Pathological caudal skeleton of an ichthyodectiform fish from the Upper Cretaceous Niobrara Formation of western Kansas, USA.

A series of 12 contiguous caudal vertebrae of an ichthyodectiform fish from the Smoky Hill Chalk Member of the Niobrara Formation is described. The vertebral centra exhibit extensive overgrowth of pathological bone and there is additional pathological bone within the centra and intervertebral spaces, which together resulted in the coossification of most centra. The extent of the pathology is greatest on preural vertebrae 1-3 and decreases anteriorly, which suggests that the pathology began posteriorly and progressed anteriorly. In addition to the pathological overgrowth on bones, the specimen preserves features interpreted as calcified and/or ossified soft tissues associated with the neural and haemal canals. The pathologies are unlike previously described examples of bony pathologies in fish, and it is suggested that they resulted from combined bacterial and fungal infections. As the pathologies developed, they would have adversely impacted the fish's swimming and feeding abilities, and presumably eventually led to the fish's death.

Histology and chronological magnetic resonance images of congenital spinal deformity: An experimental study in mice model.

BACKGROUND: The natural history of the congenital spinal deformity and its clinical magnitude vary widely in human species. However, we previously reported that the spinal deformities of congenital scoliosis mice did not progress throughout our observational period according to soft X-ray and MRI data. In this study, congenital vertebral and intervertebral malformations in mice were assessed via magnetic resonance (MR) and histological images. METHODS: Congenital spinal anomalies were chronologically assessed via soft X-ray and 7 T MR imaging. MR images were compared to the histological images to validate the findings around the malformations. RESULTS: Soft X-ray images showed the gross alignment of the spine and the contour of the malformed vertebrae, with the growth plate and cortical bone visible as higher density lines, but could not be used to distinguish the existence of intervertebral structures. In contrast, MR images could be used to distinguish each structure, including the cortical bone, growth plate, cartilaginous end plate, and nucleus pulposus, by combining the signal changes on T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI). The intervertebral structure adjacent to the malformed vertebrae also exhibited various abnormalities, such as growth plate and cartilaginous end plate irregularities, nucleus pulposus defects, and bone marrow formation. In the chronological observation, the thickness and shape of the malformed structures on T1WI did not change. CONCLUSIONS: Spinal malformations in mice were chronologically observed via 7 T MRI and histology. MR images could be used to distinguish the histological structures of normal and malformed mouse spines. Malformed vertebrae were accompanied by adjacent intervertebral structures that corresponded to the fully segmented structures observed in human congenital scoliosis, but the intervertebral conditions varied. This study suggested the importance of MRI and histological examinations of human congenital scoliosis patients with patterns other than nonsegmenting patterns, which may be used to predict the prognosis of patients with spinal deformities associated with malformed vertebrae.

Vertebral metastasis of hepatocellular carcinoma secondary to viral hepatitis B: case report of 2 patients.

Bone metastases from liver cancer are rare. We report two cases of bone metastases revealing HBV-induced HCC. A 26-year-old african man presented with 4 months of low back pain in the context of general deterioration. Examination revealed a lumbar spinal syndrome and hepatomegaly. Abdominal ultrasound revealed a multinodular liver, and a CT scan of the spine revealed osteolytic lesions. Biological tests revealed a hepatic cytolysis syndrome, hepatic cholestasis and hepatocellular insufficiency. Alpha foetoprotein levels were elevated and hepatitis B serology was positive. We adopted the diagnosis of HCC of viral B origin with bone metastasis. The second case involved a 44-year-old African man admitted for 10 days with back pain. Examination revealed a spinal syndrome, paraplegia and hepatomegaly. A thoracic-abdominal-pelvic CT scan revealed typical HCC lesions and osteolytic lesions on the ribs, pelvis and vertebrae. The biology revealed a biological inflammatory syndrome, hepatic cytolysis, a hepatocellular insufficiency syndrome and a cholestasis syndrome. Alfa-feto proteins were elevated and HBV serology was positive. The diagnosis of bone metastasis of HCC secondary to HBV infection was accepted.

A statistical symptomatic evaluation on SAPHO syndrome from 56 cases of confirmed diagnosis and 352 cases of non-SAPHO involvement.

OBJECTIVE: To report a statistical evaluation of symptomatology based on 56 cases of SAPHO syndrome and 352 non-SAPHO involvement cases, to propose a symptomatic scoring system in consideration of early warning for SAPHO syndrome. METHODS: A cohort comprising 56 subjects diagnosed with SAPHO syndrome was reported, as well as 352 non-SAPHO involvement cases, including their chief complaints, skin manifestations, radiological findings, and laboratory tests. We systematically reviewed previous published five representative huge cohorts from different countries to conclude several specific features of SAPHO by comparing with our case series. The score of each specific index is based on respective incidence and comparison of two cohorts was performed. RESULT: In terms of complaint rates, all subjects of two cohorts suffered from osseous pain, which appeared in the anterior chest wall, spine, and limb which were calculated. In respect to dermatological lesions, SAPHO patients suffered from severe acne, and other patients (82.14%) accompanied with palmoplantar pustulosis. Having received radiological examinations, most SAPHO subjects rather than non-SAPHO involvement cases showed abnormal osteoarticular lesions under CT scanning and more detailed information under whole-body bone scintigraphy. Differences also emerged in elevation of inflammation values and rheumatic markers like HLA-B27. Based on our cases and huge cohorts documented, the early warning standard is set to be 5 scores. CONCLUSIONS: SAPHO syndrome case series with 56 subjects were reported and an accumulative scoring system for the early reminder on SAPHO syndrome was proposed. The threshold of this system is set to be 5 points. Key Points • Fifty-six patients diagnosed by SAPHO syndrome with detailed symptoms and radiological findings were reported. • Comparison was made between the 56 SAPHO patients and 352 non-SAPHO involvement cases. • An accumulative scoring system for the early reminder on SAPHO syndrome was proposed and the threshold of this system is set to be five points.

Clinical and imaging outcomes of different phenotypes of axial spondyloarthritis: 5-year analysis of the DESIR cohort.

OBJECTIVES: To compare the long-term outcomes of three phenotypes of axial SpA (axSpA). METHODS: Patients with a clinical diagnosis of axSpA from the DESIR cohort were grouped into three phenotypes at baseline: 'Pure axSpA' ('Axial'), 'axSpA with peripheral signs' ('IBP+Peripheral') and 'axSpA at risk' ('At risk') by latent class analysis. Clinical and imaging data were collected up to 5 years. Clinical outcomes, measured in each visit, included disability (BASFI) and quality of life (QoL; SF36). Imaging outcomes included inflammatory and structural lesions on MRI and radiographs of spine and SIJ. The association between phenotype membership at baseline and each outcome was tested in multivariable GEE models. RESULTS: In total, 576 patients with axSpA were included. 'At risk' patients had worse disability and QoL than 'Axial' patients over time. For instance, 'At risk' patients had on average 0.4 more points in BASFI over time than 'Axial' patients [ß (95 % CI): 0.4 (0.2; 0.7)]. This difference was mostly noted in female patients who were HLA-B27 positive. In addition, the difference between the 'At risk' and 'Axial' phenotypes was higher in patients receiving bDMARDs than in those not (ß=0.6 vs 0.5), since BASFI improved more in 'Axial' (∆BASFI: -1.3) than in 'At risk' (∆BASFI: -0.9) treated patients. There were no differences in disability and QoL between 'Axial' and 'IBP+Peripheral' patients. Imaging outcomes were worse in the 'Axial' phenotype than in the others over time. CONCLUSION: Patients with 'axSpA at risk' show worse self-reported outcomes over time and are less likely to benefit from anti-inflammatory treatment than those with a classical axSpA phenotype.

Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future Applications.

Native vertebral osteomyelitis, also termed spondylodiscitis, is an antibiotic-resistant disease that requires long-term treatment. Without proper treatment, NVO can lead to severe nerve damage or even death. Therefore, it is important to accurately diagnose the cause of NVO, especially in spontaneous cases. Infectious NVO is characterized by the involvement of 2 adjacent vertebrae and intervertebral discs, and common infectious agents include Staphylococcus aureus, Mycobacterium tuberculosis, Brucella abortus, and fungi. Clinical symptoms are generally nonspecific, and early diagnosis and appropriate treatment can prevent irreversible sequelae. Advances in pathologic histologic imaging have led physicians to look more forward to being able to differentiate between tuberculous and septic spinal discitis. Therefore, research in identifying and differentiating the imaging features of these 4 common NVOs is essential. Due to the diagnostic difficulties, clinical and radiologic diagnosis is the mainstay of provisional diagnosis. With the advent of the big data era and the emergence of convolutional neural network algorithms for deep learning, the application of artificial intelligence (AI) technology in orthopedic imaging diagnosis has gradually increased. AI can assist physicians in imaging review, effectively reduce the workload of physicians, and improve diagnostic accuracy. Therefore, it is necessary to present the latest clinical research on NVO and the outlook for future AI applications.

Chordoma of the Oropharynx.

Background: Chordoma is a rare malignant neoplasm that predominantly arises from the axial skeleton, but can also develop in unusual locations. However, there are also rare cases of "NOS" chordoma involving the oropharyx and epithelial-myoepithelial carcinoma of the parotid gland in the same patient. According to contemporary research, chordoma is a rare malignant neoplasm that arises from the embryonic remnants of the notochord. and typically involves the clivus, sacrococcygeal bones or vertebrae. Studies have shown that the incidence of chordoma has been estimated to be one per one million people per year. Chordoma can occur at any age, but most commonly it is diagnosed in the 40-60 year old age group with the male predominance. Objective: The aim of this article was to review the case of a 74-year-old female patient with epithelial-myoepithelial carcinoma of the parotid gland and a case of "NOS" chordoma involving the oropharyx. Methods: Diagnostic methods were used to examine a female patient with two primary malignant tumors: CT neck scan, CT of paranasal sinuses, ultrasound examination, scintigraphy and operative finding. Case presentzation: Due to the anatomy complexity, complete resection of the tumor through a transoral-transpharyngeal approach was not possible. Intraoperative palpation of the mass revealed well defined submucosal lesion 20x43x46mm beginning at the level of the oro- and hypopharynx and extending superiorly to the nasopharynx, and posteriorly into the spinal canal and intervertebral foramen causing near complete occlusion of the oro and hypopharynx. The patient also underwent extracapsular dissection of the parotid tumor. Postoperative palliative radiotherapy was performed. Conclusion: Surgical treatment remains the mainstay of treatment for EMC and radiation is imperative for patients who refuse surgery and for those with advanced or inoperable diseases.

Intraosseous hemangioma with aneurysmal bone cyst-like changes of the hyoid bone: Case report and literature review.

RATIONALE: Intraosseous hemangioma is a rare benign vascular tumor of the bone that can affect any body part; however, the most common site is the vertebra, followed by calvarial bones. PATIENT CONCERNS: We present a case of intraosseous hemangioma in a 23-year-old male who presented a feeling of fullness in the throat for 3 months. The hyoid bone level had a hard mass of about 5 cm. Fine needle aspiration showed 5 mL dark bloody aspirates. Magnetic resonance image showed a 5.3 cm mixed signal intensity lesion in the hyoid body. DIAGNOSIS: Histopathologic examination showed intraosseous hemangioma with aneurysmal bone cyst (ABC)-like changes in the hyoid bone. INTERVENTIONS: The mass was completely removed without significant problems. OUTCOMES: Complete mass excision and symptomatic improvements were achieved, and no subsequent relapses were observed. LESSONS: The authors experienced a case of intraosseous hemangioma with ABC-like changes. There has been no case report of intraosseous hemangioma in the hyoid bone. This case showed a spectral pattern of the ABC-like changes developing from the underlying bone tumor as a secondary change. ABC-like changes in bone tumors can mislead the diagnosis. Careful examination of the tumor is essential for the correct diagnosis of ABC or ABC-like changes.

Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on the progression of structural damage in the spine over 2 years in patients with radiographic axial spondyloarthritis from the randomised-controlled CONSUL trial.

OBJECTIVES: The study aimed to evaluate the effect of adding a non-steroidal anti-inflammatory drug (NSAID), celecoxib (CEL), to a tumour necrosis factor inhibitor (TNFi), golimumab (GOL), compared with TNFi monotherapy on radiographic spinal progression in patients with radiographic axial spondyloarthritis (r-axSpA) over 2 years. METHODS: R-axSpA patients, having risk factors for radiographic progression (high disease activity plus C reactive protein >5 mg/L and/or ≥1 syndesmophyte(s)), underwent a 12-week run-in phase with GOL 50 mg every 4 weeks. In the core phase (96 weeks), only patients with a good clinical response at week 12 were randomised (1:1) to GOL+CEL 200 mg two times per day (combination therapy) or GOL monotherapy. The primary endpoint was radiographic progression assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change at week 108 in the intent-to-treat population. RESULTS: A total of 128 patients were enrolled in the run-in phase; and 109 patients were randomised at week 12 to monotherapy (n=55) or combination therapy (n=54). At week 108, 97 (52 vs 45) patients completed the study. The change in mSASSS at week 108 was 1.7 (95% CI 0.8 to 2.6) in the monotherapy vs 1.1 (95% CI 0.4 to 1.8) in the combination therapy groups (p=0.79). New syndesmophytes occurred in 25% of patients in the monotherapy vs 11% of patients in the combination therapy groups (p=0.12). During the study, no significant differences in adverse events and serious adverse events were observed between the groups. CONCLUSIONS: Combination therapy with GOL+CEL did not demonstrate statistically significant superiority over GOL monotherapy in retarding radiographic spinal progression over 2 years in r-axSpA.

A comprehensive coding and microRNA transcriptome of vertebral bone in postlarvae and juveniles of Senegalese sole (Solea senegalensis).

Understanding vertebral bone development is essential to prevent skeletal malformations in farmed fish related to genetic and environmental factors. This is an important issue in Solea senegalensis, with special impact of spinal anomalies in postlarval and juvenile stages. Vertebral bone transcriptomics in farmed fish mainly comes from coding genes, and barely on miRNA expression. Here, we used RNA-seq of spinal samples to obtain the first comprehensive coding and miRNA transcriptomic repertoire for postlarval and juvenile vertebral bone, covering different vertebral phenotypes and egg-incubation temperatures related to skeleton health in S. senegalensis. Coding genes, miRNA and pathways regulating bone development and growth were identified. Differential transcriptomic profiles and suggestive mRNA-miRNA interactions were found between postlarvae and juveniles. Bone-related genes and functions were associated with the extracellular matrix, development and regulatory processes, calcium binding, retinol and lipid metabolism or response to stimulus, including those revealed by the miRNA targets related to signaling, cellular and metabolic processes, growth, cell proliferation and biological adhesion. Pathway enrichment associated with fish skeleton were identified when comparing postlarvae and juveniles: growth and bone development functions in postlarvae, while actin cytoskeleton, focal adhesion and proteasome related to bone remodeling in juveniles. The transcriptome data disclosed candidate coding and miRNA gene markers related to bone cell processes, references for functional studies of the anosteocytic bone of S. senegalensis. This study establishes a broad transcriptomic foundation to study healthy and anomalous spines under early thermal conditions across life-stages in S. senegalensis, and for comparative analysis of skeleton homeostasis and pathology in fish and vertebrates.

Total spine MRI for the preoperative evaluation of adolescent idiopathic scoliosis: Part 2 - spinal cord tumors, dysraphisms, diastematomyelia, and vertebral anomalies.

Adolescent idiopathic scoliosis is a commonly encountered condition often diagnosed on screening examination. Underlying, asymptomatic neural axis abnormalities may be present at the time of diagnosis. At certain institutions, total spine MRI is obtained preoperatively to identify these abnormalities. We provide a framework for the radiologist to follow while interpreting these studies. In part 1, we discuss Arnold Chiari malformations, syringomyelia, and the tethered cord. In part 2, we focus on spinal cord tumors, dysraphisms, to include diastematomyelia, and vertebral anomalies.

Predictive Value of Vertebral Bone Destruction Classification Based on Computed Tomography in Diagnosing on Adult Spinal Tuberculosis.

OBJECTIVE: Although magnetic resonance imaging (MRI) is well-established for evaluation of spinal tuberculosis (TB), the importance of computed tomography (CT) should not be overlooked. The purpose of this study was to determine the characteristics of spinal TB and the relationship between spinal TB and the bone lesion pattern seen on three-dimensional CT images. METHODS: One hundred and sixty-one subjects were divided into a TB-positive group and a TB-negative group based on laboratory (X-pert mycobacterium tuberculosis/ rifampin) results and then subdivided further according to whether the bone lesion pattern seen on three-dimensional CT images was fragmentary, osteolytic, sclerotic, or had no evidence of bone destruction. The diagnostic value of the bone lesion pattern was compared between the TB-positive and TB-negative groups. RESULTS: Ninety-nine of the 161 patients were TB-positive and 62 were TB-negative. Fifty-six (34.8%) of the 161 patients had fragmentary/osteolytic lesions, seventy-four (45.9%) had absolute osteolytic lesions, 13 (8.1%) had osteosclerotic lesions, and 18 (11.2%) had no evidence of bone destruction. The fragmentary/osteolytic lesion pattern was strongly predictive of spinal TB (odds ratio 3.33), and when combined with 3 MRI findings (thin abscess wall, more than one half of the vertebral body destroyed, and subligamentous spread) had an even stronger diagnostic value (odds ratio 15.58). CONCLUSIONS: The absolute osteolytic pattern was the most common of the bone lesion patterns. The fragmentary/osteolytic pattern is highly suggestive of spinal TB, especially when combined with MRI findings of a thin abscess wall, destruction of more than one half of the vertebral body, and subligamentous spread.

A Deep-Learning Model for Diagnosing Fresh Vertebral Fractures on Magnetic Resonance Images.

BACKGROUND: The accurate diagnosis of fresh vertebral fractures (VFs) was critical to optimizing treatment outcomes. Existing studies, however, demonstrated insufficient accuracy, sensitivity, and specificity in detecting fresh fractures using magnetic resonance imaging (MRI), and fall short in localizing the fracture sites. METHODS: This prospective study comprised 716 patients with fresh VFs. We obtained 849 Short TI Inversion Recovery (STIR) image slices for training and validation of the AI model. The AI models employed were yolov7 and resnet50, to detect fresh VFs. RESULTS: The AI model demonstrated a diagnostic accuracy of 97.6% for fresh VFs, with a sensitivity of 98% and a specificity of 97%. The performance of the model displayed a high degree of consistency when compared to the evaluations by spine surgeons. In the external testing dataset, the model exhibited a classification accuracy of 92.4%, a sensitivity of 93%, and a specificity of 92%. CONCLUSIONS: Our findings highlighted the potential of AI in diagnosing fresh VFs, offering an accurate and efficient way to aid physicians with diagnosis and treatment decisions.

Treatment and Diagnose of Spinal Phosphaturic Mesenchymal Tumor: A Case Report and a Systematic Literature Review.

BACKGROUND: Spinal phosphaturic mesenchymal tumor (PMT) is a rare disorder but can be cured once the diagnosis is clear and a complete removal by surgery is performed. To the best of our knowledge, only 22 cases in the spine have been described, and we report a case with the largest number of spinal segments (T12-L5) affected among spine PMT cases. METHODS: A comprehensive literature search was performed until May 23, 2023, following the Preferred Reporting Items for Systematic Reviews guidelines. Studies were chosen through relevant PubMed, Web of Science, and EMBASE searches to prioritize obtaining the largest studies. The Medical Subject Headings and Boolean operators employed for this search were ("PMT" or "TIO" or "Tumor-induced osteomalacia" or "phosphaturic mesenchymal tumor") and ("spine" or "spinal"). Two researchers (L.S.Z. and D.B.C) independently reviewed and evaluated the included articles. Any differing opinions were discussed until a consensus was reached. A total of 18 studies were included. A case report is also presented. RESULTS: We report a case of spinal PMT. The full text of the relevant articles was construed. A total of 18 studies were reviewed and consolidated. These articles are roughly divided into the following 5 subcategories: 1) clinical features and baseline distribution, 2) laboratory and imaging findings, 3) pathological manifestations, and 4) surgical methods and treatment options. CONCLUSIONS: Spinal PMT is very rare with a high rate of misdiagnosis and debilitating complications, so it is of significance to increase awareness of the disease among spine surgeons consulted by patients with spinal PMT. 68Ga-DOTATOC-PET/CT shows very high sensitivity to the spinal PMT but there is no way to exactly determine the location of the tumor. PMT has unique immunohistochemical characteristics and malignant PMT is rare. Once diagnosed, complete surgical excision is the recommended treatment. Burosumab is one of the available options, especially in cases that are recurrent and difficult to surgically resect.

Development of a novel prediction model for differential diagnosis between spinal myxopapillary ependymoma and schwannoma.

Spinal myxopapillary ependymoma (MPE) and schwannoma represent clinically distinct intradural extramedullary tumors, albeit with shared and overlapping magnetic resonance imaging (MRI) characteristics. We aimed to identify significant MRI features that can differentiate between MPE and schwannoma and develop a novel prediction model using these features. In this study, 77 patients with MPE (n = 24) or schwannoma (n = 53) who underwent preoperative MRI and surgical removal between January 2012 and December 2022 were included. MRI features, including intratumoral T2 dark signals, subarachnoid hemorrhage (SAH), leptomeningeal seeding, and enhancement patterns, were analyzed. Logistic regression analysis was conducted to distinguish between MPE and schwannomas based on MRI parameters, and a prediction model was developed using significant MRI parameters. The model was validated internally using a stratified tenfold cross-validation. The area under the curve (AUC) was calculated based on the receiver operating characteristic curve analysis. MPEs had a significantly larger mean size (p = 0.0035), higher frequency of intratumoral T2 dark signals (p = 0.0021), associated SAH (p = 0.0377), and leptomeningeal seeding (p = 0.0377). Focal and diffuse heterogeneous enhancement patterns were significantly more common in MPEs (p = 0.0049 and 0.0038, respectively). Multivariable analyses showed that intratumoral T2 dark signal (p = 0.0439) and focal (p = 0.0029) and diffuse enhancement patterns (p = 0.0398) were independent factors. The prediction model showed an AUC of 0.9204 (95% CI 0.8532-0.9876) and the average AUC for internal validation was 0.9210 (95% CI 0.9160-0.9270). MRI provides useful data for differentiating spinal MPEs from schwannomas. The prediction model developed based on the MRI features demonstrated excellent discriminatory performance.

Dynamic Contrast Enhanced MR Perfusion and Diffusion-Weighted Imaging of Marrow-Replacing Disorders of the Spine: A Comprehensive Review.

Significant advancements in cancer treatment have led to improved survival rates for patients, particularly in the context of spinal metastases. However, early detection and monitoring of treatment response remain crucial for optimizing patient outcomes. Although conventional imaging methods such as bone scan, PET, MR imaging, and computed tomography are commonly used for diagnosing and monitoring treatment, they present challenges in differential diagnoses and treatment response monitoring. This review article provides a comprehensive overview of the principles, applications, and practical uses of dynamic contrast-enhanced MR imaging and diffusion-weighted imaging in the assessment and monitoring of marrow-replacing disorders of the spine.

Beyond Anatomy: Fat-Suppressed MR and Molecular Imaging of Spinal Pain Generators.

Spine pain is highly prevalent and costly, but evaluation with clinical features and anatomic imaging remain limited. Fat-suppressed MR imaging and molecular imaging (MI) may help identify inflammatory, lesional, and malignant causes. Numerous MI agents are available, each with advantages and disadvantages. Herein, FDG PET, prostate-specific membrane antigen (PSMA), bone radiotracers, and others are highlighted. No specific pain MI agents have been identified, but mechanisms of key agents are shown in video format, and the mechanism of PSMA as a theranostic agent is displayed. A multidisciplinary approach is needed to master this topic.

Molecular landscape of congenital vertebral malformations: recent discoveries and future directions.

Vertebral malformations (VMs) pose a significant global health problem, causing chronic pain and disability. Vertebral defects occur as isolated conditions or within the spectrum of various congenital disorders, such as Klippel-Feil syndrome, congenital scoliosis, spondylocostal dysostosis, sacral agenesis, and neural tube defects. Although both genetic abnormalities and environmental factors can contribute to abnormal vertebral development, our knowledge on molecular mechanisms of numerous VMs is still limited. Furthermore, there is a lack of resource that consolidates the current knowledge in this field. In this pioneering review, we provide a comprehensive analysis of the latest research on the molecular basis of VMs and the association of the VMs-related causative genes with bone developmental signaling pathways. Our study identifies 118 genes linked to VMs, with 98 genes involved in biological pathways crucial for the formation of the vertebral column. Overall, the review summarizes the current knowledge on VM genetics, and provides new insights into potential involvement of biological pathways in VM pathogenesis. We also present an overview of available data regarding the role of epigenetic and environmental factors in VMs. We identify areas where knowledge is lacking, such as precise molecular mechanisms in which specific genes contribute to the development of VMs. Finally, we propose future research avenues that could address knowledge gaps.