Key words: shock wave therapy, musculoskeletal system, mechanism.
Historic background

During World War II, engineers from Dornier factory (Germany) had observed the patterns of injuries in tank crews when the turrets were struck by shell, and pitting of metal surfaces was observed associated with supersonic flight.(1) The influence of shock wave on human tissue was first documented when the lung tissue of castaways was disrupted because of the explosion of water bombs even though no external symptoms of violence existed.(2) The wife of one engineer suggested the possible application of this knowledge to fragmentation of kidney stones and this idea had led to the development of lithotripsy in mid 1970 in Munich, Germany. The interaction between shock waves and biologic tissues in animals were investigated in Germany between 1968 and 1971.(6,31) In 1974, a research grant "Application of Extracorporeal Shock Wave Lithotripsy" was approved. The first patient with kidney stone was treated with shock wave in Munich, Germany (Dornier lithotriptor HM1) in 1980. In 1983, the first commercial lithotriptor (HM3, Dornier) was installed in Stuttgart, Germany. The first case of gallstone treated with ESWL was performed in Munich, Germany in 1985.(2,13) Twenty some years later, lithotripsy has become the gold standard for the initial treatment of urolithiasis.(1,2)
In musculoskeletal system, the application of shock waves to the loosening of cement in the revision of total hip was thought to be feasible at that time. Karpman RR et al(3) performed a study in canine femoral model, and demonstrated microfractures within the bone cement and a definite disturbance of the bone/cement interface when the specimens were examined with scanning electron microscopy and reflected light microscopy. Using the same principles, other authors reported the potential use of shock wave for bone cement removal.(4,5)
In mid 1980, incidental observations during animal studies found an osteoblastic response pattern that generated an interest in the potential application of extracorporeal shock wave therapy to numerous orthopedic disorders.(1,2,6-8) In the past 10 to 15 years, shock wave therapy had shown effects in the treatment of certain orthopedic disorders including non-union of long bone fractures, calcific tendinitis of the shoulder, lateral epicondylitis of the elbow and proximal plantar fasciitis.(1,7,9-24) More recently, several studies had extended shock wave therapy to patellar tendinits (jumper's knee), osteochondritis dessicans and avascular necrosis of the femoral head and had shown satisfactory results.(13,2,25-27) The use of extracorporeal shock wave therapy has gained significant acceptance in Europe, especially Germany, Austria, Italy and in Taiwan, and has led to the change of European Society for Musculoskeletal Shockwave Therapy to International Society for Musculoskeletal Shockwave Therapy (ISMST) in 2000. In USA, FDA (Food and Drug Administration) approved in Oct 2000 on specific shock wave device (OssaTron, High Medical Technology, Lengwil, Switzerland) for the indication of proximal plantar fasciitis, with many other clinical trials under study including lateral epicondylitis of the elbow, calcific tendinitis of the shoulder, non-union of fracture.(1,7,13,27,28) Based on our extensive clinical results in the past 3 to 4 years, and the innovative findings on the mechanism of shock wave therapy, the Department of Health of Taiwan Government had approved the OssaTron shock wave therapy for patients with proximal plantar fasciitis in May 2001, with conditional approval on several other orthopedic conditions including tendinitis of the shoulder, lateral epicondylitis of the elbow and non-union of long bone fractures. In the past, the Annual Congress of The International Society of Musculoskeletal Shockwave Therapy (ISMST) was traditionally held in European countries and cities including Izmir, Turkey in 1998, London, England in 1999, Naples, Italy in 2000, Munich, Germany in 2001, Winterhur, Switzerland in 2002. The first ISMST Congress outside the Europe was held in Orlando, Florida, USA in February 2003. During the general meeting of the association members from 34 countries, I was elected as the new president of the association. The Managing Board of ISMST has decided to hold the 7th Annual Congress of ISMST meeting in Kaohsiung, Taiwan in April 2004.

Principle of shock wave therapy

Shock waves are generated by an underwater high-voltage condenser spark discharge and then focused at the diseased area, using an elliptical reflector (Fig. 1).(7,29,30) Shock waves are high amplitude sound waves from a transient pressure disturbance that propagate in three-dimension space with a sudden rise from ambient pressure to its maximum pressure at the wave front. A shock wave is a sonic pulse that has certain physical characteristics. There is an initial rise of a high peak pressure, sometimes more than 100 MPa (500 bar) within less than 10 ns (nanoseconds), followed with a low tensile amplitude (up to 10 MPa), a short life cycle of approximately 10 盜 and a broad frequency spectrum in the range of 16 to 20 MHz. There are two basic effects of shock waves: the primary effect is direct generation of mechanical forces that result in the maximally beneficial pulse energy concentrated at the point where treatment is to be provided; and the secondary effect is the indirect mechanical forces by cavitation which may cause negative effect or damage to the tissues.(1,7,29)
Shock wave differs from ultrasound wave that is typically biphasic and has a peak pressure of 0.5 bar (Fig 2).(1,7,29,30) In essence, the peak pressure of shock wave is approximately 1000 times that of ultrasound wave. Shock waves change their physical properties through attenuation and steepening when traveling through a medium and through reflection and refraction at the boundaries when subsequently moving into another medium.(1,7,29,30) At the boundary layer between two media one part of an approaching shock wave will be reflected and the other part will be transmitted. Losses through attenuation in water are approximately 1000 times lower than an air. Shock waves are generated within water and subsequently transferred to the human body by means of a contact medium.(1,7,8,29,30) These ensure small losses attributable to attenuation and reflection by any boundary area, and the energy of shock wave will be concentrated in the treatment focus. It is along the boundaries between different media such as muscle and bone or lung tissue that the sound field experiences the biggest changes and emits the highest energy, and where the most biologic effects are expected.(1,7,8,30,31)
The focal volume of shock wave on target tissue is shown in Fig. 3. Shock wave pressure (in MegaPascals) measures the tensile force with fiberoptic hydrophone. Energy flux density describes the maximum amount of acoustic energy that is transmitted through an area of 1 mm2 per pulse. The energy describes the total acoustical energy per released shock wave. Therefore, the total energy is the accumulated energy flux density as they integrated over the entire region. In addition to the primary focal point, a second focal point (6dB) is defined the volume area of tissue within which the pressure is at least 1/2 its peak pressure. Shock wave propagation into biological tissue is shown in Fig. 4.

Methods of shock wave generation

There are three main techniques through which shock waves are generated. These are the electrohydraulic, electromagnetic, and piezoelectric principles, each of which represents a different technique of generating the shock wave. All involve the conversion of electrical energy to mechanical energy.(1,30)
Shock wave generation through the electrohydraulic principle represents the first generation of orthopedic shock wave machine. It is characterized by large axial diameters of the focal volume and high total energy within that volume.(30,32) Shock wave generation through the electromagnetic technique involves the electric current passing through a coil to produce a strong magnetic field. A lens is used to focus the wave, with the focal therapeutic point being defined by the length of the lens. The amplitude of the focused waves increases by non-linearity when the acoustic wave propagates toward the focal point.(1,30) Shock wave of piezoelectric technique involves a large number (usually > 1000) of piezocrystals mounted in a sphere and receives a rapid electrical discharge that induces a pressure pulse in the surrounding water steepening to a shock wave. The arrangements of the crystals cause self-focusing of the wave toward the center (target), and lead to an extremely precise focusing and high-energy within a defined focal volume.(1)
When comparing different shock wave devices, the important parameters include pressure distribution, energy density and the total energy at the second focal point in addition to the principle of shock wave generation of each device.
Mechanism of shock wave therapy

The processes that shock waves induced in biologic tissue are not fully understood, especially as they relate to the induction of bone healing. The most important physical parameters of shock wave therapy for the treatment of orthopedic disorders include the pressure distribution, energy density and the total acoustic energy.(1,30,33) In contrast to lithotripsy in which shock waves disintegrate renal stones, shock waves are not being used to disintegrate tissue, but rather to microscopically cause interstitial and extracellular responses.(1,30) Currently, the therapeutic mechanism of shock wave therapy in musculoskeletal problems and the specific biologic effects on the various tissues (bone, cartilage, tendon and ligament) are not fully understood. The effects from direct forces and cavitation from indirect forces cause trabecular microfractures or interstitial gaps and hematoma formation, as well as focal cell death, which then stimulate new bone or tissue formation.(1,30,34-38) When shock waves hit the cortical bone, 65% are transmitted and 35% reflected. The maximum stimulation of osteogenesis occurs at the interface of cortical and cancellous bones, while the tensile waves cause cavitation and osteocyte death, followed by osteoblast migration and new bone formation.(1,4,18,34,38-46)
The exact mechanism of shock wave therapy remains unknown. Some authors hypothetically described that shock waves cause microfracture or micro-trauma and hematoma formation that eventually lead to osteoblastic activities, increased callus formation and bone healing.(1,7,8,30,35,36) Others postulated that shock wave therapy relieves pain due to insertional tendinopathy by provoking painful level of hyper-stimulation analgesia. Recently, the results of our animal experiments demonstrated that shock wave therapy induces neovascularization at the tendon-bone junction associated with the early release of angiogenesis-mediating growth and proliferating factors including eNOS (endothelial nitric oxide synthase), VEGF (vessel endothelial growth factor) and PCNA (proliferating cell antinuclear antigen) that lead to improvement of blood supply and tissue regeneration (Fig. 5).(21,47) Therefore, the mechanism of shock wave therapy appears to involve a cascade of interaction between physical shock wave energy and biologic responses as shown in Fig. 6.

Shock wave therapy in orthopedic disorders

In 1986, Haupt reported the first experiment to investigate the influence of shock wave on bone.(9) The first shock wave treatment for non-union of fracture was done in Bochum, Germany in 1988. In the same year, Valchanov and Michalilov described shock wave therapy for non-unions and delayed unions, and reported a success rate of treatment of 85% despite the poor control study.(1,9,48) The first report of shock wave therapy on calcific tendonitis of the shoulder was made in 1990, with subsequent reports on lateral epicondylitis and plantar fasciitis.(1,9,49) The first orthopedic shock wave machine (OssaTron, HMT AG, Lengwil, Switzerland) was made available in 1993. As of 2002, the ISMST recommended the following indications for shock wave therapy in orthopedic disorders. These included non-unions and delayed unions of long bone fractures, calcific tendonitis of the shoulder, lateral epicondylitis of the elbow and proximal plantar fasciitis.(10,13,16,35) In addition, the effects of shock wave therapy were investigated on several other conditions including avascular necrosis of the femoral head in adults, osteochondritis dessicans of the talus and the knee, patellar tendonitis, Achilles tendonitis, medial epicondylitis of the elbow, trochanteric bursitis and non-calcific tendonitis of the shoulder.(2,25,27,30,50)

Animal experiments

Shock wave therapy versus bone healing
Several studies had investigated the effects of shock wave therapy on fracture healing and its effects on other musculoskeletal tissues including cartilage in animal experiments.(7,32,35,39,45,49,51-59) Haupt et al(48) in an experimental model in rats, confirmed a positive effect of shock wave treatment on fracture healing. Johannes et al(60) showed the promotion of bony union with shock wave therapy in hypertrophic non-unions in dogs. Wang et al(57) demonstrated that shock wave therapy enhanced callus formation and induced cortical bone formation in acute fractures in dogs at 12 weeks, and the effect of shock wave therapy seemed to be time dependent. Wang FS et al(61) had successfully created a non-union model in rats, and had shown that shock wave therapy significantly promotes fracture healing than the control. However, Forriol et al(62) reached an alternative conclusion and thought that shock wave treatment might delay bone healing and did not recommend its use in clinical orthopedics. Therefore, there are conflicting results on the effect of shock wave therapy on bone healing in animal experiments. Most studies showed a positive effect of shock wave therapy on fracture healing,(48,60,61) whereas only one study showed a negative result.(62) The possible reasons for the discrepancy included the different types of animals and the different shock wave energy flux densities used in different studies.
Wang et al had demonstrated that high-energy shock wave therapy produces a significantly higher bone mass including BMD (bone mineral density), callus size, ash and calcium contents, and better bone strength including peak load, peak stress and modulus of elasticity than the control group after fractures of the femurs in rabbits. However, the effects of low-energy shock wave therapy were less prevailing with comparable results as compared with the control. Therefore, the effect of shock wave therapy on bone mass and bone strength appeared to be dose-dependent and progression with time. There are many other studies investigating the effect of shock wave therapy on bone healing in animals.(47,61,63-65) The important findings included superoxide mediates shock wave induction of ERK-dependent osteogenic transcription factor (CBFA-1) and mesenchymal cells differentiation toward osteoprogenitors.(64) Extracorporeal shockwave promotes bone marrow stromal cell growth and differentiation toward osteo-progenitors associated with TGF-b1 and VEGF induction.(47) Physical shock wave mediates membrane hyperpolarization and Ras activation for osteogenesis in human bone marrow stromal cells.(63) Shock wave enhances fracture healing and biomechanical strength associated with increase in TGF-b1 induction.(65) Altered expression of bone morphogenetic protein in shockwave promoted healing of fracture defect.(64)

Shock wave therapy versus insertional tendinopathy at the tendon-bone junction
Many studies were devoted to investigate the effect of shock wave therapy on insertional tendinopathies at the tendon-bone junction.(11,20,23,28,31,32,54,66-68) Rompe et al.(54) demonstrated dose-related effects of shock waves on rabbit tendo Achilles, and suggested that energy flux density of more than 0.28 mJ/mm2 should not be used clinically in the treatment of tendon disorders. In their study, a statistically significant increase of capillary formation was noted with higher energy shock wave (0.60 mJ/mm2), which also caused more tissue reaction and potential damage to the tendon tissue. Wang et al(21) had demonstrated that low energy shock waves enhance neovascularization with formation of new capillary and muscularized vessels at the tendon-bone junction of the Achilles tendons in dogs. In a study in rabbit model, Wang et al further demonstrated that shock wave therapy induces a significantly higher number of neo-vessels (neovascularization) including capillary and muscularized vessels than the control without shock wave therapy at the tendon-bone junction. In the earlier stage, shock wave therapy releases a higher number of angiogenesis-mediating growth and proliferating indicators including eNOS, VEGF, and PCNA than the control without shock wave therapy. The eNOS and VEGF began to rise in as early as one week and remained high for 8 weeks, then declined in 12 weeks; whereas the increase of PCNA and neo-vessels began in 4 weeks and persisted for 12 weeks and longer. Therefore, the mechanism of shock wave therapy may have involved the early release of agniogenesis-related growth factors, which in turn induce neovascularization and improve blood supply at the tendon-bone junction of the Achilles tendon in rabbits. It is believed that the mechanism of shock wave therapy alleviates pain due to insertional tendinopathy by the induction of neovascularization and improvement of blood supply to the tissue, and initiating repairs of the chronically inflamed tissues by tissue regeneration.

Clinical applications

Non-union and delayed union of long bone fracture
Several studies on the effect of shock wave therapy for non-union and delayed union of long bone fractures, and reported the success rate ranged from 50% to 90%.(10,16-18,26,50,69-75) Wang et al(19) treated 72 patients with non-unions of long bone fracture with shock wave therapy, and reported a 49% success rate of bony union associated with complete resolution of pain and functional recovery at initial 3-month follow-up of 55 patients; the success rate of bony union was 82.4% at 6-month follow-up of 34 patients; and the success rate of bony union was 88% (22/25) at 9 to 12 month follow-up in 22 patients. Schleberger and Senge(75) showed successful fracture healing in three of four pseudoarthroses treated with 2000 shock waves. Valchanou et al(17) reported bony unions in 70 of 82 patients with delayed or chronic nonunion of fractures at various locations. Rompe et al(73,74) reported a 50% success rate in the treatment of delayed bone union with shock waves in another clinical study, whereas Vogel et al(18) reported a 60.4% union rate in 48 patients with pseudarthroses treated with 3000 shock wave impulses. Schaden et al(16) reported a success of 85% in the treatment of 115 delayed and non-unions.