A retrospective, controlled trial evaluation of pulsed electromagnetic field stimulation for fusion success following lumbar spinal surgery

Introduction

Surgical intervention for degenerative spinal pathologies has increased steadily over the past few decades. This is partly due to an aging global population with increased life expectancy. In general, the prevalence of degenerative diseases, including spinal degeneration, is expected to continuously increase due to the aging population, and, subsequently, the number of required spine surgeries will increase in parallel (1). Lumbar spinal fusion surgery can be either a primary procedure or an adjunct to decompression for patients with these conditions with the goal to reduce pain and secure spinal stability (2). A larger frequency of procedures are being conducted in patients >65 years of age who have existing co-morbidities and significant risk factors for nonunion (3).

Evolutionary steps in technique and surgical protocol, with an additional advantage of improved knowledge of the underlying science, continue to innovate operative procedures (3-5). Altogether, these advancements have been instrumental in increasing the prevalence and impact of these procedures while driving improved patient outcomes. Even with this progression, the incidence of nonunion in lumbar spine varies greatly, with a reported range from 5% to 35% of patients (6). Nonunion occurs when the bones fail to heal and fuse as intended post-surgery. This can lead to changes in alignment, neurological injury, persistent pain, spinal instability, and the need for additional revision surgeries to achieve a successful fusion (7). These outcomes are detrimental and lead to a decline in patient quality of life, lost productivity, and significant financial burden. Indeed, spinal fusion is considered one of the most expensive operative procedures with direct hospital costs estimated at up to $12.8 billion per year (8).

One strategy that can be implemented in post-operative care is the use of treatment approaches that aid in fusion success. Pulsed electromagnetic field (PEMF) stimulation therapy is a non-invasive biotechnology that utilizes electromagnetic fields to directly induce changes in the targeted tissue. PEMF imparts a dual effect on tissue: the magnetic field modulates magnetic reactive properties within the tissue, and the electrical field exerts a force on the ions present in the tissue to induce a change in the electrical gradient. Both mechanisms force movement of ions or charged particles within the target tissue, leading to changes at the biological level through activation of signaling systems that underlie inflammation and regenerative processes (9-11).

PEMF treatment has been utilized in a variety of medical indications with favorable responses in orthopedic applications including musculoskeletal injury, wound healing, and sports medicine (11-13). In orthopedics, PEMF is reported to reduce potential risks by promoting osteogenic stimulus and reducing healing times (9). PEMF is used as an adjunct therapy that can be implemented postoperatively to heal nonunited fractures (14). Considering the high prevalence and long-term impact of degenerative lumbar spinal disease, exploration into surgical strategies that optimize patient fusion success, especially in those at risk for nonunion, is of interest. The current study used a controlled trial design to evaluate the effect of PEMF on lumbar fusion in patients with risk factors for nonunion.

Methods

Study design

Study details have been previously reported for subjects that were included in a PEMF interventional treatment group (15). Data were collected from a prospective, multicenter clinical trial (registration number: NCT03176303; registration date: 2017-06-05) conducted at 10 study sites across the USA. The study sites included the following: University of Virginia, Florida Orthopaedic Institute, Aspirus Spine and Neurosciences Institute, Spine Institute of Louisiana, University of Colorado School of Medicine, Institute of Neuro Innovation, Inova Neurosurgery, Rothman Institute, University of Michigan, and the Carolina Neurosurgery and Spine Associates. The study aimed to assess the safety and efficacy of PEMF treatment as an adjunct therapy following lumbar spinal fusion. The SpinalStim^TM medical device (Orthofix US LLC, Lewisville, TX, USA) was utilized by subjects post-operatively to deliver PEMF treatment. Data collected from the PEMF group (interventional arm) were compared to a retrospective cohort of subjects (control arm) that were not treated with PEMF.

Fusion status was assessed at 12-months post-operation and determined by clinical site investigators. Fusion status was evaluated using anterior/posterior (A/P), lateral, and flexion/extension radiographs and computed tomography (CT) (without contrast). Specific level assessments were measured as fused based on the presence of bridging bone, absence of lucencies at the graft-bone or implant-bone, and lack of motion on flexion/extension. All treated levels had to demonstrate bony fusion for the patient to be considered a fusion success. Along with fusion status, the impact of risk factors was evaluated for successful fusion. Risk factors for nonunion included previous failed lumbar spinal fusion, diabetes, osteoporosis, smoking, multilevel (≥2 levels) procedures, age, and body mass index (BMI). Safety outcomes including adverse event (AE) reporting, were assessed only for the PEMF group throughout the study duration.

Subjects

Subjects enrolled in the PEMF group were eligible for the study if they were undergoing lumbar fusion surgery and had risk factors for nonunion, were ≥18 years of age, and had a BMI ≤45 kg/m². Exclusion criteria for the study included active or prior history of malignancy within the previous five years, a diagnosis of scoliosis (>30°), and psychiatric or any drug addiction illness that prevented the subject from completing study outcome measurements. Subjects were enrolled in the control arm who underwent lumbar spinal surgery and were prescribed PEMF, but did not receive PEMF treatment (e.g., insurance denial, refused the PEMF treatment).

PEMF interventional treatment

Subjects in the PEMF group received treatment using the SpinalStim^TM device. The SpinalStim device is a home-wearable bone growth stimulation device approved by the Food and Drug Administration (FDA) as an adjunctive, noninvasive lumbar spinal fusion treatment for patients post-surgery. SpinalStim is designed to be used in the home setting and was instructed for use for six months following surgery. When in active mode, the SpinalStim device generates repeating burst groups of multiple pulses of electromagnetic energy by delivering time-varying electrical signals to a treatment coil, where the groups of multiple pulses repeat at a constant interval. SpinalStim provides even distribution of PEMF treatment around the fusion site across tissue, bone, and fixation. Subjects were instructed to start PEMF treatment within 14 days of spinal surgery and to wear the device for two hours/day. This study met all compliance requirements with the protocol. Good Clinical Practice guidelines and all other applicable regulatory body requirements were followed, as well as the guidelines set by the Declaration of Helsinki and its subsequent amendments. This study was approved by the Central Western Institutional Review Board (IRB) (No. 20170923) and local IRBs where applicable [at the Aspirus Research Institute (No. 17.07.488), University of Virginia (No. HSR# 20855), and Rothman Institute (No. RP# 15-042ex)]. All institutions are informed and have agreed to the study. Informed consent was obtained from all subjects involved in the study.

Statistical analyses

PEMF and control group data were analyzed for counts and percentages for categorical baseline variables. The mean ± standard deviation (SD) and range are reported for continuous variables. Correlation of outcomes to risk factors was calculated by Chi-squared test or by Fisher’s exact test if a count was less than 5. Alpha was set at 0.05 and a P value ≤0.05 was considered significant. Further analyses using a logistic regression were performed for risk factors and treatment effects on fusion at 12 months. Examination of the relationship between patient risk factors, treatment group assignment, and fusion outcomes at 12 months included four model evaluations with progressively increasing complexity, including individual risk factor effects and composite risk factor approaches, providing insights into the relative importance of different covariates and treatment effects. Available data were analyzed using the SAS Version 9.4 (SAS Institute, Cary, NC).

Results

Subjects

For the PEMF treatment group, a total of 224 subjects were enrolled in the study, with 142 subjects available for fusion assessment at 12 months. Data was compared to the control group, which included 47 subjects. CT scans were available for fusion assessment in 56.3% of PEMF treatment subjects and 59.6% of control subjects. PEMF and control groups enrolled subjects with a similar mean age (PEMF, 63.3±10.3 years; control, 66.6±9.4 years) and mean BMI (PEMF, 31.0±5.9 kg/m²; control, 31.5±8.2 kg/m²). Both PEMF and control groups had over half of the subjects enrolled with BMI >30 kg/m² (obese) (PEMF, 55.6%; control, 51.1%). The control group included a larger number of females (70.2%; n=33/47) compared to the PEMF group (55.6%; n=79/142) (Table 1). A small percentage of PEMF subjects presented with a single risk factor (7.7%; n=11), 92.3% (n=131) with >2 risk factors, 51.4% (n=73) with ≥3 risk factors, and 16.9% (n=24) with ≥4 risk factors for nonunion. In the control group, 4.3% (n=2) of subjects presented with 0 risk factors, 23.4% (n=11) with 1 risk factor, 72.3% (n=34) with >2 risk factors, 42.6% (n=20) with ≥3 risk factors, and 17.0% (n=8) with ≥4 risk factors for nonunion. The majority of PEMF subjects had 2 levels fused (50.0%, n=71) with others having a single level (7.0%, n=10), 3 levels (27.5%, n=39), or ≥4 levels fused (15.5%, n=22). In the control group, the majority of subjects had a single level fused (61.7%; n=29) with others having 2 levels fused (6.4%; n=3), 3 levels (2.1%; n=1), or >4 levels fused (29.8%, n=14) (Figure 1, Table 2).

Figure 1 Number of fusion levels and risk factors. PEMF, pulsed electromagnetic field.

Fusion rate at 12-month post-operation

In the PEMF group, 88.0% (n=125/142) showed successful fusion (all levels graded as fused) with 12.0% (n=17/142) graded as non-fused. Fusion success was 88.0% for subjects with at least one risk factor, 82.4% for subjects with ≥2 risk factors, 46.5% for subjects with ≥3 risk factors, and 14.8% for subjects with ≥4 risk factors. In the control group, 68.1% (n=32/47) of subjects showed successful fusion, with 31.9% (n=15/47) graded as non-fused (Figures 2,3). Fusion success was 63.8% for subjects with at least one risk factor, 40.4% for subjects with ≥2 risk factors, 25.5% for subjects with ≥3 risk factors, and 10.6% for subjects with ≥4 risk factors. Fusion rates were statistically significant in the PEMF group compared to control with subjects who had at least one risk factor (P=0.002), ≥2 risk factors (P<0.001), and ≥3 risk factors (P=0.003). Subjects treated with PEMF showed statistically improved fusion rates with prior failed fusion (P=0.04), multi-level fusion surgery (P<0.001), and advanced age (P<0.001) when compared to controls (Table 3).

Figure 2 High rates of fusion following PEMF treatment. (A) A significant increase in fusion success was observed following PEMF treatment (88.0%) compared to control (68.1%). (B) The PEMF treatment group showed significantly higher rates of fusion in subjects with at least 1, ≥2, ≥3, and ≥4 risk factors compared to control (*, P<0.01). PEMF, pulsed electromagnetic field.

Figure 3 Pre- and post-operative representative imaging for control (A-D) and PEMF subjects (E-H). PEMF, pulsed electromagnetic field.

Linear regression analyses showed a significant effect of PEMF on positive fusion (P=0.003) and remained highly significant after adjusting for all individual risk factors (P<0.001). Analysis of individual risk factors showed no effect on fusion for prior fusion history, diabetes, osteoporosis or multi- vs. single-level fusion (P>0.05). A significant negative effect confirmed that nicotine use (P=0.048), high BMI (P=0.045), and advanced age (P=0.03) were predictors for reduced fusion success. Even in the presence of these risk factors, fusion success remained high with PEMF treatment (P<0.001). Analysis of fusion success using either 5 (P<0.001) or 7 (P<0.001) risk factor composites also showed a highly significant effect of the treatment on fusion success (Table 4).

Safety assessment

Over the 12-month study, 553 AEs were reported in the PEMF group, with 119 subjects (53.1%) reporting ≥1 AE. Most AEs were rated as mild (n=312, 56.3%), followed by moderate (n=170, 30.7%) and severe (n=71, 12.8%). A total of 547 AEs (98.7%) were considered unrelated to the PEMF intervention, with only 6 AEs (1.1%) considered related. The details surrounding related AEs reports are presented in Table 5. Safety events were not recorded for the control group.

Discussion

Treatment approaches that complement spinal fusion surgery to enhance successful healing and clinical outcomes are of continued interest as the frequency of surgeries increases each year. PEMF represents a noninvasive post-operative approach that can easily be added as an adjunct therapy with mounting evidence demonstrating positive impact for its utility in musculoskeletal indications. The current analysis is one of few conducted in the lumbar spine that has evaluated spinal fusion following PEMF in a controlled format and thereby adds to the previous study report (15) by including a comparative arm of subjects enrolled into the study who did not receive PEMF treatment. Post-operative PEMF treatment significantly improved fusion success by approximately 20% compared to the control group. Furthermore, PEMF showed significant improvements in fusion success in subjects with single and multiple risk factors for nonunion.

Given that spinal surgery is a common procedure conducted in older patients who develop degenerative spinal disease, it is not surprising that this patient population presents with multiple challenges to consider for best practices to optimize patient outcomes. Aging patients generally present with co-morbidities that may be risk factors for poor surgical success. Clinical and surgical risk factors such as obesity, nicotine use, age, osteoporosis, diabetes, prior surgery, multilevel surgery, multiple risk factors, and surgical approach may negatively impact fusion success. The current study evaluated seven risk factors for nonunion and not only showed a worsening of fusion success in subjects with a higher number of risk factors, but also a statistically significant improvement in fusion rates in these risk factor subgroups following PEMF treatment compared to control. These findings are consistent with other studies that have evaluated PEMF in cervical (16-18) and lumbar spinal fusion (14,18-22).

This study joins only a few other controlled studies that have evaluated PEMF following lumbar spinal surgery and corroborates others by showing positive effect of PEMF on successful fusion. Collectively, these studies show an average of about 20% improvement in PEMF vs. control groups (21,23,24). Most notably, Mooney et al. showed an approximate 24% improvement at 12-month follow-up with PEMF compared to control on successful fusion rate in subjects who had lumbar fusion surgery (24). Patel et al. similarly showed a 90.5–100% fusion success in subjects treated with PEMF with multiple risk factors (25) although no control served as a comparator. In another study conducted by Simmons et al., subjects who presented with symptomatic pseudarthrosis more than 9 months following lumbar spine fusion were treated with PEMF and achieved 67% successful fusion. Subjects demonstrated equivalent fusion effectiveness across patients with risk factors including smoking, use of allograft, absence of fixation, and multilevel fusions (14).

While PEMF stimulation technology has been around for decades, the scientific evidence for its benefit in skeletal applications is still being elucidated. Advancing research indicates a role for PEMF influence on electric charge at the bone level resulting in increased bone tissue deposition around a broken or fractured segment (26). Additionally, PEMF directly increases the membrane potential of osteoblasts, inducing intracellular mechanisms responsible for anti-inflammation, angiogenesis, and growth factor release (27). Altogether, the mechanistic underpinnings present a unique and appealing approach to improve post-surgical outcomes following spinal fusion surgery. PEMF is poised to bridge the gap for successful fusion in patients who are at risk for nonunion by potentially mitigating the magnitude of risk factor impact at the cellular level.

The study presented limitations that should be considered when reviewing the data. While a control group provides direct comparison for fusion status, groups were not analyzed for additional outcome measurements, which does not allow for other comparative analyses. In the context of real-world examination of PEMF post-surgical procedures, the performance of surgeons and individual site standards were not controlled, which introduces variability among surgical processes.

The noninvasive nature of PEMF is appealing for this patient population. As evidenced by the number of studies evaluating clinical factors influencing nonunion, elderly patients are more likely to present with multiple co-morbidities and risk factors given their age. Elderly patients are also likely to be on multi-drug therapies due to these conditions. This can make interventional therapies complicated due to treatment interactions and noncompliance. The non-invasive nature of PEMF and its lack of drug interactions promote its utility in this patient population.

Conclusions

This study adds to the growing literature demonstrating efficacy for the use of PEMF post-operatively in patients who are at risk for nonunion after spinal surgery. Given the non-invasive nature and favorable safety profile of PEMF therapy, this modality represents an appealing adjunct treatment approach to improving nonunion in lumbar spinal surgery patients who present with single and multiple risk factors for nonunion.

Acknowledgments

We thank Stephanie E. Tedford, PhD, from Pharmacologics, Inc, who on behalf of Orthofix US LLC, assisted in the implementation of manuscript revisions, and Deanna Naomi Schreiber-Gregory, MS, Biostatistician for data analysis.

Footnote

Data Sharing Statement: Available at https://jss.amegroups.com/article/view/10.21037/jss-25-106/dss

Peer Review File: Available at https://jss.amegroups.com/article/view/10.21037/jss-25-106/prf

Funding: This study was supported by Orthofix US LLC (Lewisville, TX, USA).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-25-106/coif). H.H. has conflicts of interest from activity with Orthofix, Nuvasive, Medtronic, Depuy, Pfizer, and SRS. M.A.W. has conflicts of interest from activity with Expanding Innovations. P.C. has conflicts of interest from activity with Nexus Spine, and Stryker Speakers Bureau. V.P. reports ongoing institutional research support, consulting, and advisory relationships with Globus, SIBone, Mainstay Medical, Simplify Medical, Medical Metrics, Inc., Cerapedics, Zygofix, SpineWelding, Orthobond Corporation, Johnson & Johnson, Ecential Robotics, Pfizer, Performat, and Orthofix. All relationships are paid to the institution. A.V. has conflicts of interest from activity with Orthofix, Synergy, SpineArt, Globus Medical, and Institute of Neuro Innovation. J.J.W. has conflicts of interest from activity with Orthofix. K.R. has conflicts of interest from activity with Orthofix, 4 web, Stryker, and Orthoson. I.A. has received consulting and honorarium fees from Orthofix in the past 36 months. V.M. has conflicts of interest from activity with Orthofix. I.C. and J.R. are employees of Orthofix US LLC. D.C. reports receiving royalty payments from Medtronic, Globus Medical/Nuvasive, and Spine Wave; receiving consulting payments from Spine Welding and SI Joint and receiving speaking honoraria from Mainstay Medical. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Good Clinical Practice guidelines and all other applicable regulatory body requirements were followed as well as the guidelines set by the Declaration of Helsinki and its subsequent amendments. This study was approved by the Central Western Institutional Review Board (IRB) [No. 20170923] and local IRBs where applicable (at the Aspirus Research Institute [No. 17.07.488], University of Virginia [No. HSR# 20855], and Rothman Institute [No. RP# 15-042ex]). All institutions are informed and agreed with the study. Informed consent was obtained from all subjects involved in the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Parenteau CS, Lau EC, Campbell IC, et al. Prevalence of spine degeneration diagnosis by type, age, gender, and obesity using Medicare data. Sci Rep 2021;11:5389. [Crossref] [PubMed]
2. Esses SI, Huler RJ. Indications for lumbar spine fusion in the adult. Clin Orthop Relat Res 1992;87-100.
3. Passias PG, Jalai CM, Worley N, et al. Adult Spinal Deformity: National Trends in the Presentation, Treatment, and Perioperative Outcomes From 2003 to 2010. Spine Deform 2017;5:342-50. [Crossref] [PubMed]
4. Patil PG, Turner DA, Pietrobon R. National trends in surgical procedures for degenerative cervical spine disease: 1990-2000. Neurosurgery 2005;57:753-8; discussion 753-8.
5. Kim CW, Siemionow K, Anderson DG, et al. The current state of minimally invasive spine surgery. Instr Course Lect 2011;60:353-70.
6. Chun DS, Baker KC, Hsu WK. Lumbar pseudarthrosis: a review of current diagnosis and treatment. Neurosurg Focus 2015;39:E10. [Crossref] [PubMed]
7. Tsutsumimoto T, Shimogata M, Yoshimura Y, et al. Union versus nonunion after posterolateral lumbar fusion: a comparison of long-term surgical outcomes in patients with degenerative lumbar spondylolisthesis. Eur Spine J 2008;17:1107-12. [Crossref] [PubMed]
8. Weiss AJ, Elixhauser A, Andrews RM. Characteristics of Operating Room Procedures in U.S. Hospitals, 2011. 2006.
9. Barnaba S, Papalia R, Ruzzini L, et al. Effect of pulsed electromagnetic fields on human osteoblast cultures. Physiother Res Int 2013;18:109-14. [Crossref] [PubMed]
10. Bassett CA. Fundamental and practical aspects of therapeutic uses of pulsed electromagnetic fields (PEMFs). Crit Rev Biomed Eng 1989;17:451-529.
11. Ross CL, Zhou Y, McCall CE, et al. The Use of Pulsed Electromagnetic Field to Modulate Inflammation and Improve Tissue Regeneration: A Review. Bioelectricity 2019;1:247-59. [Crossref] [PubMed]
12. Hu H, Yang W, Zeng Q, et al. Promising application of Pulsed Electromagnetic Fields (PEMFs) in musculoskeletal disorders. Biomed Pharmacother 2020;131:110767. [Crossref] [PubMed]
13. Sorrell RG, Muhlenfeld J, Moffett J, et al. Evaluation of pulsed electromagnetic field therapy for the treatment of chronic postoperative pain following lumbar surgery: a pilot, double-blind, randomized, sham-controlled clinical trial. J Pain Res 2018;11:1209-22. [Crossref] [PubMed]
14. Simmons JW Jr, Mooney V, Thacker I. Pseudarthrosis after lumbar spine fusion: nonoperative salvage with pulsed electromagnetic fields. Am J Orthop (Belle Mead NJ) 2004;33:27-30.
15. Weinstein MA, Beaumont A, Campbell P, et al. Pulsed Electromagnetic Field Stimulation in Lumbar Spine Fusion for Patients With Risk Factors for Pseudarthrosis. Int J Spine Surg 2023;17:816-23. [Crossref] [PubMed]
16. Foley KT, Mroz TE, Arnold PM, et al. Randomized, prospective, and controlled clinical trial of pulsed electromagnetic field stimulation for cervical fusion. Spine J 2008;8:436-42. [Crossref] [PubMed]
17. Coric D, Bullard DE, Patel VV, et al. Pulsed electromagnetic field stimulation may improve fusion rates in cervical arthrodesis in high-risk populations. Bone Joint Res 2018;7:124-30. [Crossref] [PubMed]
18. Patel V, Wind JJ, Aleem I, et al. Adjunctive Use of Bone Growth Stimulation Increases Cervical Spine Fusion Rates in Patients at Risk for Pseudarthrosis. Clin Spine Surg 2024;37:124-30. [Crossref] [PubMed]
19. Di Silvestre M, Savini R. Pulsing electromagnetic fields (PEMFs) in spinal fusion: preliminary clinical results. Chir Organi Mov 1992;77:289-94.
20. Bose B. Outcomes after posterolateral lumbar fusion with instrumentation in patients treated with adjunctive pulsed electromagnetic field stimulation. Adv Ther 2001;18:12-20. [Crossref] [PubMed]
21. Linovitz RJ, Pathria M, Bernhardt M, et al. Combined magnetic fields accelerate and increase spine fusion: a double-blind, randomized, placebo controlled study. Spine (Phila Pa 1976) 2002;27:1383-9; discussion 1389. [Crossref] [PubMed]
22. Mooney V. Pulsed electromagnetic fields: an adjunct to interbody spinal fusion surgery in the high risk patient. Surg Technol Int 1993;2:405-10.
23. Marks RA. Spine fusion for discogenic low back pain: outcomes in patients treated with or without pulsed electromagnetic field stimulation. Adv Ther 2000;17:57-67. [Crossref] [PubMed]
24. Mooney V. A randomized double-blind prospective study of the efficacy of pulsed electromagnetic fields for interbody lumbar fusions. Spine (Phila Pa 1976) 1990;15:708-12. [Crossref] [PubMed]
25. Patel VV, Billys J, Okonkwo DO, et al. Three- and 4-Level Lumbar Arthrodesis Using Adjunctive Pulsed Electromagnetic Field Stimulation: A Multicenter Retrospective Evaluation of Fusion Rates and a Review of the Literature. Int J Spine Surg 2021;15:228-33. [Crossref] [PubMed]
26. Markov MS. Expanding use of pulsed electromagnetic field therapies. Electromagn Biol Med 2007;26:257-74. [Crossref] [PubMed]
27. Strauch B, Herman C, Dabb R, et al. Evidence-based use of pulsed electromagnetic field therapy in clinical plastic surgery. Aesthet Surg J 2009;29:135-43. [Crossref] [PubMed]