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Ultrasound Accelerated Fracture Healing Device

Policy Number: MP-331

Latest Review Date: April 2019

Category:  DME                                                                    

Policy Grade: B

Description of Procedure or Service:

Low-intensity pulsed ultrasound (LIPUS) has been investigated as a technique to accelerate healing of fresh fractures, surgically treated closed fractures, delayed unions, nonunions, stress fractures, osteotomy sites, and distraction osteogenesis. LIPUS is administered using a transducer applied to the skin surface overlying the fracture site.

Bone Fractures

An estimated 7.9 million fractures occur annually in the United States. Most bone fractures heal spontaneously over the course of several months following standard fracture care (closed reduction if necessary, followed by immobilization with casting or splinting). However, approximately 5% to 10% of all fractures have delayed healing, resulting in continued morbidity and increased utilization of health care services. Factors contributing to a nonunion include which bone is fractured, fracture site, degree of bone loss, time since injury, extent of soft tissue injury, and patient factors (e.g., smoking, diabetes, systemic disease).

Fracture Nonunion

There is no standard definition of a fracture nonunion. The Food and Drug Administration has defined nonunion as when “a minimum of 9 months has elapsed since injury and the fracture site shows no visibly progressive signs of healing for a minimum of 3 months." Other definitions cite 3 to 6 months of time from the original injury, or simply when serial radiographs fail to show any further healing. These definitions do not reflect the underlying conditions in fractures that affect healing, such as the degree of soft tissue damage, alignment of the bone fragments, vascularity, and quality of the underlying bone stock.

Delayed Union

Delayed union is generally considered a failure to heal between 3 and 9 months post fracture, after which the fracture site would be considered a nonunion. Delayed union may also be defined as a decelerating bone healing process, as identified in serial radiographs. (In contrast, nonunion serial radiographs show no evidence of healing.) It is important to include both radiographic and clinical criteria to determine fracture healing status. Clinical criteria include the lack of ability to bear weight, fracture pain, and tenderness on palpation.

Treatment

Low-intensity pulsed ultrasound (LIPUS) has been proposed to accelerate healing of fractures. LIPUS is believed to alter the molecular and cellular mechanisms involved in each stage of the healing process (inflammation, soft callus formation, hard callus formation, and bone remodeling). The mechanism of action at the cellular level is not precisely known, but it is theorized that LIPUS may stimulate the production or the activities of the following compounds that contribute to the bone healing process: cyclooxygenase-2, collagenase, integrin proteins, calcium, chondroblasts, mesenchymal cells, fibroblasts, and osteoblasts.

Low intensity pulsed ultrasound treatment is self-administered with 1 daily 20 minute treatment, continuing until the fracture has healed, usually for about 5 months.

Policy:

Fresh Fracture

Low-intensity ultrasound treatment (E0760) may be considered medically necessary 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. Candidates for ultrasound treatment are those at high risk for delayed fracture healing or nonunions. These risk factors may include either locations of fractures or patient morbidities and include any one of the following:

  • Patient Comorbidities
    • Diabetes
    • Steroid therapy
    • Osteoporosis
    • Alcoholism history
    • Smoking
    • Obesity greater than 50% over ideal weight
    • Severe anemia
    • End Stage Renal disease

  • Fracture locations
  • Radial fractures that are closed & posteriorly displaced (Colles fx)
  • Tibial diaphysis fractures that are closed or grade I open (wound <1cm with minimal soft tissue injury, wound bed is clean and bone injury is simple with minimal comminution)
  • Jones Fracture, 5th metatarsal
  • Navicular (scaphoid) fracture
  • Fractures associated with extensive soft tissue or vascular damage
  • Metatarsal fracture

Delayed Union

Low intensity ultrasound treatment (E0760) may be considered medically necessary as a treatment of delayed union of bones, including nonunion of previously surgically-treated fractures, and excluding the skull and vertebra, when the following criteria are met:

  • A decelerating healing process is documented by a lack of clinical and radiologic (serial x-rays) 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.

Non-union

Low-intensity ultrasound treatment (E0760) may be considered medically necessary as a treatment of fracture non-unions of bones, including nonunion of previously surgically-treated fractures, and excluding the skull and vertebra, when all of the following criteria are met:

  • The treatment is for nonunion of bones other than the skull or vertebrae (e.g., radius, ulna, humerus, clavicle, tibia, femur, fibula, carpal, metacarpal, tarsal and metatarsal).
  • The nonunion is not related to, or due to, a malignancy.
  • It is ≥ 90 days from the date of initial treatment of the fracture.
  • The fracture nonunion is documented by at least 2 sets of appropriate imaging studies, multiple views, separated by a minimum of 90 days confirming that clinically significant healing has not occurred, with written interpretation by a physician stating such.
  • A fracture gap of ≤1 cm.
  • The patient can be adequately immobilized and is of an age where he/she is likely to comply with non-weight bearing (if fracture is of a weight-bearing bone).

Non-covered/Investigational

Low-intensity ultrasound treatment (E0760) is considered not medically necessary and investigational when utilized for other applications including but not limited to:

  • Congenital pseudarthrosis
  • Fractures that are Open Grade II or III
  • Fresh surgically-treated closed fractures (with or without internal fixation)
  • Fractures too unstable for closed reduction/casting
  • Fractures involving immature skeletal system
  • Pathological fractures due to bone pathology or malignancy
  • Treatment of Charcot foot disorder
  • Avascular necrosis of the femoral head
  • Fractures, failed fusions, or nonunions of the axial skeleton (skull and vertebrae)
  • Chronic epicondylitis
  • Prosthesis loosening following hip arthroplasty
  • Stress fractures

Key Points:

The most recent literature update was performed through February 27, 2019.

Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life (QOL), and ability to function including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology,two domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Low-Intensity Pulsed Ultrasound

Systematic Reviews

A systematic review by Schandelmaier et al (2017) provides the most comprehensive and rigorous overview and analysis of the existing evidence, including 26 RCTs that used LIPUS for bone healing. Additional systematic reviews or meta-analyses are listed in Table 1. However, because there is a substantial degree of overlap in the studies included in these reports (see Table 2), we will primarily focus on the findings of Schandelmaier et al (2017), which include analyses that highlight the results of RCTs identified as 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. The systematic review by Lou et al (2017) focused on fresh fractures and the review by Leighton et al (2017) focused on nonunions. All systematic reviewers acknowledged that the evidence for the use of LIPUS has methodologic limitations (see Table 1).

Table 1. Systematic Reviews Assessing Use of LIPUS to Treat Fractures

Study

No. of Studies

Study Designs

No. of Subjects

Types of Fractures

Main Conclusions on LIPUS

Schandelmaier et al (2017)

26

RCT

1593

Multiple types

Based on moderate- to high-quality evidence in fresh fracture, LIPUS does not improve outcomes important to patients and is unlikely to affect radiographic bone healing

Seger et al (2017)

5

CSRegistry

166

Nonunion

Encouraging results for consideration as nonoperative alternative in select cases

Lou et al (2017)

12

RCTQuasi-RCT

1099

Fresh fracture

Positive results though strength of the evidence is limited

Leighton et al (2017)

13

RCTCSCohortRegistry

1441

Nonunion

Potential benefit of LIPUS; however, no evidence that LIPUS can be used instead of surgery. May be useful in patients for whom surgery is high-risk.

Griffin et al (2014)

12

RCTQuasi-RCT

648

Multiple types

Cannot rule out potential benefit but evidence insufficient

Busse et al (2009)

13

RCT

563

Multiple types

Promising results but moderate- to low-quality evidence

TEC Assessment (1995)

2

RCT

128

Fresh fracture

Meets TEC criteria for FDA-labeled indications in tibia and distal radius

CS: case series; FDA: Food and Drug Administration; LIPUS: low-intensity pulsed ultrasound; RCT: randomized controlled trial.

 

 

Table 2. Studies Included in Systematic Reviews

Systematic Reviews by Fracture Type

Studies

N

Study Design

Schandelmaier (2017) Multiple

Seger (2017) Nonunion

Lou (2017)

Fresh

Leighton (2017)

Nonunion

Griffin (2014) Multiple

Busse (2009)

Multiple

TEC Assessment (1995) Fresh

Busse et al (2016)

51

RCT

Busse et al (2014)

501

RCT

Dudda et al (2011)

36

RCT

El-Mowafi et al (2005)

20

RCT

Emami et al (1999)

32

RCT

Exogen et al (1994)

85

RCT

Farkash (2015)

29

CS

Gan et al (2014)

30

RCT

Gebauer et al (2005)

66

CS

Handolin et al (2005a)

22

RCT

Handolin et al (2005b)

30

RCT

Heckman et al (1994)

97

RCT

Hemery et al (2010)

14

CS

Jingushi et al (2007)

72

CS

Kamath et al (2015)

60

RCT

Kristiansen et al (1997)

85

RCT

Lerner et al (2004)

17

CS

Leung et al (2004)

30

RCT

Liu et al (2014)

81

RCT

Lubbert et al (2008)

120

RCT

Mayr et al (2002)

100

CS

Mayr et al (2000)

30

RCT

Nolte et al (2001)

28

CS

Patel et al (2014)

28

RCT

Pigozzi et al (2004)

15

CS

Ricardo (2006)

21

RCT

Roussignol et al (2012)

60

CS

Rubin et al (2001)

118

Reviewa

Rue et al (2004)

40

RCT

Rutten et al (2007)

20

RCT

Salem et al (2014)

21

RCT

Schofer et al (2010)

101

RCT

Schortinghuis et al (2008)

9

RCT

Schortinghuis et al (2005)

8

RCT

Strauss et al (1999)

20

RCT

Tsumaki et al (2004)

42

RCT

Urita et al (2013)

27

RCT

Wang et al (2007)

59

RCT

Watanabe et al (2013)

151

Cohort

Yadav et al (2008)

67

RCT

Zacherl et al (2009)

52

RCT

Zura et al (2015)

767

Registry

No. of studies

26

5

12

13

12

13

2

CS: case series; RCT: randomized controlled trial.a This review contained data from a registry analysis.

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 (e.g., 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 fractures.

Meta-analysis results are summarized in Tables 3 and 4. Variation in results was observed for days to full weight bearing, pain, or radiographic healing. When only trials with low risk of bias were included, there was no difference between treatment and control groups (see Table 3).

Table 3. Summary of LIPUS Results From the Schandelmaier Meta-Analysis

Outcomes

No. of Trials and Results (95% Confidence Intervals)

Heterogeneity

High Risk of Bias

Low Risk of Bias

Total

p

I2

n

Results

n

Results

n

Results

Percent difference in days to return to work

Not reported separately

Not reported separately

3

2.7 (-7.7 to 14.3)

0.76

0%

Percent difference in days to full weight bearing

1

-40.0 (-48.4 to -30.3)

2

4.8 (-4.0 to 14.4)

3

-16.6 (-44.9 to 26.1)

<0.001

95%

Mean difference in pain reduction on 1-100 VAS (follow-up, 4-6 wk)

1

-28.1 (-37.1 to -19.2)

3

-0.9 (-2.5 to 0.6)

4

-6.9 (-15.4 to 1.6)

<0.001

91%

RR of subsequent operations (follow-up, 8 wk to 44 mo)

Not reported separately

Not reported separately

7

0.8 (0.6 to 1.2)

0.67

0%

Percent difference in days to radiographic healing

12

-32.8 (-39.5 to -25.3)

3

-1.7 (-11.2 to 8.8)

15

-27.3 (-34.7 to -19.0)

<0.001

85%

Risk difference in adverse events

Not reported separately

Not reported separately

9

0.0 (-0.0 to 0.03)

0.40

4%

RR: relative risk; VAS: visual analog scale; LIPUS: low-intensity pulsed ultrasound.

Adapted from Schandelmaier et al (2017).

Table 4. Summary of Findings and Quality of Evidence

Outcomes

QOE

LIPUS Effect on Outcome

1

Percent difference in days to return to work

Moderatea

Probably little or no impact

2

Percent difference in days to full weight bearing

High

No impact

3

Mean difference in pain reduction on 1-100 VAS (follow-up, 4-6 wk)

High

No impact

4

Relative risk of subsequent operations (follow-up, 8 wk to 44 mo)

Moderatea

Probably little or no impact

5

Percent difference in days to radiographic healing

Moderatea

Probably little or no impact

6

Risk difference in adverse events

High

No impact

Adapted from Schandelmaier et al (2017).

LIPUS: low-intensity pulsed ultrasound: QOE: quality of evidence: VAS: visual analog scale.

a Due to serious imprecision.

Fresh Fractures

Clinical Context and Therapy Purpose

The purpose of LIPUS in patients who have fresh fractures (either surgically managed or non-surgically managed) is to provide an adjunctive treatment option to standard of care.

The question addressed in this evidence review is: Does the use of LIPUS improve net health outcomes in patients with fresh fractures (either surgically or non-surgically managed) compared with standard care without the adjunctive use of LIPUS?

The following PICOTS were used to select literature to inform this review.

Patients

The relevant population of interest are patients with fresh fractures (either surgically or non-surgically managed). A fracture is most commonly defined as fresh for seven days after the fracture occurs.

Interventions

The therapy being considered is LIPUS. LIPUS is believed to alter the molecular and cellular mechanisms involved in each stage of the healing process (inflammation, soft callus formation, hard callus formation, and bone remodeling). The mechanism of action at the cellular level is not precisely known, but it is theorized that LIPUS may stimulate the production or the activities of the following compounds that contribute to the bone healing process: cyclooxygenase-2, collagenase, integrin proteins, calcium, chondroblasts, mesenchymal cells, fibroblasts, and osteoblasts. LIPUS would be an adjunctive therapy following setting and immobilizing the bone. LIPUS is a 20 minute/day self-administered treatment.

Comparators

The comparator is standard fresh fracture management without LIPUS as an adjunctive therapy.

Outcomes

The general outcome of interest is time to healing, which may be measured radiologically and assessed by an orthopedic surgeon. Clinically meaningful measures for healing would involve functional outcomes such as assessment of pain, use of analgesics, the need for secondary procedures, and ability to return to activities of daily living.

Timing

Follow-up should extend for months, the duration of time required for fracture healing.

Setting

The patient takes the LIPUS device home and self-administers the treatment. Recommended time of treatment administration is 20 minutes/day.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

  • To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
  • In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies;
  • Studies with duplicative or overlapping populations were excluded.

Systematic Reviews

Lou et al (2017) conducted a meta-analysis focusing on fresh fractures. The literature search, conducted through November 2016, included 12 studies, all of which were included in the Schandelmaier et al (2017) meta-analysis, except for a small study (n=20) by Strauss et al (1999), which only appeared in a conference abstract. Studies included patients that had been surgically managed and conservatively managed. Results from the Lou et al(2017) meta-analysis showed that time to fracture union was significantly lower in patients receiving LIPUS than in patients not receiving LIPUS (standard mean difference, -0.65; 95% 95% confidence interval [CI], -1.13 to -0.17). However, 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 in the Lou et al (2017) meta-analyses.

Surgically Managed

Randomized Controlled Trials

Busse et al (2016) reported on results from a concealed, blinded, sham-controlled, randomized trial (TRUST) evaluating LIPUS for the treatment of patients who underwent intramedullary nailing for fresh tibial fractures. This is the largest RCT to date, enrolling 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 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% CI, 0.86 to 1.34; p=0.55). Additionally, there was no difference in the 36-Item Short-Form Health Survey 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.

Tarride et al (2017) provided additional analyses using data from the TRUST trial, comparing health care resource use among patients using LIPUS with patients using the sham device. There were no significant differences between groups (11% in patients receiving LIPUS vs 10% in patients receiving sham) in need for secondary procedures (e.g., 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.

Emami et al (1999) conducted a double-blind, sham-controlled trial that randomized 32 patients who had a fresh tibial fracture fixed with an intramedullary rod to additional treatment with an active (n=15) or inactive (n=17) LIPUS device. 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 for LIPUS vs 37 days for sham; p=0.44); time to radiographic healing assessed by radiologist (mean, 155 days [median, 113 days] for LIPUS vs mean, 125 days [median, 112 days] for sham; p=0.76); and time to radiographic healing assessed by orthopedic surgeon (mean, 128 days, for LIPUS vs mean, 114 days for sham; p=0.40).

Nonsurgically Managed

Randomized Controlled Trial

Lubbert et al (2008) performed a multicenter, double-blind RCT (n=101) of LIPUS treatment of fresh (<5 days) clavicle shaft fractures. 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 a 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 for pain also did not differ significantly.

Section Summary: Fresh Fractures

Evidence for the use of LIPUS following fresh fracture includes three RCTs that evaluated patients that were surgically managed and one RCT that evaluated patients that were nonsurgically managed. The RCTs reported no statistically significant differences in radiographic healing, physical component score of the 36-Item Short-form Health Survey, use of physical therapy, need for secondary procedures, use of nonsteroidal anti-inflammatory drugs, and time to first visible callus.

Fracture Nonunion or Delayed Union Fracture

Clinical Context and Therapy Purpose

The purpose of LIPUS in patients who have fracture nonunion or delayed union fracture is to provide an adjunctive treatment option to standard of care.

The question addressed in this evidence review is: Does the use of LIPUS improve net health outcomes in patients with fracture nonunion or delayed union fracture compared with standard care without the adjunctive use of LIPUS?

The following PICOTS were used to select literature to inform this review.

Patients

The relevant population(s) of interest are patients with fracture nonunion or delayed union fracture. There is not a consensus definition of nonunion or delayed union. In general, these conditions are considered if serial radiographs either do not show progressive healing, or show a decelerating healing process after three months since the fracture occurrence.

Interventions

The therapy being considered is LIPUS. LIPUS is believed to alter the molecular and cellular mechanisms involved in each stage of the healing process (inflammation, soft callus formation, hard callus formation, and bone remodeling). The mechanism of action at the cellular level is not precisely known, but it is theorized that LIPUS may stimulate the production or the activities of the following compounds that contribute to the bone healing process: cyclooxygenase-2, collagenase, integrin proteins, calcium, chondroblasts, mesenchymal cells, fibroblasts, and osteoblasts. LIPUS would be an adjunctive therapy following setting and immobilizing the bone. LIPUS is a 20 minute/day self-administered treatment.

Comparators

The comparator is standard nonunion or delayed union fracture management without LIPUS as an adjunctive therapy.

Outcomes

The general outcome of interest is time to healing, which may be measured radiologically and assessed by an orthopedic surgeon. Clinically meaningful measures for healing would involve functional outcomes such as assessment of pain, use of analgesics, the need for secondary procedures, and ability to return to activities of daily living.

Timing

Follow-up should extend for months, the duration of time required for fracture healing.

Setting

The patient takes the LIPUS device home and self-administers the treatment. Recommended time of treatment administration is 20 minutes/day.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

  • To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
  • In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies;
  • Studies with duplicative or overlapping populations were excluded.

Systematic Reviews

The meta-analysis by Seger et al (2017) included 5 studies focused on scaphoid nonunions and analyzed healing index and average time to union following LIPUS. 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 conducted.

The meta-analysis by Leighton et al (2017) included 13 studies, one of which was an RCT. The date of the literature search was not provided. Quality of the studies was assessed using the Methodological Index for Non-Randomized Studies. Quality scores ranged from 5 to 12 (an “ideal” is 16 for nonrandomized trials). While the pooled estimate of effect size for the healing rate was 82% (95% CI, 77% to 87%), significant heterogeneity was detected (=62). A separate analysis, excluding studies with quality scores of 6 or lower, resulted in a comparable heal rate of 80% (95% CI, 74% to 85%). Because some patients in the analysis were treated conservatively and some underwent surgical interventions, the authors could not recommend LIPUS as a replacement for surgery or as an adjunct to surgery. Reviewers contended that LIPUS might be useful in patients for whom surgery is high risk.

The systematic review by Schandelmaier et al (2017) included 3 RCTs of nonunion fractures operatively managed.Because all the RCTs were rated at high-risk of bias, the authors could not adequately assess the efficacy of LIPUS for nonunion fractures. Two of theRCTs are discussed below; One is not discussed below because it was published only as a thesis.

Randomized Controlled Trials

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 (Table 5) 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 mm2in 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) (Table 6). This trial did not report functional outcomes or pain assessment, limiting the utility of results.

Ricardo (2006) published a blinded RCT evaluating 21 subjects with scaphoid nonunion who were treated with LIPUS or a sham device following a pedicled vascularized bone graft (Table 5). Time to healing was defined as the number of days from the operation to healing both clinically (solid and not causing tenderness or pain) and radiographically (bridging cortices). Additional outcomes included pain, wrist range of motion, radiographic evidence of union, carpal height index, and scapholunate-capitolunate angles; however, the authors did not report these outcome by treatment arm.The authors reported a statistically significant reduction in time to radiographic healing (-40.4%; 95% CI, -48.7% to -30.8%) with LIPUS (Table 6).

Table 5. Summary of Key RCT Characteristics

Study

Countries

Sites

Dates

Participants

Interventions

Active

Comparator

Schofer (2010)

Germany

6

2002 to 2005

Patients with tibial delayed unions

LIPUS (n=51)

sham device (n=50)

Ricardo (2006)

Cuba

1

1999 to 2004

Patients with scaphoid nonunion fractures treated wtihpedicledvascularized bone grafts from the distal radius

LIPUS (n=10)

sham device (n=11

LIPUS: low-intensity pulsed ultrasound; RCT: randomized controlled trial.

Table 6. Summary of Key RCT Results

Study

Healing

p value

LIPUS

Sham device

Schofer (2010)

physician assessed 65% healed

physician assessed 46% healed

0.07

Ricardo (2006)

56+ 3 days

94+ 5 days

<0.0001

RCT: randomized controlled trial; .

The purpose of the gaps tables (see Tables 7 and 8) is to display notable gaps identified in each study. This information is synthesized as a summary of the body of evidence following each table and provides the conclusions on the sufficiency of evidence supporting the position statement.

Table 7. Relevance Gaps

Study

Populationa

Interventionb

Comparatorc

Outcomesd

Follow-Upe

Schofer (2010)

2. Primary outcome was bone mineral density and secondary outcome was gap area. Physicians judged patients as healed/not healed, but no description of criteria used by physician

Ricardo (2006)

The evidence gaps stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
aPopulation key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.

bIntervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4.Not the intervention of interest.

c Comparator key:1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.

d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.

e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Table 8. Study Design and Conduct Gaps

Study

Allocationa

Blindingb

Selective Reportingc

Data Completenessd

Powere

Statisticalf

Schofer (2010)

1. Drop out rate for LIPUS group was 10% and drop out rate for sham device was 24%

Ricardo (2006)

No description of randomization procedure

1. Power calculations not reported and sample size is small (N=21)

4. Only time to healing was compared statistically; additional outcomes (pain, return to activities) were not reported by treatment group

The evidence gaps stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.

aAllocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.

bBlinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.

c Selective Reporting key:1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.

d Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).

e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.

f Statistical key: 1. Analysis is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Analysis is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4.Comparative treatment effects not calculated.

Observational Study

Nolte et al (2016) conducted a retrospective comparison of patients with metatarsal fractures treated by LIPUS and by surgical techniques. For the comparative analysis, patients from a Food and Drug Administration-required LIPUS registry (n=594) were propensity-matched 1:1 with patients treated surgically from a health claims database. The overall heal rates for all types of fractures combined was comparable for LIPUS (97%) and surgery (95%) (p=0.07). A subgroup analysis of patients with delayed or nonunion metatarsal fractures (n=226) also showed comparable rates of healing among the LIPUS group (96%) and the surgery group (96%).

Section Summary: Fracture Nonunion or Delayed Union Fracture

The evidence for LIPUS treatment of fracture nonunion consists only of lower quality and uncontrolled studies. There are 2 meta-analyses (2017) without controlled comparative results. A third meta-analysis, which included all types of fractures, identified three RCTs of patients with nonunion; however, all three trials were considered at high-risk of bias (one published as a thesis).Of the two RCTs, the larger one had primary and secondary outcomes that were physiological assessments, rather than functional measures. It is unclear how healing status was determined in this study, as the outcome was described as "physician-assessed". Limitations of the second published RCT include no description of the randomization process and a small sample size.

Stress Fractures, Osteotomy Sites, or Distraction Osteogenesis

Clinical Context and Therapy Purpose

The purpose of LIPUS in patients who have stress fractures, osteotomy sites or distraction osteogenesis, is to provide an adjunctive treatment option to standard of care.

The question addressed in this evidence review is: Does the use of LIPUS improve net health outcomes in patients with stress fractures, osteotomy sites, or distraction osteogenesis compared with standard care without the adjunctive use of LIPUS?

The following PICOTS were used to select literature to inform this review.

Patients

The population of interest consists of patients with stress fractures, osteotomy sites, or distraction osteogenesis.

Interventions

The therapy being considered is LIPUS. LIPUS is believed to alter the molecular and cellular mechanisms involved in each stage of the healing process (inflammation, soft callus formation, hard callus formation, and bone remodeling). The mechanism of action at the cellular level is not precisely known, but it is theorized that LIPUS may stimulate the production or the activities of the following compounds that contribute to the bone healing process: cyclooxygenase-2, collagenase, integrin proteins, calcium, chondroblasts, mesenchymal cells, fibroblasts, and osteoblasts. LIPUS would be an adjunctive therapy following setting and immobilizing the bone. LIPUS is a 20 minute/day self-administered treatment.

Comparators

The comparator is standard stress fracture, osteotomy sites, or distraction osteogenesis management without LIPUS as an adjunctive therapy.

Outcomes

The general outcome of interest is time to healing, which may be measured radiologically and assessed by an orthopedic surgeon. Clinically meaningful measures for healing would involve functional outcomes such as assessment of pain, use of analgesics, the need for secondary procedures, and ability to return to activities of daily living.

Timing

Follow-up should extend for months, the duration of time required for fracture healing.

Setting

The patient takes the LIPUS device home and self-administers the treatment. Recommended time of treatment administration is 20 minutes/day.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

  • To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
  • In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies;
  • Studies with duplicative or overlapping populations were excluded.

Stress Fractures

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. 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.

Osteotomy Sites

Urita et al (2013) 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. 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 at high-risk of bias in the meta-analysis by Schandelmaier.

Distraction Osteogenesis

The Schandelmaier systematic review also included six trials of LIPUS for distraction osteogenesis following surgery. Four of six studies were rated at high-risk of bias. Four studies were in the tibia. No clinically meaningful results were reported for the mandible studies in the meta-analysis. 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) in the meta-analysis. Four of the studies were included in the meta-analysis for time to radiographic healing with mixed results, three not reporting statistically significant results.

Lou et al (2018) conducted a systematic review and meta-analysis on the use of LIPUS for the treatment of patients with distraction osteogenesis. The literature search, conducted in May 2018, identified 7 RCTs (172 patients) for inclusion. The Cochrane risk of bias tool was used to assess trial quality. Three of the trials were considered low-riskof bias and four were considered to have high-risk of bias. Main limitations in the trials were related to the lack of treatment allocation details and outcome assessors knowledge of treatment. Pooled results did not find statistically significant differences in: treatment time, radiological gap fill area, histological gap fill length, or bone density..

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 and were 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. A meta-analysis ofthree trials on the use of LIPUS for patients with distraction osteogenesis reported no statistically significant differences in treatment time, gap fill, or bone density.

Summary of Evidence

For individuals who have fresh fractures (surgically or nonsurgically managed) who receive LIPUS as an adjunct to routine care, the evidence includes RCTs and several meta-analyses. Therelevant outcomes are symptoms, morbid events, functional outcomes, and QOL. 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 and 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 events.

For individuals who have fracture nonunion or delayed union fracture who receive LIPUS as an adjunct to routine care including surgery, if appropriate, the evidence includes only lower quality studies consisting of a small systematic review in scaphoid nonunions, a meta-analysis of nonunion in various locations, two low-quality RCTs, and one observational comparative study. Therelevant outcomes are symptoms, morbid events, functional outcomes, and QOL. Of thetwo RCTs, onedid not include functional outcomes. The second RCT had a small sample size and did not describe the randomization procedure. The observational study reported similar healing rates with LIPUS and surgery, though the retrospective nature of the study , limits 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.

For individuals who have stress fractures, osteotomy sites, or distraction osteogenesis who receive LIPUS as an adjunct to routine care, the evidence includes only lower quality studies consisting of small RCTsand one meta-analysis for distraction osteogenesis. Therelevant outcomes are symptoms, morbid events, functional outcomes, and QOL. Results do not generally include functional outcomes and results across various outcomes, primarily time to radiographic healing, are inconsistent. The meta-analysis of three trials using LIPUS for distraction osteogenesis reported no statistically significant differences in physiological or functional outcomes. 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 (BMJ) Rapid Recommendation

TheBMJ Rapid Recommendations are a series of articles, produced by BMJ in collaboration with the MAGIC group, to provide clinicians with practice guidelines. BMJ Rapid Recommendations (2017) published guidelines on the use of low-intensity pulsed ultrasound (LIPUS) for bone healing. 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. 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. "After extensive deliberations, the panel found no compelling anatomical or physiological reasons why LIPUS would probably be beneficial in these other patient populations."

National Institute for Health and Clinical Excellence

TheNICE(2018) published a guidance on the use of LIPUS to promote healing of fresh fractures at low-risk of non-healing. The guidance states that the "current evidence does not show efficacy. Therefore, this procedure should not be used for this indication."

The NICE (2018) published a guidance on the use of LIPUS to promote healing of fresh fractures at high-risk of non-healing. The guidance states that the "current evidence on efficacy is very limited in quantity and quality. Therefore, this procedure should only be used in the context of research.

The NICE (2018) published a guidance on the use of LIPUS to promote healing of delayed and nonunion fractures. The guidance states that the "current evidence on efficacy is inadequate in quality. Therefore, this procedure should only be used with special arrangements for clinical governances, consent and audit or research."

The NICE (2013) published guidance on Exogen for the treatment of long-bone fractures with nonunion and delayed fracture healing.The NICE concluded that use of the Exogen bone healing system to treat long-bone 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 three 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 of this guidance is in 2018.

American Academy of Orthopaedic Surgeons

The American Academy of Orthopaedic Surgeons (AAOS) has published 2009 guidelines on the treatment of distal radius fractures. The AAOS issued a limited recommendation for use of ultrasound for adjuvant treatment of distal radius fractures. While evidence from one study demonstrated an increased rate in healing (measured by absence of pain and radiographic union), the additional cost of LIPUS, resulted in a “limited” recommendation.

U.S. Preventive Services Task Force Recommendations

Not applicable.

Key Words:

Fracture, nonunion, delayed union, bone growth stimulator, ultrasound accelerated fracture healing device, low intensity ultrasound stimulator, osteogenesis stimulator, percutaneous, pseudarthrosis, pseudoarthrosis, Exogen 2000™, Exogen 3000, SAFHS® Model 2A, SAFHS® Model 2000, Exogen 4000

Approved by Governing Bodies:

In 1994, the Sonic Accelerated Fracture Healing System (SAFHS®; later renamed Exogen 2000® and since 2006, Exogen 4000+; Bioventus) was approved by the U.S. Food and Drug Administration (FDA) through the premarket approval process for 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.

Benefit Application:

Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP: Special benefit consideration may apply. Refer to member’s benefit plan. FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.

Current Coding:

CPT Codes:

20979

Low intensity ultrasound stimulation to aid bone healing, non-invasive (nonoperative)

HCPCS:

E0760

Osteogenesis stimulator, low intensity ultrasound; non-invasive

References:

  1. American Academy of Orthopaedic Surgeons. The treatment of distal radius fractures. 2009. Available online at: www.aaos.org/research/guidelines/drfguideline.pdf. Accessed February 27, 2019.

  2. Bhandari M, Fong K, Sprague S et al. 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 2012; 94(15):e1091-6.

  3. Biglari B, Yildirim TM, Swing T, Bruckner T, Danner W, Moghaddam A. Failed treatment of long bone non-unions with low intensity pulsed ultrasound. Arch Orthop Trauma Surg. Aug 2016; 136(8):1121-1134.

  4. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Ultrasound accelerated fracture healing. TEC Assessments 1995; Volume 10, Tab 14.

  5. Busse JW, Bhandari M, Kulkarni AV, et al. The effect of low-intensity pulsed ultrasound therapy on time to fracture healing: a meta-analysis. CMAJ 2002; 166(4):437-41.

  6. Busse JW, et al. Low intensity pulsed ultrasonography for fractures: Systematic review of randomized controlled trials. BMJ 2009; 338:b351.

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

  8. 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. Oct 25 2016; 355:i5351.

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

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

  11. Dudda M, Hauser J, Muhr G et al. Low-intensity pulsed ultrasound as a useful adjuvant during distraction osteogenesis: a prospective, randomized controlled trial. J Trauma 2011; 71(5):1376-80.

  12. El-Mowafi H, Mohsen M. The effect of low-intensity pulsed ultrasound on callus maturation in tibial distraction osteogenesis. Int Orthop. Apr 2005;29(2):121-124.

  13. Emami A, Petren-Mallmin M and Larsson S. No effect of low-intensity ultrasound on healing time of intramedullary fixed tibial fractures. J Orthop Trauma 1999; 13(4):252-7.

  14. Griffin XL, Smith N, Parsons N et al. Ultrasound and shockwave therapy for acute fractures in adults. Cochrane Database Syst Rev 2012; 2:CD008579.

  15. Griffin XL, Parsons N, Costa ML, et al. Ultrasound and shockwave therapy for acute fractures in adults. Cochrane Database Syst Rev. 2014; 6:CD008579.

  16. Heckman JD, Ryaby JP, et al. Acceleration of tibial fracture-healing by non-invasive, low-intensity pulsed ultrasound. Am J bone Joint Surg, January 1994; 76(1): 26-34.

  17. Jingushi S, Mizuno K, Matsushita T, et al. Low-intensity pulsed ultrasound treatment for postoperative delayed union or non-union of long bone fractures. J Orthop Sci 2007; 12(1):35-41.

  18. Kristiansen TK, Ryaby JP, et al. Accelerated healing of distal radial fractures with the use of specific, low-intensity ultrasound. A multicenter, prospective, randomized, double-blind, placebo-controlled study. Am J Bone Joint Surg, July 1997; 79(7): 961-973.

  19. Leighton R, Watson JT, Giannoudis P, et al. Healing of fracture nonunions treated with low-intensity pulsed ultrasound (LIPUS): A systematic review and meta-analysis. Injury. Jul 2017;48(7):1339-1347.

  20. Leung KS, Lee WS, Tsui HF, et al. Complex tibial fracture outcomes following treatment with low-intensity pulsed ultrasound. Ultrasound Med Biol 2004; 30(3):389-95.

  21. Lou S, Lv H, Li Z, et al. The effects of low-intensity pulsed ultrasound on fresh fracture: A meta-analysis. Medicine (Baltimore). Sep 2017;96(39):e8181.

  22. Lubbert PH, van der Rijt RH, et al. Low-intensity pulsed ultrasound (LIPUS) in fresh clavicle fractures: A multi-centre double blind randomized controlled trial. Injury, December 2008; 39(12): 1444-1452.

  23. MAGIC: Making GRADE the Irrestible Choice. n.d.; www.magicproject.org. Accessed February 1, 2018.

  24. Mayr E, Rudzki MM, Rudzki M, et al. [Does low intensity, pulsed ultrasound speed healing of scaphoid fractures?]. Handchir Mikrochir Plast Chir. Mar 2000; 32(2):115-122.

  25. National Institute for Health and Care Excellence. NICE medical technology guidance 12: EXOGEN ultrasound bone healing system for long bone fractures with non-union or delayed healing. 2013. Available online at: www.nice.org.uk/nicemedia/live/14018/62289/62289.pdf. Accessed February 1, 2018.

  26. National Institute for Health and Care Excellence. Low-intensity pulsed ultrasound to promote fracture healing. IPG 374. 2010; https://www.nice.org.uk/guidance/ipg374/chapter/1-Guidance. Accessed February 1, 2018.

  27. National Institute for Health and Care Excellence (NICE). Low-intensity pulsed ultrasound to promote healing of fresh fractures at low risk of non-healing [IPG621]. 2018; https://www.nice.org.uk/guidance/ipg621. Accessed February 27, 2019.

  28. National Institute for Health and Care Excellence (NICE). Low-intensity pulsed ultrasound to promote healing of fresh fractures at high risk of non-healing [IPG622]. 2018; https://www.nice.org.uk/guidance/ipg622. Accessed February 27, 2019.

  29. National Institute for Health and Care Excellence (NICE). Low-intensity pulsed ultrasound to promote healing of delayed-union and non-union fractures [IPG623]. 2018; https://www.nice.org.uk/guidance/ipg623. Accessed February 27, 2019.

  30. Nolte P, Anderson R, Strauss E, et al. Heal rate of metatarsal fractures: A propensity-matching study of patients treated with low-intensity pulsed ultrasound (LIPUS) vs. surgical and other treatments. Injury. Nov 2016; 47(11):2584-2590.

  31. Poolman RW, Agoritsas T, Siemieniuk RA, et al. Low intensity pulsed ultrasound (LIPUS) for bone healing: a clinical practice guideline. BMJ. Feb 21 2017; 356:j576.

  32. Ricardo M. The effect of ultrasound on the healing of muscle-pediculated bone graft in scaphoid non-union. Int Orthop. Apr 2006;30(2):123-127.

  33. Rue JP, Armstrong III DW, et al. The effect of pulsed ultrasound in the treatment of tibial stress fractures. Orthopedics, November 2004; 27(11): 1192-1195.

  34. Rutten S, Nolte PA, Guit GL, et al. Use of low-intensity pulsed ultrasound for posttraumatic non-unions of the tibia: A review of patients treated in the Netherlands. J Trauma 2007; 62(4):902-8.

  35. Rutten S, Klein-Nulend J, Guit GL, et al. Low-intensity pulsed ultrasound stimulation of delayed unions of the osteotomized fibula: a prospective randomized double-blind trial. Low-intensity pulsed ultrasound treatment in delayed bone healing [thesis]. Amsterdam, the Netherlands: Vrije Universiteit Amsterdam; 2012.

  36. Salem KH, Schmelz A. Low-intensity pulsed ultrasound shortens the treatment time in tibial distraction osteogenesis. Int Orthop. Jul 2014; 38(7):1477-1482.

  37. Schandelmaier S, Kaushal A, Lytvyn L, et al. Low intensity pulsed ultrasound for bone healing: systematic review of randomized controlled trials. BMJ. Feb 22 2017; 356:j656.

  38. Schofer MD, Block JE, Aigner J et al. Improved healing response in delayed unions of the tibia with low-intensity pulsed ultrasound: results of a randomized sham-controlled trial. BMC Musculoskelet Disord 2010; 11:229.

  39. Schortinghuis J, Bronckers AL, Stegenga B, et al. Ultrasound to stimulate early bone formation in a distraction gap: a double blind randomised clinical pilot trial in the edentulous mandible. Arch Oral Biol. Apr 2005;50(4):411- 420.

  40. Schortinghuis J, Bronckers AL, Gravendeel J, et al. The effect of ultrasound on osteogenesis in the vertically distracted edentulous mandible: a double-blind trial. Int J Oral Maxillofac Surg. Nov 2008;37(11):1014-1021.

  41. Seger EW, Jauregui JJ, Horton SA, et al. Low-intensity pulsed ultrasound for nonoperative treatment of scaphoid nonunions: a meta-analysis. Hand (N Y). Apr 01, 2017: 1558944717702470.

  42. Strauss E, Ryaby JP, McCabe J. Treatment of Jones' fractures of the foot with adjunctive use of low-pulsed ultrasound stimulation [abstract]. J Orthop Trauma. 1999;13(4):310.

  43. Summary of Safety and Effectiveness Data. Exogen 2000® or Sonic Accelerated Fracture Healing System (SAFHS®). Exogen®, a Smith and Nephew Company, Piscataway, NJ.

  44. Tarride JE, Hopkins RB, Blackhouse G, et al. Low-intensity pulsed ultrasound for treatment of tibial fractures: an economic evaluation of the TRUST study. Bone Joint J. Nov 2017;99-B(11):1526-1532.

  45. Tsumaki N, Kakiuchi M, Sasaki J, et al. Low-intensity pulsed ultrasound accelerates maturation of callus in patients treated with opening-wedge high tibial osteotomy by hemicallotasis. J Bone Joint Surg Am. Nov 2004;86-A(11):2399-2405.

  46. Urita A, Iwasaki N, Kondo M et al. Effect of low-intensity pulsed ultrasound on bone healing at osteotomy sites after forearm bone shortening. J Hand Surg Am 2013; 38(3):498-503.

  47. Watanabe, YY, Arai, YY, Takenaka, NN, Kobayashi, MM, Matsushita, TT. Three key factors affecting treatment results of low-intensity pulsed ultrasound for delayed unions and nonunions: instability, gap size, and atrophic nonunion.. J Orthop Sci, 2013 Jun 19;18(5).

  48. 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. Oct 2015; 46(10):2036-2041.

  49. Zura R, Mehta S, Della Rocca GJ, et al. A cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): findings in the elderly versus all patients. BMC Musculoskelet Disord. 2015; 16:45.

Policy History:

Medical Policy Group, October 2008 (4)

Medical Policy Administration Committee, November 2008

Available for comment November 20, 2008-January 5, 2009

Medical Policy Group, February 2009 (4)

Medical Policy Administration Committee, March 2009

Available for comment February 27-April 13, 2009

Medical Policy Group, October 2009 (1)

Medical Policy Administration Committee, October 2009

Available for comment October 20-December 3, 2009

Medical Policy Group, November 2009 (1)

Medical Policy Administration Committee, December 2009

Available for comment December 4, 2009-January 19, 2010

Medical Policy Group, February 2010 (1)

Medical Policy Administration Committee, April 2010

Available for comment April 7-May 21, 2010

Medical Policy Group, February 2010; Regular update (1)

Medical Policy Group, November 2011 (1): Electrical bone stimulator portion removed and put into separate policy #082; Update to Description, Policy, Key Points, and References with criteria for coverage for delayed union

Medical Policy Administration Committee, January 2012

Available for comment January 11 – February 27, 2012

Medical Policy Panel, December 2012

Medical Policy Group, March 2013 (1): Update to policy statement with clarifications, no change to coverage criteria; update to Key Points and References, also.

Medical Policy Panel, January 2014

Medical Policy Group, January 2014 (1): Update to Policy, Key Points and References related to clarification of coverage concerning surgically-treated fractures, fresh versus nonunion; policy statements prior to March 2010 removed

Medical Policy Administration Committee, February 2014

Available for comment February 15 through March 31, 2014

Medical Policy Panel, February 2015

Medical Policy Group, (6): 2015 Update to Key Points and References; no change to policy statement.

Medical Policy Panel, August 2016

Medical Policy Group, August 2016, (6): Updates to Description, Key Points, Summary and References. No change to policy statement.

Medical Policy Panel, March 2017

Medical Policy Group, March 2017 (6): Updates to Key points, Key Words, Governing Bodies, Practice guidelines and References; removed previous policy statement from 2013.

Medical Policy Panel, July 2017

Medical Policy Group, August 2017 (6): Updates to Description, Key Points, and References. No change to policy statement.

Medical Policy Panel March 2018

Medical Policy Group, April 2018 (6): Updates to Key Points, Practice Guidelines and References.

Medical Policy Panel, March 2019

Medical Policy Group, April 2019 (6): Updates to Description, Key Points, Practice Guidelines and References. Title changed to “Ultrasound Accelerated Fracture Healing Device”. No change to policy statement.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.