Coverage Policy Manual
Policy #: 1998023
Category: DME
Initiated: February 1998
Last Review: August 2018
  Ultrasound Accelerated Fracture Healing Device

Description:
The majority of bone fractures heal spontaneously over the course of several months following injury. However, approximately 5-10% of all fractures have delayed healing, resulting in continued morbidity and increased utilization of healthcare services. Ultrasound may accelerate healing of fractures by stimulating new bone growth, and therefore, has been proposed as a treatment for fractures with delayed healing or at high risk for non-healing.
 
The current policy does not limit the use of the device to specific fracture sites. According to orthopedic anatomy, the skeleton consists of long bones, short bones, flat bones, and irregular bones. Long bones act as levels to facilitate motion, while short bones function to dissipate concussive forces. Short bones include those comprising the carpus and tarsus. Flat bones, such as the scapula or pelvis, provide a broad surface area for attachment of muscles. Despite their anatomic classification, all bones are composed of a combination of cortical and trabecular (also called cancellous) bone. Depending on their function, bones are composed of a varying combination of cortical and trabecular bone. However, at the cellular level, the type of bone cannot be distinguished histologically. The inclusion of all bones regardless of the anatomic site is based on this histologic similarity of all bones; it is not anticipated that the efficacy of ultrasound-accelerated healing would vary according to the anatomic site and function of the bone.
 
The definition of a fracture nonunion has remained controversial. For electrical bone growth stimulators, the U.S. Food and Drug Administration (FDA) labeling defined nonunion as follows: "A nonunion is considered to be established when a minimum of 9 months has elapsed since injury and the fracture site shows no visibly progressive signs of healing for minimum of 3 months." Others have contended that 9 months represents an arbitrary cut-off point that does not reflect the complicated variables that are present in fractures, i.e., degree of soft tissue damage, alignment of the bone fragments, vascularity, and quality of the underlying bone stock. Other proposed definitions of nonunion involve 3 to 6 months’ time from original healing, or simply when serial x-rays fail to show any further healing. According to the FDA labeling for a low-intensity pulsed ultrasound device, “a nonunion is considered to be established when the fracture site shows no visibly progressive signs of healing.”
 
Delayed union is generally considered a failure to heal between 3 and 9 months after fracture, after which the fracture site would be considered to be a nonunion. Delayed union may also be defined as a decelerating bone healing process, as identified in serial x-rays. (In contrast, nonunion serial x-rays show no evidence of healing.) Together, delayed union and nonunion are sometimes referred to as "ununited fractures." To determine the status of fracture healing, it is important to include both radiographic and clinical criteria. Clinical criteria include the lack of ability to bear weight, fracture pain, and tenderness on palpation.
 
Ultrasound treatment can be self-administered with one daily 20-minute treatment, continuing until the fracture has healed. The mechanism of action at the cellular level is not precisely known but is thought to be related to a mechanical effect on cell micromotion/deformation, causing an increase in stimulation of transmembrane cell adhesion molecules and upregulation of cyclooxygenase-2.
 
Regulatory Status
The Sonic Accelerated Fracture Healing System, SAFHS® (also referred to as Exogen 2000®) was initially cleared for marketing by the FDA in October 1994 as a treatment of fresh, closed, posteriorly displaced distal radius (Colles’) fractures and fresh, closed, or grade-I open tibial diaphysis fractures in skeletally mature individuals when these fractures are orthopedically managed by closed reduction and cast immobilization. In February 2000, the labeled indication was expanded to include the treatment of established nonunions, excluding skull and vertebra.
 
Note: Electrical stimulation of bone healing is considered separately in policy No.1997057.
 

Policy/
Coverage:
Effective November 2017
 
Low-intensity pulsed ultrasound as a treatment of fresh fractures, fracture nonunion and delayed union fractures, stress fractures, osteotomy, distraction osteogenesis or any other indication does not meet member benefit certificate primary coverage criteria.
 
For members with contracts without primary coverage criteria, low-intensity pulsed ultrasound as a treatment of fresh fractures, fracture nonunion and delayed union fractures, stress fractures, osteotomy, distraction osteogenesis or any other indication is considered not medically necessary. Services that are considered not medically necessary are specific contract exclusions in most member benefit certificates.
 
Effective February 2017 – October 2017
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Low-intensity ultrasound treatment meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when used as an adjunct to conventional management (i.e., closed reduction and cast immobilization) for the treatment of acute (defined as within 7 days after fracture occurs), closed fractures in skeletally mature individuals.
 
Low-intensity ultrasound treatment meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes as a treatment of fracture nonunions of bones excluding the skull and vertebra when the following criteria are met:
 
    • At least 3 months have passed since the date of the fracture, AND  
    • Serial radiographs have confirmed that no progressive signs of healing have occurred, AND  
    • The fracture gap is 1 cm or less, AND  
    • The patient can be adequately immobilized and is of an age where he/she is likely to comply with non-weight bearing.  
 
Low-intensity ultrasound treatment as a treatment of delayed union of bones meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes. Delayed union of bones is defined by the following criteria:
 
    • decelerating healing process as determined by serial radiographs, AND
    • a lack of clinical and radiologic evidence of union, bony continuity, or bone reaction at the fracture site for no less than 3 months from the index injury or the most recent intervention.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Other applications of low-intensity ultrasound treatment, including but not limited to treatment of open fractures, or congenital pseudoarthroses, is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For contracts without primary coverage criteria, other applications of low-intensity ultrasound treatment, including but not limited to treatment of open fractures, or congenital pseudoarthroses, are considered investigational.  Investigational services are specific exclusions in most member benefit certificates of coverage.
 
Effective October 2012 – January 2014
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Low-intensity ultrasound treatment meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when used as an adjunct to conventional management (i.e., closed reduction and cast immobilization) for the treatment of fresh, closed fractures in skeletally mature individuals.
 
Low-intensity ultrasound treatment meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes as a treatment of fracture nonunions of bones excluding the skull and vertebra.  The following patient selection criteria are suggested, consistent with those proposed for electrical stimulation as a treatment of nonunions:
        • At least 3 months have passed since the date of the fracture, AND
        • Serial radiographs have confirmed that no progressive signs of healing have occurred, AND
        • The fracture gap is 1 cm or less, AND
        • The patient can be adequately immobilized and is of an age where he/she is likely to comply with non-weight bearing.
 
Low-intensity ultrasound treatment as a treatment of delayed union of bones meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
  
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Other applications of low-intensity ultrasound treatment, including but not limited to treatment of open fractures, or congenital pseudoarthroses, is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For contracts without primary coverage criteria, other applications of low-intensity ultrasound treatment, including but not limited to treatment of open fractures, or congenital pseudoarthroses, are considered investigational.  Investigational services are specific exclusions in most member benefit certificates of coverage.
 
Effective prior October 2012
Low-intensity ultrasound treatment meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when used as an adjunct to conventional management (i.e., closed reduction and cast immobilization) for the treatment of fresh, closed fractures in skeletally mature individuals.
 
Low-intensity ultrasound treatment meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes as a treatment of fracture nonunions of bones excluding the skull and vertebra.  The following patient selection criteria are suggested, consistent with those proposed for electrical stimulation as a treatment of nonunions:
    • At least 3 months have passed since the date of the fracture, AND
    • Serial radiographs have confirmed that no progressive signs of healing have occurred, AND
    • The fracture gap is 1 cm or less, AND
    • The patient can be adequately immobilized and is of an age where he/she is likely to comply with non-weight bearing.
 
Other applications of low-intensity ultrasound treatment, including but not limited to treatment of delayed unions (defined as a decelerating healing process as determined by serial x-rays), open fractures, or congenital pseudoarthroses, is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For contracts without primary coverage criteria, other applications of low-intensity ultrasound treatment, including but not limited to treatment of delayed unions (defined as a decelerating healing process as determined by serial x-rays), open fractures, or congenital pseudoarthroses, are considered investigational.  Investigational services are an exclusion in the member certificate of coverage.

Rationale:
LOW-INTENSITY PULSED ULTRASOUND
 
Systematic Reviews
A recently published systematic review by Schandelmaier et al (2017) provides the most comprehensive and rigorous overview and analysis of the existing evidence, including 26 randomized controlled trials (RCTs) that used low-intensity pulsed ultrasound (LIPUS) for bone healing (Schandelmaier, 2017).  There is a substantial degree of overlap in previously published systematic reviews or meta-analyses (TEC Assessment, 1995; Busse, 2009; Griffin, 2014; Schandelmaier, 2017; Seger, 2017). Therefore, we will primarily focus this review of evidence on the findings of Schandelmaier et al (2017) and highlight the results of RCTs identified to be of higher quality. The recently published meta-analysis by Seger et al (2017) analyzed healing index and average time to union following use of LIPUS in cases of scaphoid nonunion, but it did not report control group comparisons (Seger, 2017).
 
The study populations in RCTs included by Schandelmaier et al (2017) examined multiple types of fractures including patients with fresh fractures surgically managed (n=7), fresh fractures not surgically managed (n=6), distraction osteogenesis (n=5), nonunion fractures (n=3), osteotomy (n=3), and stress fractures (n=2). The RCTs had a median population size of 30 patients (range, 8-501 patients). The outcomes examined by this systematic review emphasized those outcomes reported by patients to be most important: functional recovery (eg, time to return to work, time to full weight bearing); pain reduction; and number of subsequent operations. Additional outcomes included time to radiographic healing, since this may be used by physicians to influence clinical decision making and adverse effects associated with LIPUS.
 
In this systematic review, 2 reviewers independently assessed the quality of the included RCTs, using GRADE, a modified Cochrane risk of bias tool. Generation of randomization sequence, concealment of allocation, and blinding of patients, caregivers, and outcome reporting were evaluated in each trial. Each outcome within each trial was assessed for blinding of outcome assessors, loss to follow-up, and additional limitations. Trial authors were contacted if there was uncertainty in the quality assessment. Of the 26 included trials, 6 were considered to have a low risk of bias, with the remaining 20 trials considered to have a high risk of bias. Reasons for high risk of bias designation included failure to report a method for allocation concealment (15 trials), high or unclear numbers of patients excluded from the analysis (13 trials), unblinded patients (10 trials), and unblinded caregivers or outcome assessors (10 trials). Of the 6 trials rated to be at low risk of bias, 4 were conducted in individuals with fresh fracture, 3 of which were operatively managed tibial fractures8,9 and one of which was nonoperatively managed clavicle fractures (Lubbert, 2008).The other 2 trials rated at low risk of bias included operatively managed mandibular fractures related to distraction osteogenesis (Schortinghuis, 2005; Schortinghuis, 2008).
 
None of the overall results from the meta-analysis (Schandelmaier, 2017)  demonstrated statistically significant differences supporting LIPUS. Variation in results was observed for days to full weight bearing, pain, or radiographic healing, and when only trials with low risk of bias were included, there was no difference between treatment and control groups.
 
Fresh Fractures
Surgically Managed
In 2016, Busse et al reported results from a concealed, blinded, sham-controlled, randomized trial evaluating LIPUS for the treatment of patients who underwent intramedullary nailing for fresh tibial fractures (Busse, 2016). The trial enrolled 501 patients; 250 received a LIPUS device, and 251 received a sham device. Treatment was self-administered for 20 minutes a day until there was radiographic evidence of healing. Coprimary end points were radiographic healing and return to function (as measured by the 36-Item Short-Form Health Survey [SF-36] Physical Component Summary score). Both radiographic and functional assessments had to show a clinically important effect for the results to be considered positive. All patients, clinicians, investigators, data analysts, and the industry sponsor were blinded to allocation until data analysis was complete. Patient compliance was considered moderate, with 73% of patients administering over half of all recommended treatments. There was no difference in time to radiographic healing between the treatment groups (hazard ratio, 1.07; 95% confidence interval [CI], 0.86 to 1.34; p=0.55). Moreover, there was no different in SF-36 Physical Component Summary scores (mean difference, 0.55; 95% CI, -0.75 to 1.84; p=0.41). A previously conducted pilot double-blind RCT by Busse et al (2014), including 51 subjects not assessed in the 2016 study, also did not find any statistically significant differences in pain reduction, subsequent operations, or radiographic healing time (Busse, 2014).
 
Emami et al (1999) conducted a double-blind, sham-controlled trial that randomized 32 patients with a fresh tibial fracture fixed with an intramedullary rod to additional treatment with an active (n=15) or inactive (n=17) LIPUS device (Emammi, 1999). LIPUS treatment began within 3 days of surgery (1 patient began treatment within 7 days of injury), and was self-administered for 20 minutes a day for 75 days. Radiographs were taken every third week until healing. Results showed that LIPUS did not shorten healing time based on any of the following measures: time to first visible callus (mean, 40 days, SD=3 for LIPUS vs 37 days, SD=3 for sham; p=0.44); time to radiographic healing assessed by radiologist (mean, 155 days, SD=days [median, 113 days] for LIPUS vs mean, 125 days, SD=11 [median, 112 days] for sham; p=0.76); and time to radiographic healing assessed by orthopedic surgeon (mean, 128 days, SD=13, for LIPUS and mean, 114 days, SD=9 for sham; p=0.40).
 
Nonsurgically Managed
Lubbert et al (2008) performed a multicenter, double-blind RCT (N=101) of LIPUS treatment of fresh (<5 days) clavicle shaft fractures (Lubbert, 2008). Patients used the LIPUS devices for 20 minutes once daily for 28 days and recorded their subjective feeling as to whether the fracture healed (the primary outcome measure), pain on visual analog scale, level of daily activities (hours of work, household work, sport), and analgesic use. Patient perception of the day the fracture healed was determined in 92 patients (47 active, 45 placebo); mean time to healing was 26.77 days in the active group and 27.09 days in the placebo group (p=0.91). Between-group differences regarding analgesic use and mean visual analog scale scores also did not differ significantly.
 
Section Summary: Fresh Fractures
Evidence for the use of LIPUS following fresh fracture, either surgically or nonsurgically managed, consists of a 2017 systematic review including 13 RCTs, 4 of which rated low risk for bias. The overall results of the systematic review and meta-analysis and particularly the results including only RCTs with a low risk of bias did not demonstrate statistically significant improvements for LIPUS on functional outcomes, pain, or radiographic healing time.
 
Fracture Nonunion or Delayed Union Fracture
The 2017 meta-analysis by Seger et al included 5 studies focused on scaphoid nonunions and analyzed healing index and average time to union following LIPUS.4 Among 166 cases in the analysis, 78.6% (range, 33%-100%) were reported to show healing following LIPUS with an average time to union of 4.2 months (range, 2.3-5.6 months). Comparative results were not the focus of the analysis.
 
The 2017 systematic review published by Schandelmaier included 3 RCTs in nonunion fractures that were operatively managed; however, all studies were rated at high risk of bias(Schandelmaier, 2017).  Schofer et al (2010) reported on a multicenter, randomized, double-blinded, sham-controlled trial of LIPUS in 101 patients with delayed union of the tibia (Schofer, 2010). Delayed union was defined as a lack of clinical and radiologic evidence of union, bony continuity, or bone reaction at the fracture site for no less than 16 weeks from the index injury or the most recent intervention. Roughly one-third of patients had an open fracture. Patients were randomized to LIPUS (n=51) or to an inactive sham device (n=50), to be administered 20 minutes a day for 16 weeks. The primary outcome was change in bone mineral density assessed by computed tomography attenuation coefficients. Gap area was a secondary outcome. Intention-to-treat analysis showed that LIPUS improved mean bone mineral density by 34% (90% CI, 14% to 57%) compared with sham treatment. The mean reduction in bone gap area was -0.13 mm2 in the LIPUS group and -0.10 mm2 in the sham group (effect size, -0.47; 95% CI, -0.91 to -0.03 mm2). At the end of 16 weeks, physicians judged 65% of patients in the LIPUS group healed and 46% of the patients in the sham group healed (p=0.07). This trial did not report functional outcomes or pain assessment limiting the utility of results.
 
Rutten et al (2012), published only as a thesis, reported on a blinded RCT with 20 subjects with tibial fracture nonunion that found a statistically significant reduction in time to radiographic healing (percent difference in days, -57.2%; 95% CI, -74.7% to -27.6%) (Rutten, 2012). However, there was a 45% loss to follow-up rate raising significant concerns about potential bias of these findings.
 
Ricardo et al (2006) published a blinded RCT in 21 subjects with scaphoid nonunion that also found a statistically significant reduction in time to radiographic healing (-40.4%; 95% CI, -48.7% to -30.8%) (Ricardo, 2006). Biglari et al (2016) conducted a prospective, single-institution, observational study on 61 nonunions in long bones of the lower extremity treated with LIPUS (Biglari, 2016). To be included in the study, patients could not have had an intervention at least 90 days before beginning LIPUS treatment. Successful therapy was defined as a radiographically confirmed consolidation and no further surgical revision needed for the next year. All patients were available for all follow-up visits. The average age of the patients was 45 years (range, 18-63 years). Twenty (32.8%) cases met the successful therapy definition. An analysis comparing successful and unsuccessful outcomes found that LIPUS was more beneficial in patients with a fracture gap size less than 1 cm, a fracture age of less than 6 months, and a low Non-Union Scoring System score.
 
Zura et al (2015) published an industry-sponsored analysis of the effect of LIPUS on patients with nonunion, defined as a failure to heal for more than 12 months using clinical and radiographic criteria (Zura, 2015).Patients were a subset in a U.S. Food and Drug Administration-required postmarket registry of consecutive patients who have used the Exogen LIPUS device. The registry had 1286 patients with nonunion. The analysis was performed on 767 (60%) records. Reasons for being excluded from the analysis included: 18% lost to follow-up, 9% for noncompliance, 8% withdrawals, and 5% other factors. The reported healing rate was 86.2% with the average time for healing 6.0 months.
 
Section Summary: Fracture Nonunion or Delayed Union Fracture
The evidence for LIPUS treatment of fracture nonunion consists only of lower quality and mostly uncontrolled studies including a 2017 meta-analysis without controlled comparison results, 3 RCTs at high risk of bias (one published as a thesis) and 2 observational studies (a prospective study and a registry study). Reported outcomes do not include functional outcomes, and a wide range of healing rates were reported across the studies with a lack of comparison with routine surgical care in the observational studies, limiting meaningful interpretation of these results.
 
Stress Fractures, Osteotomy Sites, or Distraction Osteogenesis
Rue et al (2004) reported on a double-blind RCT that examined the effects of 20 minutes of daily LIPUS on tibial stress fracture healing issues such as pain, function, and resumption of professional and personal activities in 26 military recruits (Rue, 2004). The delay from onset of symptoms to diagnosis was 32 days in the LIPUS group and 28 days in the placebo group. This trial found no significant difference in healing times between LIPUS treatment and sham, with a mean time of return to duty of 56 days for both groups. The trial was rated with a high risk of bias in the 2017 Schandelmaier meta-analysis (Schandelmaier, 2017).
 
In 2013, Urita et al published a small (N=27) quasi-randomized study (alternating assignment) of LIPUS after ulnar-shortening osteotomy for ulnar impaction syndrome or radial-shortening osteotomy for Kienböck disease (Urita, 2013).  Patients in the LIPUS group received a daily 20-minute treatment for at least 12 weeks postoperatively. Blinded evaluation of radiographic healing showed that LIPUS reduced the mean time to the cortical union by 27% (57 days vs 76 days) and endosteal union by 18% (121 days vs 148 days) compared with sham treatment. At the time of endosteal healing, the osteotomy plus LIPUS group and the osteotomy-only group had similar results, as measured using the Modified Mayo Wrist Score and no pain at the osteotomy site. The study was rated with a high risk of bias in the 2017 meta-analysis by Schandelmaier (Schandelmaier, 2017).
 
The 2017 systematic review by Schandelmaier included 6 trials of LIPUS for distraction osteogenesis following surgery and 4 of 6 studies were rated at high risk of bias (Schandelmaier, 2017).  Four studies were in the tibia, (Dudda, 2011; Salem, 2014; El-Mowafi, 2005; Tsumaki, 2004) and the other two were in the mandible (Schortinghuis, 2005; Schortinghuis, 2008). No clinically meaningful results were reported for the mandible studies in the meta-analysis (Schandelmaier, 2017). The remaining studies in the tibia were all unblinded. No statistically significant difference was noted in subsequent operations (relative risk, 0.63; 95% CI 0.13 to 2.99) as reported by Dudda et al (Dudda, 2011) in the meta-analysis (Schandelmaier, 2017).  Four of the studies (Dudda, 2014; Salem, 2014; El-Mowafi, 2005; Tsumaki, 2004)  were included in the metaanalysis  (Schandelmaier, 2017) for time to radiographic healing with mixed results, three not reporting statistically significant results.
 
Section Summary: Stress Fractures, Osteotomy Sites, or Distraction Osteogenesis
The evidence for LIPUS treatment of stress fractures, osteotomy sites, or distraction osteogenesis consists only of lower quality RCTs all rated to have a high risk of bias. Results do not generally include functional outcomes and results across various outcomes, primarily including time to radiographic healing, are inconsistent.
 
SUMMARY OF EVIDENCE
For individuals who have fresh fractures (surgically or nonsurgically managed) who receive low-intensity pulsed ultrasound (LIPUS), the evidence includes randomized controlled trials (RCTs) and a 2017 cumulative meta-analysis of RCTs. Relevant outcomes are symptoms, morbid events, functional outcomes, and quality of life. The evidence base has recently evolved with the publication of a large RCT and meta-analysis significantly shifting the weight of the evidence. Conclusions based on several earlier small RCTs, rated at high risk of bias, showed a potential benefit of LIPUS; however, the large RCT published in 2016, rated at low risk of bias, showed no benefit. A 2017 meta-analysis including only trials with low risk of bias found no difference in days to full weight bearing, pain reduction, or days to
radiographic healing. Similarly, the overall results of the meta-analysis found no significant difference in return to work, subsequent operations, or adverse effect. The evidence is insufficient to determine the effects of the technology on health outcomes.
 
For individuals who have fracture nonunion or delayed union fracture who receive LIPUS, the evidence includes only lower quality studies including a small systematic review in scaphoid nonunions, 3 low-quality RCTs, and 2 observational studies. Relevant outcomes are symptoms, morbid events, functional outcomes, and quality of life. Reported outcomes in this subgroup of fractures do not include functional outcomes. A wide range of healing rates have been reported across the observational studies with a lack of comparison with routine surgical care, limiting any meaningful interpretation of these results. Additionally, the evidence base on the use of LIPUS in the management of fresh fractures has evolved as described above and there is no demonstrated physiologic mechanism suggesting differential results of
LIPUS in fracture nonunion or delayed union. The evidence is insufficient to determine the effects of the technology on health outcomes.
 
For individuals who have stress fractures, osteotomy sites, or distraction osteogenesis who receive LIPUS, the evidence includes only lower quality studies including small RCTs. Relevant outcomes are symptoms, morbid events, functional outcomes, and quality of life. Results do not generally include functional outcomes and results across various outcomes, primarily time to radiographic healing, are inconsistent. Additionally, the evidence base on the use of LIPUS in the management of fresh fractures has evolved as described above and there is no demonstrated physiologic mechanism suggesting differential results of LIPUS in stress fractures, osteotomy sites, or distraction osteogenesis. The evidence is insufficient to determine the effects of the technology on health outcomes.
 
PRACTICE GUIDELINES AND POSITION STATEMENTS
British Medical Journal Rapid Recommendation
The British Medical Journal (BMJ) Rapid Recommendations are a series of articles, produced by BMJ in collaboration with the MAGIC group,(MAGIC, 2017) to provide clinicians with practice guidelines. In 2017, BMJ Rapid Recommendations published guidelines on the use of e of low-intensity pulsed ultrasound (LIPUS) for bone healing (Poolman, 2017). The guidelines were based on a 2017 systematic review, which included 26 randomized controlled trials evaluating patients with fresh fractures not surgically managed, fresh fractures surgically managed, nonunion fractures, osteotomy, and distraction osteogenesis (Schandelmaier, 2017).  The committee concluded that there is “moderate to high certainty evidence to support a strong recommendation against the use of LIPUS for bone healing.” Furthermore, the guideline expert panel discussed whether the results of higher quality studies in patients with fresh fractures reported in Schandelmaier et al (2017) would apply to other types of fractures including nonunions and osteotomies (Schandelmaier, 2017).  “After extensive deliberations, the panel found no compelling anatomical or physiological reasons why LIPUS would probably be beneficial in these other patient populations” (Poolman, 2017).
 
National Institute for Health and Care Excellence
The U.K.’s National Institute for Health and Care Excellence (NICE) published guidance in 2010 on LIPUS to promote fracture healing (NICE, 2017).  NICE concluded that this procedure “can reduce fracture healing” and is particularly beneficial for “delayed healing and fracture non-union.”
 
In 2013, NICE published guidance on Exogen for the treatment of long bone fractures with nonunion and delayed fracture healing (NICE, 2013).  NICE concluded that use of the Exogen bone healing system to treat longbone fractures with nonunion is supported by “clinical evidence” and “cost savings … through avoiding surgery.” For long-bone fractures with delayed healing, defined as no radiologic evidence of healing after 3 months, there was “some radiologic evidence of improved healing.” However, due to “substantial uncertainties about the rate at which bone healing progresses without adjunctive treatment between 3 and 9 months after fracture” and need for surgery, “cost consequences” were uncertain. The next review by NICE of the Exogen system is scheduled to begin in April 2017.
 
American Academy of Orthopaedic Surgeons
The American Academy of Orthopaedic Surgeons published 2009 guidelines on the treatment of distal radius fractures (American Academy of Orthopaedic Surgeons, 2009). The Academy issued a limited recommendation for the use of LIPUS for adjuvant treatment of distal radius fractures. While evidence from 1 study demonstrated an increased rate of healing (measured by the absence of pain and radiographic union), the additional cost of LIPUS, resulted in a “limited” recommendation.
 
2018 Update
A literature search was conducted through July 2018.  There was no new information identified that would prompt a change in the coverage statement.  The key identified literature is summarized below.
 
Fresh Fractures
Lou et al conducted a meta-analysis focusing on fresh fractures (Lou, 2017). The literature search, conducted through November 2016, included 12 studies, all of which were included in the Schandelmaier et al meta-analysis, except for a small study (N=20) by Strauss et al, which only appeared in a conference abstract (Schandelmaier, 2016; Strauss, 1999). Studies included patients that had been surgically managed and conservatively managed. Time to fracture union was significantly lower in patients receiving LIPUS than inpatients not receiving LIPUS (standard mean difference, -0.65; 95% 95% confidence interval [CI], -1.13 to -0.17). Subgroup analysis showed that this significant reduction in healing time with LIPUS was seen only among patients conservatively managed, while there was no difference in healing time among patients surgically managed. Reviewers concluded that patients with fresh fractures might benefit from the use of LIPUS but warned that there were methodologic limitations in the trials. Separate analyses using only low risk of bias trials was not conducted.
 
Tarride et al provided additional analyses using data from the TRUST trial, comparing health care resource use among patients using LIPUS with patients using the sham device (Tarride, 2017). There were no significant differences between groups (11% in patients receiving LIPUS vs 10% in patients receiving sham) in need for secondary procedures (eg, removal of lock screw, implant exchange or removal. There were also no statistically significant differences in use of physical therapy (44% vs 46%), use of anticoagulants (42% vs 36%), or use of nonsteroidal anti-inflammatory drugs (28% vs 35%) among patients receiving LIPUS compared with patients receiving sham, respectively.

CPT/HCPCS:
20979Low intensity ultrasound stimulation to aid bone healing, noninvasive (nonoperative)
E0760Osteogenesis stimulator, low intensity ultrasound, noninvasive

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Accelerated fracture healing. 1995 Blue Cross Blue Shield Association Technology Evaluation Center Assessment; tab 14.

American Academy of Orthopaedic Surgeons.(2017) The treatment of distal radius fractures. 2009; http://www.aaos.org/research/guidelines/drfguideline.pdf. Accessed January 30, 2017.

Bhandari M, Fong K, Sprague S, et al.(2012) Variability in the definition and perceived causes of delayed unions and nonunions: a cross-sectional, multinational survey of orthopaedic surgeons. J Bone Joint Surg Am. Aug 1 2012;94(15):e1091-1096. PMID 22854998

Biglari B, Yildirim TM, Swing T, et al.(2016) Failed treatment of long bone nonunions with low intensity pulsed ultrasound. Aug 2016;136(8):1121-1134. PMID 27383218

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Busse JW, Bhandari M, Einhorn TA, et al.(2014) Trial to re-evaluate ultrasound in the treatment of tibial fractures (TRUST): a multicenter randomized pilot study. Trials. 2014;15:206. PMID 24898987

Busse JW, Bhandari M, Einhorn TA, et al.(2016) Re-evaluation of low intensity pulsed ultrasound in treatment of tibial fractures (TRUST): randomized clinical trial. BMJ. Oct 25 2016;355:i5351. PMID 27797787

Busse JW, Bhandari M, et al.(2002) The effect of low-intnsity pulsed ultrasound therapy on time to fracture healing: a meta-analysis. CMAJ 2002; 166:437-41.

Busse JW, Bhandari M, Kulkarni AV, et al.(2002) The effect of low-intensity pulsed ultrasound therapy on time to fracture healing: A meta-analysis. CMAJ 2002; 166:437-41.

Busse JW, Kaur J, Mollon B, et al.(2009) Low intensity pulsed ultasonography for fractures: systematic review of randomised controlled trials. BMJ 2009; 338:b351.

Buza JA, 3rd, Einhorn T.(2016) Bone healing in 2016. Clin Cases Miner Bone Metab. May-Aug 2016;13(2):101-105. PMID 27920804

Coverage Issues Manual. http://www.hcfa.gov/pubforms/06_cim/ci35.htm#_1_53. Accessed October 22 2000.

Dijkman BG, Busse JW, Walter SD et al.(2011) The impact of clinical data on the evaluation of tibial fracture healing. Trials 2011; 12:237.

Dudda M, Hauser J, Muhr G, et al.(2011) Low-intensity pulsed ultrasound as a useful adjuvant during distraction osteogenesis: a prospective, randomized controlled trial. J Trauma. Nov 2011;71(5):1376-1380. PMID 22071933

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