Melatonin Improves the Resistance of Oxidative Stress-Induced Cellular Senescence in Osteoporotic Bone Marrow Mesenchymal Stem Cells.

Accumulation of senescent bone marrow-derived mesenchymal stem cells (BMMSCs) has led to an age-related bone loss. However, the role of stem cell senescence in estrogen deficiency-induced osteoporosis remains elusive. Though melatonin plays a vital role in bone metabolism regulation, the underlying mechanisms of melatonin-mediated antiosteoporosis are partially elucidated. Therefore, this study purposed to explore (1) whether estrogen deficiency causes cellular senescence of BMMSCs, and if so, (2) the potential of melatonin in preventing bone loss via senescence signaling inhibition. BMMSCs derived from ovariectomized (OVX) rats (OVX BMMSCs) showed an impaired osteogenic capacity, albeit having comparable levels of senescence biomarkers than the sham cells. When exposed to low levels of hydrogen peroxide (H2O2), OVX BMMSCs rapidly exhibited senescence-associated phenotypes such as the increased activity of senescence-associated ß-galactosidase (SA-ß-gal) and upregulation of cell cycle inhibitors. Notably, the in vitro treatment with melatonin hindered H2O2-induced senescence in OVX BMMSCs and restored their osteogenic capacity. Treatment with either SIRT1 inhibitor (sirtinol) or melatonin receptor antagonists (luzindole and 4-P-PDOT) eliminated melatonin protective effects, thus indicating its potential in preventing stem cell senescence via SIRT1 activation through the melatonin membrane receptors. Following in vivo intravenous administration with melatonin, it successfully protected the bone microstructure and preserved the antisenescence property of BMMSCs in OVX rats. Collectively, our findings demonstrated that melatonin protected against estrogen deficiency-related bone loss by improving the resistance of BMMSCs to cellular senescence. Therefore, melatonin-mediated antisenescence effect on stem cells provides vital information to facilitate the development of a novel and effective strategy for treating postmenopausal OP.

The effects of dementia on the prognosis and mortality of hip fracture surgery: a systematic review and meta-analysis.

OBJECTIVES: Dementia is a common mental disorder that affects the life quality in elders. Recently, emerging studies reported the negative impacts of dementia on prognosis after hip surgeries. However, the integrated and reliable role of dementia in hip surgery is not illustrated. METHODS: We searched the relevant literatures before June 2020 and extracted the data that met the inclusion criteria. The influence of dementia on postoperative walking ability, complications including infection, cardiovascular complications, hip dislocation, delirium, and respiratory complications, and survival rate at different periods were evaluated. Qualitative and quantitative analysis were conducted using Review Manager Version 5.3. RESULTS: The meta-analysis enrolled a total of 30 studies with 1,037,049 patients. The pooled results revealed that there were significant negative impacts of dementia on the recovery of postoperative walking ability, postoperative infection, hip dislocation, delirium and respiratory complications and mortality at different periods. CONCLUSIONS: Dementia is a crucial risk factor for the poor prognosis after hip fracture surgery. Therefore, when making clinical strategies for hip fracture patients with dementia, countermeasures for possible complications should be generated.

Identification of Key Genes and Pathways in Osteoarthritis via Bioinformatic Tools: An Updated Analysis.

OBJECTIVE: Osteoarthritis (OA) is a severe and common degenerative disease; however, the exact pathology of OA is undefined. Our study is designed to investigate the underlying molecular mechanism of OA with bioinformatic tools. DESIGN: Three updated GEO datasets: GSE55235, GSE55457, and GSE82107 were selected for data analyzing. R software was utilized to screen and confirm the candidate differentially expressed genes in the development of OA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway were performed to identify the enriched GO terms and signaling pathways. Protein and protein interaction (PPI) models were built to observe the connected relationship among each potential protein. RESULTS: A total of 113 upregulated genes and 161 downregulated genes were found by integrating 3 datasets. GO enrichment indicated that cell differentiation, cellular response to starvation, and negative regulation of phosphorylation were important biological processes. KEGG enrichment indicated that FoxO, IL-17 signaling pathways, and osteoclast differentiation mainly participated in the progression of OA. Combining the molecular function and PPI results, ubiquitylation was identified as a pivotal bioactive reaction involved in OA. CONCLUSION: Our study provided updated candidate genes and pathways of OA, which may benefit further research and treatment for OA.

Which is the most effective treatment for lumbar spinal stenosis: Decompression, fusion, or interspinous process device? A Bayesian network meta-analysis.

OBJECTIVE: To compare the clinical efficacy, complications, and reoperation rates among three major treatments for lumbar spinal stenosis (LSS): decompression, fusion, and interspinous process device (IPD), using a Bayesian network meta-analysis. MATERIALS AND METHODS: Databases including Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science were used for the literature search. Randomized Controlled Trials (RCTs) with three treatment methods were reviewed and included in the study. R software (version 3.6.0), Stata (version 14.0), and Review Manager (version 5.3) were used to perform data analysis. RESULTS: A total of 10 RCTs involving 1254 patients were enrolled in the present study and each study met an acceptable quality according to our quality assessment described later. In direct comparison, IPD exhibited a higher incidence of reoperation than fusion (OR â€‹= â€‹2.93, CI: 1.07-8.02). In indirect comparison, the rank of VAS leg (from best to worst) was as follows: IPD (64%) â€‹> â€‹decompression (25%) â€‹> â€‹fusion (11%), and the rank of ODI (from best to worst) was: IPD (84%) â€‹> â€‹fusion (13%) â€‹> â€‹decompression (4%). IPD had the lowest incidence of complications; the rank of complications (from best to worst) was: IPD (60%) â€‹> â€‹decompression (27%) â€‹> â€‹fusion (14%). However, for the rank of reoperation, fusion showed the best results (from best to worst): fusion (79%) â€‹> â€‹decompression (20%) â€‹> â€‹IPD (1%). Consistency tests at global and local level showed satisfactory results and heterogeneity tests using loop text indicated a favorable stability. CONCLUSION: The present study preliminarily indicates that non-fusion methods including decompression and IPD are optimal choices for treating LSS, which achieves favorable clinical outcomes. IPD exhibits a low incidence of complications, but its high rate of reoperation should be treated with caution. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: For the treatment of LSS, several procedures including decompression, fusion, and IPD have been reported. However, each method has its own advantages and disadvantages. To date, the golden standard treatment for LSS is still controversial. In this network meta-analysis, our results demonstrate that both decompression and IPD obtain satisfactory clinical effects for LSS. IPD is accompanied with a low incidence of complications, however, its high rate of reoperation should be acknowledged with discretion.

Predictors of postoperative acute kidney injury in patients undergoing hip fracture surgery: A systematic review and meta-analysis.

BACKGROUND: The present study aimed to summarize the predictors of acute kidney injury (AKI) in patients after hip surgery. METHODS: A literature search was performed using PubMed, EMBASE, Cochrane Library, and Web of Science for studies assessing the predictors of AKI after hip fracture surgery. Pooled odds ratio (OR) and mean difference (MD) of those who experienced AKI compared to those who did not were calculated for each variable. Evidence was assessed using the Newcastle-Ottawa Scale. RESULTS: Ten studies with 34 potential factors were included in the meta-analysis. In the primary analysis, 12 factors were associated with AKI, comprising males (OR 1.25; 95% confidence interval (CI) 1.14-1.36), advanced age (MD 2.28; 95% CI 0.80-3.75), myocardial infarction (OR 1.39; 95% CI 1.18-1.63), hypertension (OR 1.46; 95% CI 1.13-1.89), diabetes (OR 1.84; 95% CI 1.40-2.42), chronic kidney disease (OR 3.66; 95% CI 2.21-6.07), hip arthroplasty (OR 1.35; 95% CI 1.22-1.50), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers use (OR 2.28; 95% CI 1.68-3.08), more intraoperative blood loss (MD 44.06; 95% CI 2.88-85.24), higher preoperative blood urea nitrogen levels (MD 5.29; 95% CI 3.38-7.20), higher preoperative serum creatinine levels (MD 0.4; 95% CI 0.26-0.53), and lower preoperative estimated glomerular filtration rate (MD -19.59; 95% CI -26.92--12.26). Another 13 factors related to AKI in individual studies were identified in the systematic review. CONCLUSION: Related prophylaxis strategies should be implemented in patients involved with the above-mentioned characteristics to prevent AKI after hip surgery.

Comparison of cervical disc arthroplasty and anterior cervical discectomy and fusion for the treatment of cervical disc degenerative diseases on the basis of more than 60 months of follow-up: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis was designed to investigate the long-term efficacy and safety between cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) in treating cervical disc degenerative diseases (CDDDs). METHODS: Literature search was performed on Pubmed, Embase, Cochrane Library, and Web of Science before Jan 2019. Surgical details, clinical outcomes, range of motion (ROM), complications, and reoperation rates between CDA and ACDF groups were compared and analyzed. A fixed- or random-effects model was applied based on different heterogeneity. STATA (Version 11.0) software was used to perform data analysis. RESULTS: A total of 13 randomized controlled trial studies with more than 60 months of follow-up (mean 83.1 months) were enrolled in this meta-analysis. Pool results indicated that the CDA group exhibited significantly better outcomes in clinical scores (odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.15-2.08, p = 0.004) and preservation of ROM (mean difference = 1.77, 95% CI: 1.60-1.95, p < 0.001) than the ACDF group. Meanwhile, the incidence of adjacent segment disease (ASD) (OR = 0.51, 95% CI: 0.35-0.76, p = 0.001) and occurrence of reoperation (OR = 0.41, 95% CI: 0.25-0.69, p = 0.001) were lower in the CDA group than in the ACDF group. CONCLUSIONS: At long-term follow-up, CDA showed better efficacy in terms of clinical outcomes, ROM, ASD, and reoperation than ACDF for treating CDDDs. However, our results require further validation in large-sample and high-quality studies.

Melatonin restores the osteoporosis-impaired osteogenic potential of bone marrow mesenchymal stem cells by preserving SIRT1-mediated intracellular antioxidant properties.

Postmenopausal osteoporosis (OP) is one of the most common bone diseases that affects millions of aging women. Reduced osteogenesis and increased oxidative stress have been implicated in bone marrow mesenchymal stem cells (BMMSCs) derived from OP patients. Melatonin has shown positive effects on osteoblast differentiation and bone formation; however, it was unknown whether melatonin could restore OP-impaired osteogenic potential of BMMSCs and what the underlying mechanisms entailed. The objective of this study is to investigate (1) whether melatonin can restore the impaired osteogenic potential of OP BMMSCs by preserving their antioxidant functions, and if so, (2) whether intravenous administration of melatonin can prevent OP-induced bone loss in ovariectomized (OVX) rats. Ovariectomies were performed in female rats and BMMSCs were isolated from the osteoporotic rats 3 months later. In vitro treatment with melatonin successfully improved the osteogenic differentiation of OP BMMSCs, as evidenced by increased levels of matrix mineralization and osteoblast-specific genes. In melatonin-treated OP BMMSCs, intracellular oxidative stress was significantly attenuated, while levels of intracellular antioxidant enzymes were noticeably up-regulated - particularly superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPX1). Silent information regulator type 1 (SIRT1) was involved in the melatonin-mediated recovery of osteogenesis and antioxidant functions. Meanwhile, in vivo injections of melatonin via the tail vein successfully ameliorated the bone micro-architecture in ovariectomized rat femurs. Further experiments confirmed that BMMSCs derived from melatonin-treated OVX rats exerted well-preserved antioxidant properties and osteogenic potential. Our findings demonstrate that the administration of melatonin is a promising strategy for treating patients with postmenopausal OP by preserving the antioxidant properties and osteogenic potential of their BMMSCs.

Reperfusion Revision Surgery for Augmented Vertebral Nonunion with Movable Cement.

BACKGROUND: Osteoporotic vertebral nonunion is a special type of osteoporotic vertebral fracture and can gain satisfactory clinical outcomes using vertebral augmentation. In the rare occurrence that augmented vertebral nonunion occurs postoperatively, pedicle screw fixation is the primary strategy. However, is a different method like the second shot of cement reliable? The purpose of this study is to introduce the reperfusion revision surgery strategy for treatment of osteoporotic vertebral nonunion. CASE DESCRIPTION: An 80-year-old female patient experienced vertebral re-nonunion in situ after receiving kyphoplasty at the T11 vertebrae. During revision surgery, we tried a new, minimally invasive surgical method in which we inserted cement into the intravertebral cleft around the movable cement without obvious leakage. Special bone cement perfusion techniques (incremental temperature cement delivery and secondary cement preparation based-perfusion and blocking) were used. The cement tail was performed to increase the anchor and fastness between the cement and vertebral body. CONCLUSIONS: The patient gained immediate pain relief and vertebral stability after the revision surgery. A 2-year postoperative radiograph and follow-up showed sufficient vertebral height and clinical outcomes. Using special puncture and bone cement perfusion techniques, reperfusion revision surgery in situ is an effective strategy for the treatment of vertebral re-nonunion.

Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation via Targeting MicroRNA-140.

Osteoarthritis (OA) is characterized by the progressive destruction of articular cartilage, which is involved in the imbalance between extracellular matrix (ECM) synthesis and degradation. MicroRNA-140-5p (miR-140) is specifically expressed in cartilage and plays an important role in OA-induced matrix degradation. The aim of this study was to investigate (1) whether intra-articular injection of melatonin could ameliorate surgically induced OA in mice and (2) whether melatonin could regulate matrix-degrading enzymes at the posttranscriptional level by targeting miR-140. In an in vitro OA environment induced by interleukin-1 beta (IL-1ß), melatonin treatment improved cell proliferation of human chondrocytes, promoted the expression of cartilage ECM proteins (e.g., type II collagen and aggrecan), and inhibited the levels of IL-1ß-induced proteinases, such as matrix metalloproteinase 9 (MMP9), MMP13, ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4), and ADAMTS5. Both the microarray and polymerase chain reaction (PCR) experiments revealed that miR-140 was a melatonin-responsive microRNA and melatonin upregulated miR-140 expression, which was suppressed by IL-1ß stimulation. In vivo experiments demonstrated that intra-articular injection of melatonin prevented disruptions of cartilage matrix homeostasis and successfully alleviated the progression of surgery-induced OA in mice. Transfection of miR-140 antagomir completely counteracted the antiarthritic effects of melatonin by promoting matrix destruction. Our findings demonstrate that melatonin protects the articular cartilage from OA-induced degradation by targeting miR-140, and intra-articular administration of melatonin may benefit patients suffering from OA.

Intermediate screws or kyphoplasty: Which method of posterior short-segment fixation is better for treating single-level thoracolumbar burst fractures?

PURPOSE: To compare intermediate screws (IS) with kyphoplasty (KP) in posterior short-segment fixation (PSSF) for patients with single-level thoracolumbar burst fractures. METHODS: Between 2010 and 2016, 1465 patients were retrospectively reviewed; 48 patients were enrolled with a minimal follow-up of 2 years. Perioperative and functional outcomes were compared. The regional Cobb angle (CA) was included in radiographic analysis. Implant failures or CA correction loss over 10° were regarded as surgical failures. Multiple linear regression was performed to investigate the risk factors of kyphosis recurrence. RESULTS: Fluoroscopic time (23.7 ± 3.6 vs. 79.3 ± 12.1 s, p < 0.001), operative time (109.6 ± 13.1 vs. 123.8 ± 19.0 min, p = 0.006) and blood loss (104.6 ± 34.9 vs. 129.1 ± 21.7 ml, p = 0.005) were all lower in the IS group. The KP group had lower Visual Analogue Scale scores (3.3 ± 0.9 vs. 2.7 ± 0.8, p = 0.028) and greater anterior body height (ABH) (30.3 ± 9.0 vs. 36.3 ± 11.0%, p = 0.044) after surgery, and less correction loss (5.6 ± 2.7 vs. 0.4 ± 1.2%, p < 0.001). Both groups had a CA correction loss of 4° with a 10% failure rate. The A3 Magerl subclassification, smaller preoperative ABH and smaller postoperative CA had positive correlations with CA correction loss. CONCLUSION: PSSF with KP provides better back pain relief, greater ABH reduction and less correction loss, while IS has the advantages of less operative time, fluoroscopic time and blood loss. Magerl subclassification of burst fracture is a potential predictor for recurrent kyphosis. Reducing fractured vertebral body height rather than segmental curvature may be more important in PSSF. STUDY DESIGN: Retrospective, non-randomized controlled study. These slides can be retrieved under Electronic Supplementary Material.