Rate of fusion using novel synthetic bone graft mixed with allograft stem cell product in lumbar fusions

Introduction

Background

There are over 400,000 spinal fusions performed in the United States each year with roughly 75% involving the lumbar region (1). It is the indicated treatment for many chronic spinal conditions that are resistant to conservative management. Spondylolisthesis and degenerative disc disease are the most common with scoliosis, vertebral disc herniation, and spinal stenosis also being reasons for its utilization (1,2). The operation varies depending on the surgical approach; however, common to all interbody techniques is the removal of the intervertebral disc and the insertion of a cage filled with bone graft which promotes arthrodesis (3).

Rationale and knowledge gap

The capability of the bone graft to stimulate bone regeneration is determined by its osteogenicity (ability to form new bone), osteoinductivity (capacity for ingrowth of supportive structures), and osteoconductivity (capability to promote differentiation of mesenchymal stem cells to osteoblasts and chondroblasts via scaffolding structural properties) (4). Iliac crest autografts have long been regarded as the “gold standard” bone graft material for lumbar interbody fusions as they possess all three characteristics of a suitable bone graft, are easily accessible from the fusion site, and provide a sufficient amount of graft (1,5). However, iliac crest autografts face scrutiny due to the high risk of morbidity posed by the procedure. Post-procedural side effects include numbness and chronic pain at the harvest site, and disability that interferes with activities of daily living (5). These post-operative sequelae have incentivized the creation of graft material from allogeneic or synthetic sources.

Allogeneic bone graft is harvested from cadaveric donors and processed to reduce the risk of adverse immune responses which could result in rejection. Until recently, allogeneic bone grafts were considered inferior to their autogenous counterparts due to the extensive processing which destroys their osteogenecity and osteoinductivity (6). However, recently developed allografts have shown promise in their ability to be used as bone grafts. The product used in this study, a mixture of cortical fiber allograft with fully synthetic allograft, is combined with growth factors and stem cells that allow it to display all three characteristics of a successful bone graft which render it as effective as its autograft counterpart (6,7).

Objective

This study aims to observe how the allograft mixture will affect the rate of arthrodesis in patients undergoing lumbar interbody and lateral mass fusions. Secondary objectives of the study were to compare the effect of non-modifiable and modifiable risk factors on the arthrodesis rate and to evaluate pre-operative and post-operative radiographic parameters. We present this article in accordance with the STROBE reporting checklist (available at https://jss.amegroups.com/article/view/10.21037/jss-24-87/rc).

Methods

Study design

An IRB-approved retrospective chart review (Parkview Health, IRB00003435) was conducted in accordance with the Declaration of Helsinki (as revised in 2013) on patients who received a lumbar interbody fusion using the mixture of Vimax^® and Osteoflo^® from SurGenTec between May 26, 2021, to December 31, 2022. Individual consent for this retrospective analysis was waived. The same board-certified orthopedic spine surgeon conducted the procedures. Patients meeting study criteria were required to be over the age of 18 years, have pre- and post-operative radiographs from each follow-up interval studied, and receive an interbody fusion involving T12–S1 vertebrae, using the allograft mixture for graft material. Patients with active malignancy, patients who underwent additional procedures in the T12–S1 region before the end of the follow-up period, and patients who received an osteotomy were excluded from the study among other criteria. Patients with additional T12–S1 procedures were not included due to reoperation from pseudoarthrosis but rather other pathology at different levels unrelated to the fusion with the allogeneic bone graft. The primary reason for excluding these patients was to ensure radiographic parameter measurements were not altered due to secondary procedures throughout the follow-up period. A complete list of inclusion and exclusion criteria is displayed in Table 1. Throughout the identified time period, 211 patients underwent interbody fusions with the allogeneic graft material with only 129 fulfilling inclusion and exclusion criteria.

Surgical technique

Interbody fusions were completed according to the standard technique for each approach. Lateral mass fusions (posterolateral inter-transverse process fusions) were accomplished using Bovie cautery and Cobb tool to reveal the lateral gutter space. A burr was used to decorticate the transverse process and the bone graft was then packed in the lateral gutters.

Data collection

Demographic information was recorded from the electronic medical record system including age, sex, body mass index (BMI), surgical approach, surgical level, allograft amount, and comorbidities. The Bridwell Fusion Grading System as outlined in the study by Hsieh et al. was used to assess 2-week, 6-week, 3-month, 6-month, and 1-year post-operative radiographs by a board-certified, fellowship-trained orthopedic spine surgeon to determine lateral mass and interbody fusion grades (8). For the sake of reporting, we presumed all patients at 2 weeks were not fused and scored a 4, even though there was no lucency of the implants or collapse of the cage. This allowed us to track the progression of bone graft incorporation and maturation. Pre- and post-operative radiographs at the same time points were viewed to measure spondylolisthesis, anterior disc height, posterior disc height, and foraminal height.

Statistical analysis

IBM SPSS Statistics [Version 29.0.1.0 (171)] was used to perform all statistical analyses. The Kruskal-Wallis test was used to assess if there were any significant differences between Bridwell grades of the interbody and lateral mass fusions at each follow up time period. Each interval was compared to the subsequent follow-up interval to evaluate for significance. The 2-week was compared to the 6-week; the 6-week was compared to the 3-month; the 3-month was compared to the 6-month; and the 6-month was compared to the 1-year.

When looking for significant differences in comorbidities, the patients with the comorbidity were compared to patients without the comorbidity at each time interval. For example, the Bridwell grades of patients with hypertension were compared to the Bridwell grades of patients without hypertension at the 2-week follow-up period. This was repeated for the 6-week, 3-month, 6-month, and 1-year intervals for each comorbidity studied. The same comparisons were made for patients undergoing different surgical approaches. The Kruskal-Wallis test was used to compute significance for both comorbidities and surgical approach.

Data retrieved from taking measurements on the radiographs were assessed for significant differences using the paired-samples t-test. Data from each post-operative timepoint was compared to the pre-operative measurement.

Bias

Patients with incomplete follow-up data were removed from the study to eliminate bias. Bias was minimized by having one board-certified, fellowship-trained orthopedic surgeon grade all interbody and lateral mass fusions, and one medical student who received proper training take measurements on all radiographs.

Results

A total of 129 out of 171 patients met the inclusion and exclusion criteria for the study. The 129 patients included in the study had an average age of 61.0 years and an average BMI of 31.9 kg/m². About 48.8% of the patients were female. Of the comorbidities noted, hypertension, depression, anxiety, and diabetes mellitus were prevalent in over 32% of the studied group. Percutaneous trans-kambin triangle interbody fusion and transforaminal lumbar interbody fusion (TLIF) were the two most utilized surgical approaches for interbody fusions, comprising 79% of the total procedures. Additional demographic information and surgical details are shown in Table 2.

There was a total of 199 interbody fusions completed on the 129 patients studied. Fifty-one patients underwent multi-level interbody fusions. Two hundred and eleven lateral mass fusions were performed on the 129 patients included in the study. Fifty-four patients received lateral mass fusions at two or more levels, meaning some lateral mass fusions were completed at levels to an adjacent interbody fusion. More information about the levels the fusions were performed is displayed in Table 3.

Arthrodesis rate

The number and percent of lateral mass and interbody fusions that received a Bridwell Grade I (complete fusion) at each time interval are recorded in Tables 4,5. About 23.3% of fusions were classified as a Bridwell Grade I at 3 months, 70.9% at 6 months, and 92.8% at 1 year. At the 1-year timepoint, all remaining unfused fusions were a Bridwell Grade II. There was a significant difference between each time interval in the fusion gradings according to the Kruskal Wallis test (Figures 1,2).

Figure 1 Mean lateral mass bridwell fusion grades.

Figure 2 Mean interbody bridwell fusion grades.

Demographics

Patients were divided into two groups: under and over 65 years old. A significant delay in the progression toward arthrodesis was found for patients over 65 years at the 3-month time period for interbody fusions, while no difference was observed in lateral mass fusion grading (Figures 3,4).

Figure 3 Effects of age (years) on lateral mass fusion grade.

Figure 4 Effects of age (years) on interbody fusion grade.

The fusion grades were also compared when patients were divided between sex assigned at birth. Patients assigned female sex at birth exhibited a decrease in progression toward fusion at the 6-week mark for lateral mass fusions and at 3 months for interbody fusions (Figures 5,6).

Figure 5 Effects of sex at birth on lateral mass fusion grade.

Figure 6 Effects of sex at birth on interbody fusion grade.

Obesity is defined by the Center for Disease Control as a BMI greater than 30 kg/m². The patients were divided into a non-obese and obese group, and their fusion grades were compared. Comparable rates of fusion were seen across all timepoints for lateral mass and interbody fusions (Figures 7,8). When BMI was subdivided at 35 kg/m², the BMI >35 kg/m² group displayed slower arthrodesis rates for lateral mass fusions at 6 weeks and 3 months for lateral mass fusions and 3 months for interbody fusions (Figures 9,10).

Figure 7 Effects of BMI >30 kg/m² on lateral mass fusion grade. BMI, body mass index.

Figure 8 Effects of BMI >30 kg/m² on interbody fusion grade. BMI, body mass index.

Figure 9 Effects of BMI >35 kg/m² on interbody fusion grade.BMI, body mass index.

Figure 10 Effects of BMI >35 kg/m² on interbody fusion grade. BMI, body mass index.

Comorbidities

No significant difference in lateral mass fusion grade was found for patients diagnosed with COPD, osteoporosis, diabetes mellitus, heart disease, thyroid disease, or renal disease (Table 6). Patients with depression, and anxiety exhibited delayed progression towards arthrodesis of lateral mass fusions at one or more time intervals compared to those without the corresponding diagnoses while patients with hypertension showed quicker progression towards fusion at the 6-week, 6-month, and 1-year marks (Table 6).

Heart disease and thyroid disease displayed significant changes in the rate of interbody fusions at 6 months (Table 7). Renal disease notably demonstrated a delayed progression towards fusion at 6 weeks and 3 months while osteoporosis significantly impacted interbody fusion grades at 3 months (Table 7). The presence of the other comorbidities did not affect interbody fusion grades.

Surgical approach

The arthrodesis rates were assessed based on the surgical approach. Results of the comparisons for lateral mass fusions and interbody fusions are shown in Figures 11,12. The arthrodesis rates were compared between surgical techniques for each time interval. For lateral mass fusions, significant differences in fusion rates were observed among the surgical techniques at 6 weeks, 3 months, and 6 months. Extreme lateral interbody fusion (XLIF) exhibited slower rates of fusion compared to the other techniques throughout this time period, while TLIF and oblique lateral lumbar interbody fusion (OLIF) were consistently quicker throughout these same time periods. Among interbody fusions, the fusion rates significantly differed only at 6 weeks. Minimally invasive surgery (MIS) TLIF and XLIF displayed the lowest rates of fusion at 6 weeks, while the two quickest techniques were anterior lumbar interbody fusion (ALIF) and OLIF.

Figure 11 Effect of surgical approach on lateral mass fusion grade. MIS ALIF, minimally invasive surgery anterior lumbar interbody fusion. TLIF, transforaminal lumbar interbody fusion; ALIF, anterior lumbar interbody fusion; XLIF, extreme lateral interbody fusion; OLIF, oblique lateral lumbar interbody fusion; MIS TLIF, minimally invasive surgery transforaminal lumbar interbody fusion.

Figure 12 Effect of surgical approach on interbody fusion grade. MIS ALIF, minimally invasive surgery anterior lumbar interbody fusion. TLIF, transforaminal lumbar interbody fusion; ALIF, anterior lumbar interbody fusion; XLIF, extreme lateral interbody fusion; OLIF, oblique lateral lumbar interbody fusion; MIS TLIF, minimally invasive surgery transforaminal lumbar interbody fusion.

Radiographic measurements

Table 8 shows the results of the analyses on the various post-operative measurements taken when compared to the pre-operative measurements. Significant improvements were seen for spondylolisthesis reduction, anterior disc height, posterior disc height, and foraminal height at each post-operative time period.

Discussion

Arthrodesis rate

Key findings

The arthrodesis rate was acceptable at 1-year post-operative with a 92.0% fusion rate amongst interbody fusions and a 77.8% fusion rate among lateral mass fusions. Only one case of non-union was identified in the study, which occurred in a two-level interbody and lateral mass fusion in a patient with diabetes mellitus and hypertension. At the 1-year follow-up appointment, their interbody fusions were Bridwell Grade II, and their lateral mass fusions were Bridwell Grade IV. The patient was asymptomatic and never required revision surgery. Lumbar CT images obtained after the patient was involved in a motor vehicle accident 14 months after the procedure showed progression of the interbody fusions to Grade I and lateral mass fusions to Grade II, suggesting a slowed arthrodesis rate likely due to the patient’s comorbid conditions.

Comparison with similar research

The arthrodesis rate was followed using radiologic assessment is typical of other studies (9,10). A recent systematic review and meta-analysis evaluating 64 studies by Tavares et al. found the interbody fusion rate for iliac crest autografts to be 88.6% (10). There is little data expressing an acceptable fusion rate for lateral mass fusions. The 1-year fusion rate of 77.8% in this study suggests a lower rate of fusion when compared to interbody fusions.

Implications and actions needed

The similar fusion rates among the iliac crest autografts and the allogeneic mixture used in this study support the utilization of an allogeneic bone graft as grafting material. The use of only allogeneic compounds in interbody fusions is substantiated by these results and has preliminarily proven to be as effective as iliac crest autografts which carry a significant side effect profile.

Demographics

Non-modifiable and modifiable risk factors have been shown to impact the bone healing process (11-13). Prior research has shown mixed results on how these risk factors affect the arthrodesis rate after interbody fusion. Some studies have identified risk factors such as obesity and old age; however, others report no significant difference in their findings (12,14). This study aimed to assess the impact of specific risk factors on the rate of arthrodesis to observe if allografts could be used effectively in a wide patient population.

Female sex displayed slower progression towards arthrodesis in both lateral mass and interbody fusions at 6 weeks and 3 months, respectively. This is likely due to the gender-related differences in bone mineral density, exaggerated by the onset of menopause. Elderly individuals (age >65 years) had significantly faster progression towards fusion at 3 months post-operative compared to younger individuals but this difference disappeared at later timepoints. A well-established correlation exists between increasing age and decreased bone mineral density, resulting in a decelerated rate of arthrodesis in the elderly population. Similar fusion rates at 1 year post-operative between gender and age groups mitigates the significance of the findings noted at earlier timepoints, suggesting this graft mixture is equally as effective in both sexes and across all ages. Furthermore, obesity (BMI >30 kg/m²) has been associated with higher rates of reoperation; however, current studies do not report a slowed arthrodesis rate in obese individuals (15). This study found no difference in arthrodesis rates amongst obese and non-obese patients; however, when BMI was divided at 35 kg/m², those with a BMI >35 kg/m² displayed delayed arthrodesis at 6 weeks in both lateral mass and interbody fusions as well as 3 months in interbody fusions. No differences were noted at later timepoints suggesting that there are no long-term differences in fusions capabilities when using this graft in obese versus non-obese individuals, corroborating its use in all patient populations.

Comorbidities

Anxiety, renal disease, heart disease, and osteoporosis all negatively impacted the rate of arthrodesis in either the interbody or lateral mass fusion rates at the 6-week, 3-month, or 6-month time intervals. The impact of these comorbidities on arthrodesis rate is mixed among prior research studies. The differences noted vanished by the 1-year post-operative assessment showing there is no lasting effect on the arthrodesis rate. Thyroid disease showed significantly faster progression at 6 months post-operative in interbody fusions. Thyroid disease is known to accelerate bone turnover which leads to decreased bone mineral density and higher rates of non-union (16). The reason for the improved arthrodesis rate in this study is unknown. It was not seen in lateral mass fusions, and the rate was comparable to patients without thyroid disease at the 1-year post-operative timepoint; therefore, there is no likely clinical difference.

The aforementioned studies included hypertension as a risk factor for non-union and reoperation, but none of them investigated the impact on the arthrodesis rate. This study found that lateral mass fusions in those with hypertension were quicker to reach arthrodesis at the 6-week, 6-month, and 1-year periods. Importantly, interbody fusions showed no difference between patients with hypertension and those without. The lack of a clear mechanism for this cause and the lack of significant findings reflected in interbody fusions most likely makes this result an anomaly. Another significant finding revealed patients with depression exhibited slower lateral mass fusion rates than those without depression across the 3-month, 6-month, and 1-year intervals. Again, this result was not reflected in the interbody fusions which question the existence of a true correlation. The absence of a notable impact on the majority of comorbid conditions studied suggests the effective use of newly developed allografts mixtures, like the one in this study, across a broad range of patients.

Surgical approach

Significant differences between surgical approaches were not expected as demonstrated in a study by Lee et al. (17). The significant findings displayed at the 6-week, 3-month, and 6-month intervals is likely explained by the extreme variability in the number of patients receiving each surgical approach. For example, the average lateral mass fusion rate for the XLIF approach was weighted more heavily by the patients who experienced non-union in their lateral mass fusions due to only eight patients undergoing XLIF. Comparable rates of fusion at 1-year post-operative suggest that no significant differences truly exists if the study groups were to have been equal in size.

Radiographic measurements

Nerve compression from degenerative disc disease which leads to stenosis is the most common indication for interbody fusions (18). The surgical intent is to increase the space for the nerves to relieve pressure placed on it. The significant increases in anterior disc height, posterior disc height, and foraminal height illustrate the surgeries were successful in achieving this goal. Greater increases in disc height are linked to lower incidences of reoperation (19).

Interbody fusions are the preferred method for the treatment of spondylolisthesis as they preserve lumbar alignment and provide decompression (20). When the vertebral bodies slip out of place, it can cause nerve compression which leads to pain. Spinal fusions attempt to restore the natural placement of the vertebral bodies in relation to each other while preventing them from shifting out of place. The significant decrease in spondylolisthesis displays that this objective was accomplished in the surgeries.

Limitations of the study

Although this study included a substantial number of patients, the authors acknowledge that certain results are constrained by lack of data for some of the groups of patients studied. This point is best illustrated when examining the results of how surgical approaches affect the arthrodesis rate. Extreme variance in the number of patients included in each surgical approach group may have exaggerated the perceived impact the surgical approach has on the rate of arthrodesis. A future study with similar group sizes is needed to accurately examine its actual effect.

An additional limitation of the study, common to all retrospective chart reviews, is misreported or underreported data in the electronic medical records. The comorbidities of the patients were extracted accurately to the author’s knowledge; however, patients who go undiagnosed or have missing information in the medical record system would have been evaluated in the incorrect group during data analysis. This has the potential to influence the observed impact of some comorbidities on the arthrodesis rate, although the authors consider this to be minimal. Similarly, due to the retrospective nature of the study, the volumes of graft material utilized could not be controlled for. While all patients received the same cortical fiber allograft and fully synthetic allograft product, some surgical cases instances required allograft bone chips to extend the graft volume. Other admixtures such as bone matrix protein, bone marrow aspirate, and local autograft were included in the grafts in rare instances.

A substantial limitation of this study was the lack of previous research observing the effect of comorbidities and demographic data on fusion rates. Among the studies found, there are conflicting results which becomes problematic when trying to compare fusion rates of the allograft mixture to previous graft materials in specific patient populations.

The study exhibited significant decompressive results on radiographs. The original intention of the authors was to include patient-reported outcomes and quality-of-life data to provide further interpretation of this data. However, this data was significantly incomplete due to the patient’s lack of survey completion which would have yielded unreliable analysis. The authors acknowledge this limitation and intend to collect more robust data regarding patient-reported outcomes and quality of life data in future studies to provide further interpretation of the decompressive findings observed on the radiographs.

Additionally, radiographic interpretation was performed by an orthopedic spine surgeon. The authors recognize that having an independent radiologist review the radiographs would eliminate possible bias; however, spine surgeons more routinely analyze images in a manner that was required by this study.

Conclusions

The lateral mass and interbody fusions progressed at an acceptable rate using the allograft mixture of 77.8% of lateral fusions and 92.0% of interbody fusions received a Bridwell Grade I at 1 year. These rates are comparable to fusion rates in studies utilizing iliac crest autografts which support allograft mixtures as an effective alternative to iliac crest autografts. Although there were instances where demographics and comorbidities displayed a slower progression towards arthrodesis early in the recovery process, the 1-year arthrodesis rates were comparable, with the exception of cases involving hypertension and depression. These two comorbidities only impacted either lateral mass fusions or interbody fusions in each scenario, and not both, for which we do not have an explanation, making the likelihood of this being a statistical anomaly very likely. Future data collection pertaining to these comorbidities will be analyzed to determine if these significant findings are consistent. The similar 1-year arthrodesis rates among most demographic categories and comorbidities studied support the use of allogeneic bone grafts across all patient populations. This finding, along with the large patient cohort in the study, makes the findings generalizable to a broad range of patients undergoing a spine fusion. Finally, the procedures demonstrated exceptional decompressive abilities, significantly increasing anterior disc height, posterior disc height, and foraminal height.

Acknowledgments

Prior to completion of the project in its entirety, a portion of this study was presented at a medical school research symposium [Rate of Fusion Using Novel Synthetic Bone Graft Mixed with Allograft Stem Cell Product in Lumbar Interbody Fusions (Bartrom S, Smith M. Poster Presented at: Indiana University Medical Student Program for Research and Scholarship (IMPRS) Research Symposium; July 27–28, 2023; Indianapolis, IN).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jss.amegroups.com/article/view/10.21037/jss-24-87/rc

Data Sharing Statement: Available at https://jss.amegroups.com/article/view/10.21037/jss-24-87/dss

Peer Review File: Available at https://jss.amegroups.com/article/view/10.21037/jss-24-87/prf

Funding: This work was supported by SurGenTec, Indiana Clinical and Translational Sciences Institute, and the National Institute of Health (No. UL1TR002529).

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-24-87/coif). Both authors report fundings from SurGenTec, Indiana Clinical and Translational Sciences Institute, and the National Institute of Health (No. UL1TR002529). M.S. reports relationships with Ventris Medical (consultant) and SurGenTec (consultant, royalties, and stock options). 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. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the institutional review board of Parkview Health (IRB00003435) and individual consent for this retrospective analysis was waived.

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/.

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