The predictive value of albumin to alkaline phosphatase ratio for vertebral refractures in postmenopausal women.

INTRODUCTION: To investigate the clinical value of serum albumin to alkaline phosphatase ratio (AAPR) in predicting the risk of osteoporotic vertebral refractures group (OVRFs) after percutaneous vertebral augmentation (PVA) in postmenopausal women. MATERIALS AND METHODS: This is a retrospective case-control study including a series of postmenopausal women patients with osteoporotic vertebral fracture (OVF) and underwent PVA. Patients were divided into OVRFs and non-OVRFs. COX model was used to evaluate the correlation between preoperative AAPR and OVRFs after PVA. The receiver operating characteristic (ROC) curve and Kaplan-Meier method were used to analyze the predictive value of AAPR for the incidence of OVRFs. RESULTS: A total of 305 patients were included in the final study, and the incidence of postoperative OVRFs was 28.9%. Multivariate COX analysis showed that advanced age (HRs = 1.062, p = 0.002), low BMI (HRs = 0.923, p = 0.036), low AAPR (HRs = 0.019, p = 0.001), previous fall history (HRs = 3.503, p = 0.001), denosumab treatment (HRs = 0.409, p = 0.007), low L3 BMD (HRs = 0.977, p = 0.001) and low L3 paravertebral muscle density (PMD)value (HRs = 0.929, p = 0.001)) were closely related to the incidence of OVRFs. The area under the curve (AUC) of AAPR for predicting OVRFs was 0.740 (p < 0.001), and the optimal diagnostic cut-off value was 0.49. Kaplan-Meier curve analysis showed that low AAPR group (< 0.49) was significantly associated with lower OVRFs-free survival (p = 0.001; log-rank test). CONCLUSION: AAPR is an independent risk factor for OVRFs after PVA in postmenopausal women, and it can be used as an effective index to predict OVRFs.

The efficacy of nutritional screening indexes in predicting the incidence of osteosarcopenia and major osteoporotic fracture in the elderly.

INTRODUCTION: The effect of nutritional status on osteosarcopenia (OS) and major osteoporotic fracture (MOF) among the elderly is still unclear. So we aimed to compare the efficacy of the Mini-Nutrition Assessment-Short Form (MNA-sf), the Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status (CONUT) for predicting OS and MOF among the elderly. MATERIALS AND METHODS: A total of 409 participants were enrolled in this prospective study. Blood biochemical indexes, nutritional status, and bone- and muscle-related examinations were assessed at initial visit to the outpatient. Participants were divided into 4 groups: (1) control; (2) osteopenia/osteoporosis; (3) sarcopenia; (4) osteosarcopenia, and then followed for 5 years, recording the occurrence time of MOF. RESULTS: The frequency values of osteopenia/osteoporosis, sarcopenia, and OS, at baseline, were respectively 13.4, 16.1, and 12% among the study samples. Correlation analysis showed that nutritional status scores were associated with body mass index, handgrip strength, albumin, bone mineral density, and physical functions. According to multivariate models, poor nutritional status was significantly associated with a higher risk of OS and MOF (P < 0.05). Survival analysis showed that the MOF rate in malnutrition group was significantly higher than normal nutrition group (P < 0.05). The receiver operator characteristic curve shows that the value of MNA-sf to diagnose OS and MOF is greater (P < 0.05). CONCLUSION: The poor nutritional status was associated with a higher risk of both OS and MOF. MNA-sf showed a superior diagnostic power for OS and MOF among the elderly. Early nutrition assessments and interventions may be key strategies to prevent OS and fractures.

α-Ketoglutaric acid ameliorates intervertebral disk degeneration by blocking the IL-6/JAK2/STAT3 pathway.

Intervertebral disk degeneration (IVDD) is the major cause of low back pain. Alpha-ketoglutaric acid (α-KG), an important intermediate in energy metabolism, has various functions, including epigenetic regulation, maintenance of redox homeostasis, and antiaging, but whether it can ameliorate IVDD has not been reported. Here, we examined the impacts of long-term administration of α-KG on aging-associated IVDD in adult rats. In vivo and in vitro experiments showed that α-KG supplementation effectively ameliorated IVDD in rats and the senescence of nucleus pulposus cells (NPCs). α-KG supplementation significantly attenuated senescence, apoptosis, and matrix metalloproteinase-13 (MMP-13) protein expression, and it increased the synthesis of aggrecan and collagen II in IL-1ß-treated NPCs. In addition, α-KG supplementation reduced the levels of IL-6, phosphorylated JAK2 and STAT3, and the nuclear translocation of p-STAT3 in IL-1ß-induced degenerating NPCs. The effects of α-KG were enhanced by AG490 in NPCs. The underlying mechanism may involve the inhibition of JAK2/STAT3 phosphorylation and the reduction of IL-6 expression. Our findings may help in the development of new therapeutic strategies for IVDD.NEW & NOTEWORTHY Alpha-ketoglutaric acid (α-KG) exerted its protective effect on nucleus pulposus cells' (NPCs) degeneration by inhibiting the senescence-associated secretory phenotype and extracellular matrix degradation. The possible mechanism may be associated with negatively regulating the JAK2/STAT3 phosphorylation and the decreased IL-6 expression, which could be explained by a blockage of the positive feedback control loop between IL-6 and JAK2/STAT3 pathway.

Computed tomography-based paravertebral muscle density predicts subsequent vertebral fracture risks independently of bone mineral density in postmenopausal women following percutaneous vertebral augmentation.

BACKGROUND: The risk of subsequent vertebral fractures (SVF) after the primary vertebral fracture cannot be explained by lower bone mineral density (BMD) alone. Computed tomography (CT) measurements of paravertebral muscle density (PMD) are recognized radiographic markers used to predict physical function, fragile fractures. AIMS: This study aims to investigate the relationship between PMD and the risk of SVF in cohorts of postmenopausal women, and to determine if combining both PMD and BMD measures derived from CT can improve the accuracy of predicting SVF. METHODS: This study enrolled 305 postmenopausal women between the ages of 50 and 88 for 3 years of follow-up studies. Trabecular attenuation (Hounsfield units, HU) was measured at L1 level and muscle attenuation of paravertebral muscle at L3 level on preoperative lumbar CT scans to determine the L1 BMD and L3 PMD. Kaplan-Meier analysis was applied to evaluate SVF-free survival. The hazard ratios (HRs) of PMD for SVF events were estimated with the Cox proportional hazards model. The predictive values of L1 BMD and L3 PMD for SVF were quantified using the Receiver-Operating Characteristic (ROC) curve. RESULT: During the 3 years of follow-up studies, 88 patients (28.9%) suffered an SVF. ROC curve analysis demonstrated that an L3 PMD threshold of 32 HU had a sensitivity of 89.8% and a specificity of 62% for the prediction of SVF. Kaplan-Meier analysis showed that L3 PMD ≤ 32 HU was significantly associated with lower SVF-free survival (p < 0.001; log-rank test). After adjusting for age, BMI, diabetes, postoperative osteoporosis treatment, handgrip strength, L1 BMD, multivariate analyses also indicated a persistent modest effect of L3 PMD on SVF-free survival. The area under the ROC curve of L3 PMD and L1 BMD, combined to predict the risk of SVF, was 0.790, which was significantly higher than the value for L1 BMD alone (0.735). L3 PMD and L1 BMD significantly improved the accuracy of SVF risk prediction compared with L1 BMD alone, which was confirmed by reclassification improvement measures. The inclusion of handgrip strength and postoperative osteoporosis treatment in the model further improved SVF prediction accuracy, and PMD remained significant in the model. CONCLUSION: Decreased L3 PMD is an independent risk predictor of SVF. Combined CT-based L1 BMD and L3 PMD can significantly improve the accuracy of predicting the risk of SVF in postmenopausal women who have suffered prior osteoporotic vertebral fractures.

Magnesium-sensitive upstream ORF controls PRL phosphatase expression to mediate energy metabolism.

Phosphatases of regenerating liver (PRL-1, PRL-2, and PRL-3, also known as PTP4A1, PTP4A2, and PTP4A3) control magnesium homeostasis through an association with the CNNM magnesium transport regulators. Although high PRL levels have been linked to cancer progression, regulation of their expression is poorly understood. Here we show that modulating intracellular magnesium levels correlates with a rapid change of PRL expression by a mechanism involving its 5'UTR mRNA region. Mutations or CRISPR-Cas9 targeting of the conserved upstream ORF present in the mRNA leader derepress PRL protein synthesis and attenuate the translational response to magnesium levels. Mechanistically, magnesium depletion reduces intracellular ATP but up-regulates PRL protein expression via activation of the AMPK/mTORC2 pathway, which controls cellular energy status. Hence, altered PRL-2 expression leads to metabolic reprogramming of the cells. These findings uncover a magnesium-sensitive mechanism controlling PRL expression, which plays a role in cellular bioenergetics.

Association between handgrip strength and subsequent vertebral-fracture risk following percutaneous vertebral augmentation.

INTRODUCTION: The aim of this study was to investigate the association between handgrip strength (HGS) and the risk of subsequent vertebral fracture (SVF) after percutaneous vertebral augmentation (PVA). MATERIALS AND METHODS: A total of 340 patients aged over 50 years with osteoporotic vertebral fracture were enrolled in this 3-year follow-up investigation. HGS was measured with a hand-held dynamometer before PVA. Female patients and male patients were grouped using the HGS threshold recommended by the Asian Working Group for Sarcopenia (AWGS). Kaplan-Meier analysis was used to evaluate SVF-free survival. The hazard ratios (HRs) of HGS for SVF events were estimated with the Cox proportional hazards model. RESULTS: During the follow-up period, a total of 93 patients (27.4%) experienced SVF. Kaplan-Meier analysis showed that the HGS of female patients < 18.0 kg and male patients < 28 kg was significantly associated with lower SVF-free survival (female patients: p < 0.001, male patients: p = 0.038; log-rank test). Among women, each 1-kg increase in HGS was associated with a 9% lower risk of SVF (HR 0.91, p = 0.035) after adjustment for potential risk factors. Among men, although the associations between low HGS and increased risk of SVF were significant in the crude model (HR 0.79, p < 0.001), this significance disappeared after adjustment for bone mineral density of the femoral neck. CONCLUSIONS: Low HGS was significantly associated with lower SVF-free survival among elderly patients who underwent single-level PVA for osteoporotic vertebral fracture.

Estimation of the ideal correction of lumbar lordosis to prevent reoperation for symptomatic adjacent segment disease after lumbar fusion in older people.

BACKGROUND: Symptomatic adjacent segment disease (ASDis) is a major complication following spinal fusion. Sagittal spinopelvic imbalance may contribute to the development of ASDis. However, the exact ideal correction of lumbar lordosis (LL) is unknown for different ages of people to prevent ASDis. The purpose of this study was to estimate the ideal correction of LL required to prevent symptomatic ASDis requiring revision surgery in patients of various ages, and to determine the radiographic risk factors for ASDis. METHODS: 468 patients who underwent lumbar fusion between January 2014 and December 2016, were enrolled in the present study. The patients were classified into the ASDis and N-ASD group. These two matched groups were compared regarding surgery-related factors and radiographic features. Multivariate logistic regression analysis was used to evaluate the risk factors for ASDis. RESULTS: Sixty-two patients (13.25%) underwent reoperation for ASDis during a mean follow-up duration of 38.07 months. Receiver operating characteristic curve analysis showed that the postoperative LL - preoperative LL (△LL) cutoff value was 11.7°for the development of ASDis. Logistic regression analysis revealed that the risk factors for symptomatic ASDis were a smaller LL angle, △LL > 12°, and PI-LL > 10° (p <  0.05). For patients > 60 years, the incidence of ASDis was higher in patients with a LL correction of ≥10° and a lumbar-pelvic mismatch (PI-LL) of > 20°. CONCLUSIONS: The significant predictors of the occurrence of ASDis were a smaller LL angle, △LL > 12°, and PI-LL > 10°. However, in patients older than 60 years, the incidence of ASDis after lumbar fusion was higher in those with a LL correction of ≥10° and PI-LL of > 20°. More attention should be paid to patient age and the angle of correction of LL before lumbar fusion.

Preoperative vitamin D status and its effects on short-term clinical outcomes in lumbar spine surgery.

BACKGROUND: Many studies have found that vitamin D deficiency has a high incidence rate worldwide, but we found few studies on the role of vitamin D in spinal degenerative diseases. We investigated the determinants of preoperative vitamin D deficiency and its effects on postoperative outcomes among patients undergoing elective lumbar spine surgery. METHODS: 360 patients treated from July 2017 to July 2018 were retrospectively identified for inclusion. The patients' fasting serum levels of 25(OH)D, N-terminal midfragment of osteocalcin (N-MID), and ß typeⅠcollagen carboxyl terminal peptide (ß-CTX) were measured by electrochemiluminescence before the operation. The visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) and Oswestry Disability Index scores (ODI) were used to evaluate the clinical outcomes. Standard demographic data and all perioperative complications occurring within 3 months follow-up after operation were recorded. RESULTS: The mean serum level of 25(OH)D was 20.81 ± 8.55 ng/mL, the rates of deficiency (<20 ng/ml) was 53.6%. The abnormal proportion of N-MID and ß-CTX were 8.61% and 34.44%, bone turnover markers serum level was higher in older age groups (p < 0.05). Female sex (p < 0.001), a high body mass index (BMI) (p = 0.012), lack of vitamin D supplementation (p = 0.018), smoking (p = 0.033), moderate (p < 0.001) to severe pain (p = 0.005) were significant predictors of vitamin D deficiency after the multivariate analysis. The VAS, JOA and ODI scores showed significantly better outcomes compared to deficient group at post-operative and final follow-up (p < 0.05). CONCLUSION: Vitamin D deficiency was common in patients undergoing elective lumbar spine surgery. Female sex, high BMI, lack of vitamin D supplementation, smoking and moderate to severe pain were risk factors for vitamin D deficiency. Moreover, preoperative hypovitaminosis D (<20 ng/ml) was correlated with worse surgical outcomes in short-term.

Does the C3/4 disc play a role in cervical spondylosis with dizziness? A retrospective study.

PURPOSE: To investigate the effect of C3/4 disc degeneration on cervical spondylosis with dizziness (CSD) and to assess the curative effect of anterior cervical decompression and fusion (ACDF) in patients with CSD. METHOD: Four hundred nineteen patients who underwent ACDF for treatment of myelopathy or radiculopathy were divided into dizziness and non-dizziness group. The visual analog scale (VAS) score and Japanese Orthopaedic Association (JOA) score were used to determine the intensity of dizziness and neurological symptoms, respectively. Cervical disc degeneration was evaluated using Miyazaki's classification system. Some parameters were measured using cervical radiographs. The surgical effects on CSD were compared between surgery with and without C3/4 level. Multivariate logistic regression analysis was used to determine the risk factors for CSD. RESULTS: The pre-operative incidence of CSD was 33.9%. Women were more likely to develop dizziness than men (p < 0.05), CSD was significantly associated with C3/4 disc degeneration (69.7%, p < 0.001), and smokers were more subject to dizziness (p < 0.05). Regression analysis showed that female (OR = 1.611, p = 0.031), smoking (OR = 1.719, p = 0.032), Miyazaki grade of C3/4 ≥ IV (OR = 2.648, p < 0.001), and instability on C3/4 (OR = 1.672, p = 0.024) were risk factors for CSD. Treatment of CSD by ACDF involving C3/4 was more effective than not involving C3/4 (efficacy rate, 73.2% vs 51.7%, p < 0.05). CONCLUSION: The CSD is a common clinical manifestation in elderly patients, especially patients with cervical spondylosis at the C3/4 level. Female, smoking, instability on C3/4, and C3/4 Miyazaki grade ≥ IV could be considered significant risk factors for CSD. CSD is more likely to be alleviated by ACDF involving C3/4.

Sagittal imbalance, muscle atrophy, and osteoporosis: risk factors for revision posterior lumbar fusion surgery in patients with Parkinson's disease.

OBJECTIVE: The aim of our study was to evaluate features and complications of patients with Parkinson's disease (PD) who underwent posterior lumbar fusion surgery for lumbar degenerative diseases (LDD), as well as the risk factors for revision. METHODS: Between January 2010 and December 2016, 132 patients were retrospectively identified for inclusion. Patients were divided into a 29 revision PD group and a 103 non-revision PD group. Patient factors included bone mineral density (BMD) and severity of PD using the Hoehn and Yahr staging system. Surgical factors included surgical levels and fusion methods. Radiographic measurements included pre-operative spinopelvic parameters, paraspinal muscle atrophy, and fatty infiltration. Logistic regression analysis was used to determine independent predictors for revision posterior lumbar fusion. RESULTS: The average age of the PD patients was 67.96 years, and the follow-up time was 49.01 months. R-PD patients accounted for 21.97% of all PD patients who underwent lumbar fusion surgery. Multivariable analysis indicated that low BMD (p = 0.012), fatty infiltration (p = 0.038), a smaller relative cross-sectional area (rCSA) of the paraspinal muscle (p = 0.008), larger pelvic incidence-lumbar lordosis (PI-LL) (p = 0.01), and sagittal vertical axis (SVA) (p = 0.004) were significant independent risk factors for revision posterior lumbar fusion in PD patients. CONCLUSION: PD patients with low pre-operative BMD, fatty infiltration, a smaller rCSA of the paraspinal muscle, and larger PI-LL and SVA had a higher rate of revision lumbar fusion. Maintaining sagittal balance, functional exercises, and anti-osteoporosis treatment were important in preventing complications in PD patients.

Leptin regulates disc cartilage endplate degeneration and ossification through activation of the MAPK-ERK signalling pathway in vivo and in vitro.

Recent findings demonstrate that leptin plays a significant role in chondrocyte and osteoblast differentiation. However, the mechanisms by which leptin acts on cartilage endplate (CEP) cells to give rise to calcification are still unclear. The aim of this study was to evaluate the effects of leptin that induced mineralization of CEP cells in vitro and in vivo. We constructed a rat model of lumbar disc degeneration and determined that leptin was highly expressed in the presence of CEP calcification. Rat CEP cells treated with or without leptin were used for in vitro analysis using RT-PCR and Western blotting to examine the expression of osteocalcin (OCN) and runt-related transcription factor 2 (Runx2). Both OCN and Runx2 expression levels were significantly increased in a dose- and time-dependent manner. Leptin activated ERK1/2 and STAT3 phosphorylation in a time-dependent manner. Inhibition of phosphorylated ERK1/2 using targeted siRNA suppressed leptin-induced OCN and Runx2 expression and blocked the formation of mineralized nodules in CEP cells. We further demonstrated that exogenous leptin induced matrix mineralization of CEP cells in vivo. We suggest that leptin promotes the osteoblastic differentiation of CEP cells via the MAPK/ERK signal transduction pathway and may be used to investigate the mechanisms of disc degeneration.

Comparison of unilateral versus bilateral pedicle screw fixation in degenerative lumbar diseases: a meta-analysis.

PURPOSE: Traditionally, lumbar spinal surgery is performed with bilateral pedicle screw fixation to provide stability as the fusion heals. However, many studies have reported that unilateral pedicle screw fixation is as effective as bilateral constructs. To compare the clinical outcomes, complications, and surgical trauma between the two techniques for treatment of degenerative lumbar diseases, we conducted a meta-analysis. METHODS: We searched MEDLINE, EMBASE, PubMed, Google Scholar, and Cochrane databases for relevant controlled studies up to August 2013 that compared unilateral with bilateral fixation for the treatment of degenerative lumbar diseases. We independently performed title/abstract screening and full-text screening. A random effects model was used for heterogeneous data; otherwise, a fixed effect model was used, pooling data using mean difference (MD) for continuous outcomes and odds ratio (OR) for dichotomous outcomes. RESULTS: A total of 12 articles (865 participants) were eligible. Overall, there were significant differences between the two groups for blood loss (MD = -171.73, 95 % CI = -281.70 to -61.76; p = 0.002), operation time (MD = -66.02, 95 % CI = -115.52 to -16.51; p = 0.009), and fusion rate (OR = 0.50, 95 % CI = 0.26-0.96; p = 0.004). However, there were no significant differences in hospital stay (MD = -4.44, 95 % CI = -13.37 to 4.50), ODI (MD = -0.09, 95 % CI = -0.59 to 0.42; p = 0.74), JOA (MD = 0.18, 95 % CI = -0.77 to 1.14; p = 0.71), VAS (MD = -0.04, 95 % CI = -0.16 to 0.08; p = 0.49), SF-36 (PF: MD = -1.11, 95 % CI = -4.38 to 2.17, p = 0.51; GH: MD = 1.22, 95 % CI = -2.17 to 4.60, p = 0.48; MH: MD = -0.22, 95 % CI = -3.83 to 3.38, p = 0.90) and complications (OR = 1.15, 95 % CI = 0.72-1.85; p = 0.56). CONCLUSIONS: This meta-analysis shows that there was significantly less blood loss in unilateral group and less operating time; however, the fusion rate was significantly higher in the bilateral group. The outcomes of hospital stay, ODI, JOA, VAS, SF-36 score, and complications are similar in the two groups.

Fusion techniques for adult isthmic spondylolisthesis: a systematic review.

INTRODUCTION: Various fusion techniques have been used to treat lumbar spine isthmic spondylolisthesis (IS) in adults, including anterior lumbar interbody fusion (ALIF), posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), posterolateral fusion (PLF), and circumferential fusion. The objective of this study was to evaluate which fusion technique provides the best clinical and radiological outcome for adult lumbar IS. MATERIALS AND METHODS: A systematic review was performed. MEDLINE databases and reference lists of selected articles were searched. Inclusion criteria stated that the studies had to be controlled and that they compared clinical and radiological outcomes of various fusion techniques for treating adult IS. Exclusion criteria were use of only one treatment and non-English language articles. Two reviewers independently extracted relevant data from each included study. Statistical comparisons were made when appropriate. RESULTS: Nine studies that compared two surgical approaches to IS were included in this systematic review. Three were prospective studies, and six were retrospective studies. Two studies compared ALIF with instrumented PLF and ALIF with percutaneous pedicle screw fixation, two studies compared ALIF and TLIF, and five studies compared PLIF and PLF. ALIF was superior to other techniques regarding restoration of disc height, segmental lordosis, and whole lumbar lordosis. TLIF had lower complication rates. ALIF combined with PLF showed lower nonfusion rates than other techniques. However, there were no significant differences in clinical outcomes between any two techniques. CONCLUSION: Compared to other fusion techniques, TLIF shows fewer complications, ALIF shows better sagittal alignment, and circumferential fusion showed better fusion rates. It was difficult to make recommendations about the optimal approach because of the methodological variance in the publications.

Anterior cervical discectomy and fusion with a zero-profile VA spacer device: a clinical and radiological study with two-year follow-up.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to compare clinical and radiological outcomes of the anterior cervical discectomy and fusion (ACDF) with a novel zero-profile variable-angle (Zero-P VA) spacer and a traditional poly-ether-ether-ketone (PEEK) cage and plate system in cases pertaining to cervical radiculopathy/myelopathy. There are two conventional types of ACDF procedures aimed at treating symptomatic cervical spondylosis. The first one involves an uninstrumented "stand-alone" approach utilizing bone graft/cage, while the second incorporates bone graft/cage in conjunction with a front plate positioned before the vertebral bodies. Both procedures have their own inherent advantages and disadvantages. The Zero-P VA spacer, however, represents a unique synthesis by amalgamating the advantages of both traditionally typical procedures. Notably, this spacer can potentially circumvent the issue related to prevertebral soft-tissue disturbance and reduce the occurrence of dysphagia. METHODS: Using our surgical database, the authors systematically conducted a retrospective analysis encompassing all patients who underwent single-level ACDF between January 2018 and January 2019, with a minimum two-year follow-up. Patients either received a Zero-P VA implant or PEEK cage coupled with plating. The Japanese Orthopedic Association (JOA) score and Visual Analogue Scale (VAS) for arm and neck pain were documented. Dysphagia was evaluated using the Eating Assessment Tool-10 (ETA-10). Additional parameters such as cervical alignment, fusion rate and the incidence of postoperative complications were assessed. RESULTS: According to the outcomes of the statistical analysis, there was no substantial disparity that emerged in the advancements observed in the JOA and VAS metrics between the two study cohorts. Noteworthy, however, the ETA-10 scores were statistically significantly reduced in the Zero-P VA group compared to the cage and plating group (p < 0.05). At the final follow-up, there were no statistically significant differences in the height of the operated segment, Cobb angle of the fused segment, C2-C7 Cobb angle and fusion rate between the two groups (p > 0.05). However, postoperative complications were slightly lower in patients with the Zero-P VA group (7.69%) as compared to the cage and plating group (16.67%). CONCLUSION: The clinical outcomes observed with the Zero-P VA spacer used for single-level ACDF were found to be satisfactory. The performance of this device is comparable or even superior to the traditional cage and plating method in preventing postoperative dysphagia and mitigating potential complications associated with the use of a plate.

Inhibition of Mettl3 ameliorates osteoblastic senescence by mitigating m6A modifications on Slc1a5 via Igf2bp2-dependent mechanisms.

Age-related osteoporosis is characterized by a marked decrease in the number of osteoblasts, which has been partly attributed to the senescence of cells of the osteoblastic lineage. Epigenetic studies have provided new insights into the mechanisms of current osteoporosis treatments and bone repair pathophysiology. N6-methyladenosine (m6A) is a novel transcript modification that plays a major role in cellular senescence and is essential for skeletal development and internal environmental stability. Bioinformatics analysis revealed that the expression of the m6A reading protein Igf2bp2 was significantly higher in osteoporosis patients. However, the role of Igf2bp2 in osteoblast senescence has not been elucidated. In this study, we found that Igf2bp2 levels are increased in ageing osteoblasts induced by multiple repetition and H2O2. Increasing Igf2bp2 expression promotes osteoblast senescence by increasing the stability of Slc1a5 mRNA and inhibiting cell cycle progression. Additionally, Mettl3 was identified as Slc1a5 m6A-methylated protein with increased m6A modification. The knockdown of Mettl3 in osteoblasts inhibits the reduction of senescence, whereas the overexpression of Mettl3 promotes the senescence of osteoblasts. We found that administering Cpd-564, a specific inhibitor of Mettl3, induced increased bone mass and decreased bone marrow fat accumulation in aged rats. Notably, in an OVX rat model, Igf2bp2 small interfering RNA delivery also induced an increase in bone mass and decreased fat accumulation in the bone marrow. In conclusion, our study demonstrated that the Mettl3/Igf2bp2-Slc1a5 axis plays a key role in the promotion of osteoblast senescence and age-related bone loss.

Vitamin D delays intervertebral disc degeneration and improves bone quality in ovariectomized rats.

Known to be involved in bone-cartilage metabolism, Vitamin D (VD) may play a role in human's disc pathophysiology. Given that postmenopausal women are prone to suffer VD deficiency and intervertebral disc degeneration (IDD), this study is intended to investigate whether VD can delay IDD in ovariectomized rats by improving bone microstructure and antioxidant stress. Female Sprague-Dawley rats were randomly allocated into four groups: sham, oophorectomy (OVX)+VD deficiency (VDD), OVX, and OVX+VD supplementation (VDS). In vivo, after a 6-month intervention, imaging and pathology slice examinations showed that IDD induced by OVX was significantly alleviated in VDS and deteriorated by VDD. The expressions of aggrecan and Collagen II in intervertebral disc were reduced by OVX and VDD, and elevated by VDS. Compared with the OVX+VDD and OVX group vertebrae, OVX+VDS group vertebrae showed significantly improved endplate porosity and lumbar bone mineral density with increased percent bone volume and trabecular thickness. Furthermore, 1α,25(OH)2D3 restored the redox balance (total antioxidant capacity, ratio of oxidized glutathione/glutathione) in the disc. The cocultivation of 1α,25(OH)2D3 and nucleus pulposus cells (NPCs) was conducted to observe its potential ability to resist excessive oxidative stress damage induced by H2O2. In vitro experiments revealed that 1α,25(OH)2D3 reduced the senescence, apoptosis, and extracellular matrix degradation induced by H2O2 in NPCs. In conclusion, VDS exhibits protective effects in OVX-induced IDD, partly by regulating the redox balance and preserving the microstructure of endplate. This finding provides a new idea for the prevention and treatment of IDD.

The Effects of Abdominal Obesity and Sagittal Imbalance on Sacroiliac Joint Pain After Lumbar Fusion.

BACKGROUND: Postoperative sacroiliac joint pain (SIJP) is a common manifestation of failed back surgery syndrome after a posterior lumbar interbody fusion (PLIF). However, there is currently no consensus on the risk factors for SIJP after PLIF. OBJECTIVES: We explored the effects of abdominal obesity and sagittal imbalance on SIJP after PLIF. STUDY DESIGN: This is a prospective observational cohort study. SETTING: This study occurred at the Department of Spinal Surgery at a hospital affiliated with a medical university. METHODS: A total of 401 patients who underwent PLIF from June 2018 to June 2021 were enrolled in this study. 36 patients experienced postoperative SIJP. In contrast, a matched group comprised 72 non-SIJP patients. We used 1:2 propensity score matching to compare obesity features and sagittal spine parameters in the 2 groups. Inflammatory cytokines and visual analog scale (VAS) scores were measured in the SIJP group. RESULTS: A total of 36 patients (8.98%) experienced SIJP during the follow-up. Compared with the non-SIJP group, patients with postoperative SIJP had a higher body mass index (BMI), greater abdominal obesity, a higher incidence of pelvic incidence-lumbar lordosis greater than 10°, and a higher incidence of a sagittal vertical axis greater than 5 cm (P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve for waist circumference was greater than that for BMI (0.762 vs. 0.650, P = 0.049). Logistic regression analysis revealed that the risk factors for SIJP were abdominal obesity, a pelvic incidence-lumbar lordosis of greater than 10°, and a sagittal vertical axis greater than 5 cm (P < 0.05). In patients with SIJP, interleukin 6, tumor necrosis factor-α, and VAS scores were higher in the abdominal obesity group than in the non-abdominal obesity group (P < 0.05). LIMITATIONS: There was no uniform diagnosis of SIJP, so the incidence rate of SIJP might not be accurate. CONCLUSIONS: The significant predictors of SIJP were abdominal obesity and sagittal imbalance. Patients with abdominal obesity showed higher levels of inflammatory markers and pain intensity. More attention should be paid to body shape and the angle of correction of lumbar lordosis before lumbar surgery.

Stage specific effect of leptin on the expressions of estrogen receptor and extracellular matrix in a model of chondrocyte differentiation.

Endochondral ossification is a dynamic process. The interaction between leptin and estrogen in this process is complicated. Whether there is a stage specific crosstalk between leptin and estrogen in the differentiation process of the chondrocytes in the growth plate remains unknown. The aim of our study was to investigate the effect of leptin on the expression of estrogen receptors and extracellular matrix in ATDC5 cells, an in vitro model of endochondral ossification. First, we quantified the physiological expressions of estrogen receptors α, ß (ERα, ERß), leptin receptor (Ob-Rb), type II and type X collagens in definite stages of endochondral ossification in ATDC5 cells using real-time PCR. Dynamic and stage specific expression characteristics of these target genes were observed. Simultaneous expressions of Ob-Rb with ERα or ERß in ATDC5 cells were also found with dual-label confocal immunofluorescency. Then using Western blotting analysis and/or real-time PCR, we detected that, leptin treatment up-regulated the expressions of ERα, ERß and type II collagen, but down-regulated type X collagen expression and the ERα/ERß ratio in the chondrogenic differentiation stage. Meanwhile, leptin down-regulated the expressions of ERα, type II and type X collagens, and the ERα/ERß ratio, but up-regulated the expression of ERß in the hypertrophic differentiation stage. Significant positive correlation existed between ERα and type II collagen expression, and between the ratio of ERα/ERß and type X collagen production. In summary, the crosstalk between leptin and estrogen receptor might be differentiation stage specific in ATDC5 cells.

Role of ferroptosis and immune infiltration in intervertebral disc degeneration: novel insights from bioinformatics analyses.

Background: Intervertebral disc degeneration (IVDD), which contributes to stenosis of the spinal segment, commonly causes lower back pain. The process of IVDD degradation entails gradual structural adjustments accompanied by extreme transformations in metabolic homeostasis. However, the molecular and cellular mechanisms associated with IVDD are poorly understood. Methods: The RNA-sequencing datasets GSE34095 and GSE56081 were obtained from the Gene Expression Omnibus (GEO) database. Ferroptosis-related differentially expressed genes (DEGs) were identified from these gene sets. The protein-protein interaction (PPI) network was established and visualized using the STRING database and Cytoscape software, and the key functional modules of ferroptosis-related genes were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs. Weighted gene co-expression network analysis (WGCNA), immune infiltration analysis in the GEO database, and other GSE series were used as validation datasets. The xCELL algorithm was performed to investigate the immune cell infiltration differences between the degenerated IVDD and control groups. Results: The major genes involved in nucleus pulposus tissue immune infiltration and ferroptosis-related genes were mined by bioinformatics analysis. A total of 3,056 DEGs were obtained between the IVDD tissue and control groups. The DEGs were enriched in the cell cycle; apoptosis; necroptosis; and the PI3K-Akt, Hippo, and HIF-1 signaling pathways. PCR and Western blot techniques were utilized to confirm the differential ferroptosis-related genes. The results indicated that the protein expression levels of NCOA4 and PCBP1 were elevated, while the protein expression level of GPX4 was reduced in NPCs following IL-1ß treatment. Our study has found that severe disc tissue degeneration leads to a noteworthy increase in the expression of CD8A in naive T cells, CCR7 in memory CD4+ cells, GZMB in natural killer (NK) cells, and CD163 and CD45 in macrophages. Conclusion: Our data demonstrate that ferroptosis occurs in IVDD, suggesting that ferroptosis may also increase IVDD improvement by triggering immune infiltration. This work was conducted to further understand IVDD pathogenesis and identify new treatment strategies.

Leptin regulates estrogen receptor gene expression in ATDC5 cells through the extracellular signal regulated kinase signaling pathway.

Both estrogen and leptin play an important role in the regulation of physiological processes of endochondral bone formation in linear growth. Estrogen receptors (ERα and ERß) are known as members of the superfamily of nuclear steroid hormone receptors and are detected in all zones of growth plate chondrocytes. They can be regulated in a ligand-independent manner. Whether leptin regulates ERs in the growth plate is still not clear. To explore this issue, chondrogenic ATDC5 cells were used in the present study. Messenger RNA and protein analyses were performed by quantitative PCR and Western blotting. We found that both ERα and ERß were dynamically expressed during the ATDC5 cell differentiation for 21 days. Leptin (50 ng/ml) significantly upregulated ERα and ERß mRNA and protein levels 48 h after leptin stimulation (P<0.05) at day 14. The up-regulation of ERα and ERß mRNA by leptin was shown in a dose-dependent manner, but the most effective dose of leptin was different (100 and 1,000 ng/ml, respectively). Furthermore, we confirmed that leptin augmented the phosphorylation of ERK1/2 in a time-dependent manner. A maximum eightfold change was observed at 15 min. Finally, a specific ERK1/2 inhibitor, UO126, blocked leptin-induced ERs regulation in ATDC5 cells, indicating that ERK1/2 mediates, partly, the effects of leptin on ERs. These data demonstrate, for the first time, that leptin regulates the expression of ERs in growth plate chondrocytes via ERK signaling pathway, thereby suggesting a crosstalk between leptin and estrogen receptors in the regulation of bone formation.