Safety and Efficacy of Bioabsorbable Cervical Spacers and Low-Dose rhBMP-2 in Multi-Level ACDF

Discussion

Among the various available grafting options for multilevel ACDFs, autologous bone from the iliac crest has traditionally been considered the gold standard. ^{1, 2, 12–15} Harvesting of iliac crest autograft can be associated with potential complications such as hematoma, surgical site infection, lateral femoral cutaneous nerve injury, pelvic fracture, muscle herniation, and persistent pain, and as a result, is becoming less commonly used today.² Allograft is often used as an alternative to autologous bone, however, there may be an increased likelihood of failed fusion and need for additional revision surgery.¹⁶ In order to avoid donor morbidity, synthetic spacers filled with a graft biologic have become an increasingly popular alternative. One commonly used option for interbody spacers are polyetheretherketone (PEEK) spacers, which offer the advantages of radiolucency and an elastic modulus closer to cortical bone.^17–19 However, there exist concerns about particulate debris, as well as the limited amount of graft biologic that can be used due to their small apertures (relative to the cross-sectional endplate) and high costs.^17–19 Titanium cages are also commonly used, but have the additional disadvantages of having a modulus of elasticity much higher than cortical bone, and their lack of radiolucency make fusion assessment difficult.^{20, 21}

Given the disadvantages of PEEK and titanium spacers, intervertebral spacers derived from bioabsorbable materials have emerged as a promising alternative. In addition to its radiolucency property and modulus of elasticity similar to bone, bioabsorbable implants degrade slowly over time (maintains 90% strength until 6 months after implantation, degrades to 50% strength by 12 months postoperative), resulting in a gradual “dynamization” across the implant, graft material, and vertebral body endplates, all of which may increase the likelihood of a solid fusion. Since BCS gradually resorb, long-term problems associated with stress shielding, particulate debris, and retained foreign body are significantly minimized.^{1, 23}

While high fusion rates and clinical efficacy has been widely reported for single-level cases, there is a much wider discrepancy regarding the safety and utility of ACDF in multi-level cases.²⁵ The reported fusion rates and complications rates for these procedures can vary widely and are highly dependent upon the number of levels treated, the use of supplemental instrumentation, and the choice of graft biologic and interbody spacer.^1–9 Pseudoarthrosis rates of 0% to 44% have been reported, however, these numbers may be confounded by the lack of standardized fusion assessment and definition.^{1, 24, 25} In general, fusion rates are thought to decrease with more levels treated, the use of allograft biologic, and a lack of rigid instrumentation. Complication rates also vary widely, between 2% to 67%, particularly in regards to commonly-reported approach-related events such as dysphagia, and also generally increase with the number of levels treated and potentially the source of graft.²⁴

Although short-term dysphagia is recognized as a ubiquitous and well-known side effect following ACDF, there is nonetheless a considerable variability in the reported literature regarding incidence and prevalence rates.^24–26 This variability can largely be attributed to discrepancies in both the definition and assessment of dysphagia. The qualitative assessment of dysphagia used in the present study defined “swallowing impairment” to include difficulty with solid and/or liquid foods and pain swallowing, and symptoms were self-reported by the patient. This definition of dysphagia is largely consistent with others found in recently published literature. Incidences of dysphagia in the current study were quantified if symptoms were unresolved by the 2 week postoperative visit or if hospital readmission and additional treatment was required. Patients exhibiting symptoms past 2 weeks, but were resolved by 3 months without additional intervention or readmission, were considered to have “prolonged” dysphagia. Patients with symptoms unresolved after 3 months were considered to have “persistent” dysphagia.

Early complaints of postoperative, transient dysphagia were not uncommon in patients in the current series, but were not quantified prior to the initial postoperative visit at two weeks. Twenty-one (29%) patients had prolonged dysphagia beyond the two-week postoperative visit, with symptoms resolving by 4 weeks in 10 patients and by 3 months in the remaining 11 patients. Of these, 2 patients required hospital readmission for observation and steroid treatment, with no additional intervention. No patients had persistent dysphagia after 3 months. By comparison, a retrospective analysis of 454 patients by Riley et al. found that the incidence of dysphagia at 3 months postoperative was 33% for patients treated at two levels and 39% for patients treated at three or more levels.²⁶

Excluding patients with uncomplicated prolonged dysphagia, the overall complication rate for patients in the current series was 11% (4% major complications and 7% minor complications). By comparison, complication rates reported by Fountas et al. for two- or three-level ACDFs using autologous or allografts with or without a plate was 20%. However, this complication rate decreases to 9% after excluding patients with dysphagia that resolved by 4 weeks postoperative. In their series, a postoperative hematoma occurred in 26 (4.8%) patients, recurrent laryngeal nerve injury occurred in 18 (3.3%) patients, and esophageal perforation occurred in 2 (0.4%) patients. A CSF leak due to an intraoperative dural tear was noted in 2 (0.4%) patients.²⁴

The fusion rate for patients in the current series was 98.6%, or 99.5% of treated levels. By comparison, for patients treated with allograft or autograft, Fountas et al. reported similarly high fusion rates of 94% in two-level cases and 91% in three-level cases, giving an overall fusion rate of 93%. A meta-analysis by Fraser et al. reported an 80% fusion rate for two-level ACDFs without fixation and 95% fusion rate with fixation. For three-level cases, Fraser et al. reported a 65% fusion rate for three-level cases without fixation and 83% fusion rate with additional plate placement.²⁵ A more recent systematic literature review by Miller et al. reported fusion rates of 91% of levels treated for each allograft and autograft and 97% of levels treated with cages filled with morselized autologous local bone supplemented with bone graft substitute.²⁸

Our fusion rate of 98.6% in the current study is also consistent with other rates reported for patients treated with BCS. Park et al. reported a 95.2% fusion rate in a series of 26 patients with BCS for one- or two-level degenerative disc disease. Of the 26 patients, allograft was used for 25 patients and autologous ICBG was used for 1 patient.²⁷. In a comprehensive literature review, Vaccaro et al. also reported similarly high fusion rates of 94% of levels treated with BCS, and noted that sagittal alignment was maintained throughout the follow-up period.⁶ In comparison with other fusions rates for BCS with rhBMP-2, Lanman et al. reported a 100% fusion rate by 3 months postoperative measured by x-rays and CT. Low complication rates were also reported, with only 1 patient experiencing severe dysphagia requiring extended hospital stay.¹

In the current series, BCS were used in conjunction with an average of 0.6mg of rhBMP-2 per level. While the authors recognize that the use of rhBMP-2 in the cervical spine is both off-label and controversial, we nonetheless hope the current study demonstrates that when used in very low doses and contained within a spacer and with meticulous surgical technique, rhBMP-2 can still be considered a safe and effective option. Particularly in light of recent findings from meta-reviews by Simmonds et al., the use of rhBMP-2 has been suggested to increase fusion rates when properly utilized.¹⁰

Clinical improvements in the current series were high, with an average of 60% reduction of neck pain and 55% reduction of arm pain. Physical quality of life (QOL) improved an average of 24% and mental QOL improved an average of 18%. Additionally, disability (NDI) improved an average of 43%. In comparison, a systematic literature review by Miller et al. reported improvements in NDI as 46% for cage, 61% for allograft, and 76% for autograft.²⁸ It should be noted that the clinical indication for surgery was myelopathy in 40% of patients in the current series, and thus, the NDI, which contains questions mostly related to disability as a result of radicular symptoms, may not reflect the “true disability” for these patients. Improvements for neck pain were reported between 63% to 69% and arm pain was reported as 62% to 75%. Finally, PCS improved 42% and MCS improved 16% for patients treated with allograft.

Finally, there are several limitations in the current study, namely the lack of a control or comparative group, and the lack of routinely-collected CT scans. As this is an observational single-cohort study, conclusions regarding comparative effectiveness against conventional cage options are limited. Additionally, without an adequate control group, it is difficult to attribute clinical improvements and/or fusion efficacy to a specific component (interbody cage, biologic, etc.). The purpose of this study, instead, is to provide evidence regarding the feasibility and utility of a possible cage and graft combination. Finally, as serial CT studies were not collected, fusion status could only be determined based on symptomatic rather than radiographic confirmation.