Individuals with recognized delayed fracture unions might begin by reducing the risk factors for delayed unions or nonunions but may progress to surgical repair if it persists.

Electrical and Electromagnetic Bone Growth Stimulators

Different applications of electrical and electromagnetic fields have been used to promote healing of delayed and nonunion fractures: invasive, noninvasive, and semi-invasive.

Invasive stimulation involves the surgical implantation of a cathode at the fracture site to produce direct current electrical stimulation. Invasive devices require surgical implantation of a current generator in an intramuscular or subcutaneous space, while an electrode is implanted within the fragments of bone graft at the fusion site. The implantable device typically remains functional for 6 to 9 months after implantation, and although the current generator is removed in a second surgical procedure when stimulation is completed, the electrode may or may not be removed. Implantable electrodes provide constant stimulation at the nonunion or fracture site but carry increased risks associated with implantable leads.

Noninvasive electrical bone growth stimulators generate a weak electrical current within the target site using pulsed electromagnetic fields, capacitive coupling, or combined magnetic fields. In capacitive coupling, small skin pads/electrodes are placed on either side of the fusion site and worn for 24 hours a day until healing occurs or up to 9 months. In contrast, pulsed electromagnetic fields are delivered via treatment coils placed over the skin and worn for 6 to 8 hours a day for 3 to 6 months. Combined magnetic fields deliver a time-varying magnetic field by superimposing the time-varying magnetic field onto an additional static magnetic field. This device involves a 30-minute treatment per day for 9 months. Patient compliance may be an issue with externally worn devices.

Semi-invasive (semi-implantable) stimulators use percutaneous electrodes and an external power supply, obviating the need for a surgical procedure to remove the generator when treatment is finished.

Regulatory Status

In 1984, the noninvasive OrthoPak® Bone Growth Stimulator (BioElectron, now Zimmer Biomet) was approved by the U.S. Food and Drug Administration (FDA) through the premarket approval process for treatment of fracture nonunion. Pulsed electromagnetic field systems with the FDA premarket approval (all noninvasive devices) include Physio-Stim® (Orthofix), first approved in 1986, and OrthoLogic® 1000, approved in 1997, both indicated for treatment of established nonunion secondary to trauma, excluding vertebrae and all flat bones, in which the width of the nonunion defect is less than one-half the width of the bone to be treated; and the EBI Bone Healing System® (Electrobiology, now Zimmer Biomet), which was first approved in 1979 and indicated for nonunions, failed fusions, and congenital pseudarthrosis. No distinction was made between long and short bones. The FDA has approved labeling changes for electrical bone growth stimulators that remove any time frame for the diagnosis.

No semi-invasive electrical bone growth stimulator devices with the FDA approval or clearance were identified.

FDA product code LOF.

Related Policies

• Low Intensity Pulsed Ultrasound Fracture Healing Device (Policy #008 in the Treatment Section)
• Electrical Stimulation of the Spine as an Adjunct to Spinal Fusion Procedures (Policy #154 in the Treatment Section)
• Bone Morphogenetic Protein (Policy #056 in the Surgery Section)

1. treatment of fracture nonunions in the appendicular skeleton (includes the bones of the shoulder girdle, upper extremities, pelvis, and lower extremities) when all of the following criteria are met:
• at least 3 months have passed since the date of fracture;
• serial radiographs (defined as a minimum of 2 sets with multiple views of the fracture site separated by a minimum of 90 days) have confirmed that no progressive signs of healing have occurred; and
• the fracture gap is 1 cm or less.
2. treatment of congenital pseudoarthroses in the appendicular skeleton.

C. Implantable (E0749 Osteogenesis stimulator, electrical, surgically implanted) and semi-invasive electrical bone growth stimulators are considered investigational.

Medicare Coverage:
Medicare Advantage Products differ from the Horizon BCBSNJ Medical Policy. An implantable oteogenesis electrical bone growth stimulator is covered for nonunion of long bone fractures when NCD 150.2 criteria is met. For additional information on coverage and eligibility, please refer to National Coverage Determination (NCD) for Osteogenic Stimulators (150.2). Available at: https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=65&ncdver=2&bc=AAAAgAAAAAAAAA%3d%3d&.

A noninvasive stimulator device is covered when NCD 150.2 and LCD L33796 criteria is met. For additional information and eligibility, refer to Noridian Local Coverage Determination (LCD): Osteogenesis Stimulators (L33796). Available at: https://www.cms.gov/medicare-coverage-database/details/lcd-criteria details.aspx?LCDId=33796&ContrId=389&ver=10&ContrVer=1&CntrctrSelected=389*1&Cntrctr=389&s=38&DocType=All&bc=AggAAAQAAAAAAA%3d%3d&.

Medicaid Coverage:
For members enrolled in Medicaid and NJ FamilyCare plans, Horizon BCBSNJ applies the above medical policy.

FIDE-SNP:

For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.

Policy Guidelines: (Information to guide medical necessity determination based on the criteria contained within the policy statements above.)

Fracture Nonunion
No consensus on the definition of fracture nonunion currently exists. One proposed definition is failure of progression of fracture healing for at least 3 consecutive months (and for at least 6 months following the fracture), accompanied by clinical symptoms of delayed union or nonunion (pain, difficulty bearing weight) (Bhandari et al, 2012).

The original U.S. Food and Drug Administration (FDA) labeling of fracture nonunions defined them as fractures not showing progressive healing after at least 9 months from the original injury. The labeling states: “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.” This time frame is not based on physiologic principles but was included as part of the research design for FDA approval as a means of ensuring homogeneous populations of patients, many of whom were serving as their own controls. Others have contended that 9 months represents an arbitrary cutoff point that does not reflect the complicated variables present in fractures (i.e., degree of soft tissue damage, alignment of the bone fragments, vascularity, quality of the underlying bone stock). Some fractures may show no signs of healing, based on serial radiographs as early as 3 months, while a fracture nonunion may not be diagnosed in others until well after 9 months. The current policy of requiring a 3-month time frame for lack of progression of healing is consistent with the definition of nonunion as described in the clinical literature.

Delayed Union
Delayed union is defined as a decelerating healing process as determined by serial radiographs, together with 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. In contrast, nonunion serial radiographs (described above) show no evidence of healing. When lumped together, delayed union and nonunion are sometimes referred to as “ununited fractures.”

Fresh Fracture
A fracture is most commonly defined as “fresh” for 7 days after its occurrence. Most fresh closed fractures heal without complications with the use of standard fracture care (i.e., closed reduction, cast immobilization).

[RATIONALE: This policy was created in 1992 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through February 11, 2020.

 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, 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.

Noninvasive Electrical Bone Growth Stimulation
Fracture Nonunion
Clinical Context and Therapy Purpose

There is no standard definition of a fracture nonunion.^1,The Food and Drug Administration (FDA) labeling for one of the electrical stimulators included in this policy 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 a minimum of 3 months." Others have contended that 9 months represents an arbitrary cutoff point that does not reflect the complicated variables present in fractures (i.e., the degree of soft tissue damage, alignment of the bone fragments, vascularity, quality of the underlying bone stock). Other proposed definitions of nonunion involve 3 to 6 months from the original injury, or simply when serial radiographs fail to show any further healing. Another is the failure of progression of fracture healing for at least 3 consecutive months (and for at least 6 months following the fracture) accompanied by clinical symptoms of delayed union or nonunion (pain, difficulty bearing weight).^1,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.” Factors contributing to a nonunion include: which bone is fractured, fracture site, the degree of bone loss, time since injury, the extent of soft tissue injury, and patient factors (e.g., smoking, diabetes, systemic disease).^2,

Fractures at certain locations (e.g., scaphoid, proximal fifth metatarsal) are at greater risk of delayed union due to a tenuous blood supply. Systemic factors, including immunosuppression, cancer, and tobacco use, may also predispose patients to fracture nonunion, along with certain medications (e.g., nonsteroidal anti-inflammatory drugs, fluoroquinolones).

The purpose of noninvasive electrical bone growth stimulation of the appendicular skeleton in patients with fracture nonunion is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does noninvasive electrical bone growth stimulation of the appendicular skeleton improve the net health outcome in patients with fractures nonunion?

The following PICO was used to select literature to inform this policy.

Patients

The relevant population of interest is patients with fracture nonunion of the appendicular skeleton.

Interventions

The therapy being considered is noninvasive electrical bone growth stimulation.

Noninvasive electrical bone growth stimulators generate a weak electrical current within the target site using pulsed electromagnetic fields, capacitive coupling, or combined magnetic fields.

Electrical bone growth stimulation is generally managed by orthopedists and orthopedic surgeons.

Comparators

The following therapies and practices are currently being used to make decisions about electrical bone growth stimulation of the appendicular skeleton: conservative therapy and surgery. These therapies are generally managed by orthopedists and orthopedic surgeons.

Outcomes

The general outcomes of interest are symptoms, change in disease status, and functional outcomes.

Follow-up for the procedure would be at least 6 months or until the bone has completely healed.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

1. To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
2. In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
3. To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

The FDA approval of electrical bone growth stimulation as a treatment of fracture nonunion involving the appendicular skeleton was based on a number of case series in which patients with nonunions, primarily of the tibia, served as their controls. These studies from the 1980's have suggested that electrical stimulation results in subsequent unions in a significant percentage of patients.^3,4,5,6,7,

Review of Evidence
Systematic Reviews

Aleem et al (2016) reported on a meta-analysis of the efficacy of electrical stimulators for bone healing.^8, The review was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Reviewers searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library up to March 6, 2016, supplemented with hand searches of major orthopedic conference proceedings from March 2013 to March 2016, for RCTs comparing direct current, capacitive coupling, or pulsed electromagnetic field therapy with sham control for nonunion, delayed union, fresh fracture, osteotomy, or symptomatic spinal instability requiring fusion. Analyses were performed with the intention-to-treat principle using random-effects models. Fifteen trials were identified, of which 5 included treatment of nonunion^9,10,11, or delayed union^12,13, fractures. Nonunion or delayed-union fractures were combined in subgroup analyses including 174 participants. The estimated relative risk for electrical stimulators versus sham for the outcome of radiographic nonunion at the last follow-up or 12 months was 0.57 (95% confidence interval [CI], 0.29 to 1.12; I²=76%; p=0.002). Overall, reviewers found no evidence to support a difference in treatment effect due to treatment indication (interaction p=0.75) and moderate quality evidence supporting electrical stimulation in reducing patient-reported pain and radiographic nonunion across indications.

Griffin et al (2008) reported on a systematic review of electromagnetic bone growth stimulation that included 49 studies, 3 of which were RCTs.^14,

The 2 largest and most recent trials of nonunion fractures are described in the following section.

Randomized Controlled Trials

An RCT by Scott and King (1994) compared capacitive coupled electric fields with sham treatment (dummy unit) in 23 patients who had a nonunion fracture (at least 9 months old and without clinical or radiographic signs of progression to union within the last 3 months) of a long bone.^11, In this trial, electrodes were passed onto the skin surface through holes in the plaster cast. Twenty-one patients completed the protocol (10 treatment, 11 controls). Six months after patients began treatment, an orthopedic surgeon and a radiologist, neither of whom were involved in patient management, examined radiographs and determined that 6 of 10 in the treatment group healed, while none of those in the control group healed (p=0.004).

Simonis et al (2003) compared pulsed electromagnetic field stimulation with placebo treatment for tibial shaft fractures ununited at least 1 year after fracture, with no metal implant bridging the fracture gap, and no radiographic progression of healing in the 3 months before treatment.^9, All 34 patients received surgical treatment with osteotomy and unilateral external fixator before randomization. Treatment was delivered by external coils; control subjects received sham treatment using identical machines not passing current through the coils. Patients were assessed monthly for 6 months, and clinical and radiographic assessments were conducted at 6 months. Treatment was considered a failure if union was not achieved at 6 months. In the treatment group, 89% (16/18) of fractures healed compared with 50% (8/16) in the control group (p=0.02). While a larger percentage of smokers in the treatment group healed compared with those in the control group, there was an imbalance in the number of smokers in each group, and the difference in healing rates between groups was not statistically significant. The authors concluded the available evidence supported the use of pulsed electromagnetic field therapy in the treatment of nonunion of the tibia and suggested that future trials consider which electromagnetic stimulation modality and for which anatomic sites the treatment is most effective.

Section Summary: Fracture Nonunion

Sham-controlled randomized trials with fewer than 60 patients in total have concluded that noninvasive electrical stimulators improve fracture healing for patients with fracture nonunion. Pre-post studies of patients with nonhealing fractures have also suggested the efficacy of this treatment. There are few nonsurgical options in this population.

Delayed Fracture Union
Clinical Context and Therapy Purpose

Most bone fractures heal spontaneously over a few months postinjury. Approximately 5% to 10% of all fractures have delayed healing, resulting in continued morbidity and increased utilization of health care services.^2,2,

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. Together, delayed union and nonunion are sometimes referred to as "ununited fractures." To determine fracture healing status, 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.

The purpose of noninvasive electrical bone growth stimulation of the appendicular skeleton in patients with delayed fracture union is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does noninvasive electrical bone growth stimulation of the appendicular skeleton improve the net health outcome in patients with delayed fracture union?

The following PICO was used to select literature to inform this policy.

Patients

The relevant population of interest is patients with delayed fracture union of the appendicular skeleton.

Interventions

The therapy being considered is noninvasive electrical bone growth stimulation.

Noninvasive electrical bone growth stimulators generate a weak electrical current within the target site using pulsed electromagnetic fields, capacitive coupling, or combined magnetic fields.

Electrical bone growth stimulation is generally managed by orthopedists and orthopedic surgeons.

Comparators

The following therapies and practices are currently being used to make decisions about electrical bone growth stimulation of the appendicular skeleton: conservative therapy and surgery. These therapies are generally managed by orthopedists and orthopedic surgeons.

Outcomes

The general outcomes of interest are symptoms, change in disease status, and functional outcomes.

Follow-up for the procedure would be at least 6 months or until the bone has completely healed.

Study Selection Criteria

Methodologically credible studies were selected using the principles described in the first indication.

Review of Evidence
Systematic Reviews

The Aleem et al (2016) review (discussed previously) reported on a combined meta-analysis of delayed and nonunion fractures.^8, Similarly, the Griffin et al (2008) review also combined delayed and nonunion fractures.^14, Both included RCTs (N=92 patients) of delayed fractures, which are described in the following section.

Also, the portion of the policy on electrical stimulation for delayed unions was informed by a TEC Assessment (1992) of the RCT by Sharrard (1990; described below), which offered the following conclusion: “…Sharrard’s health outcome data do not show that noninvasive electrical bone growth stimulation delivers an advantage over placebo.”^15,

Randomized Controlled Trials

Shi et al (2013) reported on a randomized sham-controlled trial that included 58 patients with delayed union of surgically reduced long bone fractures (femur, tibia, humerus, radius ulna).^12, Delayed union was defined as a failure to heal after at least 16 weeks and not more than 9 months following surgical reduction and fixation of the fracture. Patients with fracture nonunion, defined as failure to heal after more than 9 months, were excluded from the trial. Treatment with 8 hours of pulsed electromagnetic field per day was stopped when no radiographic progression was observed over 3 months or when union was achieved, with union defined as no pain during joint stressing or during motion at the fracture site and callus bridging for 3 of 4 cortices on blinded assessment. Three months of treatment resulted in a slight, but not statistically significant, improvement in the rate of union between pulsed electromagnetic field treated patients (38.7%) and controls (22.2%). The success rate was significantly greater with pulsed electromagnetic field (77.4% vs. 48.1%) after an average of 4.8 months of treatment. The time to union did not differ significantly between pulsed electromagnetic field therapy patients (4.8 months; range, 2-12 months) and sham controls (4.4 months; range, 2-7 months).

In the double-blind RCT by Sharrard (1990), pulsed electromagnetic field stimulation was compared with a sham procedure using a dummy device in 45 patients with delayed union of the tibia.^13, Stimulators were positioned on the surface of the plaster cast. Treatment began 16 to 32 weeks after injury. Patients with fracture gaps greater than 0.5 cm after reduction, systemic disease, or who were taking steroids were excluded, as were patients with marked bony atrophy or hypertrophy. Fifty-one patients were recruited; 45 completed the protocol (20 treatment, 25 control). In the treatment group, 3 patients achieved union, 2 achieved probable union, 5 showed progression to union, and 10 showed no progress after 12 weeks. In the control group, none had united, 1 had probably united, 3 progressed toward union, and 17 showed no progress.

Griffin et al (2011) published a Cochrane review of electromagnetic field stimulation (including 3 specifically on pulsed electromagnetic field) for treating delayed union or nonunion of long bone fractures in adults.^16, In addition to the RCTs previously reviewed, the systematic review included a study by Barker et al (1984) that randomized 17 participants with tibial nonunion to electromagnetic field stimulation or sham treatment.^10, Thus, 4 studies (total N=125 participants) were analyzed. The primary outcome measure was the proportion of participants whose fractures had united at a fixed time point. For this outcome, the overall pooled effect size was small and not statistically significant (relative risk, 1.96; 95% CI, 0.86 to 4.48). Interpretation is limited due to the substantial clinical and statistical heterogeneity in the pooled analysis. Also, there was no reduction in pain found in 2 trials, and none of the studies reported functional outcomes. Reviewers concluded that electromagnetic stimulation might offer some benefit in the treatment of delayed union and nonunion but the evidence was inconclusive to inform current practice.

Section Summary: Delayed Fracture Union

Two randomized sham-controlled trials have been identified in the treatment of delayed union with pulsed electromagnetic field. In the Sharrard (1990) trial, radiographic healing was improved at 12 weeks but there were no statistically significant differences between groups for clinical outcomes. In the Shi et al (2013) trial, only the rate of healing at an average of 4.8 months was statistically significant, and it is not clear if this was a prespecified endpoint. The time to healing was not reduced by pulsed electromagnetic field. Additional study is needed to permit greater certainty on the effect of this technology on delayed unions.

Fresh Fracture(s)
Clinical Context and Therapy Purpose

The purpose of noninvasive electrical bone growth stimulation of the appendicular skeleton in patients with fresh fractures is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does noninvasive electrical bone growth stimulation of the appendicular skeleton improve the net health outcome in patients with fresh fractures?

The following PICO was used to select literature to inform this policy.

Patients

The relevant population of interest is patients with fresh fractures of the appendicular skeleton.

Interventions

The therapy being considered is noninvasive electrical bone growth stimulation.

Noninvasive electrical bone growth stimulators generate a weak electrical current within the target site using pulsed electromagnetic fields, capacitive coupling, or combined magnetic fields.

Electrical bone growth stimulation is generally managed by orthopedists and orthopedic surgeons.

Comparators

The following therapies and practices are currently being used to make decisions about electrical bone growth stimulation of the appendicular skeleton: conservative therapy and surgery. These therapies are generally managed by orthopedists and orthopedic surgeons.

Outcomes

The general outcomes of interest are symptoms, change in disease status, and functional outcomes.

Follow-up for the procedure would be at least 6 months or until the bone has completely healed.

Study Selection Criteria

Methodologically credible studies were selected using the principles described in the first indication.

Review of Evidence
Systematic Reviews

The Aleem et al (2016) systematic review (described previously) also included subgroup analyses for fresh fractures with the outcome of radiographic nonunion at last reported follow-up (to 12 months) for electrical stimulators versus sham.^8, Five trials (total N=366 patients) were included.^{17,18,19,20,21,} The combined relative risk of radiographic nonunion was 0.83 (95% CI, 0.51 to 1.35; I²=11%; p=0.35). The selected trials were of moderate-to-high quality. The 2 largest are summarized below.

Randomized Controlled Trials

Adie et al (2011) reported on results of a multicenter, double-blind, sham-controlled, randomized trial, which evaluated 12 weeks of pulsed electromagnetic field stimulation for acute tibial shaft fractures.^17, The endpoints examined were secondary surgical interventions, radiographic union, and patient-reported functional outcomes. Approximately 45% of patients were compliant with treatment (>6 hours daily use), and 218 (84%) of 259 patients completed the 12-month follow-up. The primary outcome (the proportion of participants requiring a secondary surgical intervention because of delayed union or nonunion within 12 months postinjury) was similar for the 2 groups (15% active vs. 13% sham). A per-protocol analysis comparing patients who received the prescribed dose of pulsed electromagnetic field stimulation with sham treatment also showed no significant differences between groups. Secondary outcomes, which included surgical intervention for any reason (29% active vs. 27% sham), radiographic union at 6 months (66% active vs. 71% sham), 36-Item Short-Form Health Survey Physical Component Summary scores at 12 months (44.9 active vs. 48.0 sham), and the Lower Extremity Functional Scale scores at 12 months (48.9 active vs. 54.3 sham), also did not differ significantly between the groups.

Hannemann et al (2014) reported on a multicenter, double-blind, randomized, sham-controlled trial (N=102) conducted in the Netherlands; they found little advantage to 6 weeks of pulsed electromagnetic field therapy for fresh scaphoid fractures (≤5 days from injury).^20, Outcomes included the time to clinical and radiologic union and functional outcome at 6, 9, 12, 24, and 52 weeks. Radiologic union measured by computed tomography did not differ significantly between groups. The median time to clinically defined union was 6 weeks in both groups. The return to normal range of motion at the wrist was 12 weeks in both groups. Grip strength of the dominant hand returned to normal sooner with pulsed electromagnetic field therapy but there was no significant difference in return of grip strength of the nondominant hand. Functional outcomes were reported in 2015.^20, There were no significant differences in either the pain or the function subscales of the Patient-Rated Hand/Wrist Evaluation between the pulsed electromagnetic field group and the sham group at any of the 5 follow-up time points. Each of the 5 domains of the EuroQol-5D as well as the EuroQoL visual analog scale was also compared at each time point. There was a single marginally significant difference in these domain scores (anxiety/depression domain at week 24), which would have been expected by chance given the number of statistical tests performed. The mean number of working days lost was similar in the 2 groups (10 days vs. 13 days; p=0.65), and the total mean quality-adjusted life years was 0.84 for pulsed electromagnetic field and 0.85 for sham (difference = 0.01; 95% CI, -0.01 to 0.04), respectively.

Section Summary: Fresh Fracture(s)

Five RCTs including 366 participants have compared electrical stimulators with sham in the treatment of fresh fractures. A systematic review and meta-analysis of these trials found moderate quality evidence that the risk of radiographic nonunion is about 17% lower in participants treated using electrical stimulators compared with sham, but this difference was not statistically significant. No differences in functional outcomes were reported between electrical stimulators and sham.

Stress Fracture(s)
Clinical Context and Therapy Purpose

The purpose of noninvasive electrical bone growth stimulation of the appendicular skeleton in patients with stress fractures is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does noninvasive electrical bone growth stimulation of the appendicular skeleton improve the net health outcome in patients with stress fractures?

The following PICO was used to select literature to inform this policy.

Patients

The relevant population of interest is patients with stress fractures of the appendicular skeleton.

Interventions

The therapy being considered is noninvasive electrical bone growth stimulation.

Noninvasive electrical bone growth stimulators generate a weak electrical current within the target site using pulsed electromagnetic fields, capacitive coupling, or combined magnetic fields.

Electrical bone growth stimulation is generally managed by orthopedists and orthopedic surgeons.

Comparators

The following therapies and practices are currently being used to make decisions about electrical bone growth stimulation of the appendicular skeleton: conservative therapy and surgery. These therapies are generally managed by orthopedists and orthopedic surgeons.

Outcomes

The general outcomes of interest are symptoms, change in disease status, and functional outcomes.

Follow-up for the procedure would be at least 6 months or until the bone has completely healed.

Study Selection Criteria

Methodologically credible studies were selected using the principles described in the first indication.

Beck et al (2008) reported on a well-conducted RCT (n=44) of capacitively coupled electric fields (OrthoPak) for healing acute tibial stress fractures.^22, Patients were instructed to use the device for 15 hours each day, and usage was monitored electronically. Healing was confirmed when hopping 10 cm high for 30 seconds was accomplished without pain. Although an increase in the hours of use per day was associated with a reduction in the time to healing, there was no difference in the rate of healing between treatment and placebo. Power analysis indicated that this number of patients was sufficient to detect a difference in healing time of 3 weeks, which was considered to be a clinically significant effect. Other analyses, which suggested that electrical stimulation might be effective for the radiologic healing of more severe stress fractures, were preliminary and a beneficial effect was not observed for clinical healing.

Section Summary: Stress Fracture(s)

The evidence on the use of noninvasive electrical bone growth stimulation to treat stress fracture(s) consists of an RCT. In this well-conducted trial, there was no difference in the healing rates between the stimulation and placebo groups.

Appendicular Skeletal Surgery
Clinical Context and Therapy Purpose

The purpose of noninvasive electrical bone growth stimulation in patients who have had appendicular skeletal surgery is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does noninvasive electrical bone growth stimulation improve the net health outcome in patients who have had appendicular skeletal surgery?

The following PICO was used to select literature to inform this policy.

Patients

The relevant population of interest is patients who have had appendicular skeletal surgery.

Interventions

The therapy being considered is noninvasive electrical bone growth stimulation.

Noninvasive electrical bone growth stimulators generate a weak electrical current within the target site using pulsed electromagnetic fields, capacitive coupling, or combined magnetic fields.

Electrical bone growth stimulation is generally managed by orthopedists and orthopedic surgeons.

Comparators

The following therapies and practices are currently being used to make decisions about electrical bone growth stimulation for patients who have had appendicular skeletal surgery: standard postsurgical management by an orthopedic surgeon.

Outcomes

The general outcomes of interest are symptoms, change in disease status, and functional outcomes.

Follow-up for the procedure would be at least 6 months or until the bone has completely healed.

Study Selection Criteria

Methodologically credible studies were selected using the principles described in the first indication.

A comprehensive search found 2 small RCTs on noninvasive electrical bone growth stimulation after orthopedic surgery. Borsalino et al (1988) reported on a randomized double-blind, sham-controlled trial of pulsed electromagnetic field stimulation (8 h/d) in 32 patients who underwent femoral intertrochanteric osteotomy for osteoarthritis of the hip.^23, Radiographic measurements at 90 days revealed significant increases in the periosteal bone callus and trabecular bone bridging at the lateral, but not the medial, cortex. The trial lacked clinical outcomes and enrolled few patients.

The trial by Dhawan et al (2004) randomized 64 patients (144 joints with triple arthrodesis or subtalar arthrodesis) to pulsed electromagnetic field stimulation for 12 hours a day or an untreated control condition.^24, Patients at high risk of nonfusion (rheumatoid arthritis, diabetes, or on oral corticosteroids) were excluded from the trial. The blinded radiographic evaluation found a significant decrease in the time to union (12.2 weeks for talonavicular arthrodesis vs. 17.6 weeks for controls; p=0.003; 13.1 weeks for calcaneocuboid fusion vs. 17.7 weeks for controls; p=0.01). Clinical outcomes were not assessed.

Section Summary: Appendicular Skeletal Surgery

The evidence on the use of noninvasive electrical bone growth stimulation to treat those who have had surgery of the appendicular skeleton consists of several RCTs. The trials showed some benefit of stimulation treatment, but clinical outcomes of interest were not assessed, limiting conclusions that can be drawn about treatment efficacy.

Implantable and Semi-Invasive Bone Growth Stimulation
Clinical Context and Therapy Purpose

The purpose of implantable and semi-invasive electrical bone growth stimulation in patients who have fracture, pseudoarthrosis, or have had surgery of the appendicular skeleton is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does implantable or semi-invasive electrical bone growth stimulation improve the net health outcome in patients who have fracture, pseudoarthrosis, or have had surgery of the appendicular skeleton?

The following PICO was used to select literature to inform this policy.

Patients

The relevant population of interest is patients who have fracture, pseudoarthrosis, or have had surgery of the appendicular skeleton.

Interventions

The therapy being considered is implantable or semi-invasive electrical bone growth stimulation.

Invasive stimulation involves the surgical implantation of a cathode at the fracture site to produce direct current electrical stimulation. Invasive devices require surgical implantation of a current generator in an intramuscular or subcutaneous space, while an electrode is implanted within the fragments of bone graft at the fusion site.

Semi-invasive (semi-implantable) stimulators use percutaneous electrodes and an external power supply, obviating the need for a surgical procedure to remove the generator when treatment is finished.

Electrical bone growth stimulation is generally managed by orthopedists and orthopedic surgeons.

Comparators

The following therapies and practices are currently being used to make decisions about electrical bone growth stimulation for patients who have fracture, pseudoarthrosis, or have had surgery of the appendicular skeleton: conservative therapy, surgery, or standard postsurgical management by an orthopedic surgeon or orthopedist.

Outcomes

The general outcomes of interest are symptoms, change in disease status, and functional outcomes.

Follow-up for the procedure would be at least 6 months or until the bone has completely healed.

Study Selection Criteria

Methodologically credible studies were selected using the principles described in the first indication.

A TEC Assessment (1992) indicated that semi-invasive bone growth stimulators are no longer in wide use.^15,

An updated comprehensive search for implantable bone stimulators identified a small number of case series, all of which focused on foot and ankle arthrodesis in patients at high-risk for nonunion (summarized in Petrisor and Lau [2005]^25,). Risk factors for nonunion included smoking, diabetes, Charcot (diabetic) neuroarthropathy, steroid use, and previous nonunion. The largest case series is Lau et al (2007), who described outcomes of the foot or ankle arthrodesis in 38 high-risk patients.^26, Union was observed in 65% of cases by follow-up evaluation (n=18) or chart review (n=20). Complications were reported in 16 (40%) cases, including 6 cases of deep infection and 5 cases of painful or prominent bone stimulators necessitating stimulator removal. A multicenter retrospective review by Saxena et al (2005) described outcomes from 28 high-risk patients with arthrodesis of the foot and ankle.^27, Union was reported for 24 (86%) cases at an average of 10 weeks; complications included breakage of the stimulator cables in 2 patients and hardware failure in another. Five patients required additional surgery.

Section Summary: Implantable and Semi-Invasive Bone Growth Stimulation

The evidence on the use of implantable and semi-invasive electrical bone growth stimulation to treat fractures, pseudoarthroses, or those who have had surgery of the appendicular skeleton consists of a small number of case series, reporting on small numbers of patients. Prospective controlled trials are needed to evaluate this procedure.

Summary of Evidence
Noninvasive Electrical Bone Growth Stimulation

For individuals who have fracture nonunion who receive noninvasive electrical bone growth stimulation, the evidence includes randomized controlled trials (RCTs) and systematic reviews of RCTs. Relevant outcomes are symptoms, change in disease status, and functional outcomes. The U.S. Food and Drug Administration (FDA) has approved noninvasive electrical bone growth stimulation for fracture nonunions and congenital pseudarthrosis in the appendicular skeleton, based largely on studies with patients serving as their controls. There is also evidence from 2 small sham-controlled randomized trials that noninvasive electrical stimulators improve fracture healing for patients with fracture nonunion. There are few nonsurgical options in this population, and the pre-post studies of patients with nonhealing fractures support the efficacy of the treatment. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have delayed fracture union who receive noninvasive electrical bone growth stimulation, the evidence includes RCTs and systematic reviews of RCTs. Relevant outcomes are symptoms, change in disease status, and functional outcomes. RCTs on the delayed union of fractures were limited by small sample sizes and did not show significant differences in outcomes between study groups. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have fresh fracture(s) who receive noninvasive electrical bone growth stimulation, the evidence includes RCTs and systematic reviews of RCTs. Relevant outcomes are symptoms, change in disease status, and functional outcomes. A meta-analysis of 5 RCTs found no statistically significant benefit of electrical bone growth stimulation for fresh fractures. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have stress fracture(s) who receive noninvasive electrical bone growth stimulation, the evidence includes an RCT. Relevant outcomes are symptoms, change in disease status, and functional outcomes. This well-conducted RCT found that, although an increase in the hours of use per day was associated with a reduction in the time to healing, there was no difference in the rate of healing between treatment and placebo. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have had surgery of the appendicular skeleton who receive noninvasive electrical bone growth stimulation, the evidence includes 2 small RCTs. Relevant outcomes are symptoms, change in disease status, and functional outcomes. Although the results of 1 trial suggest benefits to the bone stimulation in decreased time to union, clinical outcomes were not assessed. The evidence is insufficient to determine the effects of the technology on health outcomes.

Implantable and Semi-Invasive Bone Growth Stimulation

For individuals who have fracture, pseudarthrosis, or who have had surgery of the appendicular skeleton who receive implantable and semi-invasive electrical bone growth stimulation, the evidence includes a small number of case series. Relevant outcomes are symptoms, change in disease status, and functional outcomes. The evidence is insufficient to determine the effects of the technology on health outcomes.

SUPPLEMENTAL INFORMATION
Clinical Input From Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests, input was received from 5 academic medical centers while this policy was under review in 2012. Input supported the use of noninvasive electrical bone growth stimulation for the treatment of fracture nonunions or congenital pseudarthrosis of the appendicular skeleton. Input concurred that noninvasive electrical bone growth stimulation is investigational for the treatment of fresh fractures and immediate postsurgical treatment after appendicular skeletal surgery. Most reviewers considered the use of noninvasive electrical bone growth stimulation to be investigational for the treatment of delayed union, arthrodesis, or failed arthrodesis.

Practice Guidelines and Position Statements

No guidelines or statements were identified.

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

A search of ClinicalTrials.gov in February 2020 did not identify any ongoing or unpublished trials that would likely influence this review.
________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Electrical Bone Growth Stimulation of the Appendicular Skeleton
Bone Growth Stimulation of the Appendicular Skeleton, Electrical
Fracture Healing Device, Electrical Stimulation
Stimulation of the Appendicular Skeleton, Electrical Bone Growth
Appendicular Skeleton, Electrical Bone Growth Stimulation
Nonunion, Electrical Bone Growth Stimulation

References:
1. 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. Aug 1 2012;94(15):e1091-1096. PMID 22854998

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

3. Ahl T, Andersson G, Herberts P, et al. Electrical treatment of non-united fractures. Acta Orthop Scand. Dec 1984;55(6):585-588. PMID 6335345

4. Connolly JF. Selection, evaluation and indications for electrical stimulation of ununited fractures. Clin Orthop Relat Res. Nov-Dec 1981(161):39-53. PMID 6975690

5. Connolly JF. Electrical treatment of nonunions. Its use and abuse in 100 consecutive fractures. Orthop Clin North Am. Jan 1984;15(1):89-106. PMID 6607443

6. de Haas WG, Beaupre A, Cameron H, et al. The Canadian experience with pulsed magnetic fields in the treatment of ununited tibial fractures. Clin Orthop Relat Res. Jul 1986(208):55-58. PMID 3720140

7. Sharrard WJ, Sutcliffe ML, Robson MJ, et al. The treatment of fibrous non-union of fractures by pulsing electromagnetic stimulation. J Bone Joint Surg Br. Jan 1982;64(2):189-193. PMID 6978339

8. Aleem IS, Aleem I, Evaniew N, et al. Efficacy of electrical stimulators for bone healing: a meta-analysis of randomized sham-controlled trials. Sci Rep. Aug 19 2016;6:31724. PMID 27539550

9. Simonis RB, Parnell EJ, Ray PS, et al. Electrical treatment of tibial non-union: a prospective, randomised, double-blind trial. Injury. Apr 2003;34(5):357-362. PMID 12719164

10. Barker AT, Dixon RA, Sharrard WJ, et al. Pulsed magnetic field therapy for tibial non-union. Interim results of a double-blind trial. Lancet. May 5 1984;1(8384):994-996. PMID 6143970

11. Scott G, King JB. A prospective, double-blind trial of electrical capacitive coupling in the treatment of non-union of long bones. J Bone Joint Surg Am. Jun 1994;76(6):820-826. PMID 8200888

12. Shi HF, Xiong J, Chen YX, et al. Early application of pulsed electromagnetic field in the treatment of postoperative delayed union of long-bone fractures: a prospective randomized controlled study. BMC Musculoskelet Disord. Jan 19 2013;14:35. PMID 23331333

13. Sharrard WJ. A double-blind trial of pulsed electromagnetic fields for delayed union of tibial fractures. J Bone Joint Surg Br. May 1990;72(3):347-355. PMID 2187877

14. Griffin XL, Warner F, Costa M. The role of electromagnetic stimulation in the management of established non- union of long bone fractures: what is the evidence? Injury. Apr 2008;39(4):419-429. PMID 18321512

15. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Electrical bone growth stimulation for delayed union or nonunion of fractures. TEC Assessment. 1992:Volume 7:332-351.

16. Griffin XL, Costa ML, Parsons N, et al. Electromagnetic field stimulation for treating delayed union or non-union of long bone fractures in adults. Cochrane Database Syst Rev. Apr 13 2011(4):CD008471. PMID 21491410

17. Adie S, Harris IA, Naylor JM, et al. Pulsed electromagnetic field stimulation for acute tibial shaft fractures: a multicenter, double-blind, randomized trial. J Bone Joint Surg Am. Sep 7 2011;93(17):1569-1576. PMID 21915570

18. Faldini C, Cadossi M, Luciani D, et al. Electromagnetic bone growth stimulation in patients with femoral neck fractures treated with screws: prospective randomized double-blind study. Curr Orthop Pract. 2010;21(3):282- 287.

19. Hannemann PF, Gottgens KW, van Wely BJ, et al. The clinical and radiological outcome of pulsed electromagnetic field treatment for acute scaphoid fractures: a randomised double-blind placebo-controlled multicentre trial. J Bone Joint Surg Br. Oct 2012;94(10):1403-1408. PMID 23015569

20. Hannemann PF, van Wezenbeek MR, Kolkman KA, et al. CT scan-evaluated outcome of pulsed electromagnetic fields in the treatment of acute scaphoid fractures: a randomised, multicentre, double-blind, placebo-controlled trial. Bone Joint J. Aug 2014;96-B(8):1070-1076. PMID 25086123

21. Martinez-Rondanelli A, Martinez JP, Moncada ME, et al. Electromagnetic stimulation as coadjuvant in the healing of diaphyseal femoral fractures: a randomized controlled trial. Colomb Med (Cali). Apr-Jun 2014;45(2):67-71. PMID 25100891

22. Beck BR, Matheson GO, Bergman G, et al. Do capacitively coupled electric fields accelerate tibial stress fracture healing? A randomized controlled trial. Am J Sports Med. Mar 2008;36(3):545-553. PMID 18055921

23. Borsalino G, Bagnacani M, Bettati E, et al. Electrical stimulation of human femoral intertrochanteric osteotomies. Double-blind study. Clin Orthop Relat Res. Dec 1988(237):256-263. PMID 3191636

24. Dhawan SK, Conti SF, Towers J, et al. The effect of pulsed electromagnetic fields on hindfoot arthrodesis: a prospective study. J Foot Ankle Surg. Mar-Apr 2004;43(2):93-96. PMID 15057855

25. Petrisor B, Lau JT. Electrical bone stimulation: an overview and its use in high risk and Charcot foot and ankle reconstructions. Foot Ankle Clin. Dec 2005;10(4):609-620, vii-viii. PMID 16297822

26. Lau JT, Stamatis ED, Myerson MS, et al. Implantable direct-current bone stimulators in high-risk and revision foot and ankle surgery: a retrospective analysis with outcome assessment. Am J Orthop (Belle Mead NJ). Jul 2007;36(7):354-357. PMID 17694182

27. Saxena A, DiDomenico LA, Widtfeldt A, et al. Implantable electrical bone stimulation for arthrodeses of the foot and ankle in high-risk patients: a multicenter study. J Foot Ankle Surg. Nov-Dec 2005;44(6):450-454. PMID 16257674

28. Centers for Medicare & Medicaid Services. National Coverage Determination (NCD) for Osteogenic Stimulators (150.2). 2005; https://www.cms.gov/medicare-coverage-database/details/ncd- details.aspx?NCDId=65&ncdver=2&DocID=150.2&ncd_id=150.2&ncd_version=2&basket=ncd%25253A150%25 252E2%25253A2%25253AOsteogenic+Stimulators&bc=gAAAABAAAAAA&. Accessed February 24, 2020.

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

20974
20975

E0747
E0749