title: Mode & mechanism of low intensity pulsed ultrasound (LIPUS) in fracture repair.
abstract: It has been 30years since the first level one clinical trial demonstrated low intensity pulsed ultrasound (LIPUS) could accelerate fracture repair. Since 1994 numerous investigations have been performed on the effect of LIPUS. The majority of these studies have used the same signal parameters comprised of an intensity of 30mW/cm(2) SATA, an ultrasound carrier frequency of 1.5MHz, pulsed at 1kHz with an exposure time of 20minutes per day. These studies show that a biological response is stimulated in the cell which produces bioactive molecules. The production of these molecules, linked with observations demonstrating the enhanced effects on mineralization by LIPUS, might be considered the general manner, or mode, of how LIPUS stimulates fractures to heal. We propose a mechanism for how the LIPUS signal can enhance fracture repair by combining the findings of numerous studies. The LIPUS signal is transmitted through tissue to the bone, where cells translate this mechanical signal to a biochemical response via integrin mechano-receptors. The cells enhance the production of cyclo-oxygenese 2 (COX-2) which in turn stimulates molecules to enhance fracture repair. The aim of this review is to present the state of the art data related to LIPUS effects and mechanism.
authors.affiliation: Bioventus Cooperatief, Amsterdam, Netherlands. Electronic address: andrew.harrison@bioventusglobal.com.
authors.forename: Andrew
authors.initials: A
authors.lastname: Harrison
authors.affiliation: Department of Orthopedics, Rutgers, New Jersey Medical School, USA.
authors.forename: Sheldon
authors.initials: S
authors.lastname: Lin
authors.affiliation: Bioventus LLC, Durham, NC, USA.
authors.forename: Neill
authors.initials: N
authors.lastname: Pounder
authors.affiliation: Kanagawa Dental University, Graduate School of Dentistry, Yokosuka, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mikuni-Takagaki
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D019317:Evidence-Based Medicine; D017102:Fracture Healing / Q000502:physiology* / Q000528:radiation effects; D050723:Fractures, Bone / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology* / Q000528:radiation effects; D008954:Models, Biological; D010012:Osteogenesis / Q000502:physiology / Q000528:radiation effects; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods*; D000069453:Ultrasonic Waves
chemical_list: D051546:Cyclooxygenase 2
keywords: Bone morphogenic protein; Cyclo-oxygenase 2; Fracture; LIPUS; Mechanism; Ultrasound