Limited evidence to support demineralized bone matrix in foot and ankle surgical procedures:A systematic review

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.

Continuum of glucose and bone metabolism impairment across autonomous cortisol secretion: A cross-sectional study

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.

Unleashing the Potential of Electroactive Hybrid Biomaterials and Self‑Powered Systems for Bone Therapeutics

The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.

Impact of dietary nutrition regimens based on body composition analysis on bone metabolism in Alzheimer’s disease patients

BACKGROUND Body composition analysis(BCA)is primarily used in the management of conditions such as obesity and endocrine disorders.However,its potential in providing nutritional guidance for patients with Alzheimer’s disease(AD)remains relatively unexplored.AIM To explore the clinical efficacy of BCA-based dietary nutrition scheme on bone metabolism in AD patients.METHODS This retrospective study included 96 patients with AD complicated by osteoporosis who were admitted to The Third Hospital of Quzhou between January 2023 and December 2024.Based on data from previous similar studies,the patients were randomly assigned to either a routine diet(RD)group(n=48)or a personalized nutrition(PN)group(n=48).The RD group received conventional dietary guidance,while the PN group received individualized diet intervention measures based on human BCA.The intervention period lasted for 12 weeks.Bone mineral density(BMD),body mass index(BMI),muscle mass,mineral content,osteocalcin,25-hydroxyvitamin D,procollagen type I N-terminal propeptide(PINP),beta C-terminal telopeptide of type I collagen(β-CTX),and serum calcium were measured and compared between the two groups before and 12 weeks after the intervention.RESULTS No significant differences were observed between groups in terms of age,sex,height,BMI,or other baseline data(P>0.05).In both groups,BMI did not show significant changes after the intervention(P>0.05),whereas muscle mass and mineral content were significantly increased(P<0.05).After the intervention,BMI in the PN group did not differ significantly from that of the RD group,but muscle mass and mineral content were significantly higher in the PN group(P<0.05).After the intervention,a higher proportion of patients in the PN group had a T score>-1 compared to the RD group(P<0.05).The mini-mental state examination(MMSE)score was similar in both groups before the intervention.However,12 weeks after the intervention,the MMSE score in the PN group was significantly higher than that in the RD group(P<0.05).In both groups,the MMSE score significantly increased 12 weeks post-intervention compared to pre-intervention levels(P<0.05).Before the intervention,the levels of osteocalcin,serum calcium,PINP,β-CTX,and 25-hydroxyvitamin D were not significantly different between the two groups(P>0.05).After 12 weeks of intervention,the PN group exhibited higher levels of osteocalcin,serum calcium,and 25-hydroxyvitamin D,as well as lower levels of PINP andβ-CTX,compared to the RD group(P<0.05).In both groups,osteocalcin,serum calcium,and 25-hydroxyvitamin D levels were significantly higher,while PINP andβ-CTX levels were significantly lower after 12 weeks of intervention compared to baseline(P<0.05).CONCLUSION The human BCA-based dietary nutrition regimen plays a crucial role in improving BMD and bone metabolism,with effects that surpass those of conventional nutrition strategies.The findings of this study provide strong evidence for the nutritional management of AD patients.

Recent Strategies and Advances in Hydrogel‑Based Delivery Platforms for Bone Regeneration

Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo.Hydrogels have emerged as ideal carriers to address these challenges,offering the potential to prolong retention times at lesion sites,extend half-lives in vivo and mitigate side effects,avoid burst release,and promote adsorption under physiological conditions.This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration,encompassing applications in cranial defect repair,femoral defect repair,periodontal bone regeneration,and bone regeneration with underlying diseases.Additionally,this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery,carrier-assisted delivery,and sequential delivery.Finally,this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.

Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

AAV-mediated expression of p65shRNA and bone morphogenetic protein 4 synergistically enhances chondrocyte regeneration

BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.

Efficacy and safety of C-arm computed tomography-guided microwave ablation with percutaneous osteoplasty for flat bone metastases

BACKGROUND Flat bone metastases are common in patients with advanced cancers,often resulting in severe pain,limited mobility,and reduced quality of life(QOL).Traditional treatment options,such as radiotherapy or systemic therapies,often fail to provide sufficient pain relief or improve functional outcomes in these patients.Microwave ablation(MWA)offers advantages,such as shorter pro-cedure times and larger ablation zones,while percutaneous osteoplasty(PO)enhances bone stability and prevents pathological fractures.Despite these be-nefits,the combination of these techniques for treating flat bone metastases re-mains underexplored.AIM To evaluate the efficacy and safety of C-arm computed tomography(CT)-guided MWA combined with PO for managing painful flat bone metastases,focusing on pain relief,functional improvement,and QOL enhancement.METHODS A total of 45 patients with refractory moderate-to-severe pain resulting from flat bone metastases who underwent C-arm CT-guided MWA combined with PO between January 2015 and January 2021 were included.The efficacy of the pro-cedure was assessed by changes in the visual analog scale(VAS),Oswestry disability index(ODI),and QOL,as well as the occurrence of complications.Tumor response was evaluated using RECIST v1.1 and mRECIST criteria,with overall response rate(ORR)and disease control rate(DCR)as the primary end-points.RESULTS No serious complications were observed in any of the patients.A significant reduction in VAS and ODI was noted at 1 week,1 month,and 3 months post-procedure.A marked improvement in QOL was observed at all follow-up points.Bone cement extravasation was observed in 10 patients;however,none exhibited significant clinical symptoms.Based on RECIST v1.1,the ORR was 26.7%and the DCR was 88.9%.The mRECIST evaluation revealed a higher ORR of 51.1%and DCR of 88.9%.CONCLUSION C-arm CT-guided MWA with PO provides a dependable and effective strategy for managing flat bone metastases.It demonstrates significant pain relief,improved functional outcomes,and enhanced QOL.This treatment combination also shows promising tumor response rates with a low complication profile.

Association between body mass index and lumbar spine volumetric bone mineral density in diabetic and non-diabetic patients

BACKGROUND The association between body mass index(BMI)and bone mineral density(BMD)has shown inconsistent results,varying by sex and skeletal site.Despite normal or elevated bone mass,individuals with type 2 diabetes have an increased risk of hip and vertebral fractures.AIM To assess lumbar spine trabecular volumetric BMD(vBMD)across different BMI categories in individuals with and without diabetes.METHODS This cross-sectional study included 966 men over 50 years old and 1001 postmenopausal women from the Pinggu Metabolic Disease Study.The vBMD of lumbar vertebrae 2 through 4 was measured using quantitative computed tomography.Total adipose tissue,subcutaneous adipose tissue(SAT),visceral adipose tissue(VAT),and lumbar skeletal muscle area were also quantified.RESULTS In men with obesity(P=0.038)and overweight(P=0.032),vBMD was significantly higher in the diabetes group compared to non-diabetic men.After adjusting for age and sex,no significant saturation effect between BMI and BMD was found in participants with diabetes or in women without diabetes.However,a BMI threshold of 22.33 kg/m²indicated a saturation point for vBMD in nondiabetic men.Independent predictors of vBMD in men included age(r=-0.387,P<0.001),BMI(r=0.130,P=0.004),and VAT(r=-0.145,P=0.001).For women,significant predictors were age(r=-0.594,P<0.001),BMI(r=0.157,P=0.004),VAT(r=-0.112,P=0.001),and SAT(r=-0.068,P=0.035).CONCLUSION The relationship between BMI and trabecular vBMD differs in individuals with and without diabetes.Overweight and obese men with diabetes exhibit higher vBMD.

Bone marrow mesenchymal stem cells promote uterine healing by activating the PI3K/AKT pathway and modulating inflammation in rat models

BACKGROUND Uterine injury can cause uterine scarring,leading to a series of complications that threaten women’s health.Uterine healing is a complex process,and there are currently no effective treatments.Although our previous studies have shown that bone marrow mesenchymal stem cells(BMSCs)promote uterine damage repair,the underlying mechanisms remain unclear.However,exploring the specific regulatory roles of BMSCs in uterine injury treatment is crucial for further understanding their functions and enhancing therapeutic efficacy.AIM To investigate the underlying mechanism by which BMSCs promote the process of uterine healing.METHODS In in vivo experiments,we established a model of full-thickness uterine injury and injected BMSCs into the uterine wound.Transcriptome sequencing was per-formed to determine the enrichment of differentially expressed genes at the wound site.In in vitro experiments,we isolated rat uterine smooth muscle cells(USMCs)and cocultured them with BMSCs to observe the interaction between BMSCs and USMCs in the microenvironment.RESULTS We found that the differentially expressed genes were mainly related to cell growth,tissue repair,and angiogenesis,while the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathway was highly enriched.Quantitative reverse-transcription polymerase chain reaction was used to validate differentially expressed genes,and the results demonstrated that BMSCs can upregulate genes related to regeneration and downregulate genes related to inflammation.Coculturing BMSCs promoted the migration and proliferation of USMCs,and the USMC microenvironment promoted the myogenic differentiation of BMSCs.Finally,we validated the PI3K/AKT pathway in tissues and cells and showed that BMSCs activate the PI3K/AKT pathway to promote the regeneration of uterine smooth muscle both in vivo and in vitro.CONCLUSION BMSCs upregulated uterine wound regeneration and anti-inflammatory factors and enhanced uterine smooth muscle proliferation through the PI3K/AKT pathway both in vivo and in vitro.

Crosstalk between Wnt and bone morphogenetic protein signaling during osteogenic differentiati

Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed that many transcription factors and signaling pathways control osteogenic development.Osteogenesis is the process by which new bones are formed;it also aids in bone remodeling.Wnt/β-catenin and bone morphogenetic protein(BMP)signaling pathways are involved in many cellular processes and considered to be essential for life.Wnt/β-catenin and BMPs are important for bone formation in mammalian development and various regulatory activities in the body.Recent studies have indicated that these two signaling pathways contribute to osteogenic differen-tiation.Active Wnt signaling pathway promotes osteogenesis by activating the downstream targets of the BMP signaling pathway.Here,we briefly review the molecular processes underlying the crosstalk between these two pathways and explain their participation in osteogenic differentiation,emphasizing the canonical pathways.This review also discusses the crosstalk mechanisms of Wnt/BMP signaling with Notch-and extracellular-regulated kinases in osteogenic differentiation and bone development.

Hydrogel loaded with bone marrow stromal cell-derived exosomes promotes bone regeneration by inhibiting inflammatory responses and angiogenesis

BACKGROUND Bone healing is a complex process involving early inflammatory immune regu-lation,angiogenesis,osteogenic differentiation,and biomineralization.Fracture repair poses challenges for orthopedic surgeons,necessitating the search for efficient healing methods.AIM To investigate the underlying mechanism by which hydrogel-loaded exosomes derived from bone marrow mesenchymal stem cells(BMSCs)facilitate the process of fracture healing.METHODS Hydrogels and loaded BMSC-derived exosome(BMSC-exo)gels were charac-terized to validate their properties.In vitro evaluations were conducted to assess the impact of hydrogels on various stages of the healing process.Hydrogels could recruit macrophages and inhibit inflammatory responses,enhance of human umbilical vein endothelial cell angiogenesis,and promote the osteogenic differen-tiation of primary cranial osteoblasts.Furthermore,the effect of hydrogel on fracture healing was confirmed using a mouse fracture model.RESULTS The hydrogel effectively attenuated the inflammatory response during the initial repair stage and subsequently facilitated vascular migration,promoted the formation of large vessels,and enabled functional vascularization during bone repair.These effects were further validated in fracture models.CONCLUSION We successfully fabricated a hydrogel loaded with BMSC-exo that modulates macrophage polarization and angiogenesis to influence bone regeneration.

Icariin accelerates bone regeneration by inducing osteogenesisangiogenesis coupling in rats with type 1 diabetes mellitus

BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.

Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells

BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process.

Indication and surgical approach for reconstruction with endoprosthesis in bone-associated soft tissue sarcomas:Appropriate case management is vital

It is important for surgeons performing sarcoma surgery to know that bone resection and tumor prosthesis applications in soft tissue sarcomas(STS)have unique features in terms of indication,surgical approach and follow-up,in terms of the management of these cases.Some STS are associated with bone and major neurovascular structures.Bone-associated STS are generally relatively large and relatively deep-seated.Additionally,the tendency for metastasis is high.In some cases,the decision about which structures to resect is difficult.These cases are often accompanied by poor oncological and surgical outcomes.Management of cases should be done by a multidisciplinary team in advanced centers specialized in this field.The surgical team must have sufficient knowledge and experience in the field of limb-sparing surgery.Preoperative evaluation and especially good planning of bone and soft tissue reconstruction are vital.

Unveiling the role of hypoxia-inducible factor 2alpha in osteoporosis:Implications for bone health

BACKGROUND Osteoporosis(OP)has become a major public health problem worldwide.Most OP treatments are based on the inhibition of bone resorption,and it is necessary to identify additional treatments aimed at enhancing osteogenesis.In the bone marrow(BM)niche,bone mesenchymal stem cells(BMSCs)are exposed to a hypoxic environment.Recently,a few studies have demonstrated that hypoxiainducible factor 2alpha(HIF-2α)is involved in BMSC osteogenic differentiation,but the molecular mechanism involved has not been determined.AIM To investigate the effect of HIF-2αon the osteogenic and adipogenic differentiation of BMSCs and the hematopoietic function of hematopoietic stem cells(HSCs)in the BM niche on the progression of OP.METHODS Mice with BMSC-specific HIF-2αknockout(Prx1-Cre;Hif-2αfl/fl mice)were used for in vivo experiments.Bone quantification was performed on mice of two genotypes with three interventions:Bilateral ovariectomy,semilethal irradiation,and dexamethasone treatment.Moreover,the hematopoietic function of HSCs in the BM niche was compared between the two mouse genotypes.In vitro,the HIF-2αagonist roxadustat and the HIF-2αinhibitor PT2399 were used to investigate the function of HIF-2αin BMSC osteogenic and adipogenic differentiation.Finally,we investigated the effect of HIF-2αon BMSCs via treatment with the mechanistic target of rapamycin(mTOR)agonist MHY1485 and the mTOR inhibitor rapamycin.RESULTS The quantitative index determined by microcomputed tomography indicated that the femoral bone density of Prx1-Cre;Hif-2αfl/fl mice was lower than that of Hif-2αfl/fl mice under the three intervention conditions.In vitro,Hif-2αfl/fl mouse BMSCs were cultured and treated with the HIF-2αagonist roxadustat,and after 7 d of BMSC adipogenic differentiation,the oil red O staining intensity and mRNA expression levels of adipogenesis-related genes in BMSCs treated with roxadustat were decreased;in addition,after 14 d of osteogenic differentiation,BMSCs treated with roxadustat exhibited increased expression of osteogenesis-related genes.The opposite effects were shown for mouse BMSCs treated with the HIF-2αinhibitor PT2399.The mTOR inhibitor rapamycin was used to confirm that HIF-2αregulated BMSC osteogenic and adipogenic differentiation by inhibiting the mTOR pathway.Consequently,there was no significant difference in the hematopoietic function of HSCs between Prx1-Cre;Hif-2αfl/fl and Hif-2αfl/fl mice.CONCLUSION Our study showed that inhibition of HIF-2αdecreases bone mass by inhibiting the osteogenic differentiation and increasing the adipogenic differentiation of BMSCs through inhibition of mTOR signaling in the BM niche.

Gene expression analysis of cytokines and MMPs in melatonin and rhBMP-2 enhanced bone remodeling

BACKGROUND In the medical and dental fields,there is a need for studies of new therapeutic approaches for the treatment of bone defects that cause extensive bone loss.Melatonin may be an important endogenous biological factor for bone remodeling,and growth factors may enhance the repair process.AIM To evaluate the gene expression of cytokines(IL-1β,IL-6,IL-10 and TNF-α),markers of osteoclastogenesis(RANK,RANKL and OPG)and MMPs(MMP-1,MMP-2,MMP-8 and MMP-13)from the treatment of melatonin associated with an osteogenic membrane and rhBMP-2 on the recovery of a bone injury.METHODS Sixty-four rats were used and divided into 9 experimental groups and were formed according to the treatment carried out in the region of the bone lesion,which varied between the combination of 1,10 and 100μmol/L of melatonin.Gene Expression analysis was performed using real time-PCR by reading the concentration of total RNA and reverse transcription.RESULTS There were differences between groups when compared with clot or scaffold control,and improvement with a higher concentration of melatonin or rhBMP-2.The combination melatonin(1μg)with 5μg of rhBMP-2,using the guided bone regeneration technique,demonstrated some effects,albeit mild,on bone repair of critical bone defects.CONCLUSION This indicates that the approach for administering these substances needs to be reassessed,with the goal of ensuring their direct application to the affected area.Therefore,future research must be carried out,seeking to produce materials with these ideal characteristics.

Impacts of radiation therapy on quality of life and pain relief in patients with bone metastases

Bone metastases(BM)are a common complication in advanced cancer patients,significantly contributing to morbidity and mortality due to their ability to cause pain,fractures,and spinal cord compression.Radiation therapy(RT)is vital in managing these complications by targeting metastatic lesions to ease pain,improve mobility,and reduce the risk of skeletal-related events such as fractures.Evidence supports the effectiveness of RT in pain relief,showing its ability to provide significant palliation and lessen the need for opioid painkillers,thereby enhancing the overall quality of life(QoL)for patients with BM.However,optimizing RT outcomes involves considerations such as the choice of radiation technique,dose fractionation schedules,and the integration of supportive care measures to mitigate treatment-related side effects like fatigue and skin reactions.These factors highlight the importance of personalized treatment planning tailored to individual patient needs and tumor characteristics.This mini-review aims to provide comprehensive insights into the multifaceted impacts of RT on pain management and QoL enhancement in BM patients,with implications for refining clinical practices and advancing patient care through the synthesis of findings from various studies.

Ilizarov technique for treatment of a giant aneurysmal bone cyst at the distal femur:A case report

BACKGROUND Aneurysmal bone cyst(ABC)is a benign cystic of unknown etiology,characterized by multiple chambers and a high recurrence rate.Current treatment options include vascular embolization,surgical excision,curettage with cavity filling,sclerosing agent injection into the cavity,radiotherapy,and systemic drug therapy.Among these,surgical excision and curettage are the preferred treatment modalities.However,when the cyst reaches a large size,extensive removal of diseased tissue during surgery can hinder bone healing.In our department,we treated a case of a large ABC at the distal end of the femur in a child using the Ilizarov technique.The tumor was completely excised,and reconstruction was achieved through autologous femoral bone transfer.The follow-up at two years post-surgery indicated good results without tumor recurrence,and the growth and development of the child were essentially unaffected.CASE SUMMARY An 11-year-old boy was presented with an accidental fracture of his right leg.Despite having been examined at other hospitals,he had not received treatment.Given the potential for significant bone defects and the difficulty of the surgery,our doctors opted to use the Ilizarov technique to minimize harm to the patient.Upon admission,the patient underwent a needle biopsy and complete tumor resection-the Ilizarov technique assisted in the transport and reconstruction of the autologous femoral bone.Postoperatively,the patient exhibited regular followups,during which bone transport was gradually performed,and the external fixation frame was removed on time.Follow-up X-rays of the right lower limb displayed no tumor recurrence,with a normal appearance.Bone formation at the cutting site was satisfactory,and the union of the bone ends indicated good healing.After two years of follow-up,the patient had essentially returned to normal.CONCLUSION We successfully applied the Ilizarov technique to treat ABC,reducing the financial burden of patients and the pain of multiple surgeries.In cases where significant bone defects occur,the Ilizarov technique has demonstrated satisfactory therapeutic outcomes.

Spoon-assisted autologous particulate bone graft harvesting technique

Particulate bone plays a crucial role in various oral and maxillofacial surgical procedures,including reconstruction,implantation,and craniofacial surgery.Autologous bone and deproteinized bovine bone xenografts are the two primary resources used for such procedures,with the former demonstrating superior cost-effectiveness and reduced comorbidity rates,particularly in cases involving donor zones.However,a significant challenge lies in acquiring uniformly sized autologous particulate bone specimens,with existing tools often yielding coarse particles at a high cost.Consequently,commercial bone xenograft solutions are frequently favored despite lower standards.This technical note introduces a novel technique for swiftly,safely,and efficiently obtaining autologous particulate bone specimens.The procedure involves the use of a motor handpiece fitted with a micro drill and surgical spoon to collect the bone particles.The continuous irrigation with saline maintains a clear surgical field during the milling process.The collected bone particles are then transferred to a metal capsule for further use.This technique offers a promising solution to the challenge of inconsistent particle size associated with harvesting using traditional methods,providing surgeons with a reliable and efficient method of obtaining autologous particulate bone samples.