***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Several r and omised trials have been published on the effect of low-intensity pulsed ultrasound ( LIPUS ) on fracture healing in both distal radius and tibia fractures . Most studies showed a positive effect on time to clinical and radiological healing . We hypothesised that LIPUS has a beneficial effect on the healing of fresh clavicle fractures as well and studied its effect in non-operatively treated shaft fractures . METHODS We conducted a r and omised double blind , placebo-controlled  multi-centre trial in 101 adult patients with a non-operatively treated fresh clavicle shaft fracture . Of these patients , 49 used a placebo transducer and 52 patients had an active transducer with ultrasound stimulation ( Exogen 2000 ) . Data were analysed on intention to treat basis . Baseline parameters of both groups were not significantly different . RESULTS There were no differences in time to subjective clinical fracture healing , resumption of daily activities , sports or professional work , Visual Analogue pain Scores ( VAS ) and use of pain medication . CONCLUSION Our findings did not confirm that LIPUS accelerates clinical healing time of fresh clavicle shaft fractures . LEVEL OF EVIDENCE Level 1 evidence that low-intensity pulsed ultrasound does not accelerate clinical fracture healing in non-operatively treated fresh midshaft clavicle fractures INTRODUCTION Osteogenic cell proliferation and differentiation play an important role in adequate fracture healing , and is target for osteoinductive therapies in delayed fracture healing . The aim of this study was to investigate whether low-intensity pulsed ultrasound enhances fracture healing at the tissue level in patients with a delayed union of the osteotomized fibula through an effect on the presence of RUNX2 immunopositive osteogenic cells . The effect was studied in both atrophic and hypertrophic delayed unions . MATERIAL S AND METHODS Biopsies were obtained from 6 female and 1 male patient ( age 43 - 63 ) with a delayed union of the osteotomized fibula after a high tibial osteotomy treated for 2 - 4 months with or without low-intensity pulsed ultrasound in a r and omized prospect i ve double-blind placebo-controlled trial . Immunolocalization of RUNX2 protein was performed to identify osteogenic cells . Histomorphometrical analysis was performed to determine the number of cells expressing RUNX2 located within and around the newly formed woven bone at the fracture end ( area of new bone formation ) , and up to 3 mm distant from the fracture end . RESULTS Cells expressing RUNX2 were present in all histological sections of control and low-intensity pulsed ultrasound-treated bone evaluated . Within the area of new bone formation , RUNX2 immunopositive cells were found in the undifferentiated soft connective tissue , at the bone surface ( presumably osteoblasts ) , and within the newly formed woven bone . Low-intensity pulsed ultrasound treatment of fibula delayed unions significantly reduced the number of RUNX2 immunopositive cells within the soft connective tissue at the fracture ends , whereas the number of RUNX2 immunopositive cells at the bone surface was not affected . The number of RUNX2 immunopositive cells was similar for the atrophic and hypertrophic delayed unions . CONCLUSIONS Immunolocalization of RUNX2 positive cells in delayed unions of the fibula reveals that delayed clinical fracture healing does not result in impairment of osteogenic cell proliferation and /or differentiation at the tissue level , even if delayed unions are clinical ly regarded as atrophic . Reduced number of osteogenic RUNX2 immunopositive cells within the soft connective tissue , and unchanged number of RUNX2 immunopositive cells at the bone surface , implicate that low-intensity pulsed ultrasound does not increase osteogenic cell presence , but likely affects osteogenic cell differentiation Background The role of low-intensity pulsed ultrasound ( LIPUS ) in the management of fractures remains controversial . The purpose of this study was to assess the feasibility of a definitive trial to determine the effect of LIPUS on functional and clinical outcomes in tibial fractures managed operatively . Methods We conducted a multicenter , concealed , blinded r and omized trial of 51 skeletally mature adults with operatively managed tibial fractures who were treated with either LIPUS or a sham device . All participating centers were located in Canada and site investigators were orthopedic surgeons specializing in trauma surgery . The goals of our pilot study were to determine recruitment rates in individual centers , investigators ’ ability to adhere to study protocol and data collection procedures , our ability to achieve close to 100 % follow-up rates , and the degree to which patients were compliant with treatment . Patients were followed for one year and a committee ( blinded to allocation ) adjudicated all outcomes . The committee adjudicators were experienced ( 10 or more years in practice ) orthopedic surgeons with formal research training , specializing in trauma surgery . Results Our overall rate of recruitment was approximately 0.8 patients per center per month and site investigators successfully adhered to the study protocol and procedures . Our rate of follow-up at one year was 84 % . Patient compliance , measured by an internal timer in the study devices , revealed that 39 ( 76 % ) of the patients were fully compliant and 12 ( 24 % ) demonstrated a greater than 50 % compliance . Based on patient feedback regarding excessive question naire burden , we conducted an analysis using data from another tibial fracture trial that revealed the Short Musculoskeletal Function Assessment ( SMFA ) dysfunction index offered no important advantages over the SF-36 Physical Component Summary ( PCS ) score . No device-related adverse events were reported . Conclusions Our pilot study identified key issues that might have rendered a definitive trial unfeasible . By modifying our protocol to address these challenges we have enhanced the feasibility of a definitive trial to explore the effect of LIPUS on tibial fracture healing . Trial registration The TRUST definitive trial was registered at Clinical Trials.gov on 21 April 2008 ( identifier : NCT00667849 ) OBJECTIVE To determine whether stimulation with low-intensity ultrasound will reduce the radiologic healing time of fresh tibial shaft fractures fixed with a reamed and statically locked intramedullary rod . DESIGN Prospect i ve , r and omized , double blinded , and placebo controlled . PATIENTS AND METHODS Thirty-two adult patients were included , fifteen in the active ultrasound group and seventeen in the placebo group . They all used an ultrasound device twenty minutes daily for seventy-five days without knowing whether it was active or inactive . St and ardized radiographs were taken every third week until healing and at six and twelve months . All radiographs were assessed blinded and independently by a radiologist and an orthopaedic surgeon . The codes were not broken until all fractures had healed and all radiographs had been evaluated . RESULTS The time until the first visible callus averaged 40+/-3 days for the active group and 37+/-3 days for the placebo ( p=0.44 ) . The healing time , defined as radiologic bridging of three cortices , was on average 155+/-22 days ( median 113 days ) for the active treatment group and 125+/-11 days ( median 112 days ) for the placebo group ( p=0.76 ) as assessed by the radiologist and 128+/-13 days for the active group and 114+/-9 days for the placebo group ( p=0.40 ) as evaluated by the orthopaedic surgeon . CONCLUSION We conclude that low-intensity ultrasound treatment did not shorten healing time in fresh tibial fractures treated with a reamed and statically locked intramedullary nail . Our results are not in accordance with previous findings reporting reduced healing time in nonoperatively treated tibial shaft fractures when subjected to ultrasound The use of pedicled vascularised bone grafts from the distal radius makes it possible to transfer bone with a preserved circulation and viable osteoclasts and osteoblasts . Experiments performed at the basic science level has provided substantial evidence that low-intensity ultrasound can accelerate and augment the fracture healing process . Only an adequate double-blind trial comparing treatment by ultrasound stimulation in patients treated by similar surgical techniques can provide evidence of the true effect of ultrasound . This paper describes the results of such a trial . From 1999 to 2004 , 21 fractures of the scaphoid with established non-union treated with vascularised pedicle bone graft were selected for inclusion in a double-blind trial . All patients were males , with an average age of 26.7 years ( range 17–42 years ) and an average interval between injury and surgery of 38.4 months ( range 3 months–10 years ) .  Low-intensity ultrasound was delivered using a TheraMed 101-B bone-growth stimulator ( 30 mW/cm2 , 20 min/day ) , which was modified to accomplish double-blinding . These modifications did not affect the design ated active units . The placebo units were adjusted to give no ultrasound signal output across the transducer . Externally , all units appeared identical but were marked with individual code numbers . Patients were r and omly allocated to either an active or placebo stimulation . Follow-up averaged 2.3 years ( range 1–4 years ) . All patients achieved fracture union ( active and placebo groups ) , but compared with the placebo device ( 11 patients ) , the active device ( ten patients ) accelerated healing by 38 days ( 56±3.2 days compared with 94±4.8 days , p<0.0001 , analysis of variance).RésuméL’utilisation de greffes pediculées de l’extrémité distale du radius est possible . Elles peuvent être utilisées comme transferts osseux pourvu que l’on préserve la vascularisation garant d’une bonne circulation avec des osteoclastes et osteoblates bienvivants . De nombreuses expérimentations ont également montré que l’utilisation d’ultrasons de basse intensité peut accélérer et augmenter le processus de consolidation osseuse . Seule une étude en double aveugle stimulant l’ostéogènèse par ultrasons sur des patients opérés avec des techniques identiques peut mettre en évidence le véritable effet de ceux-ci . Le but decetravail est de décrire les résultats d’un tel essai . Entre 1999 et 2004 21 fractures du scaphoide avec pseudarthrose ont été traitées par une greffe pédiculée et sélectionnée pour cet essai en double aveugle . Tous les patients étaient de sexe masculin , l’âge moyen était de 26 ans ( 17 à 42 ans ) et le temps moyen entre le traumatisme et l’intervention chirurgicale a été de 38,4 mois ( 3 mois à 10 ans ) . Des  ultrasons de basse intensité ont été utilisés avec un stimulateur de type TheraMed 101-B ( 30 mW/cm2 , 20 minutes par jour ) en double aveugle . Un appareil de type placébo a été également utilisé . L’apparence externe des deux appareils était absolument identique . Les patients ont été r and omisés entre ceux recevant la stimulation placébo et ceux recevant une stimulation active d’ultrason . Après un suivi moyen de 2,3 ans ( de 1 à 4 ans ) , tous les patients ont consolidé , aussi bien dans la série avec ultrasons que dans la série placébo . Si l’on compare la série avec appareil de type placébo ( 11 patients ) à la série utilisant un appareil délivrant des ultrasons ( 10 patients ) , la guérison a été plus rapide dans cette dernière série de 38 jours ( 56±3,2 jours , versus 94±4,8 jours ; p<0.0001 en analyse devariance ) Since pulsed low-intensity ultrasound ( frequency : 1.5 MHz , pulsed by 1 kHz , signal burst width : 200 microseconds , intensity : 30 mW/cm2 ) has been proven to stimulate fracture healing both clinical ly and experimentally , our question was whether this therapy also accelerates healing of fresh stable scaphoid fractures . Addressing this question , we did the following prospect i ve r and omized clinical trial . Regarding the results of former clinical fresh fracture studies by Heckman and Kristiansen , we postulated that low intensity ultrasound accelerates healing by about 30 % . Based on this thesis , we calculated that 30 patients divided into two groups would be necessary to show significant differences between the st and ard treatment ( treated by casting ) and an adjunctive ultrasound treatment ( treated by casting and additional daily 20 minutes ultrasound treatment ) if present . Diagnosis and healing was assessed by CT scans every two weeks . CT 's were analyzed by two independent radiologists and one h and surgeon . Furthermore , areas of cancellous bone bridging in correlation to the diameter of the scaphoid was measured in each CT scan . The results showed  ultrasounded fractures healing in 43.2 + /- 10.9 days versus 62 + /- 19.2 days in the control group ( p < 0.01 ) . Trabecular bridging six weeks after injury showed 81.2 % + /- 10.4 % healed in the ultrasound-stimulated fractures versus 54.6 % + /- 29 % in the control ( p < 0.05 ) . Our study results confirm those of Heckman and Krist 
    Output:
    
Time to radiographic fracture union was the most common primary outcome measure evaluated .
The most reduction in time to radiographic union by LIPUS treatment was seen in fractures with a long natural healing tendency .
LIPUS treatment effectively reduces the time to radiographic fracture union , but this does not directly result in a beneficial effect of accelerated functional recovery or the prevention of delayed union or nonunion .
The increase in bone formation as a result of LIPUS treatment may provide a valuable tool in fracture repair , but it does not always lead to healing .