BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complet...BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.展开更多
The bone marrow microenvironment is critical for the maintenance and functionality of stem/progenitor cells,which are essential for bone development and regeneration.However,the composition and potential use of bone m...The bone marrow microenvironment is critical for the maintenance and functionality of stem/progenitor cells,which are essential for bone development and regeneration.However,the composition and potential use of bone marrow interstitial fluid have not been well explored.In this study,we report the role of neonatal bovine bone marrow interstitial fluid(NBIF)in enhancing the bone regeneration capacity of human bone marrow mesenchymal stem cells(hBMSCs).Unlike adult bovine bone marrow interstitial fluid(ABIF),NBIF-fed hBMSCs exhibit enhanced self-renewal and osteogenic potential and bone marrow homing ability,along with transcriptome changes as compared to hBMSCs cultured in standard fetal bovine serum(FBS)supplemented medium.Mass spectrometry analysis reveals that multiple secreted factors associated with tissue repair and bone development are enriched in NBIF compared to FBS and ABIF.The combined use of NBIF-enriched Nerve Growth Factor(NGF),Lactoferrin(LTF),and High Mobility Group Protein B1(HMGB1),together with Insulin-Like Growth Factor 1(IGF1)for culturing hBMSCs in the presence of FBS can enhance osteogenic potential and bone marrow homing ability,mimicking NBIF's effects.These findings highlight the role of interstitial fluid in the bone marrow microenvironment and its potential to optimize stem cell-based therapies.展开更多
Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,mar...Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.展开更多
Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant i...Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant interest in bone tissue engineering(BTE)because of their abundant availability,minimally invasive harvesting procedures,and robust differentiation potential into osteogenic lineages.Unlike bone marrow-derived mesenchymal stem cells,AD-MSCs can be easily obtained in large quantities,making them appealing alternatives for therapeutic applications.This review explores hydrogels containing polymers,such as chitosan,collagen,gelatin,and hyaluronic acid,and their composites,tailored for BTE,and emphasizes the importance of these hydrogels as scaffolds for the delivery of AD-MSCs.Various hydrogel fabrication techniques and biocompatibility assessments are discussed,along with innovative modifications to enhance osteogenesis.This review also briefly outlines AD-MSC isolation methods and advanced embedding techniques for precise cell placement,such as direct encapsulation and three-dimensional bioprinting.We discuss the mechanisms of bone regeneration in the AD-MSC-laden hydrogels,including osteoinduction,vascularization,and extracellular matrix remodeling.We also review the preclinical and clinical applications of AD-MSC-hydrogel systems,emphasizing their success and limitations.In this review,we provide a comprehensive overview of AD-MSC-based hydrogel systems to guide the development of effective therapies for bone regeneration.展开更多
BACKGROUND Anterior cruciate ligament(ACL)reconstruction using bone-patellar tendon-bone(BPTB)autografts remains the gold standard for young,active individuals due to its superior biomechanical strength and bone-to-bo...BACKGROUND Anterior cruciate ligament(ACL)reconstruction using bone-patellar tendon-bone(BPTB)autografts remains the gold standard for young,active individuals due to its superior biomechanical strength and bone-to-bone healing.However,donor site morbidity,particularly anterior knee pain(AKP),limits its utilization despite its advantages.Various techniques have been proposed to reduce AKP,but they show variable outcomes and several limitations.AIM To assess the incidence and severity of AKP following BPTB ACL reconstruction using an autologous bone grafting technique.METHODS We conducted a retrospective observational study of 24 patients aged 20-45 years,who had primary ACL reconstruction with BPTB grafts.During surgery,autologous cancellous bone generated from tunnel drilling was used to fill the patellar and tibial donor site voids after graft fixation.All patients were followed up for at least twelve months.Using the Kujala Anterior Knee Pain Score,clinical outcomes were evaluated,including the pain-specific subcomponent.RESULTS With scores ranging from 86 to 100,the average overall Kujala score was 95.67±4.01.No patient scored below 85.There was no complication such as patellar fracture,tibial tuberosity fracture,or infection.Grouped data showed 20.8%of patients scored 100,whereas 54.2%scored between 95 and 99,and 25%scored between 86 and 94.One patient(4.2%)had an 8/10 pain subcomponent,whereas 23 patients(95.8%)had a 10/10.CONCLUSION This procedure is easy to incorporate into routine surgical practice,cost-effective and reproducible without requiring extra incisions or raising the patient’s surgical expenses.Excellent short-term results back up this technique.展开更多
BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.A...BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.展开更多
Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological b...Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological benefits in cancer therapy,the specific molecular mechanisms and their influence on vitamin metabolism pathways in bone malignancies are not well defined.Methods:We conducted an integrated analysis of prognostic genes and survival outcomes in osteosarcoma,focusing on the expression of GPC2 and its correlation with tumor progression and patient survival rates.In order to explore the therapeutic relevance of 20 bioactive compounds extracted from Huangqi,molecular docking was performed to quantify their binding free energies to the GPC2 receptor,shedding light on their potential affinity and biological activity.Furthermore,the expression levels of GPC2 in tumor cells compared to normal cells were analyzed using qRT-PCR.Additionally,the effects of GPC2 overexpression and silencing on cellular viability,apoptotic response,and migratory capacity were systematically investigated.Results:In our study,GPC2 emerged as a significant prognostic gene,where high expression levels correlated with reduced overall survival.The molecular interactions between Astragalus components and the GPC2 receptor reveal compounds with strong affinity,suggesting their potential as effective targets.Furthermore,the overexpression of GPC2 enhanced tumor cell viability and migration,while its knockdown resulted in decreased cell viability and expanded apoptosis.Conclusion:This study demonstrates that Huangqi-derived components may exert anticancer effects by regulating the expression of the GPC2 gene within the vitamin metabolism pathway.These findings offer new insights into the therapeutic potential of traditional herbal medicine for improving bone tumor prognosis and provide a scientific foundation for future translational research.展开更多
The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is la...The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is largely unknown.In patients who underwent discontinuation after multiple injections of denosumab,the levels of tartrate-resistant acid phosphatase 5b increased compared to pretreatment levels,indicating a phenomenon known as“overshoot.”The rate of decrease in bone mineral density during the withdrawal period was higher than the rate of decrease associated with aging,suggesting that the physiological bone metabolism had broken down.Overshoot and significant bone loss were also observed in mice receiving continuous administration of anti-RANKL antibody after treatment was interrupted,resembling the original pathology.In mice long out of overshoot,bone resorption recovered,but osteoblast numbers and bone formation remained markedly reduced.The bone marrow exhibited a significant reduction in stem cell(SC)antigen 1-and platelet-derived growth factor receptor alpha-expressing osteoblast progenitors(PαS cells)and alkaline phosphatase-positive early osteoblasts.Just before the overshoot phase,the osteoclast precursor cell population expands and RANKL-bearing extracellular vesicles(EVs)became abundant in the serum,leading to robust osteoclastogenesis after cessation of anti-RANKL treatment.Thus,accelerated bone resorption due to the accumulation of RANKLbearing EVs and long-term suppression of bone formation uncoupled from bone resorption leads to the severe bone loss characteristic of denosumab discontinuation.展开更多
Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indic...Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indicate that bone and brain can influence each other’s homeostasis via multiple pathways,yet there is a dearth of systematic reviews in this area.This review comprehensively examines interactions across three key areas:the influence of bone-derived factors on brain function,the effects of brain-related diseases or injuries(BRDI)on bone health,and the concept of skeletal interoception.Additionally,the review discusses innovative approaches in biomaterial design inspired by bone-brain interaction mechanisms,aiming to facilitate bonebrain interactions through materiobiological effects to aid in the treatment of neurodegenerative and bone-related diseases.Notably,the integration of artificial intelligence(AI)in biomaterial design is highlighted,showcasing AI’s role in expediting the formulation of effective and targeted treatment strategies.In conclusion,this review offers vital insights into the mechanisms of bone-brain interaction and suggests advanced approaches to harness these interactions in clinical practice.These insights offer promising avenues for preventing and treating complex diseases impacting the skeleton and brain,underscoring the potential of interdisciplinary approaches in enhancing human health.展开更多
As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially ...As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially in the context of an imbalance between osteoblast and osteoclast activities.Therefore,the development of new biomaterials has become the key.This article reviews various design strategies and their advantages and disadvantages for biomaterials aimed at osteoporotic bone defects.Overall,current research progress indicates that innovative design,functionalization,and targeting of materials can significantly enhance bone regeneration under osteoporotic conditions.By comprehensively considering biocompatibility,mechanical properties,and bioactivity,these biomaterials can be further optimized,offering a range of choices and strategies for the repair of osteoporotic bone defects.展开更多
Large bone defects in load-bearing bone can result from tumor resection,osteomyelitis,trauma,and other factors.Although bone has the intrinsic potential to self-repair and regenerate,the repair of large bone defects w...Large bone defects in load-bearing bone can result from tumor resection,osteomyelitis,trauma,and other factors.Although bone has the intrinsic potential to self-repair and regenerate,the repair of large bone defects which exceed a certain critical size remains a substantial clinical challenge.Traditionally,repair methods involve using autologous or allogeneic bone tissue to replace the lost bone tissue at defect sites,and autogenous bone grafting remains the“gold standard”treatment.However,the application of traditional bone grafts is limited by drawbacks such as the quantity of extractable bone,donor-site morbidities,and the risk of rejection.In recent years,the clinical demand for alternatives to traditional bone grafts has promoted the development of novel bone-grafting substitutes.In addition to osteoconductivity and osteoinductivity,optimal mechanical properties have recently been the focus of efforts to improve the treatment success of novel bone-grafting alternatives in load-bearing bone defects,but most biomaterial synthetic scaffolds cannot provide sufficient mechanical strength.A fundamental challenge is to find an appropriate balance between mechanical and tissue-regeneration requirements.In this review,the use of traditional bone grafts in load-bearing bone defects,as well as their advantages and disadvantages,is summarized and reviewed.Furthermore,we highlight recent development strategies for novel bone grafts appropriate for load-bearing bone defects based on substance,structural,and functional bionics to provide ideas and directions for future research.展开更多
Bone Research is an open access,fully peer-reviewed journal publishing the foremost progress and novel understanding of all aspects of bone science.The journal highlights the breakthrough discoveries in basic and clin...Bone Research is an open access,fully peer-reviewed journal publishing the foremost progress and novel understanding of all aspects of bone science.The journal highlights the breakthrough discoveries in basic and clinical aspects of bone biology,pathophysiology and regeneration,as well as other significant findings related to bone.展开更多
BACKGROUND Demineralized bone matrix(DBM)is a commonly utilized allogenic bone graft substitute to promote osseous union.However,little is known regarding outcomes following DBM utilization in foot and ankle surgical ...BACKGROUND Demineralized bone matrix(DBM)is a commonly utilized allogenic bone graft substitute to promote osseous union.However,little is known regarding outcomes following DBM utilization in foot and ankle surgical procedures.AIM To evaluate the clinical and radiographic outcomes following DBM as a biological adjunct in foot and ankle surgical procedures.METHODS During May 2023,the PubMed,EMBASE and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following DBM for the management of various foot and ankle pathologies.Data regarding study characteristics,patient demographics,subjective clinical outcomes,radiological outcomes,complications,and failure rates were extracted and analyzed.In addition,the level of evidence(LOE)and quality of evidence(QOE)for each individual study was also assessed.Thirteen studies were included in this review.RESULTS In total,363 patients(397 ankles and feet)received DBM as part of their surgical procedure at a weighted mean follow-up time of 20.8±9.2 months.The most common procedure performed was ankle arthrodesis in 94 patients(25.9%).Other procedures performed included hindfoot fusion,1st metatarsophalangeal joint arthrodesis,5th metatarsal intramedullary screw fixation,hallux valgus correction,osteochondral lesion of the talus repair and unicameral talar cyst resection.The osseous union rate in the ankle and hindfoot arthrodesis cohort,base of the 5th metatarsal cohort,and calcaneal fracture cohort was 85.6%,100%,and 100%,respectively.The weighted mean visual analog scale in the osteochondral lesions of the talus cohort improved from a pre-operative score of 7.6±0.1 to a post-operative score of 0.4±0.1.The overall complication rate was 27.2%,the most common of which was non-union(8.8%).There were 43 failures(10.8%)all of which warranted a further surgical procedure.CONCLUSION This current systematic review demonstrated that the utilization of DBM in foot and ankle surgical procedures led to satisfactory osseous union rates with favorable wound complication rates.Excellent outcomes were observed in patients undergoing fracture fixation augmented with DBM,with mixed evidence supporting the routine use of DBM in fusion procedures of the ankle and hindfoot.However,the low LOE together with the low QOE and significant heterogeneity between the included studies reinforces the need for randomized control trials to be conducted to identify the optimal role of DBM in the setting of foot and ankle surgical procedures.展开更多
BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in pati...BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in patients with ACS using a continuous glucose monitoring system(CGMS)and dual-energy X-ray absorptiometry(DXA).METHODS Patients diagnosed with ACS,including Cushing syndrome,mild ACS(MACS),and nonfunctional adrenal incidentaloma(NFAI),were recruited for this study.Glucose variability and glycemic status were assessed using CGMS.Regional bone mineral content(BMC),bone mineral density(BMD),and bone area(BA)were evaluated using DXA.CGMS-and DXA-derived parameters were compared across the subgroups of ACS.Correlation analysis was performed to examine relationships between varying degrees of cortisol secretion,measured by cortisol after 1 mg overnight dexamethasone suppression test(DST)or 24-hour urine free cortisol(24h UFC),and CGMS-or DXA-derived parameters.RESULTS A total of 64 patients with ACS were included in this study:19 with Cushing syndrome,11 with MACS,and 34 with NFAI.Glucose variability,time above range(TAR),and time in range(TIR)along with specific areal BMC,BMD,and BA,differed significantly between groups of Cushing syndrome and NFAI.A significant positive correlation was observed between glucose variability or TAR and cortisol after 1 mg overnight DST or 24h UFC.By contrast,TIR,along with regional BMC,BMD,and BA,were negatively correlated with varying degrees of cortisol secretion.CONCLUSION Glucose and bone metabolism impairments are on a continuum alteration from NFAI to MACS and Cushing syndrome.Prompt attention should be given to these patients with ACS,especially those with mild hormone secretion.Parameters of glucose variability and glycemic status along with bone condition in regions rich in cancellous bone will provide valuable information.展开更多
BACKGROUND Tibial plateau fractures often require structural support for metaphyseal defects created during articular reduction.While autologous bone grafting has been utilized as the gold standard,bone substitutes of...BACKGROUND Tibial plateau fractures often require structural support for metaphyseal defects created during articular reduction.While autologous bone grafting has been utilized as the gold standard,bone substitutes offer advantages including reduced donor site morbidity.Our meta-analysis evaluated the comparative efficacy of these approaches across clinical and operative outcomes.AIM To conduct a systematic review and meta-analysis of randomized controlled trials comparing autologous bone grafts with bone substitutes for tibial plateau fractures.METHODS We conducted a systematic review and meta-analysis of randomized controlled trials comparing autologous bone grafts with bone substitutes for tibial plateau fractures.Primary outcomes included joint depression,secondary collapse rate,operative time,blood loss,and infection rate.Subgroup analyses were performed by fracture complexity,geographic region,and methodological factors.In addition to that,we also developed a combined outcome score integrating structural,procedural,and complication domains.RESULTS Seven randomized controlled trials with 424 patients(296 bone substitute,128 autograft)were included.No significant differences in joint depression or secondary collapse were observed across fracture complexity categories.Geographic variations were evident,with Western studies showing significantly higher risk of secondary collapse with autografts(risk ratio=1.45,P value=0.02).Both Western and Asian studies have demonstrated significantly reduced blood loss with bone substitutes(70-90 mL less),while operative time reduction was more significant in the Asian studies(23.65 vs 8.00 minutes,P value=0.04 for subgroup difference).The combined outcome score(standardized effect size-0.2481)favored bone substitutes,primarily due to procedural advantages.CONCLUSION Bone substitutes provide similar structural outcomes to autologous bone grafts while having better procedural advantages in tibial plateau fracture management.These findings support bone substitutes as a viable option across fracture patterns.Future studies should focus on specific bone substitute formulations and cost-effectiveness analyses.展开更多
BACKGROUND Thrombotic microangiopathy(TMA)is an acute syndrome characterized by microangiopathic hemolytic anemia,thrombocytopenia,and multi-organ dysfunction due to the microcirculation of platelet thrombi.Cancer-ass...BACKGROUND Thrombotic microangiopathy(TMA)is an acute syndrome characterized by microangiopathic hemolytic anemia,thrombocytopenia,and multi-organ dysfunction due to the microcirculation of platelet thrombi.Cancer-associated TMA is a rare and fatal complication,which often occurs during cancer remission.It is frequently misdiagnosed because of limited clinical awareness.CASE SUMMARY A middle-aged female patient presented to our clinic with a 15-days history of back pain,15 months post-gastrectomy.Cancer-associated TMA was confirmed through bone marrow aspiration,biopsy,and imaging.The patient received intermittent transfusions,fluids,nutrition,and microcirculation therapy with partial coagulation improvement.The family refused intensive care unit admission and plasma exchange,preferring palliative care.The patient died of cerebral hemorrhage and herniation due to disease progression.This case indicates that TMA may serve as an early manifestation of various malignancies,particularly gastric cancer.However,it is often misdiagnosed.Its pathogenesis is not well understood and needs to be further investigated.Currently,no standardized treatment have been developed.Plasma exchange is the only intervention available,though other therapies may also be effective.CONCLUSION In this case of gastric signet-ring cell carcinoma complicated by TMA,the patient achieved transient remission with supportive care but died following treatment discontinuation.Further studies are needed to elucidate the pathological mechanisms and therapeutic strategies for cancer-associated TMA.展开更多
Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of...Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.展开更多
The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,...The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.展开更多
Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was dimini...Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.展开更多
Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal t...Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal therapy hydrogel with a pulsed drug delivery mechanism.The system is predicated on a hydrogel matrix that is thermally responsive,characteristic of bone defect sites,facilitating controlled and site-specific drug release.The cornerstone of this system is the incorporation of mild photothermal nanoparticles,which are activated within the temperature range of 40–43°C,thereby enhancing the precision and efficacy of drug delivery.Our findings demonstrate that the photothermal response significantly augments the localized delivery of therapeutic agents,mitigating systemic side effects and bolstering efficacy at the defect site.The synchronized pulsed release,cooperated with mild photothermal therapy,effectively addresses infection control,and promotes bone regeneration.This approach signifies a considerable advancement in the management of infectious bone defects,offering an effective and patient-centric alternative to traditional methods.Our research endeavors to extend its applicability to a wider spectrum of tissue regeneration scenarios,underscoring its transformative potential in the realm of regenerative medicine.展开更多
基金Supported by Russian Science Foundation Grant,No.24-15-00185.
文摘BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.
基金financially supported by the Guangzhou National Laboratory(grant#GZNL2025C02022,A.M.#QNPG2317,J.Z.)partially by the National Natural Science Foundation of China(31988101)。
文摘The bone marrow microenvironment is critical for the maintenance and functionality of stem/progenitor cells,which are essential for bone development and regeneration.However,the composition and potential use of bone marrow interstitial fluid have not been well explored.In this study,we report the role of neonatal bovine bone marrow interstitial fluid(NBIF)in enhancing the bone regeneration capacity of human bone marrow mesenchymal stem cells(hBMSCs).Unlike adult bovine bone marrow interstitial fluid(ABIF),NBIF-fed hBMSCs exhibit enhanced self-renewal and osteogenic potential and bone marrow homing ability,along with transcriptome changes as compared to hBMSCs cultured in standard fetal bovine serum(FBS)supplemented medium.Mass spectrometry analysis reveals that multiple secreted factors associated with tissue repair and bone development are enriched in NBIF compared to FBS and ABIF.The combined use of NBIF-enriched Nerve Growth Factor(NGF),Lactoferrin(LTF),and High Mobility Group Protein B1(HMGB1),together with Insulin-Like Growth Factor 1(IGF1)for culturing hBMSCs in the presence of FBS can enhance osteogenic potential and bone marrow homing ability,mimicking NBIF's effects.These findings highlight the role of interstitial fluid in the bone marrow microenvironment and its potential to optimize stem cell-based therapies.
基金supported by NIH grants NIH/NIA R01AG069401(to L.Q.)NIH/NHLBI U54HL165442(to K.T.)P30AR069619(to Penn Center for Musculoskeletal Disorders).
文摘Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.
文摘Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant interest in bone tissue engineering(BTE)because of their abundant availability,minimally invasive harvesting procedures,and robust differentiation potential into osteogenic lineages.Unlike bone marrow-derived mesenchymal stem cells,AD-MSCs can be easily obtained in large quantities,making them appealing alternatives for therapeutic applications.This review explores hydrogels containing polymers,such as chitosan,collagen,gelatin,and hyaluronic acid,and their composites,tailored for BTE,and emphasizes the importance of these hydrogels as scaffolds for the delivery of AD-MSCs.Various hydrogel fabrication techniques and biocompatibility assessments are discussed,along with innovative modifications to enhance osteogenesis.This review also briefly outlines AD-MSC isolation methods and advanced embedding techniques for precise cell placement,such as direct encapsulation and three-dimensional bioprinting.We discuss the mechanisms of bone regeneration in the AD-MSC-laden hydrogels,including osteoinduction,vascularization,and extracellular matrix remodeling.We also review the preclinical and clinical applications of AD-MSC-hydrogel systems,emphasizing their success and limitations.In this review,we provide a comprehensive overview of AD-MSC-based hydrogel systems to guide the development of effective therapies for bone regeneration.
文摘BACKGROUND Anterior cruciate ligament(ACL)reconstruction using bone-patellar tendon-bone(BPTB)autografts remains the gold standard for young,active individuals due to its superior biomechanical strength and bone-to-bone healing.However,donor site morbidity,particularly anterior knee pain(AKP),limits its utilization despite its advantages.Various techniques have been proposed to reduce AKP,but they show variable outcomes and several limitations.AIM To assess the incidence and severity of AKP following BPTB ACL reconstruction using an autologous bone grafting technique.METHODS We conducted a retrospective observational study of 24 patients aged 20-45 years,who had primary ACL reconstruction with BPTB grafts.During surgery,autologous cancellous bone generated from tunnel drilling was used to fill the patellar and tibial donor site voids after graft fixation.All patients were followed up for at least twelve months.Using the Kujala Anterior Knee Pain Score,clinical outcomes were evaluated,including the pain-specific subcomponent.RESULTS With scores ranging from 86 to 100,the average overall Kujala score was 95.67±4.01.No patient scored below 85.There was no complication such as patellar fracture,tibial tuberosity fracture,or infection.Grouped data showed 20.8%of patients scored 100,whereas 54.2%scored between 95 and 99,and 25%scored between 86 and 94.One patient(4.2%)had an 8/10 pain subcomponent,whereas 23 patients(95.8%)had a 10/10.CONCLUSION This procedure is easy to incorporate into routine surgical practice,cost-effective and reproducible without requiring extra incisions or raising the patient’s surgical expenses.Excellent short-term results back up this technique.
文摘BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.
文摘Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological benefits in cancer therapy,the specific molecular mechanisms and their influence on vitamin metabolism pathways in bone malignancies are not well defined.Methods:We conducted an integrated analysis of prognostic genes and survival outcomes in osteosarcoma,focusing on the expression of GPC2 and its correlation with tumor progression and patient survival rates.In order to explore the therapeutic relevance of 20 bioactive compounds extracted from Huangqi,molecular docking was performed to quantify their binding free energies to the GPC2 receptor,shedding light on their potential affinity and biological activity.Furthermore,the expression levels of GPC2 in tumor cells compared to normal cells were analyzed using qRT-PCR.Additionally,the effects of GPC2 overexpression and silencing on cellular viability,apoptotic response,and migratory capacity were systematically investigated.Results:In our study,GPC2 emerged as a significant prognostic gene,where high expression levels correlated with reduced overall survival.The molecular interactions between Astragalus components and the GPC2 receptor reveal compounds with strong affinity,suggesting their potential as effective targets.Furthermore,the overexpression of GPC2 enhanced tumor cell viability and migration,while its knockdown resulted in decreased cell viability and expanded apoptosis.Conclusion:This study demonstrates that Huangqi-derived components may exert anticancer effects by regulating the expression of the GPC2 gene within the vitamin metabolism pathway.These findings offer new insights into the therapeutic potential of traditional herbal medicine for improving bone tumor prognosis and provide a scientific foundation for future translational research.
文摘The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is largely unknown.In patients who underwent discontinuation after multiple injections of denosumab,the levels of tartrate-resistant acid phosphatase 5b increased compared to pretreatment levels,indicating a phenomenon known as“overshoot.”The rate of decrease in bone mineral density during the withdrawal period was higher than the rate of decrease associated with aging,suggesting that the physiological bone metabolism had broken down.Overshoot and significant bone loss were also observed in mice receiving continuous administration of anti-RANKL antibody after treatment was interrupted,resembling the original pathology.In mice long out of overshoot,bone resorption recovered,but osteoblast numbers and bone formation remained markedly reduced.The bone marrow exhibited a significant reduction in stem cell(SC)antigen 1-and platelet-derived growth factor receptor alpha-expressing osteoblast progenitors(PαS cells)and alkaline phosphatase-positive early osteoblasts.Just before the overshoot phase,the osteoclast precursor cell population expands and RANKL-bearing extracellular vesicles(EVs)became abundant in the serum,leading to robust osteoclastogenesis after cessation of anti-RANKL treatment.Thus,accelerated bone resorption due to the accumulation of RANKLbearing EVs and long-term suppression of bone formation uncoupled from bone resorption leads to the severe bone loss characteristic of denosumab discontinuation.
基金financially supported by the Basic Science Center Program(T2288102)the Key Program of the National Natural Science Foundation of China(32230059)+3 种基金the Foundation of Frontiers Science Center for Materiobiology and Dynamic Chemistry(JKVD1211002)the Project supported by the Young Scientists Fund of the National Natural Science Foundation of China(32401128)Postdoctoral Fellowship Program of CPSF(GZC20230793)Shanghai Post-doctoral Excellence Program(2023251).
文摘Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indicate that bone and brain can influence each other’s homeostasis via multiple pathways,yet there is a dearth of systematic reviews in this area.This review comprehensively examines interactions across three key areas:the influence of bone-derived factors on brain function,the effects of brain-related diseases or injuries(BRDI)on bone health,and the concept of skeletal interoception.Additionally,the review discusses innovative approaches in biomaterial design inspired by bone-brain interaction mechanisms,aiming to facilitate bonebrain interactions through materiobiological effects to aid in the treatment of neurodegenerative and bone-related diseases.Notably,the integration of artificial intelligence(AI)in biomaterial design is highlighted,showcasing AI’s role in expediting the formulation of effective and targeted treatment strategies.In conclusion,this review offers vital insights into the mechanisms of bone-brain interaction and suggests advanced approaches to harness these interactions in clinical practice.These insights offer promising avenues for preventing and treating complex diseases impacting the skeleton and brain,underscoring the potential of interdisciplinary approaches in enhancing human health.
基金supported by the National Natural Science Foundation of China(Nos.82160419 and 82302772)Guizhou Basic Research Project(No.ZK[2023]General 201)。
文摘As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially in the context of an imbalance between osteoblast and osteoclast activities.Therefore,the development of new biomaterials has become the key.This article reviews various design strategies and their advantages and disadvantages for biomaterials aimed at osteoporotic bone defects.Overall,current research progress indicates that innovative design,functionalization,and targeting of materials can significantly enhance bone regeneration under osteoporotic conditions.By comprehensively considering biocompatibility,mechanical properties,and bioactivity,these biomaterials can be further optimized,offering a range of choices and strategies for the repair of osteoporotic bone defects.
基金supported by the National Natural Science Foundation of China(No.82202450).
文摘Large bone defects in load-bearing bone can result from tumor resection,osteomyelitis,trauma,and other factors.Although bone has the intrinsic potential to self-repair and regenerate,the repair of large bone defects which exceed a certain critical size remains a substantial clinical challenge.Traditionally,repair methods involve using autologous or allogeneic bone tissue to replace the lost bone tissue at defect sites,and autogenous bone grafting remains the“gold standard”treatment.However,the application of traditional bone grafts is limited by drawbacks such as the quantity of extractable bone,donor-site morbidities,and the risk of rejection.In recent years,the clinical demand for alternatives to traditional bone grafts has promoted the development of novel bone-grafting substitutes.In addition to osteoconductivity and osteoinductivity,optimal mechanical properties have recently been the focus of efforts to improve the treatment success of novel bone-grafting alternatives in load-bearing bone defects,but most biomaterial synthetic scaffolds cannot provide sufficient mechanical strength.A fundamental challenge is to find an appropriate balance between mechanical and tissue-regeneration requirements.In this review,the use of traditional bone grafts in load-bearing bone defects,as well as their advantages and disadvantages,is summarized and reviewed.Furthermore,we highlight recent development strategies for novel bone grafts appropriate for load-bearing bone defects based on substance,structural,and functional bionics to provide ideas and directions for future research.
文摘Bone Research is an open access,fully peer-reviewed journal publishing the foremost progress and novel understanding of all aspects of bone science.The journal highlights the breakthrough discoveries in basic and clinical aspects of bone biology,pathophysiology and regeneration,as well as other significant findings related to bone.
文摘BACKGROUND Demineralized bone matrix(DBM)is a commonly utilized allogenic bone graft substitute to promote osseous union.However,little is known regarding outcomes following DBM utilization in foot and ankle surgical procedures.AIM To evaluate the clinical and radiographic outcomes following DBM as a biological adjunct in foot and ankle surgical procedures.METHODS During May 2023,the PubMed,EMBASE and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following DBM for the management of various foot and ankle pathologies.Data regarding study characteristics,patient demographics,subjective clinical outcomes,radiological outcomes,complications,and failure rates were extracted and analyzed.In addition,the level of evidence(LOE)and quality of evidence(QOE)for each individual study was also assessed.Thirteen studies were included in this review.RESULTS In total,363 patients(397 ankles and feet)received DBM as part of their surgical procedure at a weighted mean follow-up time of 20.8±9.2 months.The most common procedure performed was ankle arthrodesis in 94 patients(25.9%).Other procedures performed included hindfoot fusion,1st metatarsophalangeal joint arthrodesis,5th metatarsal intramedullary screw fixation,hallux valgus correction,osteochondral lesion of the talus repair and unicameral talar cyst resection.The osseous union rate in the ankle and hindfoot arthrodesis cohort,base of the 5th metatarsal cohort,and calcaneal fracture cohort was 85.6%,100%,and 100%,respectively.The weighted mean visual analog scale in the osteochondral lesions of the talus cohort improved from a pre-operative score of 7.6±0.1 to a post-operative score of 0.4±0.1.The overall complication rate was 27.2%,the most common of which was non-union(8.8%).There were 43 failures(10.8%)all of which warranted a further surgical procedure.CONCLUSION This current systematic review demonstrated that the utilization of DBM in foot and ankle surgical procedures led to satisfactory osseous union rates with favorable wound complication rates.Excellent outcomes were observed in patients undergoing fracture fixation augmented with DBM,with mixed evidence supporting the routine use of DBM in fusion procedures of the ankle and hindfoot.However,the low LOE together with the low QOE and significant heterogeneity between the included studies reinforces the need for randomized control trials to be conducted to identify the optimal role of DBM in the setting of foot and ankle surgical procedures.
基金Supported by National Natural Science Foundation of China(General Program),No.82073909Four‘Batches’Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province,No.2023XM022The Shanxi Provincial Central Leading Local Science and Technology Development Fund Project,No.YDZJSX2022A059 and No.YDZJSX20231A059。
文摘BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in patients with ACS using a continuous glucose monitoring system(CGMS)and dual-energy X-ray absorptiometry(DXA).METHODS Patients diagnosed with ACS,including Cushing syndrome,mild ACS(MACS),and nonfunctional adrenal incidentaloma(NFAI),were recruited for this study.Glucose variability and glycemic status were assessed using CGMS.Regional bone mineral content(BMC),bone mineral density(BMD),and bone area(BA)were evaluated using DXA.CGMS-and DXA-derived parameters were compared across the subgroups of ACS.Correlation analysis was performed to examine relationships between varying degrees of cortisol secretion,measured by cortisol after 1 mg overnight dexamethasone suppression test(DST)or 24-hour urine free cortisol(24h UFC),and CGMS-or DXA-derived parameters.RESULTS A total of 64 patients with ACS were included in this study:19 with Cushing syndrome,11 with MACS,and 34 with NFAI.Glucose variability,time above range(TAR),and time in range(TIR)along with specific areal BMC,BMD,and BA,differed significantly between groups of Cushing syndrome and NFAI.A significant positive correlation was observed between glucose variability or TAR and cortisol after 1 mg overnight DST or 24h UFC.By contrast,TIR,along with regional BMC,BMD,and BA,were negatively correlated with varying degrees of cortisol secretion.CONCLUSION Glucose and bone metabolism impairments are on a continuum alteration from NFAI to MACS and Cushing syndrome.Prompt attention should be given to these patients with ACS,especially those with mild hormone secretion.Parameters of glucose variability and glycemic status along with bone condition in regions rich in cancellous bone will provide valuable information.
文摘BACKGROUND Tibial plateau fractures often require structural support for metaphyseal defects created during articular reduction.While autologous bone grafting has been utilized as the gold standard,bone substitutes offer advantages including reduced donor site morbidity.Our meta-analysis evaluated the comparative efficacy of these approaches across clinical and operative outcomes.AIM To conduct a systematic review and meta-analysis of randomized controlled trials comparing autologous bone grafts with bone substitutes for tibial plateau fractures.METHODS We conducted a systematic review and meta-analysis of randomized controlled trials comparing autologous bone grafts with bone substitutes for tibial plateau fractures.Primary outcomes included joint depression,secondary collapse rate,operative time,blood loss,and infection rate.Subgroup analyses were performed by fracture complexity,geographic region,and methodological factors.In addition to that,we also developed a combined outcome score integrating structural,procedural,and complication domains.RESULTS Seven randomized controlled trials with 424 patients(296 bone substitute,128 autograft)were included.No significant differences in joint depression or secondary collapse were observed across fracture complexity categories.Geographic variations were evident,with Western studies showing significantly higher risk of secondary collapse with autografts(risk ratio=1.45,P value=0.02).Both Western and Asian studies have demonstrated significantly reduced blood loss with bone substitutes(70-90 mL less),while operative time reduction was more significant in the Asian studies(23.65 vs 8.00 minutes,P value=0.04 for subgroup difference).The combined outcome score(standardized effect size-0.2481)favored bone substitutes,primarily due to procedural advantages.CONCLUSION Bone substitutes provide similar structural outcomes to autologous bone grafts while having better procedural advantages in tibial plateau fracture management.These findings support bone substitutes as a viable option across fracture patterns.Future studies should focus on specific bone substitute formulations and cost-effectiveness analyses.
基金Supported by the Research Project for Clinical Research on Precision Diagnosis and Innovative Treatment of Bone Marrow Failure,No.2024YFC2510500Jiangsu Provincial Traditional Chinese Medicine Science and Technology Development Plan,No.YB2020102Nantong Municipal Health Commission Research Project,No.QN2023007.
文摘BACKGROUND Thrombotic microangiopathy(TMA)is an acute syndrome characterized by microangiopathic hemolytic anemia,thrombocytopenia,and multi-organ dysfunction due to the microcirculation of platelet thrombi.Cancer-associated TMA is a rare and fatal complication,which often occurs during cancer remission.It is frequently misdiagnosed because of limited clinical awareness.CASE SUMMARY A middle-aged female patient presented to our clinic with a 15-days history of back pain,15 months post-gastrectomy.Cancer-associated TMA was confirmed through bone marrow aspiration,biopsy,and imaging.The patient received intermittent transfusions,fluids,nutrition,and microcirculation therapy with partial coagulation improvement.The family refused intensive care unit admission and plasma exchange,preferring palliative care.The patient died of cerebral hemorrhage and herniation due to disease progression.This case indicates that TMA may serve as an early manifestation of various malignancies,particularly gastric cancer.However,it is often misdiagnosed.Its pathogenesis is not well understood and needs to be further investigated.Currently,no standardized treatment have been developed.Plasma exchange is the only intervention available,though other therapies may also be effective.CONCLUSION In this case of gastric signet-ring cell carcinoma complicated by TMA,the patient achieved transient remission with supportive care but died following treatment discontinuation.Further studies are needed to elucidate the pathological mechanisms and therapeutic strategies for cancer-associated TMA.
基金Supported by Clinical Medical Research Fund of the Zhejiang Medical Association,No.2025ZYC-Z32Henan Provincial Key Research and Development Program,No.231111311000+1 种基金Henan Provincial Science and Technology Research Project,No.232102310411Clinical Medical Research Fund of the Zhejiang Medical Association,2024ZYC-Z30.
文摘Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.
基金supported by National Natural Science Foundation of China(grant numbers 82072523 to Zhiyong Hou)Postdoctoral program of Clinical medicine of Hebei Medical University(grant numbers PD2023012 to Sujuan Xu)+2 种基金Excellent postdoctoral research funding project of Hebei Province(grant numbers B2023005011 to Sujuan Xu)The 16th special grant of China Postdoctoral Science Foundation(grant numbers 2023T160182 to Sujuan Xu)Natural Science Foundation of Hebei Province,China(grant numbers H2023206230 to Yingchao Yin,H2024206186 to Sujuan Xu).
文摘The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.
基金supported by grants from National Natural Science Foundation of China(82272444,81972031,81972033)China Postdoctoral Science Foundation(2022M722382)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-032A)。
文摘Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.
基金supported by the National Natural Science Foundation of China(32171354,82222015,82171001)The National Key Research and Development Program of China2023YFC2413600Research Funding from West China School/Hospital of Stomatology,Sichuan University(No.RCDWIS2023-1).
文摘Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal therapy hydrogel with a pulsed drug delivery mechanism.The system is predicated on a hydrogel matrix that is thermally responsive,characteristic of bone defect sites,facilitating controlled and site-specific drug release.The cornerstone of this system is the incorporation of mild photothermal nanoparticles,which are activated within the temperature range of 40–43°C,thereby enhancing the precision and efficacy of drug delivery.Our findings demonstrate that the photothermal response significantly augments the localized delivery of therapeutic agents,mitigating systemic side effects and bolstering efficacy at the defect site.The synchronized pulsed release,cooperated with mild photothermal therapy,effectively addresses infection control,and promotes bone regeneration.This approach signifies a considerable advancement in the management of infectious bone defects,offering an effective and patient-centric alternative to traditional methods.Our research endeavors to extend its applicability to a wider spectrum of tissue regeneration scenarios,underscoring its transformative potential in the realm of regenerative medicine.
