A novel CCDC91 isoform associated with ossification of the posterior longitudinal ligament of the spine works as a non-coding RNA to regulate osteogenic genes.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common intractable disease that causes spinal stenosis and myelopathy. We have previously conducted genome-wide association studies for OPLL and identified 14 significant loci, but their biological implications remain mostly unclear. Here, we examined the 12p11.22 locus and identified a variant in the 5' UTR of a novel isoform of CCDC91 that was associated with OPLL. Using machine learning prediction models, we determined that higher expression of the novel CCDC91 isoform was associated with the G allele of rs35098487. The risk allele of rs35098487 showed higher affinity in the binding of nuclear proteins and transcription activity. Knockdown and overexpression of the CCDC91 isoform in mesenchymal stem cells and MG-63 cells showed paralleled expression of osteogenic genes, including RUNX2, the master transcription factor of osteogenic differentiation. The CCDC91 isoform directly interacted with MIR890, which bound to RUNX2 and decreased RUNX2 expression. Our findings suggest that the CCDC91 isoform acts as a competitive endogenous RNA by sponging MIR890 to increase RUNX2 expression.

Integrin αVß3 antagonist-c(RGDyk) peptide attenuates the progression of ossification of the posterior longitudinal ligament by inhibiting osteogenesis and angiogenesis.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL), an emerging heterotopic ossification disease, causes spinal cord compression, resulting in motor and sensory dysfunction. The etiology of OPLL remains unclear but may involve integrin αVß3 regulating the process of osteogenesis and angiogenesis. In this study, we focused on the role of integrin αVß3 in OPLL and explored the underlying mechanism by which the c(RGDyk) peptide acts as a potent and selective integrin αVß3 inhibitor to inhibit osteogenesis and angiogenesis in OPLL. METHODS: OPLL or control ligament samples were collected in surgery. For OPLL samples, RNA-sequencing results revealed activation of the integrin family, particularly integrin αVß3. Integrin αVß3 expression was detected by qPCR, Western blotting, and immunohistochemical analysis. Fluorescence microscopy was used to observe the targeted inhibition of integrin αVß3 by the c(RGDyk) peptide on ligaments fibroblasts (LFs) derived from patients with OPLL and endothelial cells (ECs). The effect of c(RGDyk) peptide on the ossification of pathogenic LFs was detected using qPCR, Western blotting. Alkaline phosphatase staining or alizarin red staining were used to test the osteogenic capability. The effect of the c(RGDyk) peptide on angiogenesis was determined by EC migration and tube formation assays. The effects of the c(RGDyk) peptide on heterotopic bone formation were evaluated by micro-CT, histological, immunohistochemical, and immunofluorescence analysis in vivo. RESULTS: The results indicated that after being treated with c(RGDyk), the osteogenic differentiation of LFs was significantly decreased. Moreover, the c(RGDyk) peptide inhibited the migration of ECs and thus prevented the nutritional support required for osteogenesis. Furthermore, the c(RGDyk) peptide inhibited ectopic bone formation in mice. Mechanistic analysis revealed that c(RGDyk) peptide could inhibit osteogenesis and angiogenesis in OPLL by targeting integrin αVß3 and regulating the FAK/ERK pathway. CONCLUSIONS: Therefore, the integrin αVß3 appears to be an emerging therapeutic target for OPLL, and the c(RGDyk) peptide has dual inhibitory effects that may be valuable for the new therapeutic strategy of OPLL.

Ossification of the posterior longitudinal ligament is linked to heterotopic ossification of the ankle/foot tendons.

INTRODUCTION: Systemic osteogenesis has been speculated to be involved in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL). Our purpose was to compare the radiologic prevalence and severity of heterotopic ossification in foot tendons of Japanese patients with OPLL and to determine their association with systemic heterotopic ossification. MATERIALS AND METHODS: Clinical and radiographic data of 114 patients with OPLL were collected from 2020 to 2022. Control data were extracted from a medical database of 362 patients with ankle radiographs. Achilles and plantar tendon ossification were classified as grades 0-4, and the presence of osteophytes at five sites in the foot/ankle joint was assessed by radiography. Factors associated with the presence and severity of each ossification were evaluated by multivariable logistic regression and linear regression analysis. RESULTS: The prevalence of Achilles and plantar tendon ossification (grade ≥ 2) was 4.0-5.5 times higher in patients with OPLL (40-56%) than in the controls (10-11%). The presence of Achilles tendon ossification was associated with OPLL, age, and coexisting plantar tendon ossification, and was most strongly associated with OPLL (standardized regression coefficient, 0.79; 95% confidence interval, 1.34-2.38). The severity of Achilles and plantar tendon ossification was associated with the severity of ossification of the entire spinal ligament. CONCLUSIONS: The strong association of foot tendon ossification with OPLL suggests that patients with OPLL have a systemic osteogenesis background. These findings will provide a basis for exploring new treatment strategies for OPLL, including control of metabolic abnormalities.

Comparative Analysis of Postoperative Sagittal Balance in Expansive Open-Door Laminoplasty versus Laminectomy with Fusion for Multilevel Ossification of Posterior Longitudinal Ligament: A Retrospective Study.

BACKGROUND This single-center study included 80 patients with multilevel cervical ossification of the posterior longitudinal ligament (OPLL) and aimed to compare postoperative sagittal balance following treatment with expansive open-door laminoplasty (LP) vs total laminectomy with fusion (LF). MATERIAL AND METHODS Data of 80 patients with multilevel OPLL treated with LP vs LF between January 2017 and January 2022 were retrospectively analyzed. The basic data, cervical sagittal parameters, and clinical outcomes of the patients were counted in the preoperative and postoperative periods, and complications were recorded. Forty patients underwent LP and 40 underwent LF. Cervical sagittal parameters were compared between and within the 2 groups. Clinical outcomes and complications were compared between the 2 groups. RESULTS At last follow-up, the postoperative C2-C7 Cobb angel, T1 slope (T1S), and C7 slope (C7S) were significantly higher in the LF group than in the LP group (P<0.001). C2-C7 SVA (cSVA) was slightly higher in the LF group (P>0.05) and significantly higher in the LP group (P<0.05). The incidence of postoperative complications in the LP group was significantly lower than in the LF group (P=0.02). The postoperative scores on the Visual Analog Scale (VAS), Neck Disability Index (NDI), and Japanese Orthopedic Association (JOA) were significantly improved in both groups (P<0.001). CONCLUSIONS Both procedures had good outcomes in neurological improvement. After posterior surgery, the cervical vertebrae all showed a tilting forward. Compared to LP, LF may change cervical balance in Cobb angel, T1S. LF has better efficacy in improving cervical lordosis compared with LP. Patients with high T1 slope after surgery may has more axial pain.

Identification of Risk Factors for Primary Osteoporosis: The Role of Cervical Ligament Ossification.

BACKGROUND Long-term clinical practice has suggested a possible association between ossification of cervical ligament (OCL) and primary osteoporosis (POP). However, there is a lack of relevant research data. This study aimed to clarify the potential relationship between OCL and POP, and propose new strategies for preventing the onset of POP. MATERIAL AND METHODS The study involved 107 patients. The patients' diagnosis included OCL (ossification of the posterior longitudinal ligament, ossification of the ligamentum flavum, and ossification of the nuchal ligament) and POP. Bone mineral density (BMD), types of OCL, types of ossification of posterior longitudinal ligament, age, sex, serum calcium, serum phosphorus, alkaline phosphatase, type I collagen amino-terminal extension peptide, type I collagen degradation products, osteocalcin N-terminal molecular fragments, 25-hydroxyvitamin D, and history of taking steroid drugs were collected. SPSS24.0 and GraphPad Prism 8 were used to obtain the risk factors for POP. RESULTS One-way analysis of variance found that OCL, ossification of posterior longitudinal ligament, alkaline phosphatase, and osteocalcin N-terminal molecular fragments had statistical significance on BMD of the femoral neck (P<0.05). The independent sample t test showed that patient sex had statistical significant effect on BMD (femoral neck) (P=0.036). Incorporating the above factors into multiple linear regression analysis, it was found that OCL, alkaline phosphatase, and osteocalcin N-terminal molecular fragments were risk factors affecting BMD of femoral neck (P<0.05). CONCLUSIONS OCL, osteocalcin N-terminal molecular fragments, and alkaline phosphatase are risk factors for POP.

Association between diabetes mellitus and ossification of the spinal ligament: a systematic review and meta-analysis.

PURPOSE: Ossification of the spinal ligament (OSL) is a spinal disorder characterized by abnormal bone formation in the spinal ligaments. Although clinical studies suggested that diabetes mellitus (DM) was associated with OSL, no consistent conclusion was drawn about the relationship between DM and the onset of OSL. METHODS: Studies with data on DM and OSL were retrieved by searching PubMed, Embase, Web of Science, and Cochrane Library from inception to August 23, 2023. Pooled estimates of odds ratios (ORs) with 95% confidence interval (95% CI) were calculated using random-effects models. Statistical analyses were performed by R 4.2.2 software. RESULTS: A total of 17 studies with 70,945 participants were included. The quantitative findings demonstrated that a higher risk of DM was related to the onset of OSL (OR = 2.19, 95% CI: 1.27-3.79, p = 0.008). Subgroup analysis showed a higher rate of DM in OSL patients from Japan (OR = 3.29, 95% CI: 1.51-7.17, [Formula: see text] = 0.009) than from other regions. Moreover, patients with OSL had a higher rate of DM in age < = 60 group (OR = 3.46, 95% CI: 1.14-10.50, p = 0.035) than age > 60 group (OR = 2.26, 95% CI: 1.07-4.79, p = 0.036). CONCLUSION: DM is significantly associated with an increased risk of developing OSL, especially in Japanese and people under 60 years old. Further studies with more participants were warranted to confirm the findings and provide new insights into the prevention and treatment of OSL.

Radiographic characterization of OPLL progression in patients receiving laminoplasty with a minimum of two-years follow-up.

Ossification of the posterior longitudinal ligament (OPLL) is a common cause of degenerative cervical myelopathy (DCM) in Asian populations. Characterization of OPLL progression following laminoplasty remains limited in the literature. 29 patients with OPLL received cervical laminoplasty and a minimum of 2-years follow-up. Clinical and radiological surveillance occurred at 3-months, 6-months, 12-months post-op and then at yearly intervals. Transverse (anteroposterior) diameter and sagittal length of OPLL in relation to their cervical vertebral level of localisation was assessed upon immediate post-op radiographs compared to those obtained at subsequent follow-up. OPLL progression was defined as an increase in transverse dimensions and/or length by ≥ 2 mm. The average period of clinical follow-up was 6.7 ± 3.3 years. Upon latest follow-up, 79% of patients demonstrated at least 2 mm of transverse or longitudinal progression of OPLL. This corresponded to 2-years and 5-year progression rates of 54% and 71% respectively. OPLL located over C5 demonstrated the greatest transverse progression rate at (0.24 ± 0.34 mm / year). The mean overall longitudinal progression rate was 1.61 ± 2.06 mm / year. No patients experienced neurological decline resulting from OPLL progression requiring revision decompression during the period of post-operative observation. Characterizing transverse and longitudinal progression by cervical level via radiographs has implications in surgical planning for OPLL and should be consolidated upon post-operative CT/MRI scans as well as larger sample sizes.

Comment on, "Radiographic characterization of OPLL progression in patients receiving laminoplasty with a minimum of two-years follow-up".

The article by Liu et al. (2024) investigates the progression of ossification of the posterior longitudinal ligament (OPLL) in 29 patients post-cervical laminoplasty. The study meticulously tracks transverse and longitudinal OPLL progression, providing crucial insights into surgical planning and patient outcomes. While the research design is commendable, reliance on X-ray imaging limits precision compared to CT or MRI scans. The sample size, though adequate for initial findings, may not fully capture OPLL variability, and the follow-up period could be extended to better assess long-term outcomes. Future studies should incorporate advanced imaging techniques, larger cohorts, and patient-reported outcomes to enhance the understanding of OPLL progression, thereby refining surgical strategies and improving personalized care for OPLL patients.

Anterior cervical controllable Antedisplacement and Fusion (ACAF) versus Anterior Cervical Corpectomy and Fusion (ACCF) for ossification of the cervical posterior longitudinal ligament (OPLL) in Chinese population: a systematic review and meta-analysis.

This study aimed to systematically review and compare the efficacy and safety of anterior cervical controllable antedisplacement and fusion (ACAF) versus anterior cervical corpectomy and fusion (ACCF) in treating ossification of the cervical posterior longitudinal ligament (OPLL), focusing on surgery-related indicators and postoperative outcomes. This review was conducted and reported in accordance with the Cochrane Handbook for Systematic Reviews of Interventions guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting standards. The methodological quality of this systematic review was assessed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) checklist. A detailed search strategy was implemented to retrieve literature from electronic databases, including PubMed, EMBASE, and the Cochrane Library, followed by quality assessment and data extraction for eligible studies. A total of 5 studies involving 366 participants were included. ACAF was associated with significantly fewer complications (OR = 0.25, 95% CI [0.12, 0.51], p = 0.000), including a lower incidence of cerebrospinal fluid (CSF) leakage (OR = 0.20, 95% CI [0.08, 0.52], p = 0.000). ACAF also showed better outcomes in postoperative neck disability index (NDI) scores (SMD = -0.48, 95% CI [-0.81, -0.15], p = 0.020), C2-C7 angle (SMD = 1.29, 95% CI [0.56, 2.03], p = 0.000), spinal canal area (SCA) (SMD = 0.93, 95% CI [0.56, 1.29], p = 0.000), and diameter of the spinal cord (DSC) (SMD = 0.38, 95% CI [0.11, 0.66], p = 0.010). Additionally, ACAF improved The Japanese Orthopedic Association (JOA) scores (SMD = 0.29, 95% CI [0.01, 0.57], p = 0.040) but required longer operation time (SMD = 1.08, 95% CI [0.01, 2.15], p = 0.049). No significant differences were found in blood loss (SMD = 0.23, 95% CI [-0.34, 0.79], p = 0.431), hospital stay (SMD = 0.65, 95% CI [-1.46, 2.76], p = 0.547), and improvement rate (IR) (SMD = 0.38, 95% CI [-0.10, 0.86], p = 0.118). The current meta-analysis indicated that ACAF surgery can effectively reduce the incidence of complications, significantly increase the spinal canal area and improve the spatial conditions of the spinal cord compared to those associated with ACCF surgery. This is more advantageous for the postoperative neurological recovery of patients. Nonetheless, it is crucial to approach these findings with a degree of caution.

Patients with a large ossification of the posterior longitudinal ligament have a higher incidence of arteriosclerosis in the carotid artery.

PURPOSE: This study aimed to investigate the impact of the severity of cervical ossification of the posterior longitudinal ligament (OPLL) on the incidence of arteriosclerosis in the carotid artery. METHODS: Patients with OPLL-induced cervical myelopathy were prospectively enrolled. The study involved analyzing patient characteristics, blood samples, computed tomography scans of the spine, and intima-media thickness (IMT) measurements of the common carotid artery. Patients were divided into two groups based on the size of the cervical OPLL to compare demographic data, comorbidities, and the presence of thickening of the carotid intima-media (max IMT ≥ 1.1 mm). RESULTS: The study included 96 patients (mean age: 63.5 years; mean body mass index: 26.9 kg/m2; 71.8% male; 35.4% with diabetes mellitus). The mean maximum anteroposterior (AP) diameter of the OPLL was 4.9 mm, with a mean occupancy ratio of 43%. The mean maximum IMT was 1.23 mm. Arteriosclerosis of the carotid artery was diagnosed in 62.5% of the patients. On comparing the two groups based on OPLL size, the group with larger OPLL (≥ 5 mm) had a higher BMI and a greater prevalence of carotid intima-media thickening. This significant difference in the prevalence of carotid intima-media thickening persisted even after adjusting for patient backgrounds using propensity score matching. CONCLUSIONS: Patients with a larger cervical OPLL showed a higher frequency of intima-media thickening in the carotid artery.

Validating the preoperative Japanese Core Outcome Measures Index for the Neck and comparing quality of life in patients with cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament by the patient-reported outcome measures.

PURPOSE: This cross-sectional study serves two main purposes. Firstly, it aims to validate the preoperative Japanese Core Outcome Measures Index for the Neck (COMI-Neck) in patients with cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL). Secondly, it seeks to elucidate differences in preoperative quality of life (QOL) between these two cervical pathologies using patient-reported outcome measures (PROMs). METHODS: A total of 103 preoperative patients (86 with CSM and 17 with OPLL) scheduled for cervical spine surgery were included in the study. Validated PROMs, including the Japanese COMI-Neck, Neck Disability Index (NDI), EuroQol-5 Dimension-3 level (EQ-5D-3L), and SF-12v2, were used to assess QOL. Baseline demographic and clinical data were collected, and statistical analyses were performed to compare the PROMs between CSM and OPLL groups. RESULTS: The Japanese COMI-Neck demonstrated good construct validity, with positive correlations with NDI and negative correlations with EQ-5D-3L and SF-12v2. Comparison of preoperative PROMs between CSM and OPLL groups revealed differences in age, body mass index, and EQ-5D-3L scores. The CSM group had higher NDI scores for concentration and lower EQ-5D-3L scores for self-care compared to the OPLL group. CONCLUSIONS: This study validated the preoperative Japanese COMI-Neck in CSM and OPLL patients and identified specific QOL issues associated with each condition. The findings highlight the importance of considering disease-specific QOL and tailoring treatment plans accordingly. Further research should include postoperative assessments and a more diverse population to enhance generalizability.

Comparison of radiological and clinical outcomes of cervical laminoplasty versus lateral mass screw fixation in patients with ossification of the posterior longitudinal ligament.

PURPOSE: This study aimed to compare cervical sagittal parameters and clinical outcomes between patients undergoing cervical laminoplasty(CL) and those undergoing lateral mass screw fixation(LMS). METHODS: We retrospectively studied 67 patients with multilevel ossification of the posterior longitudinal ligament (OPLL) of the cervical spine who underwent lateral mass screw fixation (LMS = 36) and cervical laminoplasty (CL = 31). We analyzed cervical sagittal parameters (C2-7 sagittal vertical axis (C2-7 SVA), C0-2 Cobb angle, C2-7 Cobb angle, C7 slope (C7s), T1 slope (T1s), and spino-cranial angle (SCA)) and clinical outcomes (visual analog scale [VAS], neck disability index [NDI], Japanese Orthopaedic Association [JOA] scores, recovery rate (RR), and minimum clinically significant difference [MCID]). The cervical sagittal parameters at the last follow-up were analyzed by binary logistic regression. Finally, we analyzed the correlation between the cervical sagittal parameters and each clinical outcome at the last follow-up after surgery in both groups. RESULTS: At the follow-up after posterior decompression in both groups, the mean values of C2-C7 SVA, C7s, and T1s in the LMS group were more significant than those in the CL group (P ≤ 0.05). Compared with the preoperative period, C2-C7 SVA, T1s, and SCA gradually increased, and the C2-C7 Cobb angle gradually decreased after surgery (P < 0.05). The improvement in the JOA score and the recovery rate was similar between the two groups, while the improvement in the VAS-N score and NDI score was more significant in the CL group (P = 0.001; P = 0.043). More patients reached MCID in the CL group than in the LMS group (P = 0.036). Binary logistic regression analysis showed that SCA was independently associated with whether patients reached MCID at NDI postoperatively. SCA was positively correlated with cervical NDI and negatively correlated with cervical JOA score at postoperative follow-up in both groups (P < 0.05); C2-7 Cobb angle was negatively correlated with cervical JOA score at postoperative follow-up (P < 0.05). CONCLUSION: CL may be superior to LMS in treating cervical spondylotic myelopathy caused by OPLL. In addition, smaller cervical SCA after posterior decompression may suggest better postoperative outcomes.

A rare case of intervertebral disc calcification combined with ossification of the posterior longitudinal ligament in a child: a case report and literature review.

BACKGROUND: Intervertebral disc calcification (IDC) combined with calcification in children has been sporadically reported, while ossification of the posterior longitudinal ligament (OPLL) in the cervical spine in pediatric patients is exceedingly rare. The aim of this study is to investigate the potential prognosis and outcomes associated with this condition. CASE PRESENTATION: We present an unusual case involving a 10-year-old Chinese child diagnosed with calcified cervical disc herniation and ossification of the posterior longitudinal ligament. Conservative treatment measures were implemented, and at the 1-month and 6-month follow-up, the patient's pain exhibited significant improvement. Subsequent cervical MRI and CT scans revealed the complete disappearance of OPLL and substantial absorption of the calcified disc. During the three-month follow-up, CT demonstrated slight residual disc calcification, however, the patient remained asymptomatic with no discernible limitation in cervical motion. CONCLUSIONS: We conducted a comprehensive review of several cases presenting with the same diagnosis. It is noteworthy that IDC combined with OPLL in children constitutes a rare clinical entity. Despite imaging indications of potential spinal canal occupation, the majority of such cases demonstrate complete absorption following conservative treatment, with OPLL exhibiting a faster absorption rate than calcified discs.

Perioperative complications and cost of posterior decompression with fusion in thoracic spine for ossification of the posterior longitudinal ligament and ossification of the ligamentum flavum -a comparative study using a national inpatient database.

BACKGROUND: Although posterior decompression with fusion (PDF) are effective for treating thoracic myelopathy, surgical treatment has a high risk of various complications. There is currently no information available on the perioperative complications in thoracic ossification of the longitudinal ligament (T-OPLL) and thoracic ossification of the ligamentum flavum (T-OLF). We evaluate the perioperative complication rate and cost between T-OPLL and T-OLF for patients underwent PDF. METHODS: Patients undergoing PDF for T-OPLL and T-OLF from 2012 to 2018 were detected in Japanese nationwide inpatient database. One-to-one propensity score matching between T-OPLL and T-OLF was performed based on patient characteristics and preoperative comorbidities. We examined systemic and local complication rate, reoperation rate, length of hospital stays, costs, discharge destination, and mortality after matching. RESULTS: In a total of 2,660 patients, 828 pairs of T-OPLL and T-OLF patients were included after matching. The incidence of systemic complications did not differ significantly between the T-OPLL and OLF groups. However, local complications were more frequently occurred in T-OPLL than in T-OLF groups (11.4% vs. 7.7% P = 0.012). Transfusion rates was also significantly higher in the T-OPLL group (14.1% vs. 9.4%, P = 0.003). T-OPLL group had longer hospital stay (42.2 days vs. 36.2 days, P = 0.004) and higher medical costs (USD 32,805 vs. USD 25,134, P < 0.001). In both T-OPLL and T-OLF, the occurrence of perioperative complications led to longer hospital stay and higher medical costs. While fewer patients in T-OPLL were discharged home (51.6% vs. 65.1%, P < 0.001), patients were transferred to other hospitals more frequently (47.5% vs. 33.5%, P = 0.001). CONCLUSION: This research identified the perioperative complications of T-OPLL and T-OLF in PDF using a large national database, which revealed that the incidence of local complications was higher in the T-OPLL patients. Perioperative complications resulted in longer hospital stays and higher medical costs.

[Clinical observation on the treatment of ossification of the posterior longitudinal ligament of the cervical spine using 3D printed self-stable zero-profile artificial vertebral body].

Objective: To observe the clinical efficacy of a 3D printed self-stable zero-profile artificial vertebral body for anterior cervical corpectomy decompression and fusion in the treatment of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine. Methods: In this prospective randomized controlled trial, patients diagnosed with OPLL in Luohe Central Hospital from January to July 2022 were divided into a zero-profile group (3D printed self-stable zero-profile artificial vertebral body was used for internal fixation and fusion after anterior cervical subtotal decompression,) and titanium-mesh group (titanium-mesh and titanium plate were used for internal fixation and fusion after anterior cervical subtotal decompression) according to envelope random method. Operation time, intraoperative blood loss, Japanese Orthopaedic Association (JOA) score and improvement rate, incidence of postoperative prosthesis subsidence, and bone graft fusion were recorded and compared between the two groups. Results: Finally, 21 patients in the zero notch group and 20 patients in the titanium mesh group were included in the study and were followed-up. In the zero-profile group, there were 16 males and 5 females, aged (48.0±12.7) years. In the titanium-mesh group, there were 14 males and 6 females, aged (49.8±10.2) years. All the 41 patients successfully completed the operation. In the zero-profile group, the surgical time was (50.04±8.45) minutes, the blood loss was (95.38±26.07) ml and the hospitalization cost was (42.32±6.12) thousand yuan. In the titanium-mesh group, the surgical time was (59.20±11.95) minutes, the blood loss was (93.10±27.86) ml and the hospitalization cost was (42.10±6.71) thousand yuan. The surgical time in the zero-profile group was shorter than that in the titanium-mesh group (P=0.007), and there was no statistically significant difference in blood loss and hospitalization costs between the two groups (both P>0.05). The 41 patients were followed-up for (14.29±1.45) months. Four cases (20.0%) in the titanium mesh group experienced swallowing difficulties and 0 cases in the zero incision group, the difference between the two groups was statistically significant (P=0.048). No intraoperative hematoma, spinal cord nerve recompression, airway crisis, incision infection complications, and no steel plate or screw breakage or displacement occurred after surgery. At the last follow-up, all cases had bone fusion. At the follow-up of 12 months after surgery, the JOA score of the zero incision group increased from preoperative (10.33±1.71) points to (15.47±0.81) points, with an improvement rate of 76.1%±15.7%; the JOA score of the titanium mesh group increased from (10.30±1.75) points to (15.30±0.92) points, with an improvement rate of 73.2%±16.7%; there was no statistically significant difference in improvement rate between the two groups (P=0.580). At the follow-up of 12 months after surgery, 1 case (4.8%) in the zero incision group and 8 cases (40.0%) in the titanium mesh group experienced implant sinking, and the difference between the two groups was statistically significant (P=0.009). Conclusion: Compared with titanium-mesh, 3D printed self-stable zero-profile artificial vertebral body for the treatment of OPLL of the cervical spine can achieve good surgical efficacy, shorter surgical time, lower incidence of postoperative chronic swallowing discomfort, and can provide a better bone material bonding interface and be less prone to prosthesis settlement.

IL-6/Stat3 suppresses osteogenic differentiation in ossification of the posterior longitudinal ligament via miR-135b-mediated BMPER reduction.

Interleukin-6 (IL-6) has been reported to induce osteogenic differentiation of mesenchymal stem cells for increasing bone regeneration, while the role of IL-6 in osteogenic differentiation during ossification of the posterior longitudinal ligament (OPLL) remains to be determined. The current study aims to explore the downstream mechanism of IL-6 in cyclic tensile strain (CTS)-stimulated OPLL, which involves bioinformatically identified microRNA-135b (miR-135b). Initially, we clinically collected posterior longitudinal ligament (PLL) and ossified PLL tissues, from which ossified PLL cells were isolated, respectively. The obtained data revealed a greater osteogenic property of ossified PLL than non-ossified PLL cells. The effect of regulatory axis comprising IL-6, Stat3, miR-135b, and BMPER on osteogenic differentiation of CTS-stimulated ossified PLL cells was examined with gain- and loss-of-function experiments. BMPER was confirmed as a target gene to miR-135b. Knockdown of BMPER or overexpression of miR-135b inhibited the osteogenic differentiation of CTS-induced ossification in PLL cells. Besides, IL-6 promoted the post-transcriptional process to mature miR-135b via Stat3 phosphorylation. In conclusion, IL-6 inhibited CTS-induced osteogenic differentiation by inducing miR-135b-mediated inhibition of BMPER through Stat3 activation.

Uniaxial cyclic stretch enhances osteogenic differentiation of OPLL-derived primary cells via YAP-Wnt/ß-catenin axis.

The pathogenesis of posterior longitudinal ligament ossification (OPLL) remains inadequately understood. Mechanical stimulation is one of the important pathogenic factors in OPLL. As one of the mechanical stimulation transduction signals, the yes-associated protein (YAP) interacts with the Wnt/ß-catenin signalling pathway, which plays an important role in osteogenic differentiation. This study aimed to demonstrate the role of YAP-Wnt/ß-catenin axis in cell differentiation induced by mechanical stress. Primary cells extracted from posterior longitudinal ligament tissues from OPLL or non-OPLL patients were subjected to sinusoidal uniaxial cyclic stretch (5 %, 0.5 Hz, 3 d). The expression of runt-related transcription factor 2, collagen I, osterix, osteocalcin and alkaline phosphatase were compared between the static and the experimental groups. In addition, the cytoskeleton was detected using phalloidin staining while YAP phosphorylation states and nuclear location were identified using immunofluorescence. The results showed that mechanical stretching loading increased the expression of osteogenic genes and proteins in the OPLL group, while it had no significant effect on the control group. When OPLL cells were stretched, YAP exhibited an obvious nuclear translocation and the Wnt/ß-catenin pathway was activated. Knocking down YAP or ß-catenin could weaken the impact upon osteogenic differentiation induced by mechanical stimulation. YAP-mediated mechanical stimulation promoted osteogenic differentiation of OPLL cells through Wnt/ß-catenin pathway and this progress was independent of the Hippo pathway.

Genetics of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of the Spinal Ligaments.

PURPOSE OF REVIEW: The study aims to provide updated information on the genetic factors associated with the diagnoses 'Diffuse Idiopathic Skeletal Hyperostosis' (DISH), 'Ossification of the Posterior Longitudinal Ligament' (OPLL), and in patients with spinal ligament ossification. RECENT FINDINGS: Recent studies have advanced our knowledge of genetic factors associated with DISH, OPLL, and other spinal ossification (ossification of the anterior longitudinal ligament [OALL] and the yellow ligament [OYL]). Several case studies of individuals afflicted with monogenic disorders, such as X-linked hypophosphatemia (XLH), demonstrate the strong association of fibroblast growth factor 23-related hypophosphatemia with OPLL, suggesting that pathogenic variants in PHEX, ENPP1, and DMP1 are associated with FGF23-phosphate wasting phenotype and strong genetic factors placing patients at risk for OPLL. Moreover, emerging evidence demonstrates that heterozygous and compound heterozygous ENPP1 pathogenic variants inducing 'Autosomal Recessive Hypophosphatemic Rickets Type 2' (ARHR2) also place patients at risk for DISH and OPLL, possibly due to the loss of inhibitory plasma pyrophosphate (PPi) which suppresses ectopic calcification and enthesis mineralization. Our findings emphasize the importance of genetic and plasma biomarker screening in the clinical evaluation of DISH and OPLL patients, with plasma PPi constituting an important new biomarker for the identification of DISH and OPLL patients whose disease course may be responsive to ENPP1 enzyme therapy, now in clinical trials for rare calcification disorders.

Prevalence and Risk Factors for Modic Changes in Symptomatic Cervical Ossification of the Posterior Longitudinal Ligament: A Retrospective Study of 203 Patients.

BACKGROUND Modic changes (MC) are abnormal bone signals under the vertebral endplates on magnetic resonance imaging (MRI) of the spine. Three types of MC may be seen on MRI as abnormal bone signals of the vertebral endplate and adjacent bone marrow. This retrospective study of 203 patients with symptomatic cervical ossification of the posterior longitudinal ligament (OPLL) aimed to evaluate factors associated with MC on cervical spine MRI. MATERIAL AND METHODS We included 203 patients with symptomatic cervical ossification of the OPLL. All patients underwent MRI with T1 and T2 sequences to assess the presence and type of MC. Univariate and multivariate logistic regression analyses were used to identify the risk factors for MC. RESULTS The prevalence of MC in patients with symptomatic cervical OPLL was 21.18%. Type 2 MC accounted for 88.64% of the cases. Local type and MC share the same segment (100.00%), followed by segmental type (77.27%), mixed type (75.00%), and continuous type (75.00%). Age (OR=1.05, 95% CI: 1.01-1.09, P=0.013) and neck pain (OR=2.67, 95% CI: 1.04-6.83, P=0.041) were significantly correlated with MC. Further receiver operating characteristic (ROC) analysis displayed an area under the curve (AUC) of 0.657 (P=0.002) for age, and the optimal cutoff was 60.50 years (sensitivity 0.67, specificity 0.68). CONCLUSIONS The results of this study found that older age and neck pain were significantly associated with development of cervical spine MC. Patients ≥60.5 years with symptomatic cervical OPLL had a higher probability of developing MC.

Reoperation rate and risk factors of reoperation for ossification of the posterior longitudinal ligament (OPLL): a systematic review and meta-analysis.

Revision surgery for OPLL is undesirable for both patients and physicians. However, the risk factors for reoperation are not clear. Thus, we sought to review the existing literature and determine the factors associated with higher reoperation rates in patients with OPLL. A search was performed using Pubmed, Embase, Web of Sciences, and Ovid to include studies regarding the risk factors of reoperation for OPLL. RoBANS (Risk of Bias Assessment tool for Nonrandomized Studies) was used for risk of bias analysis. Heterogeneity of studies and publication bias was assessed, and sensitivity analysis was performed. Statistical analysis was performed with a p-value < 0.05 using SPSS software (version 23). Twenty studies with 129 reoperated and 2,793 non-reoperated patients were included. The pooled reoperation rate was 5% (95% CI: 4% to 7). The most common cause of reoperation was residual OPLL or OPLL progression (n = 51, 39.53%). An increased risk of additional surgery was found with pre-operative cervical or thoracic angle (Standardized mean difference = -0.44; 95% CI: -0.69 to -0.19; p = 0.0061), post-operative CSF leak (Odds ratio, OR = 4.97; 95% CI: 2.48 to 9.96; p = 0.0005), and graft and/or hardware failure (OR = 192.09; 95% CI: 6.68 to 5521.69; p = 0.0101). Apart from the factors identified in our study, the association of other variables with the risk of second surgery could not be ruled out, owing to the complexity of the relationship and significant bias in the current literature.