title: Enhancement of Bone-Healing by Low-Intensity Pulsed Ultrasound: A Systematic Review.
abstract: Low-intensity pulsed ultrasound (LIPUS) is frequently used to enhance or to accelerate fracture-healing, but its clinical role and effectiveness as a treatment modality remain uncertain. We performed a systematic review and meta-analysis of randomized controlled trials to determine the efficiency of LIPUS on bone-healing and/or fracture union, as well as on functional recovery.
  
  
  
  The databases of PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and Embase were searched for trials concerning LIPUS stimulation and bone-healing or fracture repair, in any language, published from the inception of the database to January 2, 2015. Eligible studies were randomized controlled trials that enrolled patients with any type of fracture, delayed union, or nonunion and randomly assigned them to LIPUS treatment or a control group. Two reviewers independently agreed on eligibility, assessed methodological quality, and extracted outcome data. All relevant outcomes were pooled, and a meta-analysis was performed.
  
  
  
  Twenty-four unique randomized trials were selected for analysis after the search of all databases and the inclusion of one trial by the senior author. Time to radiographic fracture union was the most common primary outcome measure evaluated. After pooling the data concerning time to radiographic healing in the combined patient population (n = 429), LIPUS treatment resulted in a mean reduction in healing time of 39.8 days (95% confidence interval, 17.7 to 62.0 days; I = 94%). The most reduction in time to radiographic union by LIPUS treatment was seen in fractures with a long natural healing tendency. Three trials evaluating the time to return to work or active duty, as a surrogate for functional recovery, were unable to demonstrate a beneficial effect of LIPUS (n = 179). Evidence from two high-quality trials implied that LIPUS enhances fracture-healing through increased bone formation in cases of delayed and/or impaired bone-healing. The prevention of delayed union or nonunion by LIPUS treatment could not be demonstrated.
  
  
  
  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. Future studies should focus on reporting of a combination of subjective signs of clinical healing, functional recovery, and radiographic union to determine the effectiveness of LIPUS treatment in clinical fracture-healing.
  
  
  
  Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
authors: Department of Orthopaedic Surgery, Spaarne Hospital, Hoofddorp, the Netherlands.
authors: Sjoerd
authors: S
authors: Rutten
authors: Department of Orthopaedic Surgery, Onze Lieve Vrouwe Kliniek, Amsterdam, the Netherlands.
authors: Michel P J
authors: MPJ
authors: van den Bekerom
authors: Department of Orthopaedic Surgery, Spaarne Hospital, Hoofddorp, the Netherlands.
authors: Inger N
authors: IN
authors: Sierevelt
authors: Department of Orthopaedic Surgery, Spaarne Hospital, Hoofddorp, the Netherlands.
authors: Petrus A
authors: PA
authors: Nolte
mesh_terms: D017102:Fracture Healing; D050723:Fractures, Bone / Q000628:therapy*; D006801:Humans; D014464:Ultrasonic Therapy / Q000379:methods*