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Ultrasound and shockwave therapy for acute fractures in adults

  1. Xavier L Griffin1,*,
  2. Nick Parsons1,
  3. Matthew L Costa2,
  4. David Metcalfe1

Editorial Group: Cochrane Bone, Joint and Muscle Trauma Group

Published Online: 23 JUN 2014

Assessed as up-to-date: 2 JUN 2014

DOI: 10.1002/14651858.CD008579.pub3


How to Cite

Griffin XL, Parsons N, Costa ML, Metcalfe D. Ultrasound and shockwave therapy for acute fractures in adults. Cochrane Database of Systematic Reviews 2014, Issue 6. Art. No.: CD008579. DOI: 10.1002/14651858.CD008579.pub3.

Author Information

  1. 1

    University of Warwick, Warwick Orthopaedics, Warwick Medical School, Coventry, UK

  2. 2

    University of Warwick, Warwick Clinical Trials Unit, Coventry, Warwickshire, UK

*Xavier L Griffin, Warwick Orthopaedics, Warwick Medical School, University of Warwick, Clinical Sciences Building, Clifford Bridge Road, Coventry, CV2 2DX, UK. xavier.griffin@warwick.ac.uk. xgriffin@mac.com.

Publication History

  1. Publication Status: Edited (no change to conclusions), comment added to review
  2. Published Online: 23 JUN 2014

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Characteristics of included studies [ordered by study ID]
Emami 1999

MethodsRandomised, placebo-controlled study.


ParticipantsSetting: Uppsala University Hospital, Sweden.

Size: 30 participants in total, with 15 in each arm.

Baseline characteristics: mean (range) age 39 years (19 to 73), 21 males and 9 females.

Inclusion criteria: patients aged over 16 years with a closed or Gustillo and Anderson grade I open fracture of the tibial diaphysis treated with closed reduction and fixation with a reamed, intra-medullary, locked nail.

Exclusion criteria: history of alcohol or drug dependency; current steroid, anticoagulant, NSAID or bisphosphonate use; past medical history of neuropathy, arthritis, malignant disease; radiographs that showed severe comminution or open physes.


InterventionsParticipants underwent closed reduction and reamed, intramedullary nailing of the fracture. Surgery was performed by one of six experienced trauma surgeons. The fracture site was marked with a permanent skin marker.
Test: ultrasound treatment was started within three days of fixation and was continued for 75 days. The treatment consisted of one 20-minute period daily with a maximum exposure of 25 hours. The transducer head was coupled to the skin with a standard gel. The ultrasound signal was composed of a 200 µs burst of 1.5 MHz sine waves, with a repetition rate of 1 kHz and a spatial average intensity of 30 mW/cm².

Control: sham ultrasound treatment was started within three days of fixation and was continued for 75 days. The treatment consisted of one 20-minute period daily with a maximum exposure of 25 hours. The sham device was a deactivated, identical model to that provided to the test group.


OutcomesFollow-up schedule: every third week until union. Additional follow-up at 26 and 52 weeks irrespective of union status.

Primary: time to radiographic union.

Secondary: time to first radiographic evidence of callus, proportion of fractures united at six months, adverse events.


NotesOutcomes were assessed by a single-blinded radiologist and an orthopaedic surgeon independently, but were not pooled. The data used in this review are derived from the single independent radiologist.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "The study was ... randomized"

Comment: No specific report of how the sequence was generated.

Allocation concealment (selection bias)Unclear riskThe allocation method was not reported.

Blinding (performance bias and detection bias)
Objective measures
Low riskQuotes: "The codes were not broken for any device until the radiographic reviews for all patients had been completed."

"...devices were identical in every way..."

Comment: All measures were adequately blinded.

Incomplete outcome data (attrition bias)
Objective measures
Unclear riskQuote: "In one patient, it became obvious during the course of the study that he did not fulfil the inclusion/exclusion criteria."

Comment: No data were reported for this single participant and he was excluded from the analysis.

Selective reporting (reporting bias)Unclear riskNo protocol available.

Other biasLow riskNo other bias detected.

Selection bias (imbalance in baseline characteristics)Low riskBaseline data for age, sex and smoking status are reported and show a balanced distribution of these confounders between groups.

Handolin 2005

MethodsRandomised, placebo-controlled study.


ParticipantsSetting: Helsinki University Central Hospital, Finland.

Size: 30 patients in total, 15 in each arm.

Baseline characteristics: mean age 41.4 years (5 male/10 female) in intervention group and 39.4 years (8 male/7 female) in the control group.

Inclusion criteria: patients aged between 18 and 65 years with displaced Weber B fractures of the lateral malleolus.

Exclusion criteria: widening of the distal tibiofibular joint; open fracture; inability to co-operate with the requirements of the trial.


InterventionsParticipants underwent open reduction and internal fixation with a 4.5 mm self-reinforced poly-L-lactic acid screw. Surgery was carried out by one of two surgeons. The fracture was approached through a lateral incision. Post-operatively the ankle was immobilised for six weeks with a removable Soft Cast brace. Partial weight bearing was allowed at two weeks and full weight bearing at four weeks.

Test: participants self-administered daily ultrasound treatment for 20 minutes from the 3rd to 9th post-operative weeks directly over the fracture marked with an intraoperatively placed marker. Appropriate contact between the probe and the skin was maintained with standard ultrasound coupling gel. The ultrasound signal was composed of a 200 µs burst of 1.5 MHz sine waves, with a repetition rate of 1 kHz and a spatial average intensity of 30 mW/cm².

Control: participants in the control group were given a similar treatment regimen but had an externally similar sham machine instead.


OutcomesFollow-up schedule was at 2, 6, 9 and 12 weeks and, in a separate publication, 18 months.

At 18 months, the clinical outcome was assessed using the Olerud-Molander scoring as well as clinical examination; this was reported in a separate article for 16 (8 versus 8) participants.

Plain radiographic assessment at 2, 6, 9 and 12 weeks and at 18 months. Multi detector computed tomography (MDCT) at 18 months and dual-energy X-ray absorptiometry (DEXA) scan post operatively and at 18 months.


NotesBased on overlapping, but not matching, dates of recruitment we have assumed that a publication (Handolin 2005b) reporting 18 month results for 16 participants is a long-term follow-up of this trial. These reports share a common methodology and reporting framework. Efforts to contact the authors were unsuccessful.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "...prospective, randomised ... study."

Comment: The method of sequence generation is not reported.

Allocation concealment (selection bias)Unclear riskThe method of allocation concealment is not reported

Blinding (performance bias and detection bias)
Objective measures
Low riskQuote: " double blind; half of the devices were active ... half were sham."

Comment: Likely to be the same device but placebo devices were deactivated.

Incomplete outcome data (attrition bias)
Objective measures
High riskAll outcome data reported up to 12 weeks, but data from only 16 participants reported at 18 months

Selective reporting (reporting bias)Unclear riskNo protocol available

Other biasUnclear riskIt is not reported how the radiographic outcomes were assessed

Selection bias (imbalance in baseline characteristics)Unclear riskAge and sex similarly distributed, but smoking status not reported

Handolin 2005a

MethodsRandomised, placebo-controlled study


ParticipantsSetting: Helsinki Unversity Central Hospital, Finland.

Size: 22 patients, 11 in each arm.

Baseline characteristics: mean (range) age 37.5 years (18 to 54), 9 males and 2 females in intervention group. Mean (range) age 45.5 years (26 to 59), 6 males and 5 females in the control group.

Inclusion criteria: patients aged between 18 and 65 years with displaced Weber B fractures of the lateral malleolus.

Exclusion criteria: widening of the distal tibiofibular joint; open fracture; inability to co-operate with the requirements of the trial.


InterventionsParticipants underwent open reduction and internal fixation with a 4.5 mm self-reinforced poly-L-lactic acid screw. Surgery was carried out by one of two surgeons. The fracture was approached through a lateral incision. Post-operatively the ankle was immobilised for six weeks with a removable Soft Cast brace. Partial weight bearing was allowed at two weeks and full weight bearing at four weeks.

Test: participants self-administered daily ultrasound treatment for 20 minutes from the third to ninth post-operative weeks directly over the fracture marked with an intra-operatively placed marker. Appropriate contact between the probe and the skin was maintained with standard ultrasound coupling gel. The ultrasound signal was composed of a 200 µs burst of 1.5 MHz sine waves, with a repetition rate of 1 kHz and a spatial average intensity of 30 mW/cm².

Control: participants in the control group were given a similar treatment regimen but had an externally similar sham machine instead.


OutcomesFracture healing was assessed by anterior and lateral radiographs taken immediately and at 2, 6, 9 and 12 weeks postoperatively

In addition, fracture healing was assessed by multiplanar computed tomography and 2 and 9 weeks postoperatively


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "..prospective, randomized, double-blind and placebo controlled study". No comment on sequence generation.

Allocation concealment (selection bias)Low riskQuote: "The patients were randomly provided with either an active or sham ultrasound device in a double-blind manner".

Blinding (performance bias and detection bias)
Objective measures
Unclear riskQuote: "The patients were randomly provided with either an active or sham ultrasound device in a double-blind manner".

Comment: Likely to be the same device but placebo devices were deactivated.

Incomplete outcome data (attrition bias)
Objective measures
Low risk"One patient was excluded... because of a new injury" but the group to which he was randomised is unreported

Selective reporting (reporting bias)Unclear riskNo protocol available

Other biasLow riskNo additional biases identified

Selection bias (imbalance in baseline characteristics)Unclear riskSmoking status not reported

Heckman 1994

MethodsRandomised, placebo-controlled study


ParticipantsSetting: University of Texas Health Science Centre, USA.

Size: 97 patients were enrolled. Of the 48 patients in the test group, 11 violated the protocol and 4 were lost to follow-up, leaving 33 patients completing the study. Of the 49 patients in the control group, 6 violated the protocol and 9 were lost to follow-up, leaving 34 patients completing the study.

Baseline characteristics: mean age was 36 years, with 25 males and 8 females in the intervention group, and mean age 31 years with 29 males to 5 females in the control group.

Inclusion criteria: skeletally mature men and non-pregnant women aged less than 76 years with closed or grade I open, transverse or short oblique/spiral, fractures of the tibial diaphysis that could be treated with closed reduction and cast immobilisation.

Exclusion criteria: post-reduction findings of long oblique/spiral fracture, length of fracture line greater than twice the diameter of the diaphysis; fracture displacement greater than 50%; fracture gap greater than 0.5 cm or persistent shortening; persistent angulation greater than 10 degrees; metaphyseal fracture; large butterfly fragment; pathological fracture; comminution; participant inability to comply with trial procedures; current prescription of NSAID, calcium channel blockers, bisphosphonates; history of thrombophlebitis, vascular insufficiency, alcoholism or nutritional deficiency.


InterventionsParticipants were treated with closed reduction and above-knee casting. An alignment window was placed in the cast at the level of the fracture over the antero-medial aspect of the leg. Reduction of the casting to a below-knee cast, any subsequent splintage and weight bearing status was at the discretion of the clinician.

Test: participants underwent ultrasound treatment for 20 minutes each day from the second to twentieth week, or earlier if the clinician believed there was adequate evidence of union. The ultrasound signal was composed of a 200 µs burst of 1.5 MHz sine waves, with a repetition rate of 1 kHz and a spatial average intensity of 30 mW/cm².

Control: participants in the control group were given a similar treatment regimen but had an externally similar sham machine instead.


OutcomesFollow-up schedule: plain radiographs at 4, 6, 8, 10, 12, 14, 20, 33 and 52 weeks. Clinical examination at times of cast change and at the time of union.

Outcomes: time to combined radiographic and clinical union.


NotesThe weight bearing status of the patients was strictly described initially but subsequently handed over to the discretion of the treating clinician part way through the trial.

It was confirmed in personal communication with James Heckman that there was no time to union data on participants who violated protocol.

Cook 1997 describes a subgroup analysis of the study by Heckman 1994. Smoking status was collected prospectively during the study for half the participants and retrospectively for the other half. There were 33 participants in the active group and 34 in the control group. These numbers correspond with the numbers of participants that successfully completed the study by Heckman 1994. Of these smoking status was not determined in 7 participants due to loss to follow-up.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "...predetermined computer generated code."

Comment: Likely to have been a robust method.

Allocation concealment (selection bias)Low riskQuote: "...the patients were randomized, in groups of four, at each study site..."

Comment: It is likely that the sequence was held centrally and allocations were given to the distant study centres.

Blinding (performance bias and detection bias)
Objective measures
Low riskQuote: "The active and placebo devices were identical in every way..."

Comment: Likely to have been a robust method.

Incomplete outcome data (attrition bias)
Objective measures
Unclear riskQuote: "...patients who adhered to the study protocol ... inferences were drawn"

Only data from 67 fractures were presented, which represents a loss to follow-up of 31%. (From JDH: 13 lost to follow-up, 17 did not present in a timely manner so only certainty is ultimate successful union, no time to event data available.)

Selective reporting (reporting bias)Unclear riskNo protocol available.

Other biasHigh riskQuote: "Ninety-six patients, who had ... ninety-seven fractures..."

Comment: Per protocol analysis only. Also, there was no adjustment for recruiting related fractures

Selection bias (imbalance in baseline characteristics)Unclear riskSmoking status is not reported as part of the baseline characteristics of the participants.

Kristiansen 1997

MethodsRandomised, placebo-controlled study


ParticipantsSetting: multicentre trial, USA.

Size: a total of 85 fractures in 83 patients. Of the 40 fractures in the test group, there were 10 withdrawn, leaving 30. Of the 45 fractures in the control group, 3 were lost to follow-up and 11 were withdrawn, leaving 31.

Baseline characteristics: there were 6 males and 24 females in the intervention group and 4 males and 27 females in the control group.

Inclusion: men and non-pregnant women who were at least 20 years old, who had closed dorsally angulated metaphyseal fractures of the distal radius.

Exclusion: fracture extending beyond 4 cm proximally from the tip of the radial styloid, failure to satisfactorily reduce closed and immobilise in a below elbow cast, requirement for additional reduction after ultrasound treatment had begun, associated fracture of the ulnar shaft, current prescription of steroids or anticoagulant, any medical history of thrombophlebitis or vascular insuffiencey of the upper limb, current nutritional deficiency or alcohol dependency.


InterventionsPatients underwent closed reduction and immobilisation of the limb in a cast with volar flexion and ulnar deviation. A window was created on the dorsal aspect of the cast overlying the fracture and a retaining alignment fixture was placed in the window. The patients were given a device within 7 days of the fracture, were told to use it for 20 minutes a day, until their 10-week appointment.

Test: ultrasound probe that fitted into the retaining fixture was given to each participant. The ultrasound signal was composed of a 200 µs burst of 1.5 MHz sine waves, with a repetition rate of 1 kHz and a spatial average intensity of 30 mW/cm².

Control: a visually and audibly similar device was given to each participant.


OutcomesFollow-up schedule was weekly until week 6 and then 8, 10, 12 and 16 weeks. End point was defined as combined clinical and radiographic healing.

Primary: time to radiographic union.

Secondary: time to early trabecular healing, time to cortical bridging, percentage of organised trabecular healing, loss of reduction.


NotesThe protocol specified combined clinical and radiographic healing, but investigators were reluctant to remove casts, therefore no clinical data are reported and radiographic union was used as the primary outcome measure.

It was confirmed in personal communication with Joan McCabe that multiple reports with similar titles were all from the same study.

Cook 1997 describes a subgroup analysis of the study by Kristiansen 1997. Smoking status before and during the study was retrospectively collected. There were 30 participants in the active group and 31 in the control group. These numbers correspond with the numbers of participants that successfully completed the study by Kristiansen 1997. There were 10 participants who could not be located for a retrospective analysis of smoking status.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomly assigned...according to a computer generated code, developed by an independent consultant".

Allocation concealment (selection bias)Unclear riskComments: Concealment of the codes is not reported.

Blinding (performance bias and detection bias)
Objective measures
Low riskQuote: "The placebo device...was identical to the active unit". "The principle investigator and the independent radiologist...were blinded...performed independent central assessments...of the radiographic parameters of union.

Incomplete outcome data (attrition bias)
Objective measures
High riskComments: The protocol specified combined clinical and radiographic healing, but investigators were reluctant to remove casts, therefore no clinical data is reported. All patients lost to follow-up accounted for but approximately 30% loss to follow-up

Selective reporting (reporting bias)Unclear riskNo protocol available.

Other biasHigh riskTwo patients had bilateral fractures and they were treated with alternate devices. These fractures were analysed as independent events

Selection bias (imbalance in baseline characteristics)Unclear riskGender, age and fracture characteristics were similar. Smoking status is not reported.

Leung 2004

MethodsQuasi-randomised, placebo-controlled study


ParticipantsSetting: Chinese University of Hong Kong, China.

Size: a total of 30 fractures in 28 patients. The test group had 16 fractures in 15 patients and the control group had 14 fractures in 13 patients.

Baseline characteristics: mean (range) age 35.3 years (22 to 61), 25 males and 3 females.

Inclusion: patients with open or comminuted tibial fractures.

Exclusion: simple fractures, fractures of sites other than the tibia.


InterventionsPatients with closed fractures or Gustillo grade 1 or 2 open fractures in the diaphysis underwent fixation with reamed, locked intramedullary nail. Participants with fractures in the metaphysis or Gustillo grade 3 open fractures were treated with an external fixator. All open fractures were treated with emergency debridement and delayed closure.

Test: LIPUS machine was given to the patients as soon as the soft tissues were closed. The ultrasound signal was composed of a 200 µs burst of 1.5 MHz sine waves, with a repetition rate of 1 kHz and a spatial average intensity of 30 mW/cm² and was given for 20 minutes a day, for 90 days using coupling gel applied directly over the fracture site.

Control: a sham device that was externally identical to the LIPUS machine was given to the participants as soon as the soft tissues were closed.


OutcomesEnd point was combined clinical and radiographic union. Clinical union was defined as full painless weight bearing. Radiographic union was defined as 3 out of 4 cortices were bridged with bone on plain orthogonal radiograph. Follow-up times were every 3 weeks for the first 3 months, every 6 weeks for the following 3 months and every 8 weeks for the last 6 months. The radiographs were assessed by 3 independent surgeons and a mean time of union was used.

Primary: time to union.

Secondary: bone mineral density and plasma bone specific alkaline phosphatase, adverse events.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuote: "...assigned...according to the sequence of admission".

Comments: Quasi-randomised.

Allocation concealment (selection bias)High riskQuote: "...assigned...according to the sequence of admission".

Comments: No list provided. Quasi-randomised.

Blinding (performance bias and detection bias)
Objective measures
High riskQuote: "Control group were given a dummy machine".

Comments: Efforts were made to blind the patients, but the assessors were not blind as the machines were not identical and the patients were quasi-randomly allocated.

Incomplete outcome data (attrition bias)
Objective measures
Low riskThe complete dataset was presented.

Selective reporting (reporting bias)Unclear riskNo protocol available.

Other biasHigh riskQuote: "Four patients had segmental fractures..."

Some participants had two fractures, which may have been randomised independently. No statistical adjustments were reported to allow for this

Selection bias (imbalance in baseline characteristics)Unclear riskAge, gender and smoking status not separately reported.

Lubbert 2008

MethodsRandomised, placebo-controlled study


ParticipantsSetting: multicentre trial, Netherlands.

Size: there were 120 patients. Of the 61 in the test group, 9 were lost to follow-up, leaving 52 patients. Of the 59 in the control group, 7 were lost to follow-up and 3 did not complete the intervention, leaving 49 patients.

Baseline characteristics: 46 males and 6 females in the intervention group and 39 males and 10 females in the control group.

Inclusion: over 18 years of age, diaphyseal fracture of the clavicle (Allman group 1), treatment begun within 5 days of trauma.

Exclusion: multiple trama, re-fracture, pathological fracture, open fracture or threatened soft tissue envelope, metaphyseal fracture.


InterventionsAll participants were treated non-operatively with a collar and cuff sling for symptom control. Free arm movements within a range allowed by pain were allowed from day 1. Participants maintained a treatment diary.

Test: a LIPUS machine was given to the patients at the first visit. The ultrasound signal was given for 20 minutes a day, for 28 days using coupling gel applied directly over the fracture site. The unit was an Exogen 2000 battery powered Main Operating Unit and a Smith and Nephew Treatment Head Module transducer that delivered an ultrasound signal composed of a 200 µs burst of 1.5 MHz sine waves, with a repetition rate of 1 kHz and a spatial average intensity of 30 mW/cm².

Control: a sham device that was externally identical to the LIPUS machine was given to the participants with similar instructions for use.


OutcomesFollow-up schedule: 1, 2, 4, 6, 8 weeks.
Primary: patient-reported subjective clinical fracture healing.

Secondary: pain (VAS and painkiller use), operation, adverse events, resumption of sport/professional activities/sport.


NotesData from the patients excluded from the study was provided by Pieter Lubbert in personal communication; these allowed an intention-to-treat analysis.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "For each participating hospital consecutive numbered transducers were delivered in packs of four."

"Randomisation took place at the site of the manufacturer."

Comment: Distant block randomisation.

Allocation concealment (selection bias)Low riskQuotes: "Each hospital supply contained two randomly assigned active transducers and two placebo transducers."

"The placebo transducers looked identical..."

Comment: Allocation was concealed at a distant site.

Blinding (performance bias and detection bias)
Patient-reported measures
Low riskQuote: "The placebo transducers looked identical..."

Blinding (performance bias and detection bias)
Objective measures
Low riskQuote: "The placebo transducers looked identical..."

Incomplete outcome data (attrition bias)
Patient-reported measures
High riskTrial flow diagram presented clearly. Only a per-protocol analysis was presented

Incomplete outcome data (attrition bias)
Objective measures
Low riskNeed for operation following delayed or non-union thoroughly described

Selective reporting (reporting bias)Unclear riskNo protocol available

Other biasLow riskNo additional biases identified

Selection bias (imbalance in baseline characteristics)Unclear riskAge and smoking status not separately reported.

Mayr 2000

MethodsRandomised controlled trial


ParticipantsSetting: German emergency outpatient department. Single-centre study.

Size: 29 patients, 30 fractures; 15 fractures in each group.

Baseline characteristics: mean age (SD) age 37 (14) years; 5 to 1 male / female ratio.

Inclusion: skeletally mature adults with a fresh stable scaphoid fracture (AO B1 and B2).

Exclusion: unstable fractures, generalised skeletal disease, pathological fracture, fracture more than 10 days old at diagnosis.


InterventionsA forearm plaster splint was applied to include the thumb to the interphalangeal joint. After detumescence, the splint was replaced with a circular restraining forearm bandage to include the thumb to the interphalangeal joint.

Test: after appliance of the circular immobilising forearm bandage, daily 20-minute pulsed low-intensity ultrasound treatment (SAFHS, Exogen, Piscataway, NJ, USA; frequency: 1.5 MHz, pulsed with 1 kHz, signal length: 200 µsec, intensity: 30 mW/cm²) was conducted.

Control: no additional placebo treatment.


OutcomesFollow-up schedule: CT at 6 weeks and then every 2 weeks until union.
Primary outcome: time to union by CT assessment of fracture union.

Secondary outcome: percentage of ossification of the fracture gap.


NotesThe follow-up schedule was changed after 6 patients had been scanned at 6 weeks, when 3 of them had already achieved union. From that point onwards in the trial, first follow-up was at 4 weeks.

Translated from German.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskSequence generated by a random number generator.

Allocation concealment (selection bias)Unclear riskNot reported.

Blinding (performance bias and detection bias)
Objective measures
Low riskCT scans were blinded before reporting by a panel of independent radiologists and surgeons.

Incomplete outcome data (attrition bias)
Objective measures
Low riskThere was no loss of outcome data.

Selective reporting (reporting bias)Unclear riskNo protocol available.

Other biasLow riskNo additional biases identified

Selection bias (imbalance in baseline characteristics)Unclear riskSmoking status is not reported.

Rue 2004

MethodsRandomised, placebo-controlled trial


ParticipantsSetting: US Naval Academy

Size: 40 midshipmen with 58 stress fractures; data reported for 26 (14 in the treatment group and 12 in the control group) midshipmen with tibial stress fractures.

Baseline characteristics: 23 men and 17 women; mean age 19 years; fractures sites were tibia, metatarsal, femur and fibula (74%, 9%, 5% and 5% respectively)

Inclusion: new midshipmen sustaining stress fractures diagnosed on radiographic and scintigraphic examinations during initial training. Informed consent.

Exclusion: none


InterventionsWhile not stated explicitly it is likely that all participants received the standard-of-care treatment that included protected weight bearing if normal walking reproduced symptoms, alternative aerobic exercise, a daily multivitamin and calcium supplementation (twice daily 500 mg).

Test: daily 20-minute LIPUS treatment (Exogen Inc, Piscataway, NJ) administered by sports medicine personnel until stress fracture had healed.

Control: similar protocol with a sham unit.


OutcomesFollow-up schedule: daily treatments until fit to return to duty (work) defined as no pain on palpation, the ability to do a single leg hop on the affected side without pain and radiographic evidence of healing.

Primary outcome: time to return to duty (work).

Secondary outcome: adherence.


NotesAlthough 40 participants were enrolled with a variety of injured bones, only 33 were able to comply with the protocol for a variety of reasons. Of these 33, 7 further participants were excluded from the analysis as only those with fractures of the tibia were analysed (total attrition: 14 of 40). The 26 participants had 43 tibial stress fractures - time to return to duty was based on stress fracture site with the longest duration of symptoms.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "...and were randomized into one of two treatment protocols..."

Comment: No description of sequence generation.

Allocation concealment (selection bias)Unclear riskQuote: "...and were randomized into one of two treatment protocols..."

Comment: No description of allocation concealment.

Blinding (performance bias and detection bias)
Patient-reported measures
Low riskQuote: "The placebo group underwent the identical protocol, except that the stimulator unit was non-functional. This study was a double-blind, placebo-controlled investigation."

Comment: Participants were blinded to intervention.

Blinding (performance bias and detection bias)
Objective measures
Unclear riskQuote: "This study was a double-blind ... investigation."

Comment: Trial personnel administered the treatments and documented adherence. It is not explicit that they were also blind to the allocation although the study was 'double-blind'.

Incomplete outcome data (attrition bias)
Patient-reported measures
High riskOverall attrition proportion was 14 of 40 and the loss was explicitly systematic.

Incomplete outcome data (attrition bias)
Objective measures
High riskOverall attrition proportion was 14 of 40 and the loss was explicitly systematic.

Selective reporting (reporting bias)Unclear riskNo protocol available.

Other biasLow riskNo additional biases identified

Selection bias (imbalance in baseline characteristics)Unclear riskSmoking status is not reported.

Strauss 1999

MethodsRandomised controlled trial


ParticipantsSetting: USA hospital.

Size: 20 participants, 20 fractures; 10 fractures in each group.

Baseline characteristics: not reported.

Inclusion: patients with a fracture of the fifth metatarsal (zone II).

Exclusion: not stated.


InterventionsAll fractures were initially treated with short leg cast and weightbearing as tolerated for a mean of 10 days. All casts were converted to a hinged ankle foot orthosis and patients continued with weightbearing until fracture union.

Test: participants were given LIPUS therapy for 20 minutes twice each day.

Control: participants were given no additional placebo treatment.


OutcomesFollow-up schedule: not reported

Primary: time to clinical and radiographic union

Secondary: proportion of union within 20 weeks


NotesInadequate data were presented to include the primary outcome in the analysis in this review.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "...were studied in a prospective randomized setting. The twenty fractures were randomly divided..."

Comment: Method of randomisation is unclear.

Allocation concealment (selection bias)Unclear riskQuote: "...were studied in a prospective randomized setting. The twenty fractures were randomly divided..."

Comment: Method of randomisation is unclear.

Blinding (performance bias and detection bias)
Objective measures
High riskQuote: "...Group B (control or no ultrasound treatment)."

Comment: Control group received no sham LIPUS machine.

Incomplete outcome data (attrition bias)
Objective measures
Low riskAll participants were followed up to the final time point of the study.

Selective reporting (reporting bias)Unclear riskNo protocol available.

Other biasHigh riskThis study was only reported as a poster abstract. The detail contained within this report is minimal and evaluation of the risk of bias is extremely limited

Selection bias (imbalance in baseline characteristics)Unclear riskBaseline characteristics were not reported.

Wang 2007

MethodsQuasi-randomised controlled trial


ParticipantsSetting: Taiwan

Size: a total of 59 fractures in 56 patients. There was one exclusion in each group, leading to 27 fractures in 27 patients in the test and 30 fractures in 27 patients in the control.

Baseline characteristics: mean (range) age was 34.2 years (15 to 81), 40 males and 16 females.

Inclusion: patients with acute, displaced, high energy trauma diaphyseal fractures of the femur and tibia that required reduction and internal or external fixation.

Exclusion: pathological fracture, active infection, coagulopathy, immunosuppression, pregnancy, cardiac pacemaker, skeletal immaturity, poor compliance.


InterventionsAll closed fractures were treated with open or closed reduction and internal fixation with intra-medullary nailing or plate fixation. Patients with type III-C open fractures were initially treated with surgical debridement of the wounds and external fixator for fracture stabilization. Delayed open or closed reduction and internal fixation was performed when the soft tissues were optimised. All other open fractures were treated with primary open reduction and internal fixation.

Postoperative management included early ambulation with no weight bearing allowed through the affected limb; quadriceps and hamstring and lower limb joint range of motion exercises.

Test: participants in the study group received shockwave treatment immediately after surgery under the same anaesthesia. For patients with type III-C open fractures, shockwave treatment was performed after delayed open reduction and internal fixation for the fractures. The source of shockwaves was from an OssaTron (High Medical Technology, Kreulingen, Switzerland). Shockwaves were performed with patients on the fracture table. The fracture site was verified with C-arm X-rays, and the depth of treatment was confirmed with the control guide of the device under C-arm imaging. Surgical lubrication gel was applied to the area of skin in direct contact with the shockwave tube. Each fracture site was treated with 6,000 impulses of shockwave at 28 kV (equivalent to 0.62 mJ/mm² energy flux density). Shockwaves were applied in two planes with equal dosage in each plane as a single session.

Control: participants in the control group received open reduction and internal fixation without shockwave treatment after surgery.


OutcomesFollow-up schedule: 1, 3, 6 and 12 months.

Primary: proportion of union at 12 months.

Secondary: proportion of union at earlier time points, fracture alignment, pain (VAS), weight bearing status, adverse events.


NotesAuthors have assumed independence between observations from multiple fractures in a single participant.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuote: "[The study group] who had surgery on odd days of the week, and the control group ... who had surgery performed on even days of the week"

Comment: Quasi-randomised study.

Allocation concealment (selection bias)High riskQuote: "[The study group] who had surgery on odd days of the week, and the control group..who had surgery performed on even days of the week"

Comment: Unclear whether method of randomisation known, but would be easy to identify pattern.

Blinding (performance bias and detection bias)
Patient-reported measures
Unclear riskQuote: "Patients in the control group ... without shockwave treatment after surgery."

Comment: It is not reported whether the participants were blind to their allocation.

Blinding (performance bias and detection bias)
Objective measures
Low riskQuote: "An independent examiner blinded to the nature of the study protocol performed the examination."

Incomplete outcome data (attrition bias)
Patient-reported measures
High riskQuote: "Two patients were excluded from the final analysis because of postoperative deep infection and osteomyelitis."

Comment: This was consistent with the eligibility criteria but is an unusual means to handle data from participants developing adverse events.

Incomplete outcome data (attrition bias)
Objective measures
High riskQuote: "Two patients were excluded from the final analysis because of postoperative deep infection and osteomyelitis."

Comment: This was consistent with the eligibility criteria but is an unusual means to handle data from participants developing adverse events.

Selective reporting (reporting bias)Unclear riskNo protocol available.

Other biasLow riskQuote: "56 patients with 59 .... fractures"

Some participants had two fractures which may have been randomised independently. No statistical adjustments were reported to allow for this

Selection bias (imbalance in baseline characteristics)Unclear riskThe distribution of smoking status between the groups is not reported.

Yadav 2008

MethodsRandomised, placebo-controlled trial


ParticipantsSetting: Indian military recruits in training.

Size: 67 cases with stress fracture; with 39 in the treatment group and 28 in the control group.

Baseline characteristics: age not reported, gender data not reported.

Inclusion: history and examination consistent with a diagnosis of stress fracture.

Exclusion: none.


InterventionsAll participants were managed non-operatively and prescribed paracetamol and ice-packs.

Test: treated with 10 min/day using a ultrasound probe emitting a 3 MHz, 1 W/cm² ultrasound signal pulsed with a duty cycle of 50%.

Control: similar treatment with a sham unit which was identical to the test unit.


OutcomesTime to return to training. No radiological outcome measures assessed.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "...were randomly assigned ... by chit method."

Allocation concealment (selection bias)Unclear riskQuote: "...were randomly assigned ... by chit method."

Comment: It is not clear whether this was done on or off site and who had access to the results.

Blinding (performance bias and detection bias)
Patient-reported measures
Low riskQuotes: "... nonfunctioning unit identical in appearance."

"... patients ... study's researchers were blinded..."

Blinding (performance bias and detection bias)
Objective measures
Low riskQuotes: "... nonfunctioning unit identical in appearance."

"... patients ... study's researchers were blinded..."

Incomplete outcome data (attrition bias)
Patient-reported measures
Low riskThere were no missing data.

Incomplete outcome data (attrition bias)
Objective measures
Low riskThere were no missing data.

Selective reporting (reporting bias)Unclear riskNo protocol available.

Other biasLow riskNo additional biases identified

Selection bias (imbalance in baseline characteristics)Unclear riskQuote: "... matched in terms of age, height, demographics, and delay from symptom onset to diagnosis."

Comment: Sex and smoking status not reported.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Basso 1998This RCT involving a single application of ultrasound to conservatively treated distal radius fractures reported on range of motion and referral for physiotherapy at 8 weeks. It is excluded because its focus was not on fracture healing; it also not did not report any outcome measures pertinent to this review.

Busse 2005This study is a health economic analysis, which is informed using data from a systematic review.

Heckman 1997This study is a cost analysis based upon models developed from clinical data and specified assumptions. It is not a formal health economics analysis within a RCT.

ISRCTN98682811This trial ('TRUST (pilot)' in the first version of our review (Giffin 2011) was intended to be a pilot study comparing LIPUS versus sham in 50 patients with conservatively managed fractures of the tibia. It was abandoned after four months (Busse 2014) as a survey of practice showed a shift to surgical management of tibial fractures. A new pilot of surgically managed tibial fractures was set up under a new trial registration number (NCT00667849).

Urita 2013This study only included patients undergoing shortening osteotomies of the upper limb.

 
Characteristics of studies awaiting assessment [ordered by study ID]
ISRCTN90844675

MethodsRandomised controlled multicentre trial

ParticipantsAdults with closed or type I open fractures of the tibia that had been treated by reamed or unreamed locking intramedullary nails less than 10 days prior to randomisation. Patients with fractures of the lateral malleolus, fixed by plates, as well as patients with minor concomitant injuries (bruises, sprains) were offered trial participation.

Intended target population: 250

InterventionsTest: pulsed, low-energetic ultrasound (Exogen, Smith & Nephew), applied daily for three months
Control: standard of care

OutcomesFollow-up: 1 year

Primary: bony union three months (+/- 1 week) after randomisation, as assessed on plain radiographs by independent, blinded raters

Secondary (assessed after 6 weeks, 3, 6, and 12 months):

1. Delayed union and non-union rates
2. Health-related quality of life (36-item Short Form Health Survey [SF-36], EuroQoL instrument [EQ-5D])
3. Functional outcomes (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC])
4. Duration of sick leave
5. Cost-utility
6. Serious adverse events (SAE)

NotesTrial registration identified after preparation of the review. Indicated as a completed trial (01/10/2008 to 01/10/2010). Efforts to learn its current status were unsuccessful for the first version of this review but Dr Seifert indicated that data were under analysis during the update of the review. (Seifert 2013)
Contact: Dr Julia Seifert, Berlin (julia.seifert@ukb.de)

We also found that the results may have been presented in an oral presentation but have not obtained a copy of this:

Froese E, Gümbel D, Stengel D. Pulsed ultrasound to speed healing after internal fixation of tibia fractures- Results from the randomized PUSH-IT trial (ISRCTN90844675). 12th Congress European Forum For Research In Rehabilitation; 11-14 September 2013, Istanbul Turkey.

NCT00667849

MethodsRandomised controlled trial

ParticipantsPatients with tibial fractures treated with intramedullary nailing. Target population = 500

InterventionsTest: LIPUS (low-intensity pulsed ultrasound) - Exogen (Piscataway, New Jersey) Bone Healing System

Control: Sham ultrasound unit

OutcomesPrimary: radiographs at 6, 12, 18, 26, 38 and 52 weeks
Secondary: rates of nonunion of tibial fractures (6, 12, 18, 26, 38 and 52 weeks)

NotesThis multicentre study, involving centres in USA and Canada, is sponsored by Smith & Nephew (changed to BioventusLLC). It has the same name as the other trial on conservatively treated tibia fractures: TRUST (Pilot). TRUST (Full) has been completed but the data are not yet available (Busse 2013).

On 28/06/2013, the trial registration record update on status reported: "The Study was terminated due to futility". The actual population was reported as "501" but a linked report reported: "From July 5th, 2005, to June 22nd, 2007, 51 patients with 14 open and 37 closed tibial fractures were treated with reamed intramedullary nailing". However, the study start date was listed as September 2008 in the trial registration document.

The pilot study for this trial (Busse 2014), which recruited 51 patients between March 2006 to June 2007, was published after our date of last search.

 
Comparison 1. LIPUS versus control

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Time to return to work complete fractures (days)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 Resumption of work (as reported)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Resumption of work (worst case scenario)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Time to return to training/duty after stress fracture (days): as reported analysis (days)293Mean Difference (IV, Random, 95% CI)-8.55 [-22.71, 5.61]

 3 Time to fracture union (days): 'as reported' analysis8355Std. Mean Difference (IV, Random, 95% CI)-0.69 [-1.31, -0.07]

    3.1 Upper limb
3183Std. Mean Difference (IV, Random, 95% CI)-0.93 [-2.03, 0.17]

    3.2 Lower limb
5172Std. Mean Difference (IV, Random, 95% CI)-0.54 [-1.44, 0.35]

 4 Time to fracture union (days): worst case analysis8446Std. Mean Difference (IV, Random, 95% CI)-0.47 [-1.14, 0.20]

    4.1 Upper limb
3235Std. Mean Difference (IV, Random, 95% CI)-0.66 [-1.93, 0.60]

    4.2 Lower limb
5211Std. Mean Difference (IV, Random, 95% CI)-0.35 [-1.27, 0.56]

 5 Time to fracture union (days) subgrouped by operation: worst case analysis7326Std. Mean Difference (IV, Random, 95% CI)-0.62 [-1.29, 0.06]

    5.1 Operatively treated
4114Std. Mean Difference (IV, Random, 95% CI)-0.21 [-1.42, 1.00]

    5.2 Conservatively treated
3212Std. Mean Difference (IV, Random, 95% CI)-1.09 [-1.38, -0.80]

 6 Time to fracture union (days) subgrouped by smoking status: worst case analysis2111Std. Mean Difference (IV, Random, 95% CI)-1.06 [-1.47, -0.65]

    6.1 Smokers
244Std. Mean Difference (IV, Random, 95% CI)-1.17 [-2.09, -0.25]

    6.2 Non-smokers
267Std. Mean Difference (IV, Random, 95% CI)-1.06 [-1.58, -0.53]

 7 Delayed or non-union (as reported analysis)8333Risk Ratio (M-H, Random, 95% CI)0.75 [0.24, 2.28]

    7.1 Upper limb
3203Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    7.2 Lower limb
5130Risk Ratio (M-H, Random, 95% CI)0.75 [0.24, 2.28]

 8 Pain at 8 weeks (VAS: 0 no pain to 10 worst pain)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    8.1 As reported analysis
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.2 Worst case analysis
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. ECSW versus control

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Non-union at 12 months follow-up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 As reported analysis
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Sensitivity analysis
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Pain at 3 months (VAS: 0 no pain to 10 severe pain)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 As reported analysis
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Worst case analysis
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]