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.

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.

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.

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.

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.

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.

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.

Association Between Poor Nutritional Status and Increased Risk for Subsequent Vertebral Fracture in Elderly People with Percutaneous Vertebroplasty.

Background: The relationship between a poor nutritional state and the risk of fractures has not been investigated. This study aimed to investigate the ability of the Controlling Nutritional Status (CONUT) and Geriatric Nutritional Risk Index (GNRI) to predict the incidence of subsequent vertebral fracture (SVF) after percutaneous vertebroplasty (PVP). Methods: A total of 307 women and 138 men over 50 years old who underwent PVP for osteoporotic vertebral compression fracture (OVCF) were included. Blood biochemical indexes, body mass index (BMI), bone mineral density (BMD), physical function, and muscle strength were measured at baseline. Cox regression analysis was used to determine whether nutritional state was an independent predictor for SVF. Results: During follow-up, 35 (25.4%) men and 85 (27.7%) women suffered SVF. Patients with SVF had lower BMI, serum albumin levels, GNRI scores, grip strength, lumbar BMD, and Short-Physical Performance Battery (SPPB) scores and higher fall rates and CONUT scores (P < 0.05). Compared with normal nutrition, mild malnutrition was associated with higher risk for SVF (women: HR 2.37, p=0.001, men: HR 2.97, p=0.021 by GNRI; women: HR 2.36, p=0.005, men: HR 3.62, p=0.002 by CONUT) after adjusting for confounding factors. Those with moderate-severe malnutrition also had a higher risk of SVF. Kaplan-Meier analysis showed that poor nutrition state was significantly associated with lower SVF-free survival (P<0.05). The area under curve (AUC) for predicting SVF was 0.65 and 0.73 for the GNRI and 0.67 and 0.66 for the CONUT in men and women, respectively. Conclusion: GNRI and CONUT are simple and effective tools for predicting SVF in patients undergoing PVP. Health management and nutrition supplement after PVP is a potentially effective prevention strategy against SVF.

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.

Exogenous Klotho ameliorates extracellular matrix degradation and angiogenesis in intervertebral disc degeneration via inhibition of the Rac1/PAK1/MMP-2 signaling axis.

Intervertebral disc degeneration (IDD) is highly ubiquitous in the aged population and is an essential factor for low back pain and spinal disability. Because of the association between IDD and senescence, we investigated the ability of the anti-aging drug Klotho to inhibit age-dependent advancement of nucleus pulposus cell (NPC) degeneration. The results indicated that 400 pM exogenous Klotho significantly ameliorated extracellular matrix degradation and angiogenesis. Moreover, we demonstrated that the suppression of angiogenesis and extracellular matrix catabolism was related to inhibition of the Ras-related C3 botulinum toxin substrate 1 (Rac1)/PAK1 axis and matrix metalloproteinase 2 protein expression by exogenous Klotho cotreatment with a Rac1 inhibitor, gene overexpression in NPCs, and stimulation of human umbilical vein endothelial cells with conditioned medium from NPCs. The treatment also preserved the NPC phenotype, viability, and matrix content. In conclusion, these results suggest that the new anti-aging drug Klotho is a potential treatment strategy to mitigate IDD, and thus, provides an innovative understanding of the molecular mechanism of IDD. DATA AVAILABILITY: All data supporting the findings of this study are available from the corresponding authors upon reasonable request.

Ascorbic acid promotes nucleus pulposus cell regeneration by regulating proliferation during intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) affects human health. Ascorbic acid (AA) deficiency is a major factor that contributes to the development of degenerative disc disease in the elderly. Here, as a novel treatment with promising applications, we demonstrate that AA treatment inhibited senescence and maintained the proliferation of nucleus pulposus (NP) cells during long-term culture. AA-treated NP cells and acupuncture-treated rat models exhibited degenerative resistance during cell passaging and AA increased cell proliferation and decreased time-related senescence. Interestingly, Kyoto Encyclopedia of Genes and Genomes pathway mapping revealed five top enriched pathways and four pathways were associated with the aldehyde dehydrogenase (ALDH) enzyme family, especially proliferation-related ALDH1A3. Collectively, our findings demonstrate that ALDH1A3 expression was increased by AA treatment, which counteracted degeneration in NP cells over time and rejuvenated maintenance of proliferation in NP cells, which has a promising therapeutic implications in IVDD.

Association Between Abdominal Obesity and Subsequent Vertebral Fracture Risk.

BACKGROUND: Obesity had been previously considered to be a protective factor against osteoporosis or fractures; however, recent research indicates that obesity, especially abdominal obesity, may increase the risk of some types of fractures. OBJECTIVE: We explored the effects of abdominal obesity on subsequent vertebral fracture (SVF) after percutaneous vertebral augmentation (PVA). STUDY DESIGN: A prospective observational cohort study. SETTING: Department of Spinal Surgery of a hospital affiliated with a medical university. METHODS: A total of 390 women and 237 men aged > 50 years suffering from osteoporotic vertebral fracture (OVF) were included. Weight, height, bone mineral density (BMD), abdominal circumference, and other basic information were measured at baseline and 1-year follow-up visit. RESULTS: During follow-up, 80 (33.7%) men and 143 (36.7%) women incurred SVF. Greater waist circumference (WC) and waist-to-hip ratio (WHR) increased the risk of SVF in men (WC: HR 1.83, P = 0.016; WHR: HR 1.63, P = 0.045) and women (WC: HR 2.75, P = 0.001; WHR: HR 2.63, P = 0.001) after adjustment for BMD and other potential confounders. Compared with normal BMI, being overweight was associated with lower SVF risk (women: HR 0.55, P = 0.044; men: HR 0.46, P = 0.046), and obesity was associated with greater SVF risk (women: HR 4.53, P < 0.001; men: HR 3.77, P < 0.001) in both genders. We observed a nonlinear relationship between BMI and SVF with a U-shaped curve; after adjusting BMD, this became a reverse J-curve. LIMITATIONS: There was no further statistical analysis of the relationship between abdominal obesity and other fracture sites. Asymptomatic SVF may underestimate the impact of abdominal obesity on the occurrence of SVF. CONCLUSIONS: Abdominal obesity was significantly associated with a higher risk of SVF after PVA. Management of body type after PVA may be an effective prevention strategy against SVF.

Changes in intervertebral distraction: A possible factor for predicting dysphagia after anterior cervical spinal surgery.

OBJECTIVE: Dysphagia following anterior cervical spine surgery (ACSS) is common. This study aimed to determine if change in intervertebral distraction following ACSS is associated with early dysphagia. METHODS: We retrospectively examined patients who underwent ACSS for myelopathy and/or radiculopathy in our institution. The Bazaz score and the Chinese version of the Swallowing-Quality of Life survey were used to assess postoperative swallowing function. Change in intervertebral distraction was defined as the difference between the preoperative and postoperative mean values of the anterior and posterior intervertebral distances at the surgical site. Potential risk factors examined included age, gender, body mass index, operative time, blood loss volume, level of surgery, as well as radiographic data including Cobb angle, T1 slope, sagittal vertical axis, and intervertebral distraction. RESULTS: Among the 289 patients, the incidence of dysphagia was 58.1% 1 week after ACSS. Patients who underwent surgery involving C3/4 or involving three or more levels had worse Swallowing-Quality of Life and Bazaz scores. The optimal cutoff value for change in intervertebral distraction for predicting dysphagia 1 week after surgery was 6.10 mm. Change in intervertebral distraction ≥ 6.10 mm, surgery involving C3/4, and surgery involving three or more levels were significantly and independently associated with early dysphagia. CONCLUSION: A correlation between early dysphagia and change in intervertebral distraction ≥ 6.10 mm could be confirmed. In addition, patients undergoing ACSS involving C3-4 or multilevel surgery (≥3) must be monitored carefully postoperatively for dysfunctional swallowing.

Sarcopenic obesity defined by visceral adiposity was associated with osteoporotic vertebral fracture.

BACKGROUND: Previous studies have reported that the fracture risk related to sarcopenic obesity (SO) may be influenced by the distribution of fat mass. Therefore, it is useful to explore a body component suitable for defining obesity when predicting fracture risk. This study was an attempt to explore the contribution of SO defined by visceral adiposity on the incidence of osteoporotic fracture. METHODS: We enrolled 736 Chinese patients aged > 60 years in this prospective study. Sarcopenia was defined as low skeletal muscle index (SMI) with muscle strength or low SMI with low physical performance. Obesity was categorized as follows: (1) android to gynoid ratio (A/G ratio, men > 0.82, women > 0.65) as an indicator of visceral adiposity; (2) body fat percentage (men > 27.8%; women > 34.5%); and (3) body mass index (≥ 25 kg/m2). A Cox proportional hazard model was used to determine the association between SO and the risk of osteoporotic fracture. RESULTS: The incidence of SO was 8.7%; 9.0% in females and 8.1% in males. Of 223 (30.2%) patients with self-reported fractures. SO classified by A/G was associated with an increased risk of osteoporotic vertebral fracture (HR: 1.71, 95% CI: 1.07-2.72). High SMI was associated with a reduced risk of osteoporotic vertebral fracture (HR: 0.82, 95% CI: 0.72-0.93), higher BMI was associated with a higher risk vertebral fracture (HR: 1.12, 95% CI: 0.94-1.63), and higher A/G ratio was associated with a higher risk of any fracture (HR: 1.28, 95% CI: 1.14-1.43) and osteoporotic vertebral fracture (HR: 1.19, 95% CI: 1.05-1.36). CONCLUSIONS: Our findings suggest that SO, defined by visceral adiposity, was associated with the risk of osteoporotic vertebral fracture. Moreover, low SMI, low muscle strength and visceral adiposity were independently associated with osteoporotic fracture.

Relationship between Vitamin D and Nonspecific Low Back Pain May Be Mediated by Inflammatory Markers.

BACKGROUND: Vitamin D deficiency has been linked to nonspecific low back pain (Ns-LBP); however, the role of inflammation as a possible mediator between vitamin D levels and Ns-LBP is not well understood. OBJECTIVE: To explore the mediating effects of inflammatory markers on the relationship between vitamin D levels and pain outcomes. STUDY DESIGN: A retrospective study. SETTING: Department of Spinal Surgery of a hospital affiliated to a medical university. METHODS: In this cross-sectional study, we selected patients with non-specific acute low back pain (Ns-ALBP, n = 60) and non-specific chronic low back pain (Ns-CLBP, n = 78), as well as 60 people without Ns-LBP as controls, from January 2018 to January 2019. Serum 25(OH)D and inflammatory marker levels were examined. Regression and causal mediation analysis were used to evaluate the mediating effects of inflammatory markers on the association between vitamin D and pain. RESULTS: Mean serum concentrations of vitamin D in the control, Ns-ALBP, and Ns-CLBP groups were 25.70 ± 10.04, 21.44 ± 8.46 and 18.25 ± 8.05 ng/mL, respectively (P < 0.001). After adjustment for clinical factors, vitamin D deficiency was associated with Ns-LBP (P < 0.05); however, when the interleukin 6 (IL-6) level was added to the multivariable models, the association was no longer significant in Ns-CLBP patients. Mediation analysis estimated the overall mediated effect as -0.461 (P < 0.001) in Ns-CLBP patients, and the intermediary effect of IL-6 was 0.045. LIMITATIONS: A retrospective study may include inevitable bias. More sensitive biomarkers were not investigated in this study. Pain intensity evaluation using the visual analogue scale is inevitably subjective. CONCLUSION: Patients with Ns-LBP had lower vitamin D and higher inflammatory marker levels. This association between hypovitaminosis D and Ns-CLBP may be mediated by IL-6. Therefore, large-scale clinical trials are warranted to investigate the clinical efficacy of vitamin D supplementation for decreasing inflammation and relieving Ns-LBP.

Evaluation of the Use of CT Attenuation for the Prediction of Subsequent Vertebral Fracture in Patients with Osteoporosis.

BACKGROUND: Subsequent vertebral fracture (SVF) is one of the most common complications of percutaneous vertebral augmentation (PVA), which leads to lower back pain in patients. Low bone mineral density (BMD) is an independent risk factor for SVF. BMD measured using computed tomography (CT) trabecular attenuation correlates closely with BMD. OBJECTIVES: This study aims to analyze the risk factors of SVF after PVA and to estimate the predictive role of CT trabecular attenuation. STUDY DESIGN: A retrospective review. SETTING: Department of spinal surgery in an affiliated hospital of a medical university. METHODS: A total of 515 patients were retrospectively enrolled between January 2015 and December 2019 into a 5-year follow-up investigation. Trabecular attenuation (Hounsfield units [HU]) was retrospectively measured at L1 on preoperative lumbar or thoracic CT scans, and the receiver operating characteristic (ROC) curve was used to evaluate its value for the prediction of SVF. Kaplan-Meier analysis and Cox proportional hazards regression were performed to identify the risk factors for SVF. RESULTS: A total of 166 patients (32.2%) experienced SVF. ROC curve analysis demonstrated that an L1 trabecular attenuation of <= 95 HU has a sensitivity of 70.5% and a specificity of 79.9% for the prediction of SVF. Kaplan-Meier analysis showed that L1 trabecular attenuation <= 95 HU was significantly associated with lower SVF-free survival (P = 0.001; log-rank test). Multivariate analysis demonstrated that advanced age (hazard ratio [HR] = 1.03, P = 0.022), low body mass index (HR = 0.83, P = 0.001), diabetes status (HR = 1.50, P = 0.024), antiosteoporosis drugs use (HR = 0.65, P = 0.031), and decreased L1 trabecular attenuation (HR = 0.95, P = 0.001) were risk factors for SVF. LIMITATIONS: A single-center retrospective study of a consecutive cohort of patients may include the inevitable bias. We periodically reviewed the full-length x-ray of the spine at every 3 months of follow-up visit, which we may miss some patients with SVF without low back pain. CONCLUSIONS: SVF is highly prevalent in patients with osteoporotic vertebral fracture who undergo single-level PVA. Low L1 trabecular attenuation is associated with a significant reduction in SVF-free survival, and when their L1 trabecular attenuation is <= 95 HU, patients may be at higher risk of SVF. KEY WORDS: Computed tomography, Hounsfield units, vertebral fracture, osteoporosis, percutaneous vertebral augmentation.

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.

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.