eCM (Eur Cell Mater / e Cells & Materials) Not-for-Profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2021   Volume No 42 – pages 281-311

Title: Pulsed ultrasound for bone regeneration – outcomes and hurdles in the clinical application: a systematic review

Authors: R Puts, L Vico, N Beilfuß, M Shaka, F Padilla, K Raum

Address: Berlin Institute of Health Centre for Regenerative Therapies, Charité-Universitätsmedizin, Föhrer Straße 15, 13353 Berlin, Germany

E-mail: regina.puts at

Abstract: Impaired bone-fracture healing is associated with long-term musculoskeletal disability, pain and psychological distress. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive and side-effect-free treatment option for fresh, delayed- and non-union bone fractures, which has been used in patients since the early 1990s. Several clinical studies, however, have questioned the usefulness of the LIPUS treatment for the regeneration of long bones, including those with a compromised healing. This systematic review addresses the hurdles that the clinical application of LIPUS encounters. Low patient compliance might disguise the effects of the LIPUS therapy, as observed in several studies. Furthermore, large discrepancies in results, showing profound LIPUS effects in regeneration of small-animal bones in comparison to the clinical studies, could be caused by the suboptimal parameters of the clinical set-up. This raises the question of whether the so-called “acoustic dose” requires a thorough characterisation to reveal the mechanisms of the therapy. The adequate definition of the acoustic dose is especially important in the elderly population and patients with underlying medical conditions, where distinct biological signatures lead to a delayed regeneration. Non-industry-funded, randomised, double-blind, placebo-controlled clinical trials of the LIPUS application alone and as an adjuvant treatment for bones with complicated healing, where consistent control of patient compliance is ensured, are required.

Key Words: Low-intensity pulsed ultrasound, bone regeneration, surgery, acoustic dose, non-union, age, osteoporosis, compliance.

Publication date: October 14th 2021

Article download: Pages 281-311 (PDF file)

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