Treatment of chronic (&gt;1 year) fracture nonunion: Heal rate in a cohort of 767 patients treated with low-intensity pulsed ultrasound (LIPUS)

Zura, Robert; Rocca, Gregory J. Della; Mehta, Samir; Harrison, Andrew; Brodie, Christopher; Jones, John T.; Steen, R. Grant

doi:10.1016/j.injury.2015.05.042

Cited by 80 publications

(75 citation statements)

References 34 publications

(63 reference statements)

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“…Results of the healing process in non-grafted group indicated the effectiveness of ultrasound on bone repair, which is in line with previous studies (24,25). Furthermore, the use of ultrasound in the DBM group with the profile of 1 MHz and intensity of 30 mW/cm 2 and 20 minutes/day scheme, caused a slight (non-significant) delay in the healing process.…”

Section: Discussionsupporting

confidence: 89%

Evaluation of Low Intensity Pulsed Ultrasound Effects on the Osteogenesis Potential of Demineralized Bone Matrix in Experimental Tibial Defect in Rabbits

Givi

Baniadam

Esmaeilzadeh

et al. 2016

Jentashapir J Health Res

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Background: Many studies have assessed the effects of either low intensity pulsed ultrasound (LIPUS) or demineralized bone matrix (DBM) on bone repair; however, an evaluation of the combination of these modalities (LIPUS + DBM) has not yet been considered.Objectives: This study aimed to investigate combined effects of DBM and LIPUS on fracture healing. Methods: Bilateral 5-mm tibial defects were created in male Dutch rabbits (n = 30). Animals were divided to two groups of empty defect (A) and DBM group (B), in which commercial DBM putty was used in defects. In each animal left tibia was treated with LIPUS (intensity = 30 mW/cm 2 , I SATA, 1 MHz, 20 min/day, pulsed duty 1:4) and the contralateral limb was used as the control. Animals, after 14, 28 and 60 days, were submitted to radiographic or computerized tomography (CT) scanning analysis.Results: At two weeks, LIPUS had no substantial effect on bone formation. Slight increase of average rates in LIPUS group (A2) were seen compared to the empty defect group (A1) at day 21 and 28. In the DBM-treated group compared with the sham LIPUS, bone-healing rate was reduced at the end of the period (60 days) after surgery. The average healing rate in group B at the end of the 60-day period was less than group A after 21 days. Conclusions:The present study discusses systemic effect of LIPUS because of non-significant results between treated group and control group and is the first to demonstrate that LIPUS decreases bone formation induced by DBM.

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Section: Discussionsupporting

confidence: 89%

Evaluation of Low Intensity Pulsed Ultrasound Effects on the Osteogenesis Potential of Demineralized Bone Matrix in Experimental Tibial Defect in Rabbits

Givi

Baniadam

Esmaeilzadeh

et al. 2016

Jentashapir J Health Res

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“…S1A), to an intensity of 30 mW/cm 2 spatial averagetemporal average (SATA), with a power of 117 mW (Harrison et al, 2016). LIPUS shows particular efficacy in treating bone nonunion fractures (Nolte et al, 2001;Rutten et al, 2007;Zura et al, 2015a), and has been approved by the US FDA for treating both fresh fractures and nonunion fractures, and by NICE in the UK for treating nonunion fractures (Higgins et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Low Intensity Pulsed Ultrasound (LIPUS) promotes cell motility through vinculin-controlled Rac1 GTPase activity

Atherton

Lausecker

Harrison³

et al. 2017

Journal of Cell Science

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Low-intensity pulsed ultrasound (LIPUS) is a therapy used clinically to promote healing. Using live-cell imaging we show that LIPUS stimulation, acting through integrin-mediated cell-matrix adhesions, rapidly induces Rac1 activation associated with dramatic actin cytoskeleton rearrangements. Our study demonstrates that the mechanosensitive focal adhesion (FA) protein vinculin, and both focal adhesion kinase (FAK, also known as PTK2) and Rab5 (both the Rab5a and Rab5b isoforms) have key roles in regulating these effects. Inhibiting the link of vinculin to the actin-cytoskeleton abolished LIPUS sensing. We show that this vinculin-mediated link was not only critical for Rac1 induction and actin rearrangements, but was also important for the induction of a Rab5-dependent increase in the number of early endosomes. Expression of dominant-negative Rab5, or inhibition of endocytosis with dynasore, also blocked LIPUSinduced Rac1 signalling events. Taken together, our data show that LIPUS is sensed by cell matrix adhesions through vinculin, which in turn modulates a Rab5-Rac1 pathway to control ultrasound-mediated endocytosis and cell motility. Finally, we demonstrate that a similar FAK-Rab5-Rac1 pathway acts to control cell spreading upon fibronectin.

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“…6 One recent study from Zura et al showed a high healing rate of 86.2% with a total number of 767 analyzed chronic nonunions. 41 However, this study has some weaknesses that should be taken into consideration. For example, LIPUS treatment requires mechanical stability at the nonunion site, which was not discussed in this study.…”

Section: Osteitis and Nonunionsmentioning

confidence: 96%

“…42 The highly selective nature of the patient collective might have led to misleading conclusions. 41 Other clinical studies have reported the rate of healing with LIPUS therapy to be 64-88%. 6,43 However, risk profiles of patients were not often taken into account.…”

Section: Osteitis and Nonunionsmentioning

confidence: 97%

Low intensity pulsed ultrasound in the treatment of long bone nonunions: Evaluation of cytokine expression as a tool for objectifying nonunion therapy

Moghaddam

Yildirim

Westhauser

et al. 2016

Journal of Orthopaedics

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Treatment of chronic (>1 year) fracture nonunion: Heal rate in a cohort of 767 patients treated with low-intensity pulsed ultrasound (LIPUS)

Abstract: Low-intensity pulsed ultrasound enhanced HR among fractures that had been nonunion for at least 1 year, and even healed fractures that had been nonunion >10 years. LIPUS resulted in successful healing in the majority of nonunions without further surgical intervention.

Cited by 80 publications

References 34 publications

Evaluation of Low Intensity Pulsed Ultrasound Effects on the Osteogenesis Potential of Demineralized Bone Matrix in Experimental Tibial Defect in Rabbits

Evaluation of Low Intensity Pulsed Ultrasound Effects on the Osteogenesis Potential of Demineralized Bone Matrix in Experimental Tibial Defect in Rabbits

Low Intensity Pulsed Ultrasound (LIPUS) promotes cell motility through vinculin-controlled Rac1 GTPase activity

Low intensity pulsed ultrasound in the treatment of long bone nonunions: Evaluation of cytokine expression as a tool for objectifying nonunion therapy

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