 2014. Achilles tendinopathy was diagnosed based on clinical exam and pretreatment MRI. Indications for use of the LIPUS device (Exogen, Bioventus, Durham, NC) included failure of previous nonoperative therapies such as activity modification, nonsteroidal anti-inflammatory drugs, tall controlled ankle motion (CAM) boot immobilization, night splints, and AFOs for the previous 3 months. No patients had undergone prior surgery for Achilles tendon pathology and no other treatment modalities were used during the period of LIPUS stimulation such as physical therapy. The LIPUS device was loaned at no cost to the patient and placed over the area of maximum tendon tenderness for 20 min/d for 8 weeks total. Patients were individually shown how to properly apply and use the LIPUS device by the authors. Treatment was not blinded, and patients were not given any preliminary expectations by the authors regarding possible treatment outcomes. Follow-up
examinations were performed every 3 to 4 weeks after initiation of treatment to monitor patient symptoms and function. Medical comorbidities such as hypertension, coronary artery disease, diabetes, obesity, smoking history, and steroid use were all recorded. Clinical variables examined included pain, swelling, stiffness, and functional status obtained through patient interviews and focused physical examinations. Excellent clinical outcome was defined as complete resolution of pain and associated symptoms with return to full baseline activities after treatment. Good outcome was defined as significantly decreased pain and increased functional status with mild continued tendon irritation and stiffness not requiring further intervention. Minimal benefit was defined as persistent pain and functional impairment with continued pain, swelling, and tenderness over the Achilles tendon. No posttreatment MRIs were obtained due to cost and logistical restrictions. Differences between groups were evaluated using Student’s t tests and differences in proportions between groups were evaluated with Fisher’s exact tests with significance set at P < .05 (SPSS, Chicago, IL).
Results There were a total of 14 cases reviewed of Achilles tendinopathy treated with LIPUS stimulation. Average age was 50 years (range, 30-70 years) with 4 females and 10 males (Table 1). The right side was affected in 3 patients, the left side in 9 patients, and 2 patients had bilateral involvement. All patients had serial clinical examinations with an average follow-up of 12 months (range, 6-50 months). Clinical outcomes were based on pain status and patient reports of their functional status on follow-up examinations. Excellent clinical outcomes were obtained in 7 patients (50%), 2 patients (14%) had good results, and 5 patients (36%) had minimal benefit with LIPUS but had no progression of symptoms requiring surgery on final
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M
M
M
M
F
47
53
46
53
55
58
56
45
30
44
40
64
42
2
3
4
5
6
7
8
9
10
11
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12
13
14
R
L
L
L
L
L
L
Bilateral
L
L
L
R
Bilateral
R
Affected Side
Pain in Achilles, enlarged mass
Pain in Achilles, enlarged mass
Ankle pain, stiffness
Pain in Achilles, stiffness, enlarged mass
Pain in Achilles, stiffness
Pain in Achilles, stiffness, enlarged mass
Pain in Achilles, stiffness
Bilateral ankle pain, painful mass
Pain in Achilles, enlarged mass
Pain in Achilles, stiffness, enlarged mass
Pain in Achilles, stiffness, enlarged mass
Ankle pain, stiffness, painful enlarged mass
Bilateral ankle pain, painful mass
Pain in Achilles, enlarged mass
Primary Symptoms
NSAIDs, CAM boot, AFO
Night splint
Night splint, AFO
NSAIDs, CAM, night splint, AFO
NSAIDs
Night splint, AFO
NSAIDs, CAM boot, night splint
Night splint, AFO
Night splint, AFO
NSAIDs, night splint, AFO
Night splint
AFO
CAM boot
Night splint, AFO
Previous Treatments
Excellent
Excellent
Excellent
Minimal
Minimal
Minimal
Minimal
Excellent
Excellent
Good
Minimal
Good
Excellent
Excellent
Outcome
12
12
6
6
12
6
8
50
12
6
12
6
12
12
Follow-up (Months)
No pain or symptoms
No pain or symptoms
No pain or symptoms
Moderate pain, using AFO
Moderate pain
Moderate pain, using night splint and AFO
Moderate pain, using night splint and AFO
No pain or symptoms
No pain or symptoms
Minimal pain
Moderate pain, using night splint and AFO
Minimal pain
No pain or symptoms
No pain or symptoms
Follow-up Status
Abbreviations: AFO, ankle-foot orthosis; LIPUS, low-intensity pulsed ultrasound; M, male; F, female; L, left; R, right; NSAID, nonsteroidal anti-inflammatory drug; CAM, controlled ankle motion.
M
F
M
M
M
M
M
F
F
Sex
70
Age (Years)
1
Patient No.
Individual Patient Demographic and Clinical Outcomes Following LIPUS Treatment for Achilles Tendinopathy.
Table 1.
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follow-up. There were no significant differences in age, demographics, medical comorbidities, or previous treatments used between patients that had excellent, good, or minimal benefit with LIPUS.
Discussion The primary finding of this study is that more than half of patients (64%) treated with LIPUS for Achilles tendinopathy had good to excellent clinical outcomes with improved pain and function. Of the 5 patients who had minimal benefit with LIPUS treatment, none had progressive worsening of their symptoms during therapy requiring surgery. All patients had tried and failed traditional nonoperative treatment modalities for at least 3 months prior to using LIPUS, and there were no adverse reactions or complications reported with use of LIPUS over the 8-week treatment period. However, the details of the relationship between LIPUS treatment and improved pain and function remain unknown due to the retrospective, uncontrolled nature of the present case series. Achilles tendinopathy is a chronic condition characterized by noninflammatory tendon degeneration with collagen fiber disorientation, increased cellularity, calcification, tendolipomatosis, and angiofibroblastic degeneration.17 Central to this pathologic process is a poor healing response after repetitive microtrauma.18 The Achilles tendon has diminished vascularity and hypocellularity, causing it to undergo degeneration with structural loss with chronic damage rather than inflammation.2,3 Blood flow to the tendon is predominantly anterior and occurs through a series of vincula that serve as pathways for blood vessels to reach the tendon. The exact mechanism of LIPUS stimulation on chronically degenerated tendons is unknown. In animal fracture models, LIPUS has been shown to increase levels of transforming growth factor-β (TGF-β), total protein, endothelial growth factors, and overall cartilage formation.14 However, it remains
to be elucidated as to whether not these specific cellular changes caused by LIPUS take place in tendinitis and/or tendinopathy. Early studies investigating the effect of therapeutic ultrasound on Achilles tendon healing in animal models showed that early use (within the first 2 weeks) of LIPUS treatment on tenotomized tendons resulted in increased tensile strength, tensile stress, energy absorption capacity, and collagen synthesis and fiber organization compared with controls.19-24 In a rat model of Achilles tendinopathy, low-power ultrasound stimulation (100 mW/cm2) stimulated tenocyte proliferation and regulated matrix metabolism through changes in TGF-β and mitogen-activated protein kinases signaling pathways.25 It has been theorized that LIPUS works through a combination of cavitation and micro-streaming to provide mechanical energy capable of modulating inflammation and altering cell membrane activity.26 Cavitation involves the production and vibration of micrometer-sized bubbles within tissue fluids, which causes changes in the cellular activities of tissues subjected to ultrasound.27 Microstreaming is the movement of fluids along acoustic boundaries due to mechanical pressure induced by ultrasound which alters the cell permeability, vascularization, and healing potential of tendons.28,29 In vitro studies have shown that ultrasound stimulation can cause increased collagen synthesis, angiogenesis, macrophage responsiveness, and nitric oxide release.30-33 In a preclinical animal model of occluded coronary arteries, Steffen et al34 found that that a primary mechanism of ultrasound therapy on heart muscle is nitric oxide production leading to vasodilation and increased blood flow. Increased vascularization is particularly critical to recovery in Achilles tendinopathy as healthy tendon is already subject to a zone of hypovascularity 2 to 6 cm proximal to the tendon insertion seen in angiography studies.35,36 In a
randomized, sham-controlled trial investigating the effects of ultrasound on diabetic foot ulcer healing, Ennis et al37 found a significant 2.8-fold increase in wound healing with shorter time to recovery in patients treated with ultrasound stimulation. Increased healing was attributed in part to improved vascularization, and these findings were supported by Kavros et al38 who found that ultrasound therapy compared with standard of care for ischemic wounds had increased and faster rates of healing. Warden et al16 performed a randomized, double-blind, placebocontrolled study investigating the effects of LIPUS on patellar tendinopathy in 37 patients who met eligibility criteria. While visual analogue scale measurements of pain went down for all patients, there was no significant difference between placebo and LIPUS groups. When comparing these results with those of the present study, it is difficult to determine whether our results are a function of the Achilles tendon being more susceptible to the effects of LIPUS treatment or if the pathophysiology is inherently different than patellar tendinopathy. Major limitations of the present study are its retrospective nature and relatively small cohort of patients. There was no control group, and no standardized clinical or functional outcome scores were obtained before or after treatment. Routine validated questionnaires are now integrated into our regular clinical practice, but were not available at the time of this study. Given the lack of a control group in our study, it is unknown if patients would have eventually gone on to improve or worsen clinically without LIPUS treatment. In addition, since treatment was not blinded, use of the LIPUS device could have had a significant positive placebo effect on patients. All the patients in the present study had failed nonoperative treatments for a minimum of 3 months and discontinued any additional treatment modalities during the LIPUS period.
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However, we are unable to predict which patients may have improved on their own or with continued use of their previous treatment modalities after 6 to 12 months or longer. In general, it is our practice to use different treatment modalities for periods of 3 months at a time and then reassess patient symptoms and function prior to continuing or discontinuing a modality for another. We do not believe that persistent use of an ineffective treatment for more than 6 months will lead to long-term benefits. Overall, the management of Achilles tendinopathy refractory to nonoperative treatments remains challenging. While surgical intervention can improve pain and function, surgery has inherent risks and postoperative rehabilitation can be extensive and take up to 2 years to reach maximum benefit.13 The results of the present study provide preliminary data to suggest that LIPUS may be a useful treatment for Achilles tendinopathy. Alone or in conjunction with other treatment modalities such as eccentric exercises, LIPUS may provide pain relief and improved function in patients who have failed other nonoperative treatments. In our experiences, we have found LIPUS to be easy to use, well tolerated, and relatively inexpensive ($250 to $1000 depending in individual patient insurance) compared with the hospital costs associated with surgical reconstruction of the Achilles tendon. Our results indicate that that certain patients respond well to treatment although the exact mechanism of action is unknown. The indications for LIPUS treatment in patients with Achilles tendinopathy and other chronic tendon degeneration disorders require further research and comparative trials.
Conclusions The present case series shows early promising results of LIPUS for treatment of Achilles tendinopathy with decreases in pain and improvements in function at short-term follow-up. However, no definite conclusions can be made regarding the long-term outcomes of
LIPUS treatment for tendinopathy. There are numerous follow-up questions surrounding LIPUS that warrant future research including its effects and mechanism on tendinopathy in general, the potential long-term clinical benefits and disadvantages, the optimal timing and dosage of treatment, and the overall cost-effectiveness compared with established treatments.
longus tendon transfer in treatment of Achilles tendinosis. J Bone Joint Surg Am. 2013;95:54-60. 14. Coords M, Breitbart E, Paglia D, et al. The effects of low-intensity pulsed ultrasound upon diabetic fracture healing. J Orthop Res. 2011;29:181-188. 15. Larsson ME, Kall I, Nilsson-Helander K. Treatment of patellar tendinopathy—a systematic review of randomized controlled trials. Knee Surg Sports Traumatol Arthrosc. 2012;20:1632-1646.
1. Hattrup SJ, Johnson KA. A review of ruptures of the Achilles tendon. Foot Ankle. 1985;6:34-38.
16. Warden SJ, Metcalf BR, Kiss ZS, et al. Low-intensity pulsed ultrasound for chronic patellar tendinopathy: a randomized, double-blind, placebo-controlled trial. Rheumatology (Oxford). 2008;47:467-471.
2. Holmes GB, Lin J. Etiologic factors associated with symptomatic achilles tendinopathy. Foot Ankle Int. 2006;27: 952-959.
17. Sems A, Dimeff R, Iannotti JP. Extracorporeal shock wave therapy in the treatment of chronic tendinopathies. J Am Acad Orthop Surg. 2006;14:195-204.
3. Puddu G, Ippolito E, Postacchini F. A classification of Achilles tendon disease. Am J Sports Med. 1976;4:145-150.
18. Paavola M, Kannus P, Järvinen TA, Khan K, Józsa L, Järvinen M. Achilles tendinopathy. J Bone Joint Surg Am. 2002;84-A:2062-2076.
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