title: Low intensity pulsed ultrasound for bone healing: systematic review of randomized controlled trials.
abstract: ObjectiveTo determine the efficacy of low intensity pulsed ultrasound (LIPUS) for healing of fracture or osteotomy.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and trial registries up to November 2016.Study selectionRandomized controlled trials of LIPUS compared with sham device or no device in patients with any kind of fracture or osteotomy.Review methodsTwo independent reviewers identified studies, extracted data, and assessed risk of bias. A parallel guideline committee (BMJRapid Recommendation) provided input on the design and interpretation of the systematic review, including selection of outcomes important to patients. The GRADE system was used to assess the quality of evidence.Results26 randomized controlled trials with a median sample size of 30 (range 8-501) were included. The most trustworthy evidence came from four trials at low risk of bias that included patients with tibia or clavicle fractures. Compared with control, LIPUS did not reduce time to return to work (percentage difference: 2.7% later with LIPUS, 95% confidence interval 7.7% earlier to 14.3% later; moderate certainty) or the number of subsequent operations (risk ratio 0.80, 95% confidence interval 0.55 to 1.16; moderate certainty). For pain, days to weight bearing, and radiographic healing, effects varied substantially among studies. For all three outcomes, trials at low risk of bias failed to show a benefit with LIPUS, while trials at high risk of bias suggested a benefit (interaction P<0.001). When only trials at low risk of bias trials were considered, LIPUS did not reduce days to weight bearing (4.8% later, 4.0% earlier to 14.4% later; high certainty), pain at four to six weeks (mean difference on 0-100 visual analogue scale: 0.93 lower, 2.51 lower to 0.64 higher; high certainty), and days to radiographic healing (1.7% earlier, 11.2% earlier to 8.8% later; moderate certainty).ConclusionsBased on moderate to high quality evidence from studies in patients with fresh fracture, LIPUS does not improve outcomes important to patients and probably has no effect on radiographic bone healing. The applicability to other types of fracture or osteotomy is open to debate.Systematic review registrationPROSPERO CRD42016050965.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St West, Hamilton, ON L8S 4L8, Canada schandes@mcmaster.ca.|Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Spitalstrasse 12, CH-4031 Basel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schandelmaier
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St West, Hamilton, ON L8S 4L8, Canada.|Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: Alka
authors.initials: A
authors.lastname: Kaushal
authors.affiliation: Oslo University Hospital, Forskningsveien 2b, Postboks 1089, Blindern 0317 Oslo, Norway.
authors.forename: Lyubov
authors.initials: L
authors.lastname: Lytvyn
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St West, Hamilton, ON L8S 4L8, Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Heels-Ansdell
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St West, Hamilton, ON L8S 4L8, Canada.|Department of Medicine, University of Toronto, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada.
authors.forename: Reed A C
authors.initials: RA
authors.lastname: Siemieniuk
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St West, Hamilton, ON L8S 4L8, Canada.|Division General Internal Medicine and Division of Clinical Epidemiology, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, CH-1211, Geneva, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Agoritsas
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St West, Hamilton, ON L8S 4L8, Canada.|Department of Medicine, McMaster University, 1280 Main St West, Hamilton, ON L8S 4L8, Canada.
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Guyatt
authors.affiliation: Institute of Health and Society, Faculty of Medicine, University of Oslo, 0318 Oslo, Norway.|Department of Medicine, Innlandet Hospital Trust-division, Gjøvik, Norway.
authors.forename: Per O
authors.initials: PO
authors.lastname: Vandvik
authors.affiliation: Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: Rachel
authors.initials: R
authors.lastname: Couban
authors.affiliation: Orillia Soldiers' Memorial Hospital, 41 Frederick Street, Orillia, ON L3V 5W6, Canada.
authors.forename: Brent
authors.initials: B
authors.lastname: Mollon
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St West, Hamilton, ON L8S 4L8, Canada.|Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON L8S 4K1, Canada.|Department of Anesthesia, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Busse
mesh_terms: D017102:Fracture Healing; D050723:Fractures, Bone / Q000628:therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D014464:Ultrasonic Therapy