Aims. Little is known about the effect of haemorrhagic shock and resuscitation on fracture healing. This study used a rabbit model with a femoral osteotomy and fixation to examine this relationship. Materials and Methods. A total of 18 male New Zealand white rabbits underwent femoral osteotomy with intramedullary fixation with ‘shock’ (n = 9) and control (n = 9) groups. Shock was induced in the study group by removal of 35% of the total blood volume 45 minutes before resuscitation with blood and crystalloid. Fracture healing was monitored for eight weeks using serum markers of healing and radiographs. Results. Four animals were excluded due to postoperative complications. The serum concentration of osteocalcin was significantly elevated in the shock group postoperatively (p < 0.0001). There were otherwise no differences with regard to serum markers of bone healing. The callus index was consistently increased in the shock group on anteroposterior (p = 0.0069) and lateral (p = 0.0165) radiographs from three weeks postoperatively. The control group showed an earlier decrease of callus index. Radiographic scores were significantly greater in the control group (p = 0.0025). Conclusion. In a rabbit femoral osteotomy model with intramedullary fixation, haemorrhagic shock and resuscitation produced larger callus but with evidence of delayed remodelling. Cite this article: Bone Joint J 2018;100-B:1234–40

Biofilm-associated infections in wounds or on implants are difficult to treat. Eradication of the bacteria is nearly always impossible, despite the use of specific antibiotics. The bactericidal effects of high-energy extracorporeal shock waves on Staphylococcus aureus have been reported, but the effect of low-energy shock waves on staphylococci and staphylococcal biofilms has not been investigated. In this study, biofilms grown on stainless steel washers were examined by electron microscopy. We tested ten experimental groups with Staph. aureus-coated washers and eight groups with Staph. epidermidis. The biofilm-cultured washers were exposed to low-energy shock waves at 0.16 mJ/mm. 2. for 500 impulses. The washers were then treated with cefuroxime, rifampicin and fosfomycin, both alone and in combination. All tests were carried out in triplicate. Viable cells were counted to determine the bactericidal effect. The control groups of Staph. aureus and Staph. epidermidis revealed a cell count of 6 × 10. 8. colony-forming units/ml. Complete eradication was achieved using the combination of antibiotic therapy (single antibiotic in Staph. aureus, a combination in Staph. epidermidis) and shock wave application (p < 0.01). We conclude that shock waves combined with antibiotics could be tested in an in vitro model of infection

Aims: Nonunion still remains a major complication after skeletal trauma or elective surgery. In the last decade, extracorporeal shock wave therapy has become a common tool for treatment of nonunions and was even referred to as treatment of þrst choice for this condition. But so far, no prospective, randomised trial was conducted to show efþciency of this form of treatment. Methods: This study was performed to determine the value of extracorporeal shock wave therapy for the treatment of nonunions. Previous published results in literature and own clinical results of 73 consecutive patients with nonunions, treated with extracorporeal shock waves, were analysed and confronted with natural history of union. Results: Concordant to literature, union was achieved in more than 55% of treated patients; better results were achieved for hypertrophic type of nonunion (61.8%). Mean time between shock wave therapy and bony consolidation was 5.3 months, ranging from 1 to 16.5 months. Conclusions: No study could prove efþciency of extracorporeal shock wave therapy on bone healing. Clinical studies, reporting acceleration of union after application of shock waves, rather seem to misinterpret natural history of union. No evidence is given for treatment of pseudarthroses with extracor-poreal shock waves. A randomised prospective clinical trial with control group has to be performed to take a þnal decision about this indication for extracorporeal shock wave therapy

Purpose: A study was done to determine the duration of spinal shock in spinal cord injury (SCI)- the first reflex to return while recovering from spinal shock & the factors influencing duration of spinal shock. Method: 116 patients in spinal shock following SCI were included. A detailed neurological examination of sensory, motor and reflex activity was done everyday till the patients were out of spinal shock. The duration of spinal shock by appearance of any reflex, the first reflex to return & the influence of variable factors on duration of spinal shock were studied The mean duration of spinal shock was studied on factors as age, sex, nutritional status (haemoglobin, triceps skin fold thickness, & mid arm circumference), occupation (educated/uneducated, trained/untrained), mode of trauma, duration of injury, skeletal level of injury, neurological level, associated injuries, treatment modality and development of complications during spinal shock. Results: 59 patients (51%) had spinal shock duration of < 1 week; 10 (8.6%) recovered between 1st and 2nd week, 15 (13%) between 2nd and 3rd week & 4 (5%) had recovered after 3 weeks. 28 patients (25%) remained in spinal shock till discharge (6 weeks). In 76 patients (85.4%) anal wink (AW) was the first reflex to return either alone or simultaneous with BC/DPR. In none of the patients BC or DPR appeared before AW. In 7 patients (9%) cremastric reflex was first reflex to return, in 3 pathological reflexes & in 2 deep tendon reflexes (ankle) were the first to return. Conclusion: On statistical analysis mean duration of spinal shock was shorter in children as compared to adults, shorter in malnourished as compared to normal, shorter in untrained as compared to trained, shorter in patients admitted early and shorter in patients who developed complications as compared to those who did not. Mean duration of spinal shock increased progressively down the spine and spinal cord as we move from cervical to thoracic to lumbar region. Mean duration of spinal cord was not influenced by sex of patient, associated injuries to other parts of body and by different modes of treatment

Spasticity is a complex syndrome requiring extensive and complete treatment. Injections of botulinum toxin type A decrease muscle tone in spastic muscles of the hand and improve the use of the upper limb. However, rehabilitation and different non-invasive treatments should also be considered. Shock waves are defined as a sequence of single sonic pulses characterised by high peak pressure (100 MPa), fast pressure rise (< 10 ns) and short duration (10 μs). Twenty patients, with upper limb spasticity post stroke were enrolled in the study. The patients (12 men and eight women) had a mean age of 63 years (36–76 years). An electromagnetic coil lithotriptor (Modulith SLK® by Storz Medical AG) provided with in-line ultrasound, radiographic, and computerised aiming (Lithotrack® system) was used. Flexor muscles of the forearm were treated with 1500 shots, and 3200 shots were used for interosseous muscles of the hand (800 for each muscle). The energy applied was 0.030 mj/mm. The protocol consisted of one placebo treatment session in which no shock waves were applied, followed 1 week later by one active shock wave treatment session. The Ashworth Scale was used to study the muscle tone activity in patients. No changes in the Ashworth score were noted in hand and wrist flexion after placebo stimulation. After real treatment the hand muscles and finger flexion in particular showed a marked reduction in spasticity with a change in the Ashworth scale from 3 to 0. At 1, 4, and 12 weeks, a slight increase in muscle tone was observed for all subjects. Needle EMG was performed at 4 weeks. No denervation was observed. The main finding of this preliminary study is that a single active treatment of shock wave therapy in spastic muscles in a patient affected by stroke resulted in a significant reduction in muscle tone. In contrast, no effect was noted after placebo stimulation. Nitric oxide synthesis has been suggested to be one of the most important mechanisms to explain the effectiveness of shock waves in the treatment of different soft tissue diseases. Shock wave therapy appeared to be safe, non invasive and without complications. Our findings suggest that shock wave therapy may be useful in decreasing flexor tone and functional disability in patients with spasticity of the hand, with a long-lasting effect. This therapy could open a new field of research in the treatment of spasticity. Further studies with a larger group of patients are, therefore, necessary

The definition & etiology of spinal shock remain controversial. Time passed after trauma in initial recovery of any reflex is duration of spinal shock and this duration varies among patients. The factors influencing this duration and its clinical significance are not well studied. 116 patients in spinal shock following SCI were studied for duration of spinal shock with many variables & statistical analysis was done. Mean duration of spinal shock (MD of SS) was shorter in children, shorter in malnourished, shorter in untrained/laborers, shorter in patients admitted early and shorter in patients without any complications. “MD of SS” was not influenced by sex of patient, associated injuries and by different modalities of treatment. On statistical analysis of duration of spinal shock with neurological level as a variable “MD of SS “was 1.7 days in cervical cord lesions, 8.2 days in upper thoracic, 15 days in lower thoracic and 17 days in lumbar cord lesions. Such an arithmetical progression was also found at each segmental level i.e. the duration of spinal shock progressively increased at every segmental level. “MD of SS” was 1.36days at C4, 1.60 at C5, 1.72 at C6, 8.1 at T6, 12.4 at T8, 13.1 at T10, 15.3 at T12 & 21.6 at L2. Higher or proximal the SCI lesion, shorter is the spinal shock duration. Neurological level based segmental progression of spinal shock duration remains unanswered. Does the duration of spinal shock dependant on the cord length/neuronal mass involved/spared?

Aims: A review of the existing literature is presented and compared with the results of a cohort study. These data are compared with the natural course of fracture healing. Methods: In a prospective cohort study 56 patients with nonunions and 14 patients with delayed unions after fracture or osteotomy were treated with shock wave therapy and followed for 2 years or to consolidation. These results and the previous data were assembled and were compared with the results of three studies on the natural course of fracture healing. Results: Consolidation was seen in 56% of patients with nonunions after a mean of 5.2 months, and in 93% of patients with delayed unions. The success rate of shock wave therapy was strongly associated with the time between primary diagnosis and shock wave therapy. Discussion: The success rate in the own cohort was quite similar to the results reported in the literature, after 3 months 52%, 41%, 19%, 40% or 25%, and 41%, 67%, 61% or 38% after 6 months respectively. At 12 months, healing occurred in up to 80%. The fractures were usually immobilised until union was assessed. It is not likely that a single intervention of shock wave therapy causes effects that last for several months. The results were compared with the natural course of fracture healing, also showing a time dependend healing rate. Conclusion: A considerable part of the effect of shock wave therapy may be attributed to the natural course of fracture healing, where healing is seen even after 6 or 12 months. Only a randomised study will be able to show whether shock wave therapy has any effect on fracture healing

Purpose. In patients with multiple trauma delayed fracture healing is often diagnosed, but the pathomechanisms are not well known yet. The purpose of the study is to evaluate the effect of a severe hemorrhagic shock on fracture healing in a murine model. Methods. 10 male C57BL/6N mice per group (Fx, TH, THFx, Sham) and point in time were used. The Fx-group received an osteotomy after implantation of a fixateur extern. The TH-group got a pressure controlled hemorrhagic shock with a mean arterial blood pressure of 35 mmHg over 90 minutes. Resuscitation with 4 times the shed blood volume of Ringer solution was performed. The THFx group got both. Sham-animals received the implantation of a catheter and a fixateur extern but no blood loss or osteotomy. After 1, 2, 3, 4 or 6 weeks the animals were sacrificed. For the biomechanics the bones were analyzed via X-ray, µCT and underwent a 3-point bending test. The nondecalcified histology based on slices of Technovit 9100. The signaling pathway was analyzed via RT. 2. Profiler™ PCR Array Mouse Osteoporosis, Western Blot and Quantikine ELISA for RankL and OPG. Statistical significance was set at p < 0.05. Comparisons between groups were performed using the Mann–Whitney U (Fx vs. THFx) or Kruskal-Wallis Test (other groups). Results. The experiment showed that after 1 week the bones of the Fx- and THFx-mice were macroscopically instable. After 2 weeks the Fx-group showed macroscopically a stable bridging whereas the bones of the THFx-group were partly not stable bridged. 3 weeks after surgery the bones of both groups were stable bridged. Analysis via µCT showed that trauma hemorrhage leads to decreased density of the bone and callus and also to increased share of callus per bone volume after 2 weeks. The 3-point-bending test showed that the maximum bending moment is decreased in the group THFx compared to Fx after 2 weeks. The studies of the histology showed after 2 weeks a decrease in bone and cartilage after trauma-hemorrhage by optical analysis of photographs of the slices. The analyses of the signaling pathway pointed to an involvement of the RankL/Opg and IL6 pathway. Conclusion. A hemorrhagic shock has a negative effect on fracture healing in terms of reduced density of the bone and callus, increased share of callus per bone volume, decreased maximum bending moment, reduced mineralization of the callus and leads to changes in the RankL/Opg and IL6 pathways

Shock wave treatment has been shown to induce new bone formation both under physiologic conditions and during fracture repair. Whereas various underlying molecular working mechanisms have been shown in recent studies, no study has assessed the influence of varying energy flux densities (EFD) on the amount of new bone formation in vivo. Therefore, the aim of this study was to investigate whether the effect of shock waves on bone is dependent on the applied EFD and if so, to identify the minimal dose necessary to induce new bone formation in vivo to avoid unwanted side effects of high-energy shock waves. To this end, 30 New Zealand white rabbits were randomly divided in 5 groups and treated with extracorporeal shock waves at the distal femoral region (1,500 pulses at 1 Hz frequency each):. (a) control (sham treatment),. (b) EFD 0.35 mJ/mm2,. (c) EFD 0.5 mJ/mm2,. (d) EFD 0.9 mJ/mm2 and. (e) EFD 1.2 mJ/mm2. To investigate new bone formation, animals were injected with oxytetracycline at the days 5 to 9 after shock wave application and sacrificed on day 10. Histological sections of treated and untreated femora of all animals were examined using broad-band epifluorescent illumination and contact microradiography. The amount of new periosteal and endosteal bone was measured and signs of periosteal detachment, cortical fractures, and fragmented trabecular bone with callus were recorded. Application of shock waves showed new bone formation beginning with 0.5 mJ/mm2 EFD and increasing with 0.9 mJ/mm2 and 1.2 mJ/mm2. The latter EFD resulted in new bone formation also on the opposite cortical bone and cortical fractures and periosteal detachment occurred. EFD of 0.35 mJ/mm2 did not lead to any new bone formation. Here for the first time a threshold level is presented for new bone formation after applying shock waves to intact bone in vivo. We conclude that the results presented here have significant impact on further clinical applications of shock waves on bone tissue. In the present study, it is clearly demonstrated that the amount of new bone formation is directly dependent on the applied EFD. If the applied EFD is to low, no significant new bone formation will occur. If it is too high, unwanted side effects, like the formation of bone spurs in the shoulder or nerve entrapment syndromes in the elbow or feet by bony overgrowth may result

Aims. Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells. Methods. Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm. 2. , 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)’ viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene (Scx, TNC) expression were investigated using coculture system. Results. ESW-treated ACL remnant cells presented higher cell viability, proliferation, migration, and increased expression of COL-I A1, TGF-β, and VEGF. BMSC proliferation and migration rate significantly increased after coculture with ACL remnant cells with and without ESW stimulation compared to the BMSCs alone group. Furthermore, ESW significantly enhanced ACL remnant cells’ capability to upregulate the collagen gene expression and tenogenic differentiation of BMSCs, without affecting cell viability, TGF-β, and VEGF expression. Conclusion. ACL remnant cells modulated activity and differentiation of surrounding cells. The results indicated that ESW enhanced ACL remnant cells viability, proliferation, migration, and expression of collagen, TGF-β, VEGF, and paracrine regulation of BMSC proliferation, migration, collagen expression, and tenogenesis. Cite this article: Bone Joint Res 2020;9(8):457–467

Introduction: Extracorporeal shock wave therapy (ESWT) covers a multitude of different indications in modern orthopedics, however, bacterial infections are still considered as contraindications. The goal of the present study was to determine the effect of ESWT on growth of clinically relevant bacteria in orthopedic and trauma surgery. Methods: Standardised suspensions of a methicillin sensitive and a methicillin resistant strain of Staphylococcus aureus, and reference strains of Staphylococcus epidermidis, Pseudomonas aeruginosa and Enterococ-cus faecalis were subjected to 4000 impulses of high-energy shock waves with an energy flux density (EFD) of 0.96 mJ/mm2 and a frequency of 2 Hz. Furthermore, corresponding suspensions of S. aureus ATCC 25923 were exposed to different impulse rates of shock waves (1000 to 6000 impulses) and to different EFDs up to a maximum of 0.96 mJ/mm2 (2 Hz) to evaluate the influence of shock wave parameters. Subsequently, viable bacteria were quantified by culture and compared with an untreated control. Results: A highly significant antibacterial effect of the ESWT was demonstrated for all bacterial strains with a reduction of growth to values between 1,1% and 29,7% (P < 0.01). Reference strains of S. aureus and S. epidermidis reacted most sensitive whereas E. faecium demonstrated highest resistance against high-energy shock waves. After applying different energy levels to S. aureus, a significant bactericidal effect was observed only with a minimum threshold EFD of 0.59 mJ/mm2 (P < 0.05). A threshold impulse rate of more than 1000 impulses could be defined to reduce bacterial growth of S. aureus (P < 0.05). Further elevation of energy and impulse rate exponentially increased bacterial killing. Conclusions: ESWT proved to exert significant antibacterial effect in an energy-dependent manner. The results suggest that infections are not necessarily contraindications to shock wave therapy and could even represent a new indication for ESWT. However, clinical relevance should be assessed in vivo in an animal model

Excessive apoptosis has been found in torn supraspinatus tendon1 and mechanically loaded tendon cells2. Following oxidative and other forms of stress, one family of proteins that is often unregulated are Heat Shock Proteins (HSPs). The purpose of this study was to determine if HSPs were unregulated in human and rat models of tendinopathy and to determine if this was associated with increased expression of regulators of apoptosis (cFLIP, Caspases 3& 8). A running rat supraspinatus tendinopathy overuse model 3 was used with custom microarrays consisting of 5760 rat oligonucleotides in duplicate. Seventeen torn supraspinatus tendon and matched intact subscapularis tendon samples were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from ten patients undergoing arthroscopic stabilisation surgery and evaluated using semiquantative RT-PCR and immunohistochemistry. Rat Microarray: Upregulation of HSP 27 (×3.4) & 70 (×2.5) and cFLIP (×2.2) receptor was noted in degenerative rat supraspinatus tendon subjected to daily treadmill running for 14 days compared to tendons of animals subject to cage activity only. Histological analysis: All torn human supraspinatus tendons exhibited changes consistent with marked tendinopathy. Matched subscapularis tendon showed appearances of moderate-advanced degenerative change. Apoptosis mRNA expression: The expression levels of caspase 3 & 8 and HSPs 27 & 70 were significantly higher in the torn edges of supraspinatus when compared to matched subscapularis tendon and control tendon (p< 0.01). cFLIP showed significantly greater (p< 0.001) expression in matched subscapularis compared to supraspinatus and control tendon. Immunohistochemical analysis: cFLIP, Caspase 3 & 8 and HSP 27 and 70 was confirmed in all samples of torn supraspinatus tendon. Significantly increased immunoactivity of Caspase 3& 8 and HSP 27 & 70 were found in torn supraspinatus (p< 0.001) compared to matched and normal subscapularis. The proteins were localized to tendon cells. The finding of significantly increased levels of Heat Shock Proteins in human and rat models of tendinopathy with the co-expression of other regulators of apoptosis suggests that Heat Shock Proteins play a role in the cascade of stress activated-programmed cell death and degeneration in tendinopathy

The effects of extracorporeal shock waves (ESWT) on tendon healing were assessed by observing histological and biomechanical parameters in a rat model of injury to the tendo Achillis. The injury was created by inserting an 18-G needle through tendo Achillis in 48 adult Wistar albino rats. The animals were divided into three groups. The first group received radiation only after the operation. The second received no shock waves and the third had 500 15 KV shocks on the second post-operative day. All the rats were killed on the 21st day after surgery. Histopathological analysis showed an increase in the number of capillaries and less formation of adhesions in the study group compared with the control group (p = 0.03). A significantly greater force was required to rupture the tendon in the study group (p = 0.028). Our findings suggest a basis for clinical trials using ESWT

Purpose of the study. We report septic shock as postoperative complication following an instrumented posterior spinal arthrodesis on a patient with multiple body piercings. The management of this potentially catastrophic complication and outcome of treatment is been discussed. Summary of Background Data. Body piercing has become increasingly more common due to change in culture or as a fashion statement. This has been associated with local or generalized ill effects including tissue injury, skin and systemic infections, and septic shock. There is no clear guideline pathway regarding removal and reinsertion of body piercings in patients who undergo major surgery. Complications following Orthopaedic or Spinal procedures associated with body piercing have not been reported. Methods. We reviewed the medical notes and radiographs of an adolescent patient with severe Scheuermann's kyphosis and multiple body piercings who underwent an uneventful posterior spinal arthrodesis with pedicle hook/screw/rod instrumentation and autologous iliac crest bone graft and developed septic shock. Results. Septic shock developed on postoperative day 2 after reinsertion of all piercings following patient's request. The patient became systemically very unwell and required intensive medical management, as well as a total course of antibiotics of 3 months. The piercings remained in situ. She did not develop a wound infection despite the presence of bacteraemia (coagulase-negative Staphylococci/Streptococci warneri) and spinal instrumentation. The patient had no new piercings subsequent to her deformity procedure. Two and a half years after spinal surgery she reported no medical problems, had a balanced spine with no loss of kyphosis correction and no evidence of nonunion or recurrence of deformity. Conclusion. The development of septic shock as a result of piercing reinsertion in the postoperative period has not been previously reported. This is an important consideration to prevent potentially life-threatening complications following major spinal surgery. Despite the wide array of complications associated to body art there are no clear guidelines for body piercing. There is growing public awareness and several countries are laying regulations which have not yet been internationally standardized. A clear practice guideline in the perioperative management of piercings is needed as the incidence of body piercing and associated complications is rising. There is need for surgeons to be aware of the hazards of body piercing and its implications. We propose that multiple piercings should not be reinserted after major surgery and appropriate counseling should be provided to the patients as part of the consent process

The osteoclastogenesis is regulated by a complex signaling system between the pro-apoptotic factors (Bax-Cyclin E2-Cdk2) and the tumor necrosis factor family (RANKL-RANK-OPG). Extracorporeal Shock Waves Therapy (ESWT) have recently been used in orthopaedic treatments to induce bone repair, but their mechanisms of action are not sufficiently investigated. So we studied the effect of shock-waves on murine osteoblastic cells. Osteoblast cultures were subjected to a single shock-wave with combinations of low energy intensities (0.05mJ/mm2) and 500 number of shocks (impulses), whereas control cells received no treatment. We valued the cell viability quantifying the expressions of Bax and Opg by PCR. We found an immediate negative effect on cell viability, that occurs with an increase of Bax protein expression after 3 hours of treatment. After a longer time lapse a stimulatory effect on cell proliferation, as reflected by the increase of a G(1)-S phase marker, was observed. In fact, in the following 24, 48 and 72 hours after ESW treatment, we found a stronger association of Cyclin E2 and Cdk2, forming active cyclin E-Cdk2 kinase, compared to untreated cells at the same times. We further explored the molecular mechanism for the ESW induction of osteogenesis: by Real Time PCR an enhancement of Runx2 mRNA, evident 48 hours after the treatment, was found. A link between physical ESW and Runx2 activation has been already demonstrated. ESW-induced. O2- production, followed by tyrosine kinase mediated ERK activation and Runx2 activation, resulted in osteogenic cell growth and maturation. Moreover, we analyzed the cytokines RANK-L and OPG osteoblast expression, involved in regulation of osteoclastogenesis. A decrease in RANK-L/OPG ratio was found, perhaps leading to a reduced osteoclastogenesis. The Shock waves have a repair action on bone and it can been explained by the regulation on osteoclastogenesis by the apoptoic pathway of BAX and OPG

Aims: Extracorporeal Shock Waves Therapy (ESWT) has recently been used in orthopaedic treatments to induce bone repair, but their mechanisms of action are not sufficiently investigated. So we studied the effect of shockwaves on murine osteoblastic cells. Methods: Osteoblast cultures were subjected to a single shockwave with combinations of low energy intensities (0,05mJ/mm2) and 500 number of shocks (impulses), whereas control cells received no treatment. Cell division and apoptosis are interconnected and regulated by cyclins, kinases, Bax and Opg. We valued the cell viability quantifying by PCR the expressions of these molecules which regulate cell-cycle. Results: We found an immediate negative effect on cell viability, that occurs with an increase of Bax protein expression after 3 hours of treatment. After a longer time lapse a stimulatory effect on cell proliferation, as reflected by the increase of a G(1)-S phase marker, was observed. In fact, in the following 24, 48 and 72 hours after ESW treatment, we found a stronger association of Cyclin E2 and Cdk2, forming active cyclin E-Cdk2 kinase, compared to untreated cells at the same times. We further explored the molecular mechanism for the ESW induction of osteogenesis: by Real Time PCR an enhancement of Runx2 mRNA, evident 48 hours after the treatment, was found. A link between physical ESW and Runx2 activation has been already demonstrated. ESW-induced O2- production, followed by tyrosine kinase mediated ERK activation and Runx2 activation, resulted in osteogenic cell growth and maturation. Moreover, we analyzed the cytokines RANK-L and OPG osteoblast expression, involved in regulation of osteoclastogenesis. A decrease in RANK-L /OPG ratio was found, perhaps leading to a reduced osteoclastogenesis. Conclusions: The Shock waves have a repair action on bone and it can been explained by the regulation on osteoclastogenesis by the apoptoic pathway of Bax and Opg

The aim of the study was to evaluate changes in clinical results after extracorporeal shock wave therapy (ESWT) on calcified lesions of the shoulder. 963 patients with calcifying tendinitis were treated with high energy shock waves. The mean energy flux density was 0. 28 mJ/mm2. To evaluate the effect we used the visual analogue scale (VAS) and the Roles-Maudsley-score to analyse the effect on activity of daily living, and pain perception. ESWT was indicated after non operative treatment failed. At 12 months after ESWT, 73. 6% of patients reported excellent and good results, 26% scored satisfactory and poor, using the Roles-Maudsley-Score. The positive effect of the ESWT on pain perception after 12 months was statistically significant (p< 0. 001). The difference between pain perception before and after ESWT persisted in the follow up interval. No decrease was shown after 2 years. In all cases no severe side effects were observed except small petechial haemorrhages. High energy shock wave therapy is indicated to treat calcifying tendinitis which is resistant to any other non-operative treatment. The decrease in pain perception persists over a period of more than two years. Absence of side effects and its effectiveness suggest that ESWT is indicated prior to surgical intervention

A substantial body of evidence supports the use of extracorporeal shock wave therapy (ESWT) for fracture non-unions in human medicine. However, the success rate (i.e., radiographic union at six months after ESWT) is only approximately 75%. Detailed knowledge regarding the underlying mechanisms that induce bio-calcification after ESWT is limited. The aim of the present study was to analyse the biological response within mineralized tissue of a new invertebrate model organism, the zebra mussel Dreissena polymorpha, after exposure with extracorporeal shock waves (ESWs). Mussels were exposed to ESWs with positive energy density of 0.4 mJ/mm. 2. or were sham exposed. Detection of newly calcified tissue was performed by concomitantly exposing the mussels to fluorescent markers. Two weeks later, the fluorescence signal intensity of the valves was measured. Mussels exposed to ESWs showed a statistically significantly higher mean fluorescence signal intensity within the shell zone than mussels that were sham exposed. Additional acoustic measurements revealed that the increased mean fluorescence signal intensity within the shell of those mussels that were exposed to ESWs was independent of the size and position of the focal point of the ESWs. These data demonstrate that induction of bio-calcification after ESWT may not be restricted to the region of direct energy transfer of ESWs into calcified tissue. The results of the present study are of relevance for better understanding of the molecular and cellular mechanisms that induce formation of new mineralized tissue after ESWT. Specifically, bio-calcification following ESWT may extend beyond the direct area of treatment

Study Design: The effects of heat on porcine intertvertebral disc were studied experimentally. Objective: To assess the effects of in-vitro heating of porcine nucleus pulposus on expression of inducible heat shock protein 70 and subsequent modification of biochemical responses to an inflammatory insult in the heated intervertebral disc tissue. Subjects: Lumbar spines were harvested from six pigs. The nucleus pulposus was dissected from each intervertebral disc, divided into control (37°C) and heat shocked (42°C) groups then cultured in medium for one hour. All samples were then cultured at 37 C for a further two hours. After three hours tissue and supernatant were harvested from one third of the samples and the expression of inducible heat shock protein 70 (HSP70) was quantified via Western immunoblotting and enzyme linked immuno-sorbent assay (ELISA). The remaining samples were cultured either in normal medium or altered (pro-inflammatory) medium containing 5ug/ml bacterial lipopolysaccharide (LPS). At 24 hours the supernatant from these samples was analysed for both interleukin-8 (IL-8) and prostaglandin E2 (PGE2) secretion using ELISA. Outcome Measures: Western immunoblotting and enzyme linked immuno-sorbent assay (ELISA) for heat shock protein 70. ELISA for interleukin-8 (IL-8) and prostaglandin E2 (PGE2). Results: HSP70 expression was significantly increased in the heat shocked specimens. IL-8 and PGE2 secretion were significantly increased in nucleus pulposus exposed to LPS at both temperatures. The concentrations of IL-8 and PGE2 secreted in the heat shocked samples were significantly less than controls, particularly after exposure to LPS (p< 0.05, paired students t test). Conclusions: In vitro heating of porcine nucleus pulposus causes overexpression of HSP70. This heat shock effect can alter aspects of the biochemical response of the intervertebral disc tissue to an inflammatory insult. Intradiscal electrothermal therapy (IDET) may, in theory, reduce discogenic pain at temperatures as low as 42°C by generating similar heat-induced changes in the nuclear biochemistry of degenerate intervertebral discs

Introduction. The pathophysiology of osteonecrosis of femoral head (ONFH) is uncertain for most cases with speculation of vascular impairment and changes in cell biology due to multi-factorial etiologies including corticosteroid, alcohol, smoking, trauma, radiation or caisson disease and genetic. Extracorporeal shockwave therapy (ESWT) began with an incidental observation of osteoblastic response pattern during animal studies in the mid-1980 that generated an interest in the application of ESWT to musculoskeletal disorders. The mechanism of shockwave therapy is not fully understood but several reports showed better clinical outcomes and promoted bone remodelling and regeneration effect of the femoral head after ESWT in ONFH. Therefore, we compared the clinical results of the use of extracorporeal shock wave therapy (ESWT) on the patients with ONFH in radiographic staging. Methods. We evaluated 24 patients with 32 hip joints diagnosed ONFH treated with ESWT from 1993 to 2012. Average follow-up period was 27 months, and patients were average 47.8 aged. Association Research Circulation Osseous (ARCO) staging system was used to grade radiographic stage before treatment. All the patients were divided to two groups; group 1 (ARCO stage I,II), group 2 (ARCO stage III). Comparative analysis was done between two groups with visual analogue scale (VAS) score and Harris hip score (HHS) at pre-treatment, 3, 6, 12 and 24 months after treatments. The failure was defined when radiographic stage was progressed or arthroplasty surgery was needed due to clinical exacerbation. Results. Two groups showed all clinical improvements with VAS scoring at final follow-up (group 1: mean 6.3 to 1.6, p < 0.001; group 2: mean 7.1 to 3.3, p < 0.001). With HHS, group 1 showed a significant improvement from 64.4 to 95.4 (p < 0.001), while no significance in group 2 (p = 0.280). At final-follow-up, 3 hips of group 1 and 1 hip of group 2 showed radiographic improvement, but 2 patients were performed total hip arthroplasty due to persistent pain and dysfunction. Discussion and Conclusion. ESWT could be considered as an alternative option before surgical treatment in patients not only with early stage of ONFH but also with mid stage