Low intensity pulsed ultrasound (LIPUS) for bone healing: a clinical practice guidelineBMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j576 (Published 21 February 2017) Cite this as: BMJ 2017;356:j576
Choice of intervention
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All rapid responses
We understand our rapid recommendation represents a major disappointment for Bioventus, a manufacturer of low intensity pulse ultrasound (LIPUS) devices that invested vast amounts of money introducing devices to the market including speaker fees and travel reimbursement for authors of the cited publications.
As recently outlined in our letter to the editor - responding to similar criticism from M. Farrar - we disagree that there is extensive evidence that LIPUS is effective in non-unions (http://www.bmj.com/content/356/bmj.j1483). The three available RCTs are small and have serious limitations ( http://www.bmj.com/content/356/bmj.j656). None of these trials nor the two mentioned retrospective studies sponsored by Bioventus evaluated endpoints important to our patient panel members.
The argument that LIPUS is used in millions of cases does not bear on its effectiveness. Rather, this is an example of bringing a medical device to the market without trustworthy evidence - but with successful marketing - and reflects the shortcomings of the processes responsible for ensuring device effectiveness prior to dissemination. (http://www.bmj.com/content/349/bmj.g5133.long , http://www.bmj.com/content/353/bmj.i3323.long)
Rudolf W. Poolman, orthopedic surgeon, Thomas Agoritsas, assistant professor; Reed A C Siemieniuk, methodologist; Gordon H Guyatt, distinguished professor; Stefan Schandelmaier, methodologist; Per O Vandvik, associate professor.
Competing interests: No competing interests
Poolman, et al.  inappropriately extrapolate recent findings reported for LIPUS and fresh fracture healing  to include other fracture types, in particular nonunions. However, there is extensive evidence demonstrating the therapeutic and economic benefits associated with LIPUS treatment of delayed unions and established, debilitating nonunions [3-5]. Based on such evidence, the healthcare institute NICE in the UK has approved the use of LIPUS specifically for treating chronic nonunions . Neither the “Rapid Recommendation”  nor the linked systematic review article  provide any rationale to countermand such guidance; patients and physicians should therefore not be denied access to this important treatment option for nonunion healing.
The “Rapid Recommendation” , which, as disclaimed, is “not a validated clinical decision aid”, is based principally on results of the TRUST trial on surgically treated acute (fresh) tibia fractures. Data from TRUST are included in the linked review , and comprise greater than one-third of the total number of included patients across the studies analyzed. Studies on fresh fractures predominate (although these are conflated with some nonunion, distraction osteogenesis, stress fracture, and osteotomy studies), such that the results for fresh fractures constitute the findings reported from the meta-analysis. The analysis is thus heavily skewed toward the results of the TRUST fresh fracture trial, and as such is further confounded due to the low overall rate of patient adherence to treatment in that trial (average 43% compliance) .
As the leading LIPUS device in the market, EXOGEN (Bioventus LLC, Durham, NC, USA) has been available since 1994, and numerous regulatory agencies including the FDA, Health Canada, BSi, TGA, Medsafe, UAE Ministry of Health, and SFDA have granted their approval based on review of the clinical evidence. In addition, Bioventus continues to seek additional clinical data for the effect of LIPUS on the treatment of acute fractures. EXOGEN has been used to treat more than 1 million patients worldwide, with complaints for lack of efficacy averaging less than 1%. Denying the use of LIPUS to patients who stand to benefit from this therapy is unjustified.
1. Poolman RW, Agoritsas T, Siemieniuk RAC, et al. Low intensity pulsed ultrasound (LIPUS) for bone healing: a clinical practice guideline. BMJ 2017;356:j576.
2. Schandelmaier S, Kaushal A, Lytvyn L, et al. Low intensity pulsed ultrasound for bone healing: systematic review of randomized controlled trials. BMJ 2017;356:j656.
3. Zura R, Della Rocca GJ, Mehta S, et al. Treatment of chronic (>1 year) fracture nonunion: Heal rate in a cohort of 767 patients treated with low intensity pulsed ultrasound (LIPUS). Injury 2015;46(10):2036-2041.
4. Rutten S, van den Bekerom MPJ, Sierevelt IN, Nolte PA. Enhancement of bone healing by low intensity pulsed ultrasound. A systematic review. JBJS Reviews 2016;4(3)e6.
5. Mehta S, Long K, DeKoven M, Smith E, Steen RG. Low intensity pulsed ultrasound (LIPUS) can decrease the economic burden of fracture nonunion. J Med Econ 2015;18(7):542-549.
6. National Institute for Health and Clinical Excellence. Interventional procedure overview of low-intensity pulsed ultrasound to promote fracture healing. https://www.nice.org.uk/guidance/mtg12/chapter/1-Recommendations
7. Pounder NM, Phillips M, Rueger J, Heeckt P. A matter of TRUST: An issue of compliance. BMJ 2016;355:i5351
Competing interests: Dr Harrison is an employee of Bioventus and Dr Heeckt is a consultant for Bioventus
Re: Low intensity pulsed ultrasound (LIPUS) for bone healing: a clinical practice guideline - don't intervene just because you can
A recommendation not to do something just because it's possible is to be welcomed, and the authors are to be applauded for coming to such a firm conclusion in respect of LUPIS. I wonder how surgeons of yesteryear would have reacted to curtailment of their propensity to perform tonsillectomies at the drop of a hat in the days that meta-analyses and systematic reviews were futuristic limits to clinical judgement.
Competing interests: No competing interests