Biologics for fusion in adult spinal deformity: a review

Introduction

Background

Adult spinal deformity (ASD) encompasses a debilitating array of conditions which affect a significant proportion of the global population and often require surgical intervention. ASD refers to spinal derangement due to progressive and/or accelerated degeneration of native anatomy. It is highly prevalent in patients over 65 years old due to a variety of age-related predisposing factors such as osteopenia or osteoporosis, disc and facet joint degeneration, worsened mobility and balance, and neurodegenerative disorders (1). As the elderly demographic continues to expand worldwide, so too does the prevalence of ASD. From 1993 to 2003, utilization of spinal fusion increased by 89%, 31%, and 134% for cervical, thoracolumbar, and lumbar fusions, respectively (2). These utilization patterns have persisted into the 21^st century, with continued growth in the number of these procedures performed (3-5). The increased demand for surgical intervention has encouraged innovation in the surgical technologies available to manage and treat ASD.

Increased incidence of spinal fusion for ASD is inevitably followed by an increased incidence of complications associated with fusion. Pseudarthrosis is one formidable and challenging example. It is defined as failure to achieve bony fusion after operative intervention, potentially resulting in pain, structural instability, and the need for additional surgical intervention. The approximate rate of pseudarthrosis in ASD has been described in the literature at around 6.3% by some estimates but can range as high as 25–35% (6-12). Identified risk factors for pseudarthrosis include advanced age (>55 years), fusion length >12 segments, smoking history, thoracolumbar kyphosis >20 degrees, and sacral fixation (6).

To avoid pseudarthrosis in ASD surgery, a variety of augmentation strategies are used to encourage successful bony fusion. Historically, autologous iliac crest bone graft (ICBG) and/or local bone graft (spinous processes, laminae) has been favored due to inherent osteoinductive, osteoconductive, and osteogenic properties. ICBG is associated with high rates of successful fusion, described to be nearly 90% (13). However, the morbidities associated with ICBG harvest are not insignificant and include pain, superficial infection, superficial seroma or hematoma, vascular injury, iliac wing fractures, neurological injury, and deep infections or hematomas (14,15). Additionally, there are limitations to the quantity and availability of autologous bone graft, and the quality of the bone may also be patient-dependent.

Rationale and knowledge gap

The drawbacks associated with ICBG have spurred investigation into synthetic alternatives for encouraging spinal fusion. These newer technologies include: decellularized allograft, demineralized bone matrix (DBM), mesenchymal stem cells (MSCs), bone morphogenetic proteins (BMPs), ceramic hydroxyapatite (HA) grafts, bioactive glass, hydrogels, synthetic peptides, and autologous growth factors (AGFs). The efficacy, implementation, and ideal use case for these commercial synthetic graft substitutes remains an active area of research.

Prior reviews of augmentation of spinal fusion have discussed some of these technologies (16,17). The current article aims to provide a timely update on the landscape of biologics in spinal fusion, given the pace of advancements in the space. In addition, we discuss advancements since that time, including increased utilization of platelet-rich plasma (PRP) in spinal fusion. We also provide discussion of the authors’ preferred approach to utilization of biologics in spinal fusion based on experience at a high-volume urban orthopedic specialty hospital.

Objective

This article provides an up-to-date overview of synthetic biologics used to augment bony healing and decrease incidence of pseudarthrosis following spinal fusion surgeries in ASD patients. Here we characterize the current landscape of available biologics and distinguish the variety of technologies which comprise it.

Fusion and failure

The biology of spinal fusion

The overarching goal of spinal deformity correction is to achieve posterolateral or interbody vertebral fusion. The structural prerequisites for fusion are achieved using metal implants to create a rigid fixation construct involving the desired vertebral levels. This minimizes or mitigates movement among the individual segments included in the construct. Subsequently, bony fusion involves a process that takes place over the postoperative period and is supported by graft material implanted within and around the implant construct at the time of surgery.

Spinal fusion is predicated on three principles of bone grafting: osteoconduction, osteogenesis, and osteoinduction. Osteoconduction refers to the ability of a graft to provide the necessary scaffold for development of a favorable graft environment, including the development of capillary networks to provide necessary nutrients for bone growth. Osteogenesis refers to the presence of living cells within the graft that can form new bone (i.e., mesenchymal cells or osteoblasts). Osteoinduction refers to the ability of a graft to chemically stimulate osteoprogenitor cells to produce new bone.

When graft is placed at the time of surgery, it becomes immersed in hematoma. The presence of hematoma at the surgical site stimulates an inflammatory reaction, where proliferating cytokines recruit immunologic and fibroblastic cells to the fusion site. These cells form fibrinous clot. Over the following weeks, these recruited cells stimulate ingrowth of new blood vessels, which bring other growth factors including BMP, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF), granulocyte-colony-stimulating factors, and granulocyte-macrophage colony stimulating factors (18). Concurrently, the fibrinous clot is organized into a fibrovascular stroma. Subsequently, this stroma is resorbed, and osteoblastic and chondroblastic cells proliferate in its place. Eventually, newly-created cartilage is replaced with woven bone, finalizing bony fusion (19-21).

The pathophysiology of pseudarthrosis

Pseudarthrosis may arise from a variety of etiologies, including metabolic factors, patient factors, instrumentation choice, fusion material, and surgical technique (22).

Inadequate decortication is a well-established risk factor for failed arthrodesis (23). Decortication refers to removal of cortical bone at a desired fusion site to expose the underlying cancellous bone (24,25). Doing so encourages vascular ingrowth at the healing surgical site, bringing the nutrients and metabolites required to incite and encourage bone formation and graft integration (25,26). Studies have demonstrated decreased tissue neoformation in the absence of decortication (27,28). Similarly, limited bony surface area available to facilitate fusion at the graft site can increase the risk of nonunion due to inadequacy of the fusion bed.

Inadequate biologic substrate to support bone remodeling may also result in pseudarthrosis. Key players which have been identified in the bone healing process include VEGF-A, which promotes angiogenesis, as well as a variety of growth factors which encourage bony remodeling, including PIGF, FGF, PDGF, IGF, and BMP. A lack of these metabolites at the desired site of fusion may result in impaired vascularization, osteogenesis, cartilage turnover, and cortical repair, as shown in animal models (29-31).

Smoking is a well-proven risk factor for pseudarthrosis, with some studies suggesting nonunion rates of 40% vs. 8% in smokers compared to non-smokers, respectively (32,33). Animal studies have demonstrated that smoking disrupts the process of vascular ingrowth and healing which are critical to postoperative bony growth (34,35). Blood supply through neovascularizaion is essential to bone healing, as it enables recruitment of osteoblast precursors and provides necessary oxygen and nutrients to facilitate the healing process (33,36).

Finally, increased length of the fused segment is also associated with higher risk of pseudarthrosis due to greater incurred mechanical stress. Increased stress may lead to excess motion at the desired fusion site, which can result in development of fibrous tissue non-union instead of bony fusion (37). There have been a variety of patient-specific sub-factors purported to increase this risk, including kyphosis ≥20°, positive sagittal balance, antecedent osteoarthritis of the hips, advanced age, and incomplete lumbopelvic fixation (6,38,39).

Classification of biologics and bioactive augments

A summary of the described biologics and bioactive augments can be found in Table 1.

Decellularized allograft

Mechanism

Allograft bone derived from cadavers or living donors is processed for sterility, removing all cellular components while preserving the extracellular matrix (ECM). While bony tissue processing and decellularization reduces immunogenicity and disease transmission, the remaining ECM maintains biochemical properties of bone healing and spinal fusion, such as osteoconductive attachment and migration of bone-forming cells. Despite these advantages, decellularization reduces biological activity of the allograft, slowing osteoconduction and osteoinduction, graft incorporation into native bone, and subsequent increase in mechanical strength of spinal fusion (40,63,64).

Evidence

Decellularized allografts have demonstrated increasing effectiveness in ASD surgery, providing durable structural support and high fusion rates. At the turn of the century, Molinari et al. demonstrated a 98.5% incorporation rate of anterior column structural allografts, with no evidence of collapse and successful maintenance of sagittal plane correction in long-term posterior fusion patients (41). Furthermore, Buttermann et al. had previously highlighted the importance of allograft type, noting that fresh-frozen allografts yield higher fusion rates than freeze-dried alternatives in lumbar deformity correction (65). Moreover, recent literature has reported that despite the growing use of synthetic bone graft substitutes to increase spinal fusion success rates, the overall quality of evidence does not yet support the superiority of synthetic biological materials, due to a wide array of adverse events (66,67). Collectively, this evidence underscores the viability of decellularized allografts as a reliable alternative to autografts in achieving long-term sagittal stability and successful outcomes in complex spinal deformity surgeries (42,68).

Generally, synthetic bone graft substitutes lack sufficient osteoconductive, osteoinductive, and osteogenic properties compared to traditional autografts. However, allografts are often used as bone graft extenders, functioning as a “scaffold” on which more biologically active graft materials can exert their properties (Figure 1).

Figure 1 Decellularized allograft. Image courtesy of VB spine.

Clinical application

Decellularized allografts serve as a structurally robust scaffold with reduced immunogenicity, making them a reliable graft extender or substitute in long spinal fusions where mechanical stability and long-term incorporation are desired.

DBM

Mechanism

Like decellularized allograft, DBM is derived from allografts processed to remove mineralized bone components. However, it differs as it also contains osteoinductive properties. It promotes osteoinduction through exposure of bioactive organic bone matrices composed of collagen, growth factors, and other non-collagenous proteins (43). DBM is widely used in spinal surgery, as the material stimulates recruitment and differentiation of stem cells into osteoblasts. Furthermore, DBM is readily available in various forms, such as putty, gel, or strips, allowing surgeons to tailor DBM for their specific surgical needs. Despite this versatility, the osteoinductive potential of DBM varies greatly and often requires combination with other bioactive materials to increase reliability (40,63,64).

Evidence

When used in combination with other graft materials, DBM has been shown to offer comparable outcomes to traditional autografts while reducing donor site morbidity in spinal deformity patients (44,69). In 2016, Fu et al. found that DBM combined with autologous laminectomy bone achieved a fusion rate of 80.8%, compared to the 85.7% fusion rate of autogenous iliac bone grafts in long multi-segment posterolateral fusion, which confirmed an insignificant difference in fusion success (70). The American Association of Neurological Surgeons and Congress of Neurological Surgeons also support DBM as a graft extender, with Cammisa et al. showing it effectively reduces the need for autograft while maintaining similar postoperative outcomes with fewer morbidities (71,72). Finally, recent literature comparing fusion rates and clinical outcomes among three different DBM formulations in patients undergoing posterior lumbar interbody fusion (PLIF) found no significant differences across the groups (45). These findings highlight DBM as a reliable alternative to traditional autograft and allograft, providing effective fusion with fewer associated complications (Figure 2).

Figure 2 100% demineralized bone matrix, OsteoStrand. Image courtesy of OrthoFix.

Clinical application

DBM is frequently used as a graft extender or enhancer in ASD fusion due to its osteoinductive properties and versatility in form, particularly in cases where autograft volume is limited.

MSCs

Mechanism

MSCs are capable of regenerating tissue through direct differentiation into osteoblasts and/or secretion of growth factors to promote angiogenesis and osteogenesis. In challenging spinal fusions, MSCs demonstrate high osteogenic potential, as they recruit native cells to modulate inflammation and further enhance bone healing. While MSCs have garnered significant interest for adjunct use to enhance spinal fusions, stem cell therapies remain financially burdensome and require advanced techniques with subsequent monitoring to determine their efficacy in context of patient-specific goals and outcomes. Furthermore, MSCs also often require scaffolds or carriers for effective application within the surgical site (40,63,64).

Evidence

MSCs demonstrate strong potential to enhance fusion rates and improve clinical outcomes while reducing complications associated with autografts (46,47,73). A recent phase I/II clinical trial of patients with monosegmental degenerative disc disease undergoing lumbar fusion showed that autologous MSCs embedded in tricalcium phosphate were safe and effective, achieving an 80% fusion rate and significant improvements in pain and disability scores (48,49). Similarly, a retrospective study using bone marrow MSC concentrate with a collagen scaffold for posterolateral fusion reported a fusion rate of 100%, accompanied by substantial clinical improvements (50). Another recent randomized clinical trial comparing MSCs combined with allogeneic bone tissue to iliac crest grafts found higher fusion rates in the MSC group at 6 and 12 months post-op, with equivalent clinical outcomes and no increase in adverse events (74). However, these technologies are still relatively nascent, they may become more prevalent in future decades if costs can be contained.

Clinical application

MSCs are being used in challenging fusion scenarios or high-risk patients to harness their osteogenic and angiogenic potential, often combined with scaffolds or carriers to enhance localized bone healing.

BMPs

Mechanism

BMPs are potent osteoinductive agents that stimulate differentiation of MSCs into osteoblasts, initiating bone formation. Perhaps the most studied of the osteobiologics used in spinal fusion, BMPs are often delivered using carriers such as collagen sponges, which help localize proteins at the fusion site. BMPs have therefore become widely used in spine surgery and have reliably demonstrated equivalent or even improved fusion rates when compared with more traditional bone grafts. Associated complications include ectopic bone formation and generalized inflammation. These adverse effects necessitate careful dosing and delivery to ensure achievement of patient-specific care goals (40,63,64).

Evidence

BMPs, particularly recombinant human BMP-2 (rhBMP-2), have proven effective in improving fusion rates and reducing pseudarthrosis in ASD surgeries, though they come with an increased risk of certain complications (51,75). Recent meta-analysis by Poorman et al. demonstrated that BMP use significantly decreases the rate of pseudarthrosis (OR =0.23), but is associated with a higher risk of radiculitis and neurological complications (OR =2.18) (52). To date, a plethora of literature has established that rhBMP-2 outperforms ICBG in long spinal fusions, as demonstrated in Kim et al., with patients achieving lower pseudarthrosis rates (6.4% vs. 28.1%) and higher fusion rates (93.5% vs. 71.9%) (76). Additionally, Paul et al. reported a substantial reduction in reoperations for pseudarthrosis with rhBMP-2 use, with a relative risk reduction of 7.5 (53). While BMPs, particularly rhBMP-2, offer significant advantages in fusion success and reduced reoperation rates, their potential for increased complications and reduced cost-efficacy, must be carefully considered when comparing biologics during surgical planning (54) (Figure 3).

Figure 3 Bone morphogenic proteins. Image courtesy of Medtronic.

Clinical application

BMPs, especially rhBMP-2, are potent fusion enhancers commonly used in long-segment fusions or revisions to reduce pseudarthrosis rates, though they require careful dosing to mitigate complications (55).

Ceramic HA grafts

Mechanism

HA ceramics are biocompatible osteoconductive materials serving as a scaffolding for cell attachment and growth. These synthetic ceramics mimic the mineral component of bone, making it durable and ideal for structural support in spinal fusions. Ceramics are available in various forms, including granules, blocks, and coatings, allowing for versatile applications in spinal fusion. However, it lacks osteoinductive properties and is therefore often used in combination with other graft materials to enhance osteogenesis. Clinical studies have shown that HA ceramics can achieve satisfactory fusion rates, particularly when used as part of a composite graft. Its slow resorption can also delay complete bone remodeling (40,63,64).

Evidence

Ceramic HA grafts have demonstrated safety and effectiveness in spinal fusion surgeries, providing comparable fusion rates to autologous bone with fewer complications (56,57). A 5-year study involving 115 patients undergoing spinal fusion reported no complications related to HA-derived products, an excellent safety profile (58). Regarding fusion rates, Korovessis et al. found 100% fusion success in a randomized controlled trial comparing coralline HA to autologous grafts in multilevel lumbar fusions (77). A recent meta-analysis further established comparable fusion rates at 12 and 24 months between HA and autograft groups, with fewer adverse events in the HA group (78). Supported by endorsements from the American Association of Neurological Surgeons and the Congress of Neurological Surgeons, ceramic HA grafts are a reliable and safe alternative to autografts in spinal fusion for ASD (71) (Figure 4).

Figure 4 Ceramic hydroxyapatite graft. Image courtesy of OrthoFix.

Clinical application

Ceramic HA grafts provide durable, osteoconductive scaffolding and are best used in conjunction with more biologically active agents in structurally demanding fusion constructs.

Bioactive glass

Mechanism

Bioactive glass interacts with body fluids to form a hydroxycarbonate apatite layer that bonds to native bone, enhancing osteoinduction and osteoconduction. It also releases ions that stimulate osteoblast activity and angiogenesis. Its antimicrobial properties reduce infection risks, and it integrates well with other biologics. However, bioactive glass is brittle, lacks mechanical strength, and may resorb variably depending on its composition. It is often paired with other grafts for optimal results (40,79).

Evidence

Bioactive glass has emerged as an effective autograft extender for spinal fusion surgery, providing fusion rates and clinical outcomes comparable to traditional options like autograft and titanium. Cottrill et al. demonstrated that bioactive glass achieved an 84% fusion rate, and when combined with autograft, fusion rates were nearly identical to standalone autograft (89.6% vs. 91.6%), highlighting its value as a combination biologic (59). Similarly, Lee et al. compared CaO-SiO-PO-BO bioactive glass ceramic spacers to titanium cages in PLIF and found no significant difference in 12-month fusion rates (89.7% vs. 91.2%), confirming its comparable effectiveness (80). Further validation of bioactive glass by Kwon et al. showed similar fusion rates when comparing CaO-SiO2-P2O5-B2O3 bioactive glass ceramic spacer with a polyetheretherketone (PEEK) cage in PLIF. This prospective randomized controlled trial demonstrated similar 12-month fusion rates between the groups (77.8% for bioactive glass vs. 81.0% for PEEK), supporting the efficacy of bioactive glass in lumbar spine fusion (81). Similar findings have also been reported for bioactive class ceramic spacers in anterior cervical discectomy and fusion (82) (Figure 5).

Figure 5 Bioactive glass. Courtesy of Globus Medical.

Clinical application

Bioactive glass is a valuable autograft extender with osteostimulatory and antimicrobial properties, particularly suited for augmenting biologic activity in multilevel fusions.

Hydrogels

Mechanism

Hydrogels provide a hydrated matrix for cell migration and proliferation, often serving as carriers for biologics like growth factors or MSCs (60). They enhance bone healing by delivering bioactive agents directly to the fusion site. Their injectability allows minimally invasive application, however, hydrogels lack mechanical strength and require supplementation for load-bearing scenarios. Variable rates of degradation can also impact effectiveness, but their customizability makes them valuable for complex or tailored applications (40,64).

Evidence

Hydrogels have demonstrated significant promise in enhancing spinal fusion outcomes for ASD patients, particularly when combined with osteogenic factors or bone marrow aspirate. Various studies have demonstrated sustained bone growth, and thus significantly higher fusion rates (92.31% vs. 82.35% when compared to local bone graft alone) with use of recombinant BMP-2 in HA/β-TCP hydrogel or thermosensitive hydrogel composites that retain osteogenic factors within the fusion site (61,62). Similar studies have shown enhanced cell proliferation, osteogenic differentiation, and comparable fusion outcomes through photoresponsive PEGDA hydrogels with BMP-2 and Healos hydrogel with bone marrow aspirate (83-85). Collectively, these studies highlight hydrogels as a valuable adjunct in spinal fusion, enhancing fusion rates and providing a supportive environment for bone regeneration. Regardless, their use is not common in general surgical practice (Figure 6).

Figure 6 Polyethylene glycol diacrylate (PEGDA) hydrogel. Image: Courtesy of Advanced Biomatrix Inc.

Clinical application

Hydrogels function as delivery vehicles for growth factors or stem cells, allowing for minimally invasive or site-specific biologic augmentation, although they require additional structural support.

Synthetic peptides

Mechanism

Synthetic peptides mimic natural proteins involved in bone formation, promoting osteoblast activity and cell adhesion. Their precision in targeting biological pathways enhances safety and minimizes off-target effects. They are customizable and integrate well with scaffolds. However, their short half-life and lack of structural support necessitate advanced delivery methods (40).

Evidence

Synthetic peptides, such as B2A, have shown potential in enhancing spinal fusion outcomes in ASD surgeries, though evidence remains limited (86,87). A multicenter, blinded pilot study comparing B2A peptide-enhanced ceramic granules (Prefix) with autogenous ICBG in single-level transforaminal lumbar interbody fusion (TLIF) found higher fusion rates within the B2A peptide-enhanced cohort at 12 months follow-up (100% vs. 78%), though the difference was not statistically significant (88). This suggests that B2A may serve as a viable alternative to autograft, potentially offering a better safety profile. However, a systematic review emphasized the need for more robust evidence, noting that current studies on synthetic grafts, including peptides, are often limited by high bias and variability in design (89). While pilot studies are promising, further large-scale, randomized controlled trials are necessary to establish the effectiveness and safety of synthetic peptides compared to traditional graft materials (Figure 7).

Figure 7 Drug-device combination with synthetic peptide. Image courtesy of Cerapedics.

Clinical application

Synthetic peptides are emerging adjuncts designed to mimic natural osteogenic signals and may be used in select cases to stimulate localized bone formation with high precision and low immunogenicity.

AGFs

Mechanism

AGFs, derived from the patient’s own blood or bone marrow, stimulate bone formation and repair through osteoinduction. They enhance angiogenesis and modulate inflammation, creating a favorable environment for bone healing. Their autologous nature eliminates immune risks and makes them a safe option. However, their efficacy depends on patient-specific factors, and they lack structural support. Additionally, preparation can be complex, requiring specialized equipment and expertise. Despite these challenges, their safety and pro-healing properties make them a valuable adjunct in fusion surgery (40,63,64).

Evidence

AGF, particularly PRP, have shown potential in enhancing bone regeneration and fusion rates in spinal fusion surgery, but the evidence remains inconclusive (90-95). A 2020 meta-analysis by Ji-Jun et al., which included 12 studies and 661 patients, found no significant differences in fusion rates or pain relief between PRP and non-PRP groups, suggesting limited clinical impact (96). However, a 2021 study by Van Eps et al. demonstrated that combining PRP with a biomimetic, nanocomposite scaffold significantly improved bone regeneration and fusion success in a rabbit model, with 75% achieving fusion compared to the scaffold alone (97). Similarly, Landi et al. reported favorable outcomes in a small cohort of 14 patients undergoing posterolateral fusion with platelet gel, noting higher bone density in treated areas compared to controls (98). While these studies highlight the potential benefits of AGF, particularly in enhancing bone healing, further research is needed to determine the optimal methods for preparation, formulation, and application to achieve consistent and reliable outcomes in ASD patients (Figure 8).

Figure 8 Platelet-rich plasma extraction system. Image courtesy of DePuy Synthes.

Clinical application

AGFs like PRP can be used to enhance local healing in fusion beds with low donor site morbidity, though their variable efficacy warrants selective application alongside other biologics.

Strengths and limitations

The current article is not without limitations. Though our literature search included results from PubMed, Embase, OVID Medline, and ERIC, there may be sources which were inadvertently excluded from the pool of surveyed literature. Despite this limitation, the specificity the current review provides regarding new options and technologies for biologics in spine fusion outweighs these limitations and provides a thorough update to the existing literature.

Authors preferred approach

The authors preferred approach to bone grafting involves three separate components: morselized locally harvested autograft, rhBMP-2, and DBM. For an open posterolateral fusion, the authors generally use 2 BMP sponges (1.4 mg each) per level. Locally harvested autograft bone varies by case but is particularly voluminous when osteotomies or revisions are being performed. We avoid harvesting iliac crest except when revising L5/S1 pseudarthroses. Crushed cancellous allograft is mixed with DBM and used as an extender of any locally harvested bone. However, the most important component of the fusion process is adequate decortication. We are particularly specific to expose the entirety of the L5 transverse process, ala, and any portion of the superior/inner iliac wing, creating a “pocket” for a robust fusion. We have found this region to be the most problematic, but with adequate exposure and grafting we believe fusions can be obtained at the L5/S1 level without needing an interbody.

Conclusions

The role of osteobiologics in ASD surgery continues to evolve, with each alternative offering distinct advantages and limitations. Traditional autografts, particularly AICBG, remain the gold standard for spinal fusion due to their osteogenic, osteoinductive, and osteoconductive properties. However, challenges such as donor site morbidity and limited availability have spurred recent development of alternative options. These include other biologic agents, such as decellularized allografts, DBM, MSCs, and BMPs, as well as synthetic options such as ceramic HA, bioactive glass, hydrogels, PRP, and synthetic peptides.

Despite these promising advancements, variability in study design, potential biases, and limited large-scale data regarding these newer technologies necessitate cautious interpretation. Robust randomized controlled trials are essential to validate the safety, efficacy, and optimal applications of these biologics in ASD surgery.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Mark J. Lambrechts and Munish C. Gupta) for the series “Adult Spinal Deformity: Principles, Approaches, and Advances” published in AME Surgical Journal. The article has undergone external peer review.

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

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://asj.amegroups.com/article/view/10.21037/asj-25-25/coif). The series “Adult Spinal Deformity: Principles, Approaches, and Advances” was commissioned by the editorial office without any funding or sponsorship. F.L. is a Consultant for SeaSpine and SI-BONE. The authors have no other conflicts of interest to disclose.

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.

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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