Low-Intensity Pulsed Ultrasound (LIPUS) for Fracture Healing

The device. LIPUS delivers low-intensity pulsed acoustic energy to a fracture to promote bone healing. The patient places a transducer over the fracture site with coupling gel and applies it once daily at home. It is painless.

The parameters. The standard device delivers 1.5 MHz ultrasound at a low intensity of about 30 mW/cm² (spatial-average temporal-average), as pulsed bursts (200 microseconds on, at a 1 kHz pulse-repetition frequency), for 20 minutes once daily. The "low-intensity" is the point: it is far below therapeutic or high-intensity ultrasound, and it is a non-thermal, mechanical stimulus rather than the tissue-heating of higher-intensity ultrasound.

The proposed mechanism. Mechanotransduction: the micromechanical stimulus is sensed by bone cells and stimulates repair at the molecular level across the stages of fracture healing, with proposed effects on inflammation, chondrogenesis and endochondral ossification, gene and protein expression, angiogenesis and mineralisation.

The risk profile. The only reported adverse effect is minor skin irritation under the transducer. Because it is non-invasive and self-administered, it avoids the re-hospitalisation, anaesthesia and operative complications of surgery, and that is its main appeal.

The regulatory history. The FDA approved LIPUS for accelerating the healing of fresh fractures in 1994 and for established non-unions in 2000. Both approvals rested on early positive randomised trials (accelerated tibial and distal-radius union, for example), which is why the device entered practice before the later high-quality trials tempered the fresh-fracture claim.

Where the rationale is strongest. In delayed union and non-union, where LIPUS offers a non-invasive option. Case reports are encouraging, and non-inferiority trials comparing LIPUS with surgery are underway to define its role. In fresh fractures it should not be promoted as routinely accelerating ordinary fracture union.

Surgery remains the gold standard. Surgical revision is the standard treatment for an established non-union, with its known disadvantages of re-hospitalisation, anaesthesia and operative complications. LIPUS is best framed to the patient as a low-risk adjunct or, in selected cases, an alternative, with an honest account of the inconsistent evidence.

The figures follow one distal radius fracture from injury, through fixation and delayed union, to union after LIPUS.

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Who is a reasonable candidate. A motivated patient with a delayed union or a stable, well-aligned, uninfected non-union, in whom the mechanical work has been done (or is not needed), who understands the evidence and prefers to defer surgery, or in whom surgery carries disproportionate risk.

Who is not.

• An unstable or malaligned non-union needing mechanical correction
• An infected non-union: eradicate the infection first
• A fresh fracture, where the guideline recommendation against routine use applies directly

The counselling sentence. "The best trials show no benefit in fresh fractures; in non-union the honest answer is that we do not have the trial yet, the risk is essentially nil, the cost is time and money, and surgery remains the proven treatment."

Running a course. Treatment continues daily until radiographic progression is confirmed. No trial defines when to abandon it, so there is no validated stop-point; the practical rule is to review the films on the usual non-union schedule and stop if there is no progression between successive reviews.

Compliance is the weak link. Even inside TRUST, with motivated, consented patients, compliance was only moderate. In routine practice, assume adherence is imperfect and build it into the review conversation rather than discovering it at six months.

Documentation. The device is only ever an adjunct, never a substitute, so the record should show what it is an adjunct to:

• The indication: delayed union or established non-union
• The fracture's stability and alignment
• That infection has been excluded
• The host factors being addressed

Cost and funding. The BMJ Rapid Recommendation panel flagged routine use as an inefficient use of resources and raised de-implementation as a quality-improvement measure. Where funding is contested, the Poolman guideline is the document to cite.

The topics this sits between are worth reading together. The biology it claims to accelerate is set out in fracture healing, and the problem it is offered for in non-union management, with the commonest site in tibial non-union. The other non-invasive stimulus with a comparable evidence problem is electrical stimulation. The interventions that do have an effect on union - correcting the mechanics and the biology - are covered under bone grafts and, for the single most modifiable host factor, smoking cessation.

The overall picture. High-quality randomised trials and meta-analyses show inconsistent or limited benefit for acute fracture healing, so LIPUS is not established as routinely beneficial for fresh fractures. Systematic reviews of the randomised trials find no effect on functional recovery and only low-quality or inconsistent evidence for radiographic surrogates. The earlier small positive trials were at higher risk of bias.

The landmark trial. TRUST (Busse et al, BMJ 2016) randomised 501 patients (250 LIPUS, 251 sham) with operatively managed tibial fractures across 43 North American trauma centres. It was blinded and sham-controlled, with follow-up for one year. LIPUS was no better than sham:

• Function. SF-36 physical component summary mean difference 0.55 (95% CI -0.75 to 1.84, p=0.41), against a minimal important difference of 3 to 5 points, so the confidence interval excludes any clinically important benefit
• Time to radiographic healing. Hazard ratio 1.07 (95% CI 0.86 to 1.34, p=0.55)
• Safety. No difference
• Compliance. Only moderate: 73 percent administered at least half the recommended treatments

A linked BMJ Rapid Recommendation (2017) then made a strong recommendation against routine LIPUS for fresh fractures.

What TRUST excluded. Of 3,105 patients screened, only 599 were eligible. The exclusions included pathological, segmental and bilateral fractures and, critically, any fracture with less than 25 percent cortical contact and more than a 1 cm gap after fixation. That is precisely the biologically compromised fracture in which a healing stimulus would be expected to matter most. TRUST is therefore a definitive answer for the ordinary, well-reduced, well-fixed tibia, and silent on the population the non-union argument is actually about.

The bench-to-bedside gap. The in-vitro and animal data are robust, showing accelerated endochondral ossification and upregulated osteogenic genes, yet the high-quality human trials are neutral. The explanations offered:

• Surrogate (radiographic) versus patient-important (functional) outcomes
• Small-trial and publication bias
• Coupling, dosing and compliance issues
• A ceiling effect, since ordinary fractures heal well anyway

Whether the biology helps in non-union, where there is more to gain, remains the open question the ongoing trials address.