Extracorporeal Shock Wave Therapy in Orthopaedic Diseases

Th e application of extracorporeal shock wave therapy (ESWT) as a treatment for diff erent orthopaedic conditions has experienced a rapid increase over the last several years. However the mechanism of action and the therapeutic eff ect is not clear. Th e aim of this study was to review the literature about the effi cacy of ESWT in the treatment of plantar fasciitis, lateral epicondylitis, shoulder painful disorders and non-union fractures. Only randomized controlled studies published in the last  years were retrieved from electronic database and manual search. Results on effi cacy of ESWT are controversial. Studies that have claimed therapeutic benefi t did not fulfi ll scientifi c criteria and controlled randomized trials were not able to confi rm signifi cant improvement after treatment with ESWT.


Introduction
Originally used for the treatment of kidney stones ESWT has found its place in the treatment of variety of chronic orthopaedic conditions including plantar fasciitis, lateral epicondylitis (tennis elbow), calcific tendinitis of the shoulder, delayed union or non-union of fractures, osteonecrosis of the femoral head and other tendinopathies.Declared as a non invasive and safe treatment it has been applied as an alternative to surgical procedures especially in European clinics.Naturally generated shock waves can be observed in thunder and lightning, explosion and supersonic aircrafts.They can produce a dramatic increase in pressure amplitudes.Sometimes this pressure can break the windows and damage ear membranes.Th e energy released is usually expressed in joules (J) or milijoules (mJ) and pressure in kilopascals (kPa) and megapascals (MPa).Animal experiments performed  years ago revealed that shock waves had the potential to activate osteoblast cells and stimulate bone formation.Delayed and non-union fractures healed faster after being exposed to the shock waves ().This and other research papers published in the eighties and early nineties introduced the new concept of orthopaedic "Extracorporeal Shock Wave Th erapy'(ESWT)'.Before that shock waves were used mainly for kidney stone lithotripsy.

Shock Waves: Physical Principles
A shock wave can be defi ned as a sonic pulse with the following characteristics: .High Peak Pressure ( MPa) .A short lifecycle ( ms) .Fast pressure rise (less than  ns) .A broad frequency spectrum In practice there are three methods applied in shock wave generation: .Electrohydraulic principle .Electromagnetic principle .Piezoelectric principle All these techniques convert electrical to mechanical energy.Th ey are called focused shock waves and their main characteristics are a very high peak pressure ( - MPa) and a very short rise time (less than  micro second) Recently another principle for generating pressure waves was implemented, so called a ballis-tic, radial or unfocused pressure wave (Figure ).Ballistic pressure pulses are significantly lower in peak pressure (,- MPa), feature a longer rise time (more than  micro seconds) and pulse duration.The effect of ballistic pressure pulses is strongest at the surface point of impact and that is why their therapeutic effect is limited to superficial targets.Depth of penetration is  to , cm.This type of ESWT has been used mainly in physiotherapy.The shock waves propagate through a homogeneous soft tissue with a speed of  m/sec with negligible distortion.However, facing the tissue inhomogenities the shock wave will be modified by deviation from straight propagation, reflection, absorption etc.As a result a localized release of shock wave energy occurs.The direct effect of the energy released at interfaces of diff erent tissue as well as the indirect effects of colliding cavitation bubbles is assumed to initiate the healing effects of shock wave therapy ().

Mechanisms of ESWT
Although ESWT has been used in orthopedic practice for many years, the molecular mechanism of its action is poorly understood.It has been postulated that mechanical energy converted from high frequency electricity, triggers the release of free radicals, vasodilatation and successive angiogenesis.Among the free radicals the role of nitrogen oxide (NO) was particularly investigated.

Properties of NO include:
-Vasodilatation by relaxation of smooth vascular musculature through cGMP stimulation.-Macrophage activation to increase immune defense and cytotoxicity.-Neurotransmitter There are three isoenzymes of NO synthase (NOS) which using L-arginine as a substrate catalyses the synthesis of NO and citrulline.Th ese are: endothelial NOS (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS).Experimental work on rats confirmed that calcium independent NOS activity was significantly increased after treatment with ESWT.Increase was observed . day and persisted for  days after ESWT.Calcium dependent NOS activity was evidently elevated  days after treatment ().Immunohistological observation demonstrated that mesenchymal cells at fibrous tissue and chondral cells at hypertrophic cartilage displayed intensive iNOS expression.Chondral cells and osteoblasts at newly formed woven bone SUAD TREBINJAC ET AL.: EXTRACORPOREAL SHOCK WAVE THERAPY IN ORTHOPAEDIC DISEASES junction appeared evident eNOS expression.Mature osteoblasts and osteoclasts at vascularized woven bone area showed strong nNOS immuno-reactivity.Based on these results one can conclude that NOS acts an important mediator to translate physical ESW treatment into biological reaction for mesenchymal cell proliferation and diff erentiation in the area of bone defect after exposure to ESW treatment.Th e eNOS is involved in new cartilage and bone formation.Th e nNOS is probably to mediate bone remodeling and angiogenesis ().Th e role of mitogen activated protein kinase (MAPK), including extracorporal signal-regulated kinase (ERK) and p kinase (p) on bone formation was also investigated.Animal model was used for experiment.Results suggest that ERK is active in the process of bone regeneration of segmental defect.Th e p is likely act important role in signaling cartilage formation in callus.ERK and p act as an important mediator to translocate biological signal into nuclei of cells to initialize mitogenic and osteogenic transcription of osteochondrogenic cells ().
Th e relationship between these eff ects and pain relief is not clear.So far the mechanism of analgesia produced by ESWT is uncertain.Induction of neovasculariza-tion associated with mechanical and cavitation properties of shock waves are the most common proposed model ().However gate control mechanism is also suggested ().Decreased level of calcitonin gene-related peptide (CGRP) in dorsal root ganglia in rats was found after treatment with ESW.Th is could be related to pain relief ().Th e possible role of spinal endogenous opioids (met-enkephalin and dynorphin) was also investigated.Th e level of these substances remains the same at  and  hours after exposure to ESWT.According to these results there is no proof that endogeneous opioids are responsible for analgesic eff ect of ESWT ().

Clinical Studies on ESWT
Th roughout the last  years there have been many publications about ESWT in orthopaedic treatment.Most of these publications were based more on clinical than on scientifi c background.While ESWT has been proved effective particularly for treatment of plantar fasciitis and tennis elbow, there have been very few randomized, prospective placebo controlled, double blinded studies performed.After reviewing the literature published in the last  years we selected only randomized control study articles.In a prospective randomized placebo-controlled double blind study an experimental group received ESWT of  impulses of o.o mJ/mm for treatment of plantar fasciitis. were pain free or had good results.None of placebo group was pain free, only . had good results.Th e treatment group showed signifi cantly better outcome for morning and resting pain, pressure stamp-tolerance and walking ability.ESWT has been proved effective in treatment of plantar fasciitis ().
In another single blind randomized study on  patients with calcaneal enthesophytosis (calcaneal spur) it was found that the group treated with ESWT showed significant decrease of pain on the visual analog scale (VAS) and reduction of enthesophytosis larger than  mm on x-ray.Such improvement was not registered in placebo group ().Th e eff ect of ESWT in patients with chronically painful proximal plantar fasciitis was compared with conventional conservative treatment including jontophoresis with Diclofenac and oral nonsteroidal anti-infl amatory drugs.Two years after treatment both groups showed pain decrease during activities of daily living.Th ere was no statistically signifi cant diff erence between groups ().A randomized placebo -controlled, multiply blinded, crossover study conducted on patients with chronic plantar fasciitis concluded that the application of electrohydraulic high-energy shock waves to the heel is a safe and eff ective noninvasive method to treat chron-

Conclusion
For the past  years ESWT has been intensively used in orthopaedic practice.At the moment three machines have been FDA approved for the use on humans, two for plantar fasciitis and one for lateral epicondylitis (tennis elbow).Almost all study emphasized high safety of this therapy with minimal side eff ects.However, results on effi cacy of ESWT are still controversial.Many studies that claimed ESWT was effi cient in treatment of musculoskeletal conditions did not fulfi ll scientifi c criteria.On the other side, most of the well established controlled studies which included double blind or single blind trials were not able to produce such results.Th ere are multitude reasons to consider ESWT experimental and investigational rather than well documented therapeutic modality.Th e mechanism of action is speculative, diffi cult to quantify and prove.Treatment parameters have not yet been standardized and optimal dosages and frequency has not yet been established.Th ere is still no consensus on when to diff erentiate between low and high-energy applications.Th ere are no studies to compare the eff ect of focused versus ballistic (radial, not focused) techniques.One of the biggest advantages of ESWT in comparison to surgery was lower cost and faster healing of the treated tissue.However the surgery for plantar fasciitis, lateral epicondylitis and supraspinatus tendonitis with and without calcifi cation are not very often and there are no enough studies to compare effi cacy of ESWT and the surgical treatment on pain relief and functional outcomes.An opinion prevails that ESWT should be used only if other ordinary conservative treatments failed.Taking into account that in many patients, spontaneous resolution of pain and calcifi cation is possible, the abuse of ESWT in the clinical practice should be considered as a serious problem.
More studies need to be done for better understanding of the mechanism of action, to defi ne optimal parameters and to create a specifi c clinical protocol for diff erent musculoskeletal conditions.
Orthopade ; ():-.() Gross M.W., Sattler A., Haake M., Schmitt J., Hilderbrandt R., Muller H.H., Engenhart-Cabillic R. Th e eff ectiveness of radiation treatment in comparison with extra corporeal shockwave therapy in supraspinatus tendon syndrome.Strahlenther Onkol.; (): - () Haake M., Sattler A., Gross MW., Schmitt J., Hildenbrandt R., Muller HH.Comparison of extra corporeal shockwave therapy (ESWT) with Roentgen irradiation in supraspinatus tendon syndrome -a prospective randomized single-blind parallel group.Z. Orthop Ihre Grenzgeb.; (): -.() Schmitt J., Haake M., Tosch A., Hildebrand R., Deike B., Griss P. Low energy extra corporeal shock-wave treatment (ESWT) for tendonitis of the supraspinatus.A prospective randomized study.J Bone Joint Surg.; ():-.() Pan PJ., Chou CL., Chiou HJ., Ma HL., Lee HC., Chan RC.Extra corporeal shock wave therapy for chronic calcifi c tendonitis of the shoulders: a functional and sonographic study.Arch.Phys.Med.Rehabil.;  (): -.() Gerdesmeyer L., Wagenpfeil S., Haake M., Maier M., Loew M., Wortler K., Lampe R., Seil R., Handle G., Gassel S., Rompe JD.Extra corporeal shock wave therapy for the treatment of chronic calcifying tendonitis of the rotator cuff : a randomized controlled trial.JAMA.; (): - () Birbaum K., Wirtz DZ., Siebert CH., Heller KD.Use of extra corporeal shock wave therapy (ESWT) in the treatment of nonunions.A review of the literature.Arch Ortop Trauma Surg.; (): -.() Haake M., Boddeker IR., Decker T., Buch M., Vogel M., Labek G., Maier M., Loew M., Maier-Boerries O., Fischer J., Betthauser A., Rehack HC., Kanovsky W., Muller I., Gerdesmeyer L., Rompe JD.Side eff ects of extra corporeal shock wave therapy (ESWT) in the treatment of tennis elbow.Arch Orthop Trauma Surg.; (): - References SUAD TREBINJAC ET AL.: EXTRACORPOREAL SHOCK WAVE THERAPY IN ORTHOPAEDIC DISEASES ic plantar fasciitis, lasting up to and beyond one year ().Contrary to previous results, randomized, blinded multicentre trial study comprised  patients with chronic plantar fasciitis did not confi rm better result with ESWT than with placebo.Authors concluded that ESWT is ineff ective in treatment of chronic plantar fasciitis ().After reviewing clinical trials on ESWT and plantar fasciitis Boddeker and co -authors found that many studies are incomplete and methodologically inadequate.After analysis of  relevant articles authors concluded that effi cacy of ESWT can be neither confi rmed nor excluded ().Like plantar fasciitis results of treatment of lateral epicondylitis (tennis elbow) are also controversial.Perlick and co-authors evaluated the outcome of the ESWT and the operative treatment.Th ey concluded that taking into account duration of symptoms, large scale of the primary treatment and operative hazards ESWT could be considered benefi cial in the treatment of patients suff ering from lateral epicondylitis ().In a multicenter, blinded, randomized, placebo-controlled study  patients with chronic lateral epicondylitis were randomized to either active ESW treatment or to placebo group.Treated group received  shocks directed at the aff ected site at a power of  kV.Authors concluded that ESWT was more eff ective than placebo in the treatment of chronic lateral epicondylitis, although both treatments might need to be performed to enhance the level of successful outcome ().However, recently published papers were not able to confi rm effi cacy of ESWT in treatment of tennis elbow.Study performed on o patients randomly allocated to receive  session per week for  weeks of either sham or active ESWT revealed signifi cant diff erence neither in pain reduction nor in quality of life between two groups ().Review of the literature about ESWT and lateral epicondylitis was published in two articles.In the fi rst one, a total of  studies were identifi ed,  of which had been carried out as prospective, randomized and controlled studies.Regarding to clinical success, - of the patients achieved a good or very good result at follow up examinations after - months.However, in the single placebo-controlled and blinded study with the independent observer there was no diff erence between the ESWT group and the group treated with local anesthetic ().In another study,  relevant articles were ana- lyzed and it was concluded that at this point the effi cacy of ESWT can be neither confi rmed, nor excluded ().Th e next common conditions treated with ESWT were shoulder painful disorders particularly calcifying tendonitis of the rotator cuff.In prospective study  patients diagnosed as tendinosis calcarea of the rota-tive ESWT or placebo ESWT.More side eff ects were recorded in the ESWT group than in placebo group.Most frequently were reddening of the skin (,), pain (, ) and small haematomas (,).Migraine was registered in  and syncopes in  patients after receiving ESWT ().SUAD TREBINJAC ET AL.: EXTRACORPOREAL SHOCK WAVE THERAPY IN ORTHOPAEDIC DISEASES SUAD TREBINJAC ET AL.: EXTRACORPOREAL SHOCK WAVE THERAPY IN ORTHOPAEDIC DISEASES () Valchanou V., Michailov P. Use of extra corporeal shock waves in treatment of delayed and non-union fractures.J. Urol.; :- () Wess O., Physical of shock wave therapy.th International Congress of the ISMT, Orlando  () Wang F. S., Wang C. J., Chen Y. J., Kuo Y. R., Yang K. D., Sheen Chen S. M., Huang H. C., Yang Y. J., Chih S. Y. Temporal and spatial expression of Nitric Oxide Synthase (NOS) in the ESW promotion of fracture healing.th International Congress of the ISMT., Orlando  () Wang F. S., Wang C. J., Chen Y. J., Kuo Y. R., Yang K. D., Sheen Chen S. M., Huang H. C., Yang Y. J., Chih S.Y.Activation of extra cellular signal regulated kinase (ERK) and p kinase in shock wave promoted bone formation on segmental defect in rats.th International Congress of the ISMT, Orlando  () Zhu S., Zhong P. Shock wave inertial microbuble interaction: A theoretical study based on the Gilmore formulation for bubble dynamics.Acoust.Soc.Am. ;  () - () Steinbach P., Hofstaedther F., Nicolai H., Roessler W., Wieland W. Determination of energy dependent extent of vascular damage caused by high-energy shock waves in an umbilical cord model.Urol.Res.; (): - () Brummer F., Brauner T., Hulser D., Biological eff ects of shock waves World J. Urol.; :- () Leal C., Lopez J. C., Reyes O. E., Shockwave therapy in tennis elbow-Our first two years.th International Congress of the Daecke W., Kusnierczak D., Loew M. Extra corporeal shock wave therapy (ESWT) in tendinosis calcarea of the rotator cuff .Long term result and effi cacy.