NIHR Signal Ultrasound therapy doesn’t speed healing of leg fracture after surgery

Published on 7 February 2017

Low intensity pulsed ultrasound (LIPUS), sometimes used to encourage bone fractures to heal after surgery, makes no difference to how soon people can get back to their normal activities or to the speed at which bones appear to heal on x-ray.

The biggest trial of the treatment to date recruited 501 adults with a fractured tibia (shin bone) and who’d had the break fixed surgically. They were asked to use LIPUS for a year at home, or until the bone had healed. Half were given dummy equipment which looked and sounded identical.

Dropping LIPUS as a treatment after fixation surgery for tibial fractures could save NHS resources for use on other things.

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Why was this study needed?

A broken tibia is the most common long bone fracture. These fractures can take six months or longer to heal and are particularly vulnerable to non-union, when the broken pieces of bone fail to grow back together. LIPUS is commonly used in North America after fracture surgery with the intention of speeding up healing and preventing non-union and is available in the UK.

LIPUS involves applying ultrasound waves to skin over the fracture using a wand or probe and gel, similar to those used for pregnancy scans, but it is self-administered. The theory is that the ultrasound waves stimulate bone growth. It is used to promote healing of tibia fracture, both for naturally-healed and surgically-treated fractures, fresh fractures and those in which healing is delayed.

However, previous studies of LIPUS were small and produced conflicting results. A 2009 systematic review said that the studies included were of moderate to very low quality. Many previous studies focused on radiological signs of healing only rather than outcomes important to patients, such as ability to return to normal activities or rates of non-union.

What did this study do?

The TRUST trial recruited 501 adults having surgery for tibia fracture at 43 US hospitals. They were randomly assigned to use LIPUS or an identical dummy device for 20 minutes a day for 52 weeks or until the surgeon told them to stop.

They were assessed six times over a year by questionnaires about their physical health and when they were able to resume normal activities and work. Repeat X-rays were assessed by a central committee of orthopaedic surgeons, who agreed on whether the bones were healed.

The trial was stopped by the industry sponsor after an early, unplanned analysis which indicated no effect of LIPUS. The researchers continued to collect data from enrolled patients and eventually only 73 patients or 501 enrolled were followed up for fewer than 12 months. Data on patient compliance were finally available for 424 patients and there was no difference in compliance between treatment groups.

All personnel involved in the trial were blinded to treatment allocation which increases our confidence in the reliability of the results.

What did it find?

  • The researchers found no difference in physical health questionnaire results between the LIPUS and sham ultrasound groups (mean difference 0.55, 95% confidence interval [CI] -0.75 to 1.84). A 3 to 5 point difference on the 100 point short form 36 physical component summary score is considered important.
  • The researchers found no differences in the time to return to work without any limitations from the fracture (hazard ratio [HR] 1.11, 95% CI 0.82 to 1.50), household activities (HR 0.94, 95% CI 0.73 to 1.22), return to leisure activities (HR 1.06, 95% CI 0.77 to 1.46) or return to full weight-bearing (HR 0.87, 95% CI 0.7 to 1.08).
  • There was no difference in the time to radiographic healing based on X-ray results (HR 1.07, 95% CI 0.86 to 1.34).
  • The researchers described patient compliance with treatment as “moderate”, with 73% of the patients doing at least half of the recommended treatment sessions.

What does current guidance say on this issue?

A 2013 NICE technology guideline on a LIPUS machine called EXOGEN only recommends it as an option for treating long bone fractures that have failed to heal for nine months, called “non-union”. It is not recommended for fractures that have not healed for three months, termed “delayed healing”. The treatment was cost saving based on the fact that it was assumed it could avoid surgery in non-union. The cost of one machine in 2013 was £2562.50 (excluding VAT). The guidance does not cover the use of LIPUS starting immediately following a fracture that has been managed with fixation.

What are the implications?

The results imply that LIPUS does not help healing of tibial fracture when started immediately after fixation surgery and therefore should probably not be routinely used for this.

We don’t know whether LIPUS might be of benefit specifically for fractures which have failed to heal, or which are slow to heal, the topic of NICE interventional procedure guidance. This too must also be in doubt. It is likely that further advice will follow.

In the meantime the accompanying editorial to this paper makes the point that it is time for clinicians to make good use of these study results and abandon this ineffective treatment.

Citation and Funding

Busse JW, Bhandari M, Einhorn TA, et al. Re-evaluation of low intensity pulsed ultrasound in treatment of tibial fractures (TRUST): randomized clinical trial. BMJ 2016;355;pi5351.

The trial was funded by the Canadian Institutes of Health Research and an industry grant from Smith & Nephew.

Bibliography

NICE. EXOGEN ultrasound bone healing system for long bone fractures with non-union or delayed healing. MTG12. London: National Institute for Health and Care Excellence; 2013.

Jason W Busse, Jagdeep Kaur, Brent Mollon. Low intensity pulsed ultrasonography for fractures: systematic review of randomised controlled trials. BMJ. 2009;338:b351.

Griffin XL. Low intensity pulsed ultrasound for fractures of the tibial shaft. BMJ. 2016;355:i5652.

Why was this study needed?

A broken tibia is the most common long bone fracture. These fractures can take six months or longer to heal and are particularly vulnerable to non-union, when the broken pieces of bone fail to grow back together. LIPUS is commonly used in North America after fracture surgery with the intention of speeding up healing and preventing non-union and is available in the UK.

LIPUS involves applying ultrasound waves to skin over the fracture using a wand or probe and gel, similar to those used for pregnancy scans, but it is self-administered. The theory is that the ultrasound waves stimulate bone growth. It is used to promote healing of tibia fracture, both for naturally-healed and surgically-treated fractures, fresh fractures and those in which healing is delayed.

However, previous studies of LIPUS were small and produced conflicting results. A 2009 systematic review said that the studies included were of moderate to very low quality. Many previous studies focused on radiological signs of healing only rather than outcomes important to patients, such as ability to return to normal activities or rates of non-union.

What did this study do?

The TRUST trial recruited 501 adults having surgery for tibia fracture at 43 US hospitals. They were randomly assigned to use LIPUS or an identical dummy device for 20 minutes a day for 52 weeks or until the surgeon told them to stop.

They were assessed six times over a year by questionnaires about their physical health and when they were able to resume normal activities and work. Repeat X-rays were assessed by a central committee of orthopaedic surgeons, who agreed on whether the bones were healed.

The trial was stopped by the industry sponsor after an early, unplanned analysis which indicated no effect of LIPUS. The researchers continued to collect data from enrolled patients and eventually only 73 patients or 501 enrolled were followed up for fewer than 12 months. Data on patient compliance were finally available for 424 patients and there was no difference in compliance between treatment groups.

All personnel involved in the trial were blinded to treatment allocation which increases our confidence in the reliability of the results.

What did it find?

  • The researchers found no difference in physical health questionnaire results between the LIPUS and sham ultrasound groups (mean difference 0.55, 95% confidence interval [CI] -0.75 to 1.84). A 3 to 5 point difference on the 100 point short form 36 physical component summary score is considered important.
  • The researchers found no differences in the time to return to work without any limitations from the fracture (hazard ratio [HR] 1.11, 95% CI 0.82 to 1.50), household activities (HR 0.94, 95% CI 0.73 to 1.22), return to leisure activities (HR 1.06, 95% CI 0.77 to 1.46) or return to full weight-bearing (HR 0.87, 95% CI 0.7 to 1.08).
  • There was no difference in the time to radiographic healing based on X-ray results (HR 1.07, 95% CI 0.86 to 1.34).
  • The researchers described patient compliance with treatment as “moderate”, with 73% of the patients doing at least half of the recommended treatment sessions.

What does current guidance say on this issue?

A 2013 NICE technology guideline on a LIPUS machine called EXOGEN only recommends it as an option for treating long bone fractures that have failed to heal for nine months, called “non-union”. It is not recommended for fractures that have not healed for three months, termed “delayed healing”. The treatment was cost saving based on the fact that it was assumed it could avoid surgery in non-union. The cost of one machine in 2013 was £2562.50 (excluding VAT). The guidance does not cover the use of LIPUS starting immediately following a fracture that has been managed with fixation.

What are the implications?

The results imply that LIPUS does not help healing of tibial fracture when started immediately after fixation surgery and therefore should probably not be routinely used for this.

We don’t know whether LIPUS might be of benefit specifically for fractures which have failed to heal, or which are slow to heal, the topic of NICE interventional procedure guidance. This too must also be in doubt. It is likely that further advice will follow.

In the meantime the accompanying editorial to this paper makes the point that it is time for clinicians to make good use of these study results and abandon this ineffective treatment.

Citation and Funding

Busse JW, Bhandari M, Einhorn TA, et al. Re-evaluation of low intensity pulsed ultrasound in treatment of tibial fractures (TRUST): randomized clinical trial. BMJ 2016;355;pi5351.

The trial was funded by the Canadian Institutes of Health Research and an industry grant from Smith & Nephew.

Bibliography

NICE. EXOGEN ultrasound bone healing system for long bone fractures with non-union or delayed healing. MTG12. London: National Institute for Health and Care Excellence; 2013.

Jason W Busse, Jagdeep Kaur, Brent Mollon. Low intensity pulsed ultrasonography for fractures: systematic review of randomised controlled trials. BMJ. 2009;338:b351.

Griffin XL. Low intensity pulsed ultrasound for fractures of the tibial shaft. BMJ. 2016;355:i5652.

Re-evaluation of low intensity pulsed ultrasound in treatment of tibial fractures (TRUST): randomized clinical trial

Published on 1 November 2016

Busse, J. W.,Bhandari, M.,Einhorn, T. A.,Schemitsch, E.,Heckman, J. D.,Tornetta, P., 3rd,Leung, K. S.,Heels-Ansdell, D.,Makosso-Kallyth, S.,Della Rocca, G. J.,Jones, C. B.,Guyatt, G. H.

Bmj Volume 355 , 2016

OBJECTIVE: To determine whether low intensity pulsed ultrasound (LIPUS), compared with sham treatment, accelerates functional recovery and radiographic healing in patients with operatively managed tibial fractures. DESIGN: A concealed, randomized, blinded, sham controlled clinical trial with a parallel group design of 501 patients, enrolled between October 2008 and September 2012, and followed for one year. SETTING: 43 North American academic trauma centers. PARTICIPANTS: Skeletally mature men or women with an open or closed tibial fracture amenable to intramedullary nail fixation. Exclusions comprised pilon fractures, tibial shaft fractures that extended into the joint and required reduction, pathological fractures, bilateral tibial fractures, segmental fractures, spiral fractures >7.5 cm in length, concomitant injuries that were likely to impair function for at least as long as the patient's tibial fracture, and tibial fractures that showed <25% cortical contact and >1 cm gap after surgical fixation. 3105 consecutive patients who underwent intramedullary nailing for tibial fracture were assessed, 599 were eligible and 501 provided informed consent and were enrolled. INTERVENTIONS: Patients were allocated centrally to self administer daily LIPUS (n=250) or use a sham device (n=251) until their tibial fracture showed radiographic healing or until one year after intramedullary fixation. MAIN OUTCOME MEASURES: Primary registry specified outcome was time to radiographic healing within one year of fixation; secondary outcome was rate of non-union. Additional protocol specified outcomes included short form-36 (SF-36) physical component summary (PCS) scores, return to work, return to household activities, return to >/=80% of function before injury, return to leisure activities, time to full weight bearing, scores on the health utilities index (mark 3), and adverse events related to the device. RESULTS: SF-36 PCS data were acquired from 481/501 (96%) patients, for whom we had 2303/2886 (80%) observations, and radiographic healing data were acquired from 482/501 (96%) patients, of whom 82 were censored. Results showed no impact on SF-36 PCS scores between LIPUS and control groups (mean difference 0.55, 95% confidence interval -0.75 to 1.84; P=0.41) or for the interaction between time and treatment (P=0.30); minimal important difference is 3-5 points) or in other functional measures. There was also no difference in time to radiographic healing (hazard ratio 1.07, 95% confidence interval 0.86 to 1.34; P=0.55). There were no differences in safety outcomes between treatment groups. Patient compliance was moderate; 73% of patients administered >/=50% of all recommended treatments. CONCLUSIONS: Postoperative use of LIPUS after tibial fracture fixation does not accelerate radiographic healing and fails to improve functional recovery.Study registration ClinicalTrialGov Identifier: NCT00667849.

The Short Form 36 or SF-36 is a standard 36-component questionnaire which can be adapted to different healthcare situations. It includes a physical component, and asks how much physical health impacts on activities of daily living and ability to lead a normal life.

Expert commentary

Unfortunately, LIPUS, does not appear to be a solution to address the morbidity and resource burden of tibia fracture non-union. Ultrasound is attractive because it is non-invasive and safe, but it is expensive and compliance with using time-consuming devices is a practical challenge. Ultrasound treatment can be a distraction, delaying recognition of biomechanical problems that should be addressed with revision surgery. Ineffective treatment wastes money and can indirectly add morbidity by prolonging return to function. It is useful to have good evidence to support avoiding adding inappropriate cost to the treatment of tibia fracture after intramedullary nailing.

Mr Iain McFadyen, Consultant Trauma and Orthopaedic Surgeon, Royal Stoke University Hospital, University of North Midlands NHS Trust