The AO Spine Knowledge Forums: A Decade of Impactful Spine Research

Abstract

The AO Spine Knowledge Forums are independent expert-driven global study groups dedicated to improving patient care by publishing evidence-based recommendations and conducting high-impact clinical studies. Five Knowledge Forums represent 6 spine pathologies: tumor, deformity, spinal cord injury, degeneration, trauma, and infection. A summary highlighting their most impactful research achievements over the past 10 years is provided. The results illustrate the critical clinical role of these independent Knowledge Forums.

Introduction

Since its founding in 1958, research has been one of the main pillars of AO (Arbeitsgemeinschaft für Osteosynthesefragen), a medically-guided, not-for-profit organization for the surgical treatment of trauma and musculoskeletal disorders (https://www.aofoundation.org/). With the formal establishment of AO Spine as a clinical division in 2003, spine research has become more focused and structured over the years. Today, the AO Spine Research purpose and vision is to improve patient care through innovative spine research programs by positioning AO Spine as the leading global academic society in spine care and by involving its members in the scientific advancement of spine care through participation in translational and clinical studies. AO Spine research is driven by the AO Innovation Translation Center through the AO Network Clinical Research (eg, Knowledge Forums), by the AO Spine Regions (eg, regional study groups), and by the AO Research Institute located in Davos, Switzerland.

The AO Spine Knowledge Forums (KF) were launched in October of 2010 as an invention of former International Board Chairperson Dr Luiz Vialle. Their goals are to drive spine research, discovery, and innovation to promote excellence in patient care and outcomes. Since their inception, the KFs have generated and disseminated knowledge by publishing evidence-based recommendations and performing impactful clinical studies to improve patient care. ¹ Their latest advances and outcomes assist in clinical decision-making and improve patient care. Notably, the KFs maintain financial independence from third party interests and are funded through the AO Foundation’s endowment.

The 5 KFs represent 6 spine pathologies: tumor, deformity, spinal cord injury, degenerative, and trauma and infection. Each KF is led by up to 10 internationally-recognized experts (KOLs) and supported by up to 60 associated members. The KFs have grown to global clinical research networks, now comprising more than 260 expert spine clinicians and researchers from 38 countries. Over the past decade, 17 multicenter studies, 3 global registries, 9 classifications, 6 clinical practice guidelines, 4 core measurement/outcome sets, and 5 disease specific outcome measures translated into 17 languages have been developed. Overall, more than 350 peer-reviewed manuscripts and more than 500 conference abstracts have been published, earning more than 35 awards. In an effort to expedite evidence to practice, the KFs recently introduced a unique peer-reviewed article format appearing in the Global Spine Journal as the “AO Spine Clinical Practice Recommendations”. ²

The following article provides an overview of the most significant and impactful results published over the past 10 years. While it is not possible to list all the achievements, readers are encouraged to delve deeper into the publications and to follow AO Spine Research and the KFs for further insights.

Summary of Impactful Research

Knowledge Forum Tumor

The AO Spine Knowledge Forum Tumor’s (KF Tumor) mandate has been to both save and improve the lives of patients with spinal tumors through collaborative multicenter research. To achieve this end, KF Tumor has employed 3 key strategies: (1) consolidation of existing knowledge and synthesis of consensus recommendations; (2) development of instruments for patient assessment and outcome measurement; and (3) establishment of an international multicenter research network to facilitate both prospective and retrospective studies.

To date, KF Tumor has published 2 spine oncology focus issues, each providing evidence-based consensus recommendations about the treatment of primary and metastatic spinal tumors.^3-5 This international research network, which includes spinal oncology experts from North and South America, Europe, Asia and Australia, has completed 2 studies, PT-Retro and EPOSO, which focused on primary and metastatic spinal tumors, respectively, and is currently conducting 2 registry-based studies (MTRON and PTRON). To date, a staggering 6039 patients have been enrolled in these clinical studies and since its inception, KF Tumor published 85 articles. KF Tumor also completed the design and planning of a prospective study examining the effect of radiation and surgery on relieving spine tumor-associated pain, which will utilize a new electronic data capture system and is scheduled to begin enrollment in Spring of 2025.

The primary tumor registries have yielded impactful and generalizable studies on rare tumors such as chordoma, chondrosarcoma, giant cell tumor, osteosarcoma and others. ⁶ The impact of rs2305089 SNP and hTERT promoter mutations (C228 T and C250 T) on patient outcomes were explored and concluded that they are important prognostic biomarkers for chordoma patients.^7,8 Further studies demonstrated the importance of clear margins to improve disease-free survival in patients with malignant tumors. Additional research elucidated adverse event profiles and Health Related Quality of Life (HRQOL) in these complex surgical patients. ⁹

The Epidemiology, Process and Outcomes of Spine Oncology (EPOSO, ClinicalTrials.gov identifier: NCT01825161) study enrolled 442 patients, and summarily demonstrated a clear benefit of surgery in the treatment of symptomatic spinal metastases. ¹⁰ The EPOSO data were used to validate and study the Spinal Instability Neoplastic Score (SINS) ¹¹ and the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0), and psychometrically validate the Patient ExPectations in Spine Oncology (PEPSO) instrument.^12,13 The EPOSO data resulted in an additional twelve publications. We learned that even patients with short postoperative survival experience a significant improvement in HRQOL after surgery and that patients with oligometastatic disease (≤ 5 metastases) represent a distinct group with an extended postoperative survival.^14,15 We also learned that the presence of mechanical pain serves as one of the key drivers of poor HRQOL, and that surgery leads to effective relief of mechanical pain.^11,16 EPOSO also demonstrated the critical importance of neurologic function at presentation in the setting of metastatic epidural spinal cord compression, with a clear association between the severity of neurologic deficit and shorter survival, but also demonstrated that surgery leads to improvement of neurologic function. ¹⁷ Such data provide important information for clinicians when determining the optimal treatment strategy for patients with spine metastases, and help set patient expectations about recovery and potential treatment benefit, thereby improving the ability to make shared and informed treatment decisions.

Knowledge Forum Deformity

The AO Spine Knowledge Forum Deformity (KF Deformity) aims to improve the care for patients with adult spinal deformity (ASD). Its studies focus on identifying risk factors, evaluating surgical techniques, and assessing long-term outcomes. The collaborative nature of KF Deformity enables the development of evidence-based guidelines and best practices, driving advancements for ASD patients.

One main achievement of the KF Deformity was the Scoli-RISK study (ClinicalTrials.gov identifier: NCT02949245), which evaluated motor neurologic outcomes and established the gold standard for the rate of neurologic complications in patients undergoing surgery for complex ASD. ¹⁸ This award-winning multicenter prospective study enrolled 272 patients from 15 centers across 3 continents, followed patients for 5 years postoperative, and was labelled as the ‘landmark and collaborative study that changed practice’ by Drs. Lawrence Lenke and Michael Fehlings, leading spine surgeon experts and Co-Principal Investigators of the study. The study resulted in 18 publications, which identified risk factors for poor surgical outcomes, ¹⁹ highlighted the impact of mechanical complications ²⁰ and emphasized the importance of long-term follow-up ²¹ using patient-reported outcome measures (PROMs). ²² The study also revealed regional variations in outcomes and treatment protocols, underlining the need for greater standardization in practice and highlighted that measures that can anticipate and reduce the risk of postoperative neurologic complications are warranted.

Building on the experience of Scoli-RISK to reduce the risks for neurologic complications, the KF Deformity recently finalized the data collection of another international multicenter prospective study ‘Spinal Deformity Intraoperative Monitoring: SDIM’ (ClinicalTrials.gov identifier: NCT03880292), which took place in 23 centers across 5 continents and enrolled 555 patients. The study aimed to determine the incidence of intraoperative neuromonitoring (IONM) alerts in complex, high-risk ASD surgeries and identify the events that led to such alerts. The anticipated outcomes include highlighting the limitations of current IONM protocols, identifying risk factors for alerts, creating algorithms for responses to specific alerts and ultimately developing guidelines for future IONM protocols, ultimately leading to reducing the risk of neurologic complications and improving patient outcomes.

In parallel, KF Deformity is analyzing the results from their international multicenter prospective study ‘Prospective Evaluation of Elderly Deformity Surgery: PEEDS’ (ClinicalTrials.gov identifier: NCT02035280), which evaluated the long term PROMs in the elderly population, aiding clinicians identify risks and benefits for performing deformity surgery in patients 60 years and older.^23-25

Lastly, this international network established a treatment consensus for the management of adult and paediatric deformity patients,^26,27 created a classification of adult deformity patient profiles for different treatment strategies, ²⁸ and developed a core outcomes set (COSSCO). ²⁹

Knowledge Forum Spinal Cord Injury

Over the past decade, the AO Spine Knowledge Forum Spinal Cord Injury (KF SCI) has generated new knowledge related to traumatic and non-traumatic SCI, and translated this knowledge to spine surgeons, other health care providers, and patient groups worldwide. Major accomplishments have included the partnership in a multicentre international randomized controlled trial evaluating the role of riluzole in acute SCI (RISCIS trial, ClinicalTrials.gov Identifier: NCT01597518), ³⁰ a multidisciplinary effort to define research priorities in managing degenerative cervical myelopathy (RECODE-DCM)^31,32 and 2 sets of guidelines related to the management of traumatic and non-traumatic SCI.^33-38 Arguably, the greatest impact has been related to guideline development.

In 2017, the KF SCI (in partnership with the Cervical Spine Research Society) created guidelines for acute SCI and degenerative cervical myelopathy (DCM).^33-36 These guidelines were undertaken using the rigorous GRADE methodology, which established a landmark milestone in spine surgery. The guidelines examined several key questions related to the management of acute SCI including the role and timing of surgery, the role of methylprednisolone, thromboembolic prophylaxis, the role of magnetic resonance imaging and the type and timing of rehabilitation. This focus issue also articulated the first management guidelines for DCM. Based on evidence to decision framework following GRADE principles, it was recommended that surgery be the preferred treatment for moderate and severe DCM and an option for mild DCM. These guidelines have been recognized as a landmark achievement and also identified key knowledge gaps and areas for future research. Subsequent to the 2017 AOSpine-CSRS guidelines, considerable research ensued related to defining the role and timing of surgery in acute SCI and a major research effort related to DCM was launched (RECODE-DCM).^31,32

In 2024, the KF SCI, in partnership with the PRAXIS Spinal Cord Institute, published a new set of guidelines.^37,38 These guidelines focused on 3 distinct topics in the field of SCI, which were felt to represent knowledge gaps with emerging research knowledge: (1) the role and timing of surgery in acute SCI; (2) the optimal hemodynamic management of acute SCI and (3) the prevention, diagnosis and management of intraoperative SCI. Based on several new prospective, controlled studies which facilitated a rigorous meta-analysis of the literature a strong recommendation was made that surgical intervention for acute SCI be undertaken within 24 hours when medically feasible. While recommendations related to spinal cord perfusion pressure management could not be made, the guidelines articulated pragmatic management recommendations related to hemodynamics in acute SCI, which complemented the 2013 AANS/CNS guidelines. ³⁹ Importantly, the 2024 guidelines also articulated several key knowledge gaps requiring further research including: (a) the role of ultra-early (<12 h after injury) surgery for acute SCI; (b) the optimal management of patients with “mild” (ie AIS D) central cord injury; (c) the role of spinal cord perfusion monitoring to drive management and (d) the validation of the proposed AO Spine-PRAXIS care pathway to manage and prevent intraoperative SCI. These knowledge gaps are defining future areas of research of the KF SCI. ³⁸

Knowledge Forum Degenerative

The AO Spine Knowledge Forum Degenerative (KF Degen) was founded to improve patient outcomes through a deeper, evidence-based approach to treating degenerative spinal disorders. The work began with osteobiologics and expanded to encompass the full spectrum of degenerative spinal conditions, including cervical spine pathology, disc herniation, perioperative management strategies, minimally invasive surgery, and emerging technologies.

The interest in osteobiologics stemmed from recognizing inconsistencies in clinical data supporting these biologic materials for spine fusion. To address this, KF Degen developed the BOnE Classification System which categorizes osteobiologics based on the strength of available scientific evidence. ⁴⁰ This system provides surgeons and stakeholders with a simple yet effective method for assessing the potential efficacy of osteobiologic products. Building on this foundation, the AO-GO Project emerged as a major initiative aimed at clarifying the role of osteobiologics in anterior cervical discectomy and fusion (ACDF) surgery. With contributions from 73 AO Spine members worldwide, KF Degen rigorously evaluated the quality of evidence and formulated a set of evidence-based recommendations. ⁴¹ These guidelines empower surgeons, hospitals, product developers, and regulatory bodies to use osteobiologics safely and effectively, ensuring optimal outcomes for ACDF patients.

KF Degen cervical spine research has focused on improving ACDF outcomes, particularly in assessing whether solid bony fusion has been achieved. It was demonstrated that measuring interspinous process distance to assess fusion is reliable for only a minority of surgeons, with most unable to assess fusion consistently. ⁴² This finding suggests that much of the existing literature on ACDF fusion may be highly inaccurate. To address this challenge, KF Degen has shown that artificial intelligence (AI) can significantly enhance the reproducibility of fusion assessments, allowing novice personnel to achieve expert-level accuracy. KF Degen continues to explore AI applications to improve fusion assessment reliability and generate better data to guide surgical techniques and patient management.

Over the years, KF Degen expanded its research scope across a broad spectrum of degenerative spine surgery. The group has conducted a comprehensive review of global literature on chemoprophylaxis following lumbar fusion surgery, leading to the development of evidence-based usage guidelines. ⁴³ KF Degen also made significant contributions to minimally invasive spine (MIS) surgery, investigating its benefits and developing a new classification system to standardize its application. In collaboration with KF Degen, practitioners were surveyed and provided with expert recommendations on perioperative management, including wound closure techniques,^44,45 brace wear, and antibiotic protocols. ⁴⁶

KF Degen is also committed to advancing translational research through collaborations with engineers and scientists. For example, a collaboration with a scientist in Portugal to improve lumbar disc herniation resorption by stimulating macrophages. ⁴⁷ Additionally, KF Degen collaborated with a researcher in Australia to develop novel MRI techniques for the quantitative assessment of disc degeneration. ⁴⁸

The latest frontier lies in emerging technologies, including image guidance, robotic-assisted surgery, and artificial intelligence. KF Degen actively establishing collaborations with robotic engineers, technology companies, and surgeons interested in advancing these innovations.

Knowledge Forum Trauma and Infection

The AO Spine Knowledge Forum Trauma & Infection (KF T&I) has made scholarly contributions over the past decade to our global understanding of traumatic injuries to the spine and has recently expanded its focus to include primary infections of the spine.^49-53 The KF T&I aims to address the growing health care issue of spinal trauma and primary infection by leading the globe in generating the knowledge that improves patient care after suffering from spine trauma and infection.

The first step in generating a globally accepted evidenced-based treatment algorithm for spine trauma begins with having a universally accepted classification for these challenging injuries. The AO Spine Injury Classification Systems including the thoracolumbar, subaxial cervical, upper cervical, and sacral and the AO Spine-DGOU OF osteoporotic compression fracture Classification System aim to standardize decision-making and reporting using a common language among physicians.^51,52,54-56 These classifications have undergone rigorous development and have been internally and externally validated.^57-59 Additionally, a primary infection classification has been developed and is being validated.

The AO Spine Thoracolumbar Spine Injury Classification System represents a significant advancement in evaluating spinal trauma, as it incorporates the critical components of both the TLICS and Magerl classification systems. ⁵² The classification is divided into 3 main categories: Type A—Compression Injuries; Type B—Tension Band Injuries, and Type C—Displacement/Translation Injuries. However, the classification is not solely based on the morphology of the fracture, but also includes critical factors that influence treatment algorithms including the neurologic status of the patient, as well as patient specific modifiers. This classification is applicable worldwide and has provided the foundation for an AO Spine recommended treatment algorithm for thoracolumbar injuries.^49,50,53,60 The knowledge generated during the evolution of the classification and treatment algorithm was instrumental in the development of the AO Spine TLA3-A4 prospective, multinational observational study (ClinicalTrials.gov Identifier: NCT02827214) assessing the treatment for thoracolumbar (TL) burst fractures.^60-65 This is the largest modern study comparing operative and non-operative care for TL burst fractures. ⁶⁶ The results demonstrate a treatment equipoise for surgical and non-surgical management of burst fractures, however for patients with a possible injury to the posterior ligamentous complex, it demonstrates surgical treatment superiority. Furthermore, a cost-utility analysis demonstrated that at 2 years post-treatment, surgical management is cost-effective compared to non-surgical management in neurologically intact TL burst fractures from a societal perspective. ⁶⁷

Beyond classifying injuries, the KF T&I recognized that to truly determine the best treatment for patients with spinal trauma, an outcome measure for patients to interpret their recovery in relation to their pre-injury condition was developed and this is the AO Spine Patient-Reported Outcome Spine Trauma (PROST).^68,69 It has been translated into 17 languages and is one of the key metrics the KF T&I uses to evaluate patient outcomes in their studies.

Research from the KF T&I has transformed spinal trauma management, raising global standards for assessment, communication, and treatment to improve patient care and limit suffering from these devastating injuries.

Conclusion

The AO Spine Knowledge Forums have been instrumental in advancing the state of the art in spine care. The independent spine pathology-based expert groups represent a truly international perspective and focus on clinically relevant topics. The results of recent years have already been translated into clinical practice and educational programs and are having an impact.