To the Editor:

The issues and comments raised both by Buchbinder et al. and by Rompe reflect generic and specific problems related to this emerging orthopaedic technology. Those investigators studied the use of extracorporeal shock- wave therapy with electromagnetic devices that differ from the electrohydraulic device used in our study. Unfortunately, there are no recognized ways of defining high-energy or low-energy, nor are there physical means of assessing how much energy actually affects the target tissue. Furthermore, the energy was delivered in different manners in their studies (transverse versus plantar surface). Efforts certainly must be made to better define parameters, as they obviously will define improvements in treatment. Perhaps the first step was taken by Gerdesmeyer et al., who compared high and low-energy shock-wave therapy (using different device settings) with a placebo for treatment of calcific tendinopathy of the shoulder1. Both energy levels were effective compared with the placebo. However, the high-energy treatment was considerably superior to the low-energy treatment.

Both Buchbinder et al.2 and Rompe et al.3 used devices at energy settings usually considered to be low-energy. Yet their findings were quite disparate. Buchbinder et al. found no difference between patients treated with shock waves and those treated with a placebo2, while Rompe et al., in a study published in JBJS, found extracorporeal shock-wave treatment to be effective3. The protocols were quite different regarding patient selection, treatment regimen (including the amount of energy and number of doses), involvement of orthopaedists, and outcome criteria. All factors make comparison of the studies difficult. Obviously all of the studies were well planned and conducted.

We will address the various specific issues.

First, in answer to Buchbinder et al.: the previous article that we published involved preliminary data assessed at three months following shock-wave treatment4. Our recent study included the complete patient cohort in phases 1 and 2. This involved a larger number of randomized patients as well as nonrandomized patients. Furthermore, all treated patients were assessed with a different outcomes analysis, in which we used the criteria described by Roles and Maudsley (which were used in many European studies of extracorporeal shock-wave therapy). These different patient numbers and assessments led to different p values. The data submitted to the FDA were derived with multiple different statistical analyses, and we chose to report a limited number of them. The data were critically reviewed by an independent statistician, by the FDA statistician, by the orthopaedic FDA panel statistician, and by the JBJS reviewer. All felt that the data were appropriately significant, especially relative to the post-treatment outcome analysis of pain by the orthopaedists. The comments about energy levels and follow-up duration reflect differences in protocols and the aforementioned problems in energy/dose comparisons between different devices. Finally, none of our patients had ultrasound diagnosis. We felt strongly that patients who were referred with the diagnosis as made by well-trained orthopaedists and podiatrists and who were reevaluated by another orthopaedist using a specific definition of plantar fasciitis and a detailed number of inclusion criteria certainly had the disease. Ultrasound is not unequivocal in the diagnosis of this disorder.

Theodore et al.5 used the same device as Buchbinder et al. However, they used a much higher energy setting (all patients received the same dosage), ankle block anesthesia, and a placebo group. This study was instrumental in obtaining FDA approval of the device. Their study also reinforced the fact that differences in the “intensity” of the energy delivered, even by the same device, may be a major factor in the likelihood of success.

With regard to Rompe’s comments, the treatment group and placebo group as well as the nonrandomized group were all comparable at baseline. This is reflected in the values given in our publication. We certainly agree that the most significant parameter of success was the investigator’s assessment of direct heel pain using a dolorimeter. Such a method of pain measurement was not used in either the study by Buchbinder et al.2 or that by Rompe et al.3. We stated that use of pain medication was a poor differentiator between treatment and placebo groups. Neither Buchbinder et al. nor Rompe et al. assessed the use of post-treatment pain mediations.

Rompe raises the most perplexing question regarding extracorporeal shock-wave therapy. What is high energy versus what is low energy? Patients can tolerate certain levels of energy administration with electromagnetic devices. Very few can tolerate even the lowest-energy settings of the electrohydraulic device.

We agree with Rompe that injection of lidocaine or even saline solution prior to treatment may potentiate the effect of extracorporeal shock-wave therapy, especially with regard to cavitation. However, our placebo group had limited lidocaine administration at the level of the ankle, not into the plantar fascia.

We agree completely with Rompe’s comments in the final paragraph. These reflect recent detailed animal studies directed at understanding neurologic and vascular responses to extracorporeal shock-wave therapy. Additional comparable studies are necessary to understand the biologic mechanisms of action. At the same time, better definitions of the physics of differently generated shock waves are essential, not only to comprehend levels of penetration into subcutaneous and deeper target tissues, but also to be able to compare devices and studies using such devices.

John A. Ogden, MD Richard G. Alvarez, MD Richard L. Levitt, MD

Corresponding author: John A. Ogden, MD

Skeletal Educational Association 3435 Habersham Road N.W. Atlanta, GA 30305

These letters originally appeared, in slightly different form, on jbjs.org. They are still available on the web site in conjunction with the article to which they refer.

References

1. Gerdesmeyer L, Wagenpfel S, Haake M, Maier M, Loew M, Wörtler K, Lampe R, Seil R, Handle G, Gassel S, Rompe JD. Extracorporeal shock wave therapy for the treatment of chronic calcifying tendonitis of the rotator cuff: a randomized controlled trial. JAMA. 2003;290:2573-80.

2. Buchbinder R, Ptasznik R, Gordon J, Buchanan J, Prabaharan V, Forbes A. Ultrasound-guided extracorporeal shock wave therapy for plantar fasciitis: a randomized controlled trial. JAMA. 2002;288:1364-72.

3. Rompe JD, Schoellner C, Nafe B. Evaluation of low-energy extracorporeal shock-wave application for treatment of chronic plantar fasciitis. J Bone Joint Surg Am. 2002;84:335-41.

4. Ogden JA, Alvarez R, Levitt R, Cross GL, Marlow M. Shock wave therapy for chronic proximal plantar fasciitis. Clin Orthop. 2001;387:47- 59.

5. Theodore GH, Buch M, Amendola A, Bachmann C, Fleming LL, Zingas C. Extracorporeal shock-wave therapy for the treatment of plantar fasciitis. Foot Ankle Int. 2004;25: 290-7.

To the Editor:

Dr Ogden and colleagues recently reported the results of a trial of shock- wave treatment for chronic plantar fasciitis (1). We seek clarification on whether this is a reanalysis of a previously published trial (2), and if so, why the sample sizes are significantly different. While the results appear similar, the authors now claim a significant difference in the mean score of subject self-assessment of pain at 12 weeks favouring the active treatment group (p=0.014). While this cannot be verified from the data presented, as no measures of variance are provided, independent t-test comparison of mean scores for subject self-assessment of pain at 12 weeks using data published in the original trial report submitted to the US Food and Drug Administration found no statistically significant difference between groups (mean (SD) scores: 3.48 (3.11) and 4.18 (3.04) in 115 and 114 patients in the active- and placebo-treated groups respectively; mean difference = 0.7 (95% CI -0.1 to 1.5), P = 0.08)(3).

We would also like to respond to criticisms made by Dr Ogden in their recent paper about our trial (4). While the median duration of symptoms of participants in our trial was shorter than the trial by Ogden et al (6-7 months), we also found no benefit of shock-wave treatment over placebo when we restricted our analysis to only those participants with symptoms greater than 6 months. A trivial dose of shock wave was given to the placebo group (6 mJ/mm2) and it is highly unlikely that this resulted in any clinical benefit. This is supported by previous observations that high -energy shock-wave treatment is required to effect any local histological changes. Rompe et al found no sonographic or histological changes in the Achilles tendon of a rabbit model given a total dose of 80 mJ/mm2 and only transient swelling of the tendon with a minor inflammatory reaction when 280 mJ/mm2 was administered (5). The mean total dose of shock-wave that the active group received in our trial was 1401.7 mJ/mm2, which is higher than the 1300 mJ/mm2 total dose delivered to patients in the active group of previous trials of single dose high-energy ESWT (1,2,6). As we also reported, our results were consistent irrespective of total dose of ESWT received (n = 68 for ³ 1000 mJ/mm2; n = 13 for <1000 mJ/mm2)(4).

All patients in our trial were included on the basis of strict inclusion criteria, and standardised assessments were performed at each time point. The first author is a rheumatologist experienced in the management of plantar fasciitis and many patients were referred into the study by orthopaedists. An additional strength of our trial was the requirement for confirmation of the clinical diagnosis according to well- described ultrasound criteria of plantar fasciitis. These explicit criteria provide added assurance about the uniformity of the study population and increased the generalisability of the results.

Rachelle Buchbinder MBBS (Hons), FRACP, MSc Monash Department of Clinical Epidemiology, Cabrini Hospital and Department of Epidemiology and Preventive Medicine, Monash University Melbourne, Australia

Andrew Forbes PhD Department of Epidemiology and Preventive Medicine, Monash University Melbourne, Australia

Ronnie Ptasznik MBBS, FRANZCR Radiology Department, Monash Medical Centre Melbourne, Australia

REFERENCES 1. Ogden J, Alvarez RG, Levitt RL, Johnson JE, Marlow ME. Electrohydraulic high-energy shock-wave treatment for chronic plantar fasciitis. J Bone Joint Surg (Am) 2004; 86A:2216-28. 2. Ogden JA, Alvarez R, Levitt R, Cross GL, Marlow M. Shock wave therapy for chronic proximal plantar fasciitis. Clin Orthop. 2001;387:47-59.3. 3. FDA, HealthTronics OssaTronTM: Summary of safety and effectiveness data. 2000. 4. Buchbinder R, Ptasznik R, Gordon J, Buchanan J, Prabaharan V, Forbes A. Ultrasound-guided extracorporeal shock wave therapy (ESWT) for plantar fasciitis (painful heel): a randomised controlled trial. JAMA 2002;288:1364-72. 5. Rompe JD, Kirkpatrick CJ, Kullmer K, Schwitalle M, Krischek O. Dose- related effects of shock waves on rabbit tendo Achillis: A sonographic and histological study. J Bone Joint Surg( Br) 1998;80:546-552. 6. Dornier MedTech Inc. Dornier Epos TM Ultra: Summary of Safety and Effectiveness Data. Kennesaw, Ga:Dornier MedTech Inc; 2002.

Sir:

I read with great interest the article “Electrohydraulic high-energy shock-wave treatment for chronic plantar fasciitis” by John Ogden and co- workers (JBJS 2004; 86-A:2216). I congratulate them for reporting the results of the FDA trial, which, to a vast amount, had been published earlier (1,2).

Some points remain open for discussion.

(1) The alleged efficacy of this single dosed, high-energy, anaesthetically based treatment has already been discussed in an exhaustive way by Buchbinder et al.(3)in 2002: Regarding the HealthTronics sponsored FDA tria1,(4) Buchbinder critizised that the presence of plantar fasciitis was determined solely on clinical grounds. It was uncertain whether the 2 groups in the trial were comparable at baseline. Ogden et al.(1)had defined overall success of treatment at 12 weeks if all 4 of the following criteria were fulfilled: (1st) minimum 50% improvement over baseline in investigator assessment of pain (by dolorimeter), with a VAS score of 4cm or less; (2nd) minimum 50% improvement over pre-treatment baseline in subject´s self assessment of pain on first walking in the morning and VAS score of 4 cm or less; (3rd) minimum 1 point or greater improvement on a 5-point scale of distance walked without heel pain, or maintenance of baseline assessments of no pain or minimal pain; (4th) and no prescription of analgesics for heel pain int the treated heel between 10 and 12 weeks after treatment. While success in the 3 criteria other than investigator assessment of pain also favored the active treatment, none was statistically significant (subject´s self-assessment of pain criterion: 59.7% in ESWT group vs. 48.2% in placebo group, p= 0.08; subject´s self assessment of activity level: 71.4% in ESWT group vs. 67.2% in placebo group, p= 0.49; and use of pain medications: 69.7% in ESWT group vs. 67% in placebo group, p=0.41). I wonder why Ogden, who quoted the Buchbinder paper in his article, did not specifically respond to these objections. How is it possible that suddenly significant differences are calculated at 3-month follow-up while in the original FDA paper,(4) no statistically significant difference had been observed at the same follow-up?

(2) In their paper, Ogden et al. report active shock wave treatment with an energy flux density of 0.22 mJ/mm² to be high-energy? In a recent article, Rompe et al.(5)treated patients an energy flux density of 0.18 mJ/mm², calling this low-energy? I therefore question the labelling of Ogden´s concept as high-energy. I would like to know whether the authors are aware of any consensus as to how to define low-energy vs. high-energy treatment.

(3) I find it interesting to read that 47% of patients in the placebo group, having received 3 1-mL subcutaneous injections of lidocaine, reported greater than 50% improvement of morning heel pain at the 3-month follow-up. In an upcoming study(6) 86 patients with chronic plantar fasciitis had been randomly assigned to receive either low-energy ESWT without local anesthesia, given weekly for three weeks or identical ESWT with local anesthesia to the insertion of the plantar fascia. Significantly more patients achieved greater than 50% reduction of pain of first steps in the morning after ESWT without local anesthesia than after ESWT with local anesthesia (67% vs. 29%). Local anesthesia applied prior treatment reduced the efficiency of low-energy ESWT in this setup. I wonder what explanation Ogden and co-workers have for the surprisingly high rate of satisfied patients after local anesthesia only in their experimental design? With their close to 50% success rate in recalcitrant patients regarding morning pain, should subcutaneous injections of lidocaine not be given priority before shock-wave treatment?

(4) I agree with Ogden, that the mechanism of shock wave action in soft tissues is still under investigation. When discussing a possible working mechanism of shock wave application it is important to focus not only on differences of shock wave devices in clinical use. There are also different pathways for the effects of high- versus low-energy shock waves. It is important to know that the current literature(7-10) indicates that shock waves may selectively lead to dysfunction of peripheral sensory unmyelinated nerve fibers without affecting nerve fibers responsible for motor function (large myelinated fibers). For “high-energy” treatment with 0.9 mJ/mm², this selective destruction of unmyelinated sensory nerve fibers within the focal zone of ESWT may contribute to clinically evident long-term analgesia.(7) For “low-energy” application with 0.1 mJ/mm² analgesia may be a result of a shock wave-induced release of neuropeptides, such as CGRP, resulting in a local neurogenic inflammation in the focal area with subsequent prevention of sensory nerve endings from reinnervating this area.(8,9) A second application accentuated these inflammatory changes and therefore prevented reinnervation.(10) Centrally, the common findings of a reduction in the number of neurons immunoreactive to CGRP and substance P without a reduction of the total number of neurons within the lower lumbar DRG probably are a secondary effect following the (primarily induced) decrease of the number of sensory nerve fibers in the focal zone of shock wave application.9 So the peripheral and central nervous system may both play a pivotal role in mediating shock wave induced long-term analgesia. Recently, Wang(11) showed that shock wave application of 0.12 mJ/mm² resulted in increased neovascularization at the tendon-bone junction in rabbits. Chen(12) treated rats with a collagenease-induced Achilles tendinitis with a single shock wave treatment with 0, 200, 500 and 1000 impulses of 0.16 mJ/mm². Shock wave application with 200 impulses restored biomechanical and biochemical characteristics of healing tendons 12 weeks after treatment. However, shock wave treatments with 500 and 1000 impulses elicited inhibitory effects on tendinitis repair. Together, low-energy shock wave effectively promoted tendon healing. In my view it is clear from these experimental data that with increasing energy applied there is a chance of side effects that my well harm an already diseased fascia or tendon. It is also clear that even “low-energy” shock waves may induce a positive local reaction regarding down-regulation of pain transmitters, and up-regulation of cell proliferation factors. The clinical results reported by Ogden and co-workers, using an energy flux density of 0.22 mJ/mm², probably are due to these effects.

(5) I agree with Ogden and co-workers and with Speed(13) that some regimes of ESWT are a potentially helpful addition to the options for the management of soft-tissue conditions such as chronic plantar fasciitis. I support Ogden and co-workers that contrary to the opinion of Buchbinder(14) these regimes of ESWT - producing virtually no complications, allowing immediate full weight bearing without splints - should therefore be given priority before surgery.(15)

Sincerely yours,

Jan D. Rompe, MD

References

1. Ogden JA et al. Shock wave therapy for chronic proximal plantar fasciitis.Clin Orthop 387: 47-59, 2001.

2. Ogden JA. Extracorporeal shock wave therapy for plantar fasciitis: randomised controlled multicentre trial. Br J Sports Med 38: 382, 2004.

3. Buchbinder R et al. Ultrasound-guided extracorporeal shock wave therapy for plantar fasciitis: a randomized controlled trial. JAMA 288:1364-1372, 2002.

4. U.S. Food and Drug Administration. Summar of safety and effectiveness data. http://www.fda.gov/cdrh/pdf/p990086.html

5. Rompe JD et al. Shock wave application for chronic plantar fasciitis in running athletes – a prospective, randomized, placebo- controlled trial. Am J Sports Med 31:268-275, 2003.

6. Rompe JD, Meurer A, Nafe B, Hofmann A, Gerdesmeyer L. Low-energy shock wave application without local anesthesia is more efficient than low -energy extracorporeal shock wave application with local anesthesia in the treatment of chronic plantar fasciitis. J Orthop Res, in press.

7. Maier M et al. Substance P and prostaglandin E2 release after shock wave application to the rabbit femur. Clin Orthop 406:237-245, 2003.

8. Ohtori S et al. Shock wave application to rat skin induces degeneration and reinnervation of sensory nerve fibres. Neurosci Lett 315:57-60, 2001.

9. Takahashi N et al. Application of shock waves to rat skin decreases calcitonin gene-related peptide immunoreactivity in dorsal root ganglion neurons. Auton Neurosci 107:81-84, 2003.

10. Takahashi N et al. The mechanism of pain relief in extracorporeal shock wave therapy. Poster # 448, AAOS Annual Meeting San Francisco, 2004. http://www.aaos.org/wordhtml/anmt2004/poster/p448.htm.

11. Wang CJ. Shock wave therapy induces neovascularization at the tendon-bone junction. A study in rabbits. J Orthop Res 21:984-989, 2003.

12. Chen YJ et al. Extracorporeal shock waves promote healing of collagenase-induced Achilles tendinitis and increase TGF-beta1 and IGF-I expression. J Orthop Res 22:854-861, 2004.

13. Speed CA. Extracorporeal shock-wave therapy in the management of chronic soft-tissue conditions. JBJS 86-B:165-171, 2004.

14. Buchbinder R. Clinical practice. Plantar fasciitis. N Engl J Med 350:2159-2166, 2004.

15. Rompe J. Plantar fasciitis. N Engl J Med. 351:834, 2004.