What’s New in Spine Surgery

There has been a rapid progression in evidence-based medicine in spine surgery over the course of the past year. A remarkable number of innovations and clinically relevant randomized controlled trials (RCTs) have been published, with true global representation. In the field of basic science, several key genetic factors have been identified for adolescent idiopathic scoliosis (AIS) and congenital vertebral malformations. In this article, we highlight some of these potentially practice-changing studies. Maximizing Outcomes: Enhanced Recovery and Reducing Surgical Trauma Adequate postoperative pain management can help with mobility, can reduce adverse outcomes, and can prevent chronic pain. Opioids have historically been used as the mainstay treatment option. However, with the increased concerns for opioid-related adverse effects, several studies have investigated how to optimize pain control without increasing opioid consumption. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may be helpful to reduce opioid consumption while improving pain control to allow for earlier mobilization and reduced hospital length of stay. Three notable RCTs were published providing evidence to support perioperative pain management other than opioids. Ali et al.1 conducted a prospective RCT of 284 patients undergoing elective spine surgery, comparing the effect of Enhanced Recovery After Surgery (ERAS) on perioperative and 1-month postoperative opioid use. Their ERAS program included preoperative education on pain management and discharge expectations, surgical site management, and preoperative nutrition (serum albumin) and diabetes optimization, smoking cessation, pain specialist consultations, and obstructive sleep apnea control. Perioperatively, nutrition and pain control were optimized, with early mobilization within 6 hours postoperatively. Patients in the ERAS group were less likely to be using opioids at 6 months postoperatively (11% compared with 21%; p = 0.046), despite similar use in the first postoperative month. Furthermore, patients were more likely to be discharged directly home if they underwent ERAS (92% compared with 81%; p = 0.015). Li et al.2 conducted a double-blinded RCT to study the effect of NSAIDs around the incision to reduce postoperative pain in patients who underwent single-level transforaminal lumbar interbody fusion (TLIF). In this study, 80 patients who underwent TLIF were randomized into an NSAID group who had topical loxoprofen sodium cataplasm around the incision and a control group who had a topical placebo. Patients in both groups still received patient-controlled analgesia. The amount of opioid consumption and the visual analog scale (VAS) pain score were used as outcome measures measured at 0 to 12 hours, 12 to 24 hours, and 24 to 48 hours postoperatively. In the NSAID group, opioid use and VAS pain scores were reduced, with less opioid-related side effects. However, this provided no significant difference in postoperative hospital stay, postoperative drain output, or Oswestry Disability Index (ODI) scores. In this study, topical NSAIDs, with a safer profile than oral medications, provided reduced reliance on opioids while improving the postoperative pain management for patients who underwent TLIF. Iyer et al.3 published an RCT comparing the use of intravenous acetaminophen, intravenous ketorolac, and intravenous placebo on patients undergoing 1 to 2-level lumbar fusions. Patients also received oral opioids and intravenous patient-controlled analgesia as needed. The use of these opioids was studied in the first 72 hours after the surgical procedure to compare the effects of the various intravenous drugs in reducing opioid use. A total of 171 patients were recruited, but only 128 patients received all study doses per protocol. In the intravenous ketorolac group, the mean consumption of opioids was 45% lower than in the placebo group and 29% lower than in the acetaminophen group. For the secondary outcomes, the ketorolac group had lower rates of patient-controlled analgesia usage and improved pain scores overall. Importantly, there were no differences in fusion rates between groups at a mean 2.5-year follow-up, suggesting that there were no NSAID-induced increase in pseudarthrosis risk. AIS New Skeletal Maturity Parameter Most bone age parameters utilize the hand and wrist radiograph for measurements. To reduce radiation exposure in pediatric patients, utilizing a scale visible on the same spine radiograph is preferable. The Proximal Femur Maturity Index (PFMI) utilizes the proximal femoral epiphyses for staging and is visible on the same images as the spine4. The PFMI also avoids errors due to malrotation or angulation, such as are seen in the proximal humerus due to the arm position for lateral radiographs. In a prospective study, Cheung et al. examined 202 patients with AIS who were prescribed underarm bracing5. All patients were followed from brace initiation to skeletal maturity, and each patient was assessed on the risk of progression to adulthood deterioration (≥40°) or to the surgical threshold (≥50°). The PFMI was found to correlate well with these outcomes, similar to other conventional skeletal maturity parameters. For a curve of ≥30°, the risk of progression to the surgical threshold was 30% if bracing was initiated at PFMI grade 2 and 12% if initiated at PFMI grade 3. This is in spite of good compliance with brace-wear. In contrast, brace initiation at PFMI grade 4 for a curve of <30° or at PFMI grade 5 was unlikely to result in progression. Nighttime Bracing Compliance with brace-wear for the management of AIS is crucial for success in avoiding surgery. Many forms of brace treatment utilize full-time brace-wear to maximize effectiveness. However, patients do not often adhere to a full-time bracing protocol because of stigmatization and discomfort. Alternative conservative options such as scoliosis-specific exercises and nighttime bracing may be effective in preventing Cobb angle progression in moderate-grade AIS. Charalampidis et al.6 utilized a multicenter RCT to study the effects of self-mediated physical activity combined with either nighttime bracing or scoliosis-specific exercises compared with physical activity alone. There were 135 patients recruited, with 45 patients in each group. The nighttime brace group showed a significantly higher rate of treatment success (76%) compared with scoliosis-specific exercises (58%) and physical activity (53%). There were similar numbers of surgical cases in each group. This study suggested that nighttime bracing is an effective alternative for patients who cannot adhere to a full-time bracing protocol. Whether the nighttime brace can replace the full-time brace as a first-line treatment is still being debated. Regarding this point, small RCTs have shown noninferiority of the nighttime brace in terms of curve progression7,8, but these studies were likely underpowered to assess differences in surgical rates. The BASIS (Bracing Adolescent Idiopathic Scoliosis) study is a multicenter RCT investigating the effect of a nighttime brace compared with a full-time brace on progression to the surgical range9. The study is currently including patients, but results are not expected for several years. Brace Weaning Despite the abundance of literature studying the occurrence of skeletal maturity, the guidelines for how to wean brace-wear have been unclear. An immediate brace-weaning protocol allows patients to return to activities early, whereas a gradual weaning protocol theoretically may provide better maintenance of the Cobb angle and truncal balance with less back pain. To provide evidence for either practice, an open-labeled RCT of 369 patients was conducted to investigate the effects of gradual or immediate brace weaning on the Cobb angle, truncal balance, and health-related quality-of-life (HRQoL) outcomes at 6, 12, and 24-month follow-ups10. Patients at skeletal maturity were invited to participate. All patients with good brace-wear (≥18 hours) throughout the course of treatment were randomized into immediate brace weaning or 6 months of nighttime brace use before weaning. Gradual brace weaning did not demonstrate any superiority compared with immediate weaning. Similar maintenance of the Cobb angle, truncal balance, and HRQoL was observed. In addition, the numbers of cases of curve progression and curve regression were similar between groups. Hence, immediate weaning at skeletal maturity is recommended to allow patients an earlier return to normal activities. Genetics in Pediatric Deformity Several large-scale studies were published in 2024 to identify several new pathomechanisms for spinal deformities. Wang et al.11 showed that a subset of AIS could be caused by central pattern generator (CPG) defects in the neurotransmission of the central nervous system. These CPGs are important for neuromuscular coordination signaling between the body’s left and right sides. Through a study of multiple large families and >4,000 subjects, Wang et al. identified a novel SLC6A9 variant on the glycine transporter 1 gene (GLYT1). Individuals with scoliosis carried heterozygous variants of SLC6A9. The causal effects were further verified with zebrafish knockout models, and the CPGs were found to be dysfunctional, leading to discoordinated left-right neuronal activities. Specific antagonists of the glycine receptor were able to revert the abnormal phenotype substantially. This study provides insight into failed central coordination of neuromuscular activities as a cause for AIS. Yu et al.12 studied the association between an AIS genetic risk locus in an enhancer near the PAX1 gene and a variant in the collagen XI protein. Through a multicenter meta-analysis study of 10,519 individuals and 93,238 controls, a variant in COL11A1 was identified. A Pax1 knockout mouse was created. COL11A1 was observed to be downregulated in the absence of Pax1, and these mice developed spinal deformities. The intervertebral discs were also disorganized in these Pax1-deficient mice. COL11A1 also suppresses expression of MMP3, and knockdown of estrogen receptor gene Esr2 altered both Col11a1 and Mmp3 expression in chondrocytes. These genetic variations involving estrogen signaling are suggested to increase AIS disease susceptibility through the PAX1-COL11A1-MMP3 signaling axis in spinal chondrocytes. Feng et al.13 investigated the role of VANGL1 and VANGL2 in the vertebral development and their roles in congenital vertebral malformations. VANGL1 and VANGL2 are 2 core components of the Wnt/planar cell polarity signaling pathway that are important for vertebral development. A multiethnic population with congenital scoliosis was studied, and rare and deleterious variants were identified in VANGL1 and VANGL2. A zebrafish model was created to confirm pathogenicity. The penetrance and severity of vertebral malformations increased with reduced VANGL gene dosage. The findings establish the crucial role of planar cell polarity genes in the pathomechanism of congenital vertebral malformations and congenital scoliosis. Adult Spinal Deformity (ASD) Research in ASD surgery continues to focus on limiting the rate of mechanical complications and reoperation and identifying patients at risk for poor HRQoL after surgery. Pellisé et al.14 conducted a large, prospective multicenter study with 5-year follow-up and examined the effect of revision surgery on health-related quality of life. With a follow-up of 88%, the authors found that a greater number of reoperations was associated with lesser HRQoL gain at 5 years for all HRQoL measures, especially in patients in whom the adverse event could not be fully resolved with the revision surgery. The optimal surgical strategy for ASD has been debated for years and depends, to a large extent, on the surgical classification of the deformity. The most commonly reported classification systems to guide treatment are the Scoliosis Research Society (SRS)–Schwab Classification, the Global Alignment and Proportion (GAP) score, and the Roussouly classification. Onafowokan et al.15 reported on 762 patients with ASD and found that, specifically, the spinopelvic component of the GAP score independently predicted achieving the minimal clinically important differences (MCIDs) for the 22-item SRS-22 questionnaire and ODI score and was associated with a lower likelihood of developing mechanical complications (odds ratio [OR], 0.42 [95% confidence interval (CI), 0.26 to 0.73]). The Roussouly classification is a categorization of the natural variations in a standing posture of the sagittal alignment of the lumbar spine and pelvis. Theoretically, a failure to restore the spine to its original shape during ASD surgery would predispose a patient to mechanical failure. Aoun et al.16 utilized a systematic review and meta-analysis of 1,454 patients to assess the predictive power of the Roussouly classification with respect to mechanical failure. The authors found that restoring the original shape of the spine resulted in a 5 times lower rate of a mechanical complication (OR, 0.22 [95% CI, 0.12 to 0.41]). None of the above surgical strategies has been shown to alleviate the occurrence of mechanical complications, and it is important to bear in mind that these systems are all based on radiographic analysis and do not consider patient-specific factors that undoubtedly play a major role in minimizing complications in these high-risk surgical procedures. Degenerative Cervical Conditions The 20-year radiographic outcomes of artificial disc replacement (BRYAN cervical arthroplasty device; Medtronic) have been published. Foley et al.17 utilized data on roughly 80% of 47 patients who were randomized to anterior cervical discectomy and fusion (ACDF) or cervical disc arthroplasty (CDA) with a 20-year follow-up. The C2-C7 cervical range of motion was higher for the CDA group (48°) compared with the fusion group (33°) (p = 0.005). The total cervical range of motion was similar between the preoperative and 20-year follow-up time points for both groups, and the differences between the postoperative and 20-year follow-up time points were also similar for the CDA group. The final adjacent segment degeneration grading was lower in CDA compared with ACDF. The difference in the adjacent level range of motion did not reach significance. There was a 3% reduction in polyethylene height over the 20-year period, but there was no obvious radiographic osteolysis at the implant-end plate interface. The data at the 20-year follow-up were supportive of CDA compared with ACDF for improved cervical range of motion and lower rates of adjacent segment degeneration. A multicenter trial from The Netherlands18 showed, in 265 patients, that posterior cervical foraminotomy was noninferior to ACDF with regard to arm pain reduction in cervical radiculopathy. Individuals with neuroforaminal narrowing were recruited, and patients with purely axial neck pain or myelopathy were excluded. At the 2-year follow-up, the VAS scores suggested no significant differences between groups for arm pain (−2.7 less for the ACDF group compared with the posterior cervical foraminotomy group) and for the decrease in arm pain (1.5 more for the ACDF group compared with the posterior cervical foraminotomy group). Adverse events occurred in 8% of the posterior cervical foraminotomy group and 9% of the ACDF group. There were no differences in revision surgery. However, all reoperations after posterior cervical foraminotomy occurred at the index level because of persistent or reappearing radicular arm pain, whereas most ACDF revision surgeries occurred at adjacent levels (43%) or non-adjacent levels (14%), suggesting adjacent segment degeneration. Nevertheless, the success rate of reducing radicular arm pain was comparable between groups at the 2-year follow-up. Degenerative Lumbar Conditions The controversy in the debate between outcomes of decompression alone or decompression with fusion for low-grade spondylolisthesis has reached better consensus with the publication of 3 RCTs19–21. At a 2-year follow-up, the Swedish Spinal Stenosis Study showed noninferiority of decompression alone in the reduction of the ODI from baseline19. Kgomotso et al.21 published a 5-year follow-up study on 267 patients with 3-mm spondylolisthesis, regardless of instability. With a modified intention-to-treat set of 133 patients who underwent decompression-only surgery and 129 patients who underwent decompression with fusion, the ODI changes of at least 30% reduction from baseline were maintained in the groups at follow-up. Subsequent surgery was performed in 16% of the decompression group and 18% of the fusion group. Between 2 and 5 years, 5% of the decompression group required a new lumbar surgery compared with 10% of the fusion group. Karlsson et al.20 reported on a 5-year follow-up in patients with degenerative lumbar stenosis randomized to decompression or decompression with fusion. After 5 years, the ODI was similar, regardless of treatment. The mean EuroQol-5 Dimension scores were higher for the group that underwent decompression alone, and the fusion group had less improvement in leg pain compared with their preoperative status. These high-level studies support the noninferiority of decompression compared with instrumented fusion. With a possibly higher likelihood of reoperation in the fusion group, decompression may be the preferred option in most patients. 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