Fusion outcomes of structural bone allograft in cervical and lumbar spine surgery: analysis of 147 patients over a decade of follow-up

Introduction

Spinal arthrodesis is required for various spinal degenerative conditions, neoplastic diseases, and traumatic injuries (1-3). Due to steady advancements in surgical techniques and broadening indications, the number of spinal fusion procedures has increased globally in recent decades (4). Consequently, the need for optimal graft material to enhance bone healing and fusion has also increased.

Autologous iliac crest bone grafts were traditionally advocated as the best option due to their inherent integration properties. Nevertheless, the donor site’s morbidity and the challenges in meeting the increasing demand have prompted the exploration of more sustainable alternatives such as homologous structural allografts (i.e., human grafts), synthetic bone grafts, and interbody titanium cages.

Research and clinical evidence substantiate the vital role of grafts in guaranteeing structural integrity and acting as scaffolds to promote bone fusion. An ideal graft material should possess mechanical stability, vascularization, osteoconduction, osteoinduction, and osteogenesis (5-8). Specifically, osteoconduction offers a scaffold for cellular ingrowth, facilitates new cellular attachment, and enhances vascularization. Osteoinduction provides signals that promote cellular migration, proliferation, and differentiation into bone-forming cells. Lastly, osteogenesis provides viable cells sourced from the host for implantation into the bone defect, initiating the reconstruction process. While only autologous bone graft exhibits all these attributes, its use is associated with significant drawbacks, including donor site morbidity and the restricted availability of suitable harvest sites (9-16). Homologous structural allografts (i.e., human grafts) circumvent donor site damage and reduce operating time, with a proven safety profile (17).

This study aims to demonstrate that human structural allografts, provided by tissue banks, can serve as a primary or alternative scaffold for spinal arthrodesis surgery. We present this article in accordance with the STROBE reporting checklist (available at https://jss.amegroups.com/article/view/10.21037/jss-24-130/rc).

Methods

We retrospectively collected data on patients over 18 years old who were treated for cervical and lumbar spinal degenerative, traumatic, or oncologic conditions in whom structural bone allograft were used, in a single hospital (Aulss2 Marca Trevigiana, Treviso, Veneto, Italy) from January 2006 to December 2016. Clinical and radiological follow-up was conducted until December 2023. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study did not require an ethics committee approval. The hospital where the study was conducted did not require the application for the ethic committee for this retrospective study where patients, at the time of hospitalisation, agreed to the follow-up and data collection for research purposes.

Structural bone allografts are provided by the neighbouring tissue bank (Treviso Tissue Bank Foundation, Treviso, Italy). In those patients, the spine anterior column or disc substitution was reconstructed using a structural bone graft, depending on the pathology and type of intervention. The choice of structural bone graft over a synthetic interbody or expandable devices/cages depended on the surgeon’s preference, the wide availability of graft disposal, and the anatomical and sterical characteristics of the vertebral or interbody defects to be rebuilt. Indeed, this study aimed to analyse a large and heterogeneous cohort of patients with different pathologies over a 10-year follow-up.

In our practice, all spinal cases were discussed between a multidisciplinary spine team (e.g., neurosurgeons and neuroradiologists), and the best approach was considered, tailoring the choice of structural graft vs. synthetic device case by case.

The inclusion criteria were:

• Patients over 18 years old;
• Patients with cervical or lumbar spine traumatic fracture and luxation;
• Patients with cervical spondylosis;
• Patients with neoplastic vertebral body fractures;
• Patients with vertebral body fractures secondary to spondylodiscitis;
• Patients with cervical spondylosis requiring anterior decompression and fusion.

The exclusion criteria were:

• Patients who refused to be followed or were lost to follow-up.

Patients were grouped into:

• Patients who underwent anterior cervical discectomy and fusion (ACDF) with human structural bone allografts due to symptomatic spondylosis;
• Patients who underwent anterior cervical corpectomy and fusion with human structural bone allografts due to cervical fracture/luxation;
• Patients who underwent lumbar corpectomy, as part of a circumferential arthrodesis with human structural bones allograft due to lumbar fracture/luxation.

Patient selection is summarized in Figure 1.

Figure 1 Flow chart of patient’s selection.

Human structural graft procurement, processing, and storage

The “Fondazione Banca dei Tessuti del Veneto”, a non-profit tissue bank accredited by the Italian National Transplant Centre and Regional Competent Authority, provided human structural bone tissues. After obtaining proper informed consent, bone tissues were retrieved from cadaver donors within 24 hours of cardiac arrest, or 12 hours if the cadavers were not refrigerated during the first six hours after death.

Donor selection and screening were performed according to Italian requirements, which included serological and molecular tests. Bone tissues were collected in an operating theatre, and after procurement, they were immediately transferred into BASE medium (Alchimia srl, Italy) containing gentamicin 200 µg/mL (Fisiopharma, Italy), vancomycin 100 µg/mL (Pharmatex, Italy), and meropenem 200 µg/mL (Fresenius Kabi AG, Germany), a solution validated for tissue decontamination (18-20). Tissues were subsequently transported to the bank at +4 °C.

The human structural allografts used were obtained from iliac crests or fibula. At the end of the first decontamination, the processing of the bone tissues was conducted in the tissue bank’s Good Manufacturing Practice (GMP)-compliant facility, following aseptic procedures. Soft tissue residues were removed from the bone, and then cut into uniform shapes and sizes, and decontaminated again. The obtained monocortical, bicortical, or tricortical wedges were then packaged and frozen at −80 °C. This is the frozen method of conserving the grafts.

The other way to store the iliac crest segments is the freeze-drying procedure. The tissue must be processed with additional protocol to reach the final status that allows the tissue to be at room temperature for five years from the retrieval date. The freeze-dried structural allografts were obtained by cleaning the wedges with ethanol and hydrogen peroxide (Carlo Erba, Italy) to remove lipids and blood residues. The bone tissues were introduced in the freeze dryer (Scientific Products, USA), for about 24 hours. Freeze-dried structural allografts were then packaged. Samples of freeze-dried bone were analysed for residual moisture content, as the European guide recommended (21). Freeze-dried wedges were stored at +15 °C/+25 °C until use.

Several microbiological tests were conducted to verify compliance with the acceptance criteria and regulations. Samples were inoculated and incubated in BD BACTEC culture vials under the manufacturer’s instructions (BD, Becton, Dickinson, and Company, USA). Environmental monitoring was conducted according to national directives to check if classification was respected (Figure 2).

Figure 2 Preparation of structural bone allografts. (A) Frozen tricortical iliac bone graft form cadaver; (B) lyophilized bone graft form cadaver; (C) cutting the cryopreserved graft with an oscillating saw. The tissue bank technicians use this method to shape the piece to the correct dimensions. The surgeon in the operating room does the same to fit the graft onto the bone defect.

Data collection

We collected data on sex, age, location, date of intervention, fracture/luxation type, operation type, and date of clinical and radiological follow-up for either cervical or lumbar patients. The subsequent radiological follow-ups were performed at 1 month and 12 months post-surgery. The bone fusion status was examined with anteroposterior, lateral, and flexion/extension plain X-rays of the spine. Fusion was considered to be reached starting from 1-year follow-up control if bony bridges or clear signs of osseointegration were found when new bone formation was observed around the bone-implant interface (22-24). According to the clinical outcomes, additional radiological evaluation was conducted yearly using X-rays and clinical follow-ups. Patients were monitored for postoperative complications (30 days). Adverse events of interest collected were infections and bone graft misplacements.

Patients’ demographic characteristics are summarized in Tables 1,2.

Surgical procedures

The same three surgeons performed all surgical procedures (R.Z., J.D.V., E.G.). In all cases, the bone graft was hand-shaped to fill the bone defect with drills and a bone saw, the surgical goal was complete bone fusion.

In the cervical spine, in case of mild degenerative conditions such as spondylosis, the surgeon preferred ACDF of one or two levels, stand-alone structural bone graft with or with anterior plating.

In case of severe degenerative conditions, fracture luxation, or neoplastic vertebral body substitution requiring cervical corpectomy, the surgeons performed it by inserting a tailored bone graft with anterior plating or stand-alone bone graft with posterior fixation to ensure stability.

For lumbar cases, surgeons have performed lateral access to the lumbar spine, vertebral body somatectomy, and structural bone graft insertion with anterior plating or posterior fixation to ensure stability.

Statistical analysis

Descriptive statistics are reported as the median and interquartile range or mean and standard deviation for continuous variables and proportions and percentages for categorical variables.

Results

Cervical outcomes

A total of 98 patients underwent cervical surgery, with a male-to-female ratio of 2.6 to 1. The overall age at presentation was 50.7±17.6 years. Most patients (77.6%) underwent structural bone grafting consequent to fracture luxation of the cervical spine (Figure 3), 21.4% for severe degenerative conditions (Figure 4), and 1.0% for corpectomy consequent to tumour metastasis (Figure 5). The mean overall follow-up was 155±35.7 months.

Figure 3 A case of cervical post-traumatic arthrodesis. (A) A post-traumatic C4-C5 fracture in a 63 ankylosing spondylitis male (sagittal CT scan); (B) post-operative sagittal X-ray showing circumferential arthrodesis with the use of a C5 iliac crest graft with additional anterior plating, which was also fixed on the graft with screws; (C) post-operative sagittal CT at 4 years of follow-up, which shows graft subsidence on the C6 body but with adequate fusion and without misplacement. CT, computerized tomography; C, cervical.

Figure 4 A case of cervical spine fusion for degenerative conditions. (A) Sagittal T2 weighted MRI scan of C4-C5 and C5-C6 spondylosis in a 53-year-old female causing mild myelopathy symptoms; (B) post-operative sagittal CT scan showing anterior discectomy and fusion procedure with stand-alone modeled iliac crest bone grafts; (C) post-operative axial CT scan showing the position of the bone graft substituting the disc; (D) sagittal CT scan of 4 years of follow-up showing adequate arthrodesis. C, cervical; CT, computerized tomography; MRI, magnetic resonance imaging.

Figure 5 A case of cervical arthrodesis following neoplastic disorders. (A) Sagittal T1 weighted MRI scan of C5 and C6 neoplasms in a 69-year-old male; (B) sagittal CT scan showing C5 and C6 osteolytic lesions from neoplasms; (C) post-operative T1-weighted MRI scan showing C5 and C6 corpectomy and circumferential arthrodesis with stand-alone iliac crest graft; (D) postoperative axial T1 weighted MRI scan showing the graft position; (E) sagittal X-ray scan of 1 year of follow-up showing adequate arthrodesis. CT, computerized tomography; C, cervical; MRI, magnetic resonance imaging.

The mean age of traumatic patients was 48.3±19.8 years. Most grafts were reinforced with anterior plating (86.8%), while 13.2% were stand-alone. The mean follow-up time was 151.7±34.9 months.

Overall, only 3.1% of patients experienced post-operative medical adverse events (1 case of postoperative atrial fibrillation and 2 cases of pneumonia). No surgical-related complications were recorded. Over the follow-up period, no structural bone graft dislocation was documented among traumatic or spondylosis cases. Among traumatic cases, 3 cases of stand-alone bone grafting exhibited signs of lower plate subsidence but with late-confirmed radiological fusion. No subsidence was documented in the overall degenerative cases or the traumatic cases with additional anterior plating.

Three patients died during the follow-up. Results of cervical arthrodesis are summarized in Table 3.

Lumbar outcomes

A total of 49 patients underwent lumbar surgery, with a male-to-female ratio of 1.7 to 1. The average age at presentation was 42.2±13.9 years. Most patients (95.9%) underwent structural bone grafting due to fracture luxation of the lumbar spine (Figures 6,7), and only 2% due to myeloma. The mean overall follow-up was 144.7±38.9 months.

Figure 6 A case of lumbar post-traumatic arthrodesis. (A) A post-traumatic L2 type A3 according to the AO Spine classification fracture in a 51-year-old male; (B) post-operative sagittal X-ray showing the circumferential arthrodesis with the use of a stand-alone fibula graft; (C) post-operative coronal X-ray showing the correct alignment of the spine. AO, association of osteosynthesis; L, lumbar.

Figure 7 A case of dorsal and lumbar post-traumatic arthrodesis. (A) A post-traumatic D11 and L1 type A3 and type A4 according to the AO Spine classification fracture in a 53-year-old male; (B) post-operative sagittal X-ray showing the circumferential arthrodesis with the use of a stand-alone iliac crest graft; (C) post-operative sagittal T1-weighted MRI at 1 year of follow-up showing the correct position of the bone graft and the fracture healing; (D,E) postoperative sagittal and axial CT scans after 3 years showing the correct position of the grafts and the occurred fusion. AO, association of osteosynthesis; CT, computerized tomography; D, dorsal; L, lumbar; MRI, magnetic resonance imaging.

The mean age of trauma patients was 41.9±14.0 years. Most grafts were stand-alone, while 10.2% were reinforced with plating. The mean follow-up time was 143.5±39.2 months.

Overall, 14.3% of patients experienced post-operative medical adverse events, including 1 case of urinary tract infection, 1 pulmonary embolism, 1 deep vein thrombosis, and 2 instances of pneumonia. Two related complications were recorded: an early dislocation of the structural bone graft in a male patient and a wound seroma. In the first case, the graft was left standalone during the initial surgery, necessitating the addition of an anterior plate during revision surgery. Only one case showed signs of structural bone graft resorption. No subsidence was documented in either traumatic or degenerative cases with anterior plating. One case of subsidence was reported in an L2 fracture-luxation case in a 67-year-old female with osteopenia.

Two patients died during the follow-up period. Results of lumbar arthrodesis are summarized in Table 4.

Discussion

Our study, aligned with existing findings in the literature, shows that using human cadaver donor structural grafts, whether with or without extra plating, leads to successful long-term fusion outcomes in patients undergoing cervical and lumbar arthrodesis for degenerative, neoplastic, or traumatic conditions (25-27). Nearly all patients, 98.9% of cervical and 97.9% of lumbar cases, achieved and maintained fusion over the years. Adverse events were comparable to those reported in the literature for ACDF, cervical corpectomy, and lumbar somatectomy (17,28).

In the literature, autologous bone grafts have demonstrated substantial effectiveness, with reported fusion rate higher than 90% (17,29). However, the shortcomings associated with autografts are well-documented. These factors include extended surgical time from additional procedures, such as harvesting from the iliac crest, insufficient or inadequate graft material, and the risk of morbidity at the donor site. This often leads to longer hospital stays and debilitating chronic pain, the most prevalent complication (10,14,30); thereby raising costs and reducing the operative cost-effectiveness (31). These limitations were overcome by employing alternative materials such as human structural bone allografts, cages, and synthetic materials.

In cervical corpectomy, spinal reconstruction can be achieved using cages associated with anterior plating. Titanium and polyetheretherketone (PEEK) cages filled with allograft bone are commonly employed in spinal arthrodesis. The fusion rate is reported between 94% and 97% in single level discectomy interbody fusion (32,33), while discectomy alone has an average spontaneous fusion rate of 85% (33). Nevertheless, fusion failure is described as high as 70% for a multiple-level corpectomy (34).

In lumbar arthrodesis carbon fiber-reinforced PEEK cages have granted a fusion rate of 97.5% (35). However, data from the literature indicate an average cage subsidence rate ranging from 13% to 27%, reaching up to 51% (36).

Extensive research has also been conducted on synthetic materials such as ceramics, bioactive glass, and synthetic polymers. The primary benefits of synthetic grafts include their unlimited availability in various sizes and shapes, enhancing surgical efficiency.

Ceramics (e.g., hydroxyapatites, calcium sulfate, and calcium phosphates) have been used as bone grafts with osteoinductive materials to enhance osteoconductivity and osteointegration (37). In lumbar surgery, ceramics as a bone graft extender showed an overall successful fusion rate of 86%, while used alone had a fusion rate of 81% (38). In anterior cervical discectomy, ceramics displayed a fusion rate range between 78% and 100% (39). However, ceramics are known for their low mechanical strength and fragility (38).

Bioactive glasses like silicon dioxide are superior in strength to ceramics and have shown a fusion rate of 89.6% as a graft extender with autograft (40). On the other hand, the fusion rates of these synthetic materials are inferior to those reported for autologous or human grafts. When used alone, bioactive glasses have a reported fusion rate of 33.6% (41).

Human structural allografts are the most effective alternative to bone autografts in spinal arthrodesis. They promote bone fusion and improve efficacy rates, making them a significant option in salvage procedures after cage failure or subsidence for cervical and lumbar procedures (42,43). This is particularly true because the bone can be shaped in the desired form and allocated even in cases where the anatomy is altered due to tumoral and deformative conditions (44). This is especially useful in cases of corpectomy in the L4 to S1 passage or severe cervical degenerative conditions, where the shape and inclination of vertebral endplates require precise angulation to avoid malpositioning or documentation of the construct. Custom-shaped bones can assist surgeons in precisely fitting the bone defect. The key differences between synthetic grafts and devices lie in their malleability and the ability to shape the graft to the desired angle and volume. This adaptability allows for better compatibility with bone defects. In contrast, synthetic bone may not be moldable due to its properties, and devices (such as expandable cages) come in predefined shapes. As a result, the surgeon must adapt the bone defect to fit these devices, with considerable time and blood loss.

Additionally, structural bone allografts are a suitable, safe, and valid option for bone lesions requiring corpectomy and spine reconstruction. We showed that such grafts can be used in different kinds of procedures, including neoplastic diseases, in which bone graft may ensure high rates of fusions. Such results are already reported in literature for the spine’s primary and secondary neoplastic diseases (45).

Our study encompassed a broad range of pathologies for which spinal fusion is traditionally considered the standard treatment. However, it is noteworthy to mention that for patients affected by cervical and lumbar disc degeneration, total disc replacement (TDR), can be an alternative in selected cases (46,47). It allows for a greater range of motion but with reduced stability and increased mechanical stress on the posterior joints (48). Furthermore, it requires precise placement and robust anchoring on the vertebral endplates. The literature continues to debate the functional outcomes of fusion procedures compared to TDR (49-56).

Improvements in harvesting and processing methods have enabled the frozen and lyophilization of cadaveric bones, making homologous structural bone grafts available in various shapes and sizes that can be tailored to fit specific angles between vertebral bodies (25,57). The cost of processing and distributing frozen or lyophilized human structural allografts varies. Frozen bone grafts require proper storage and transportation, which can discourage their use and limit their availability to spine centres near a tissue bank. On the other hand, lyophilized grafts can be stored for up to 5 years and are easily transported (21). However, using a titanium cage or mesh with synthetic bone can be expensive. Additionally, newly developed materials like recombinant human bone morphogenetic protein-2 (rhBMP-2) are often added to titanium cages to improve fusion outcomes (58,59). The average cost of a lyophilized iliac crest used in this study is between 320 and 480 euros. In contrast, titanium cages, especially expandable ones, are priced between 800 and 4,500 euros, depending on whether they are used for cervical or lumbar procedures. Processing bone to the required dimension is a time-consuming process that requires specialized tools like a burr and trephine. The cost of the procedure can increase depending on the type of remodeling instruments used and the surgeon’s level of experience.

Limitations

This study has the inherent limitations of all retrospective studies. A significant limitation is that we did not adequately analyse the graft’s ability to restore deformity and radiological parameters. These were not considered because we view fusion outcomes as the main key point of the study. Additionally, it lacks close follow-up of patients after the first years, and it is possible that some patients did not report any adverse events that occurred over such a long-time frame, thus introducing a selection bias. However, as a specialized trauma and spine centre, any patients experiencing late adverse events would have been referred to us. The major strengths of this study are the heterogeneity of the pathology treated with structural bone human grafts and the extended follow-up, one of the longest reported in the literature, and the large sample of patients in both cervical and lumbar populations. Larger studies that directly compare patient samples treated with different grafts and reconstruction devices are necessary to gain a clearer understanding of the fusion rates and potential adverse outcomes.

Conclusions

Human structural bone grafting remains a viable and cost-effective option for spinal fusion following non-traumatic fractures, traumatic and degenerative events. Furthermore, advancements in bone harvesting and processing technology make human bone allografts a promising solution for spinal revision or as an alternative when employing expandable cages is not feasible due to spatial constraints.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jss.amegroups.com/article/view/10.21037/jss-24-130/rc

Data Sharing Statement: Available at https://jss.amegroups.com/article/view/10.21037/jss-24-130/dss

Peer Review File: Available at https://jss.amegroups.com/article/view/10.21037/jss-24-130/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-24-130/coif). The authors have no 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 did not require an ethics committee approval. The hospital where the study was conducted did not require the application for the ethic committee for this retrospective study where patients, at the time of hospitalisation, agreed to the follow-up and data collection for research purposes.

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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