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International Journal of Spine Surgery Jun 2024We sought to determine which aspect of the upper instrumented vertebrae (UIV)-tilt angle or screw angle-was more strongly associated with: (1) proximal junctional...
Comparing the Upper Instrumented Vertebrae Tilt Angle vs Screw Angle in the Development of Proximal Junction Kyphosis After Adult Spinal Deformity Surgery: Which Matters More?
BACKGROUND
We sought to determine which aspect of the upper instrumented vertebrae (UIV)-tilt angle or screw angle-was more strongly associated with: (1) proximal junctional kyphosis/failure (PJK/F), (2) other mechanical complications and reoperations, and (3) patient-reported outcome measures (PROMs).
METHODS
A single-institution, retrospective cohort study was undertaken for patients undergoing adult spinal deformity (ASD) surgery from 2011 to 2017. Only patients with UIV at T7 or below were included. The primary exposure variables were UIV tilt angle (the angle of the UIV inferior endplate and the horizontal) and UIV screw angle (the angle of the UIV screws and superior endplate). Multivariable logistic regression included age, body mass index, osteopenia/osteoporosis, postoperative sagittal vertical axis, postoperative pelvic-incidence lumbar lordosis mismatch, UIV tilt angle and UIV screw angle.
RESULTS
One hundred and seventeen patients underwent adult spinal deformity surgery with a minimum of 2-year follow-up. A total of 41 patients (35.0%) had PJK and 26 (22.2%) had PJF. (1) UIV tilt angle: 96 (82.1%) had lordotic UIV tilt angles, 6 (5.1%) were neutral, and 15 (12.8%) were kyphotic. (2) UIV screw angle: 38 (32.5%) had cranially directed screws, 4 (3.4%) were neutral, and 75 (64.1%) were caudally directed. Both lordotic-angled UIV endplate (OR = 1.06, 95% CI = 1.01-1.12, and = 0.020) and cranially directed screws (OR = 1.19, 95% CI = 1.07-1.33, and < 0.001) were associated with higher odds of PJK, with a more pronounced effect of UIV screw angle compared with UIV tilt angle (Wald test, 9.40 vs 4.42). Similar results were found for PJF. Neither parameter was associated with other mechanical complications, reoperations, or patient-reported outcome measures.
CONCLUSIONS
UIV screw angle was more strongly associated with development of PJK/F compared with tilt angle. Overall, these modifiable parameters are directly under the surgeon's control and can mitigate the development of PJK/F.
CLINICAL RELEVANCE
Surgeons may consider selecting a UIV with a neutral or kyphotically directed UIV tilt angle when performing ASD surgery with a UIV in the lower thoracic or lumbar region, as well as use UIV screw angles that are caudally directed, for the purprose of decreasing the risk of developing PJK/F.
PubMed: 38886012
DOI: 10.14444/8607 -
BioMed Research International 2024Diabetes has a significant global prevalence. Chronic hyperglycemia affects multiple organs and tissues, including bones. A large number of diabetic patients develop... (Review)
Review
Diabetes has a significant global prevalence. Chronic hyperglycemia affects multiple organs and tissues, including bones. A large number of diabetic patients develop osteoporosis; however, the precise relationship between diabetes and osteoporosis remains incompletely elucidated. The activation of the AGE-RAGE signaling pathway hinders the differentiation of osteoblasts and weakens the process of bone formation due to the presence of advanced glycation end products. High glucose environment can induce ferroptosis of osteoblasts and then develop osteoporosis. Hyperglycemia also suppresses the secretion of sex hormones, and the reduction of testosterone is difficult to effectively maintain bone mineral density. As diabetes therapy, thiazolidinediones control blood glucose by activating PPAR-. Activated PPAR- can promote osteoclast differentiation and regulate osteoblast function, triggering osteoporosis. The effects of metformin and insulin on bone are currently controversial. Currently, there are no appropriate tools available for assessing the risk of fractures in diabetic patients, despite the fact that the occurrence of osteoporotic fractures is considerably greater in diabetic individuals compared to those without diabetes. Further improving the inclusion criteria of FRAX risk factors and clarifying the early occurrence of osteoporosis sites unique to diabetic patients may be an effective way to diagnose and treat diabetic osteoporosis and reduce the risk of fracture occurrence.
Topics: Humans; Osteoporosis; Risk Factors; Osteoporotic Fractures; Fractures, Bone; Metabolic Networks and Pathways; Diabetes Mellitus; Bone Density; Osteoblasts; Signal Transduction
PubMed: 38884020
DOI: 10.1155/2024/6640796 -
Journal of Nutrition and Metabolism 2024Lycopene is a naturally occurring carotenoid predominantly found in tomatoes and tomato-based products. Like other phytochemicals, it exhibits health beneficial... (Review)
Review
Lycopene is a naturally occurring carotenoid predominantly found in tomatoes and tomato-based products. Like other phytochemicals, it exhibits health beneficial biological activities that can be exploited when it is used as a dietary supplement. and , lycopene has been demonstrated to mitigate oxidative stress-induced metabolic dysfunctions and diseases including inflammation, obesity, and diabetes mellitus. Lycopene has been shown to alleviate metabolic diseases that affect the bone, eye, kidney, liver, lungs, heart, and nervous system. This review presents the state of the art regarding lycopene's health benefits and its potential applications in health system delivery. Furthermore, lycopene's protective effects against toxins, safety in its use, and possible toxicity are explored.
PubMed: 38883868
DOI: 10.1155/2024/6252426 -
Research Square Jun 2024Apoptotic vesicles (apoVs) play a vital role in various pathological conditions; however, we have yet to fully understand their precise biological effects in rescuing...
Apoptotic vesicles (apoVs) play a vital role in various pathological conditions; however, we have yet to fully understand their precise biological effects in rescuing impaired mesenchymal stem cells (MSCs) and regulating tissue homeostasis. Here, we proved that systemic infusion of bone marrow MSCs derived from wild-type (WT) mice effectively improved the osteopenia phenotype and hyperimmune state in ovariectomized (OVX) mice. Importantly, the WT MSCs rescued the impairment of OVX MSCs both and , whereas OVX MSCs did not show the same efficacy. Interestingly, treatment with apoVs derived from WT MSCs (WT apoVs) restored the impaired biological function of OVX MSCs and their ability to improve osteoporosis. This effect was not observed with OVX MSCs-derived apoVs (OVX apoVs) treatment. Mechanistically, the reduced miR-145a-5p expression hindered the osteogenic differentiation and immunomodulatory capacity of OVX MSCs by affecting the TGF-β/Smad 2/3-Wnt/β-catenin signaling axis, resulting in the development of osteoporosis. WT apoVs directly transferred miR-145a-5p to OVX MSCs, which were then reused to restore their impaired biological functions. Conversely, treatment with OVX apoVs did not produce significant effects due to their limited expression of miR-145a-5p. Overall, our findings unveil the remarkable potential of apoVs in rescuing the biological function and therapeutic capability of MSCs derived from individuals with diseases. This discovery offers a new avenue for exploring apoVs-based MSC engineering and expands the application scope of stem cell therapy, contributing to the maintenance of bone homeostasis through a previously unrecognized mechanism.
PubMed: 38883762
DOI: 10.21203/rs.3.rs-4416138/v1 -
Frontiers in Endocrinology 2024Postmenopausal osteoporosis is a prevalent disease that affects the bone health of middle-aged and elderly women. The link between gut microbiota and bone health, known...
BACKGROUND
Postmenopausal osteoporosis is a prevalent disease that affects the bone health of middle-aged and elderly women. The link between gut microbiota and bone health, known as the gut-bone axis, has garnered widespread attention.
METHODS
We employed a two-sample Mendelian randomization approach to assess the associations between gut microbiota with osteoclasts and postmenopausal osteoporosis, respectively. Single nucleotide polymorphisms associated with the composition of gut microbiota were used as instrumental variables. By analyzing large-scale multi-ethnic GWAS data from the international MiBioGen consortium, and combining data from the eQTLGen consortium and the GEFOS consortium, we identified microbiota related to osteoclasts and postmenopausal osteoporosis. Key genes were further identified through MAGMA analysis, and validation was performed using single-cell data GSE147287.
RESULTS
The outcomes of this study have uncovered significant associations within the gut microbiome community, particularly with the Burkholderiales order, which correlates with both an increase in osteoclasts and a reduced risk of postmenopausal osteoporosis. with an odds ratio (OR) of 0.400, and a P-value of 0.011. Further analysis using single-cell data allowed us to identify two key genes, FMNL2 and SRBD1, that are closely linked to both osteoclasts and osteoporosis.
CONCLUSION
This study utilizing Mendelian randomization and single-cell data analysis, provides new evidence of a causal relationship between gut microbiota and osteoclasts, as well as postmenopausal osteoporosis. It was discovered that the specific microbial group, the Burkholderiales order, significantly impacts both osteoporosis and osteoclasts. Additionally, key genes FMNL2 and SRBD1 were identified, offering new therapeutic strategies for the treatment of postmenopausal osteoporosis.
Topics: Humans; Mendelian Randomization Analysis; Osteoporosis, Postmenopausal; Female; Osteoclasts; Gastrointestinal Microbiome; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Middle Aged; Bone and Bones; Aged
PubMed: 38883609
DOI: 10.3389/fendo.2024.1419566 -
Frontiers in Endocrinology 2024Osteoporosis (OP) is a chronic systemic bone metabolism disease characterized by decreased bone mass, microarchitectural deterioration, and fragility fractures. With the... (Review)
Review
Osteoporosis (OP) is a chronic systemic bone metabolism disease characterized by decreased bone mass, microarchitectural deterioration, and fragility fractures. With the demographic change caused by long lifespans and population aging, OP is a growing health problem. The role of miRNA in the pathogenesis of OP has also attracted widespread attention from scholars in recent years. Type H vessels are unique microvessels of the bone and have become a new focus in the pathogenesis of OP because they play an essential role in osteogenesis-angiogenesis coupling. Previous studies found some miRNAs regulate type H vessel formation through the regulatory factors, including platelet-derived growth factor-BB (PDGF-BB), hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and so on. These findings help us gain a more in-depth understanding of the relationship among miRNAs, type H vessels, and OP to find a new perspective on treating OP. In the present mini-review, we will introduce the role of type H vessels in the pathogenesis of OP and the regulation of miRNAs on type H vessel formation by affecting regulatory factors to provide some valuable insights for future studies of OP treatment.
Topics: Humans; MicroRNAs; Osteoporosis; Animals; Osteogenesis; Neovascularization, Pathologic; Bone and Bones; Microvessels
PubMed: 38883597
DOI: 10.3389/fendo.2024.1394785 -
Drug Design, Development and Therapy 2024While the role of aldosterone in bone metabolism is well established, the specific effects of the widely used aldosterone antagonist, spironolactone, on bone health are...
OBJECTIVE
While the role of aldosterone in bone metabolism is well established, the specific effects of the widely used aldosterone antagonist, spironolactone, on bone health are not fully understood. This study aimed to investigate the effects of spironolactone on osteoporosis and future fracture risk in middle-aged and elderly hypertensive patients, revealing its potential benefits for bone health.
METHODS
Propensity score matching was employed in this study to create matched groups of spironolactone users and non-users at a 1:4 ratio. We investigated the association between spironolactone use and the risk of osteoporosis using multivariate logistic regression analysis. Furthermore, we conducted multivariate linear regression analysis to explore the relationship between cumulative dosage and the FRAX score. Subgroup analysis was also performed to assess the effects under different stratification conditions.
RESULTS
In both pre-match and post-match analyses, multivariable logistic regression revealed a significant reduction in the risk of osteoporosis in the spironolactone usage group (pre-match: odds ratios [OR] 0.406, 95% confidence interval [CI], 0.280-0.588; post-match: OR 0.385, 95% CI, 0.259-0.571). Furthermore, post-match multivariable linear regression demonstrated a clear negative correlation between cumulative spironolactone dosage and the FRAX score. Subgroup analyses consistently supported these findings.
CONCLUSION
This study offers evidence supporting the significant positive impact of the antihypertensive drug spironolactone on bone health, resulting in a substantial reduction in the risk of osteoporosis and future fractures in hypertensive patients. Future research should consider conducting large-scale, multicenter, randomized controlled trials to further investigate the long-term effects of spironolactone on bone health in hypertensive patients.
Topics: Humans; Spironolactone; Hypertension; Osteoporosis; Female; Male; Aged; Middle Aged; Fractures, Bone; Risk Factors
PubMed: 38882049
DOI: 10.2147/DDDT.S466904 -
Cell Transplantation 2024Stem cells can transit between quiescence and activation, two metabolically distinct states. It is increasingly appreciated that cell metabolism assumes profound roles...
Stem cells can transit between quiescence and activation, two metabolically distinct states. It is increasingly appreciated that cell metabolism assumes profound roles in stem cell maintenance and tissue homeostasis. However, the lack of suitable models greatly hinders our understanding of the metabolic control of stem cell quiescence and activation. In the present study, we have utilized classical signaling pathways and developed a cell culture system to model reversible NSC quiescence and activation. Unlike activated ones, quiescent NSCs manifested distinct morphology characteristics, cell proliferation, and cell cycle properties but retained the same cell proliferation and differentiation potentials once reactivated. Further transcriptomic analysis revealed that extensive metabolic differences existed between quiescent and activated NSCs. Subsequent experimentations confirmed that NSC quiescence and activation transition was accompanied by a dramatic yet coordinated and dynamic shift in RNA metabolism, protein synthesis, and mitochondrial and autophagy activity. The present work not only showcases the broad utilities of this powerful NSC quiescence and activation culture system but also provides timely insights for the field and warrants further investigations.
Topics: Neural Stem Cells; Animals; Cell Differentiation; Cell Proliferation; Mice; Cell Culture Techniques; Cells, Cultured; Cell Cycle; Autophagy
PubMed: 38877676
DOI: 10.1177/09636897241259723 -
Nature Communications Jun 2024Interactions between osteolineage cells and myeloid cells play important roles in maintaining skeletal homeostasis. Herein, we find that osteolineage cells transfer...
Interactions between osteolineage cells and myeloid cells play important roles in maintaining skeletal homeostasis. Herein, we find that osteolineage cells transfer mitochondria to myeloid cells. Impairment of the transfer of mitochondria by deleting MIRO1 in osteolineage cells leads to increased myeloid cell commitment toward osteoclastic lineage cells and promotes bone resorption. In detail, impaired mitochondrial transfer from osteolineage cells alters glutathione metabolism and protects osteoclastic lineage cells from ferroptosis, thus promoting osteoclast activities. Furthermore, mitochondrial transfer from osteolineage cells to myeloid cells is involved in the regulation of glucocorticoid-induced osteoporosis, and glutathione depletion alleviates the progression of glucocorticoid-induced osteoporosis. These findings reveal an unappreciated mechanism underlying the interaction between osteolineage cells and myeloid cells to regulate skeletal metabolic homeostasis and provide insights into glucocorticoid-induced osteoporosis progression.
Topics: Animals; Mitochondria; Bone Resorption; Osteoclasts; Myeloid Cells; Osteoporosis; Mice; Ferroptosis; Glucocorticoids; Glutathione; Mice, Inbred C57BL; Cell Differentiation; Mice, Knockout; Humans; Male
PubMed: 38877020
DOI: 10.1038/s41467-024-49159-3 -
Geriatric Nursing (New York, N.Y.) Jun 2024This study aimed to understand how age, health status, and lifestyle impact bone mineral density (BMD) in middle-aged and older adults, focusing on predicting...
PURPOSE
This study aimed to understand how age, health status, and lifestyle impact bone mineral density (BMD) in middle-aged and older adults, focusing on predicting osteoporosis risk.
METHODS
This study included 2836 participants aged 50-88 from the Health Improvement Program of Bone (HOPE) conducted from 2021 to 2023. We used logistic regression to make a prediction tool. Then checked its accuracy and reliability using receiver operating characteristic (ROC) and calibration curves.
RESULTS
Factors like age, body weight, prior fractures, and smoking were independently found to affect BMD T-score distribution in men. In women, age and body weight were identified as independent factors influencing BMD T-score distribution. A nomogram was created to visually illustrate these predictive relationships.
CONCLUSIONS
The nomogram proved highly accurate in identifying men aged 50 and above and postmenopausal women based on their BMD T-score distribution, improving clinical decision-making and patient care in osteoporosis evaluation and treatment.
PubMed: 38875761
DOI: 10.1016/j.gerinurse.2024.06.010