The role and applications of extracellular vesicles in osteoporosis

Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture,which increases patient susceptibility to fragile fractures.The intricate mechanisms governing bone homeostasis are substantially impacted by extracellular vesicles(EVs),which play crucial roles in both pathological and physiological contexts.EVs derived from various sources exert distinct effects on osteoporosis.Specifically,EVs released by osteoblasts,endothelial cells,myocytes,and mesenchymal stem cells contribute to bone formation due to their unique cargo of proteins,miRNAs,and cytokines.Conversely,EVs secreted by osteoclasts and immune cells promote bone resorption and inhibit bone formation.Furthermore,the use of EVs as therapeutic modalities or biomaterials for diagnosing and managing osteoporosis is promising.Here,we review the current understanding of the impact of EVs on bone homeostasis,including the classification and biogenesis of EVs and the intricate regulatory mechanisms of EVs in osteoporosis.Furthermore,we present an overview of the latest research progress on diagnosing and treating osteoporosis by using EVs.Finally,we discuss the challenges and prospects of translational research on the use of EVs in osteoporosis.

A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis

Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.

Insights and implications of sexual dimorphism in osteoporosis

Osteoporosis,a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture,has led to a high risk of fatal osteoporotic fractures worldwide.Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis,with sex-specific differences in epidemiology and pathogenesis.Specifically,females are more susceptible than males to osteoporosis,while males are more prone to disability or death from the disease.To date,sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells.Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men.This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis,mainly in a population of aging patients,chronic glucocorticoid administration,and diabetes.Moreover,we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men.Additionally,the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.

Potential therapeutic role of spermine via Rac1 in osteoporosis:Insights from zebrafish and mice

Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

A comparison of the effect of alendronate and You-Gui-Wan on osteoporosis in female rats with kidney-yang deficiency

Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.

Exploring a novel class tryptophan hydroxylase 1 inhibitor derived from Sambucus williamsii Hance for the osteoporosis treatment

Objective:Gut-derived serotonin strongly inhibits bone formation by inhibiting osteoblast proliferation.Our previous study demonstrated that the lignan-rich fraction prepared from Sambucus willimasii Hance,a folk herbal medicine used to treat bone fractures and joint diseases in China,exerted bone-protective effects,and its actions were modulated by suppressing the synthesis of gut-derived serotonin via the inhibition of intestinal tryptophan hydroxylase 1(TPH-1).However,there is no direct evidence for the action of lignans on TPH-1.This study aimed to verify the direct action of lignans on the TPH-1 and its influence on serotonin synthesis and bone properties.Methods:Molecular docking and surface plasmon resonance were performed to determine the affinities of lignans to TPH-1.The cell viability and the protein activity and expression of TPH-1 were measured in RBL2H3 cells.The serum serotonin level and bone mineral density upon lignan treatment in ovariectomized mice were determined.Result:The lignans showed high binding scores and binding affinities to TPH-1,inhibited the activity and protein expression of TPH-1,suppressed the serum serotonin levels in ovariectomized mice as well as promoted bone mineral density.Conclusion:This is the first study to report that lignans are novel TPH-1 inhibitors and that these lignans could be potential agents for the management of serotonin-related diseases,including osteoporosis.

Calcium-fortified fresh milk ameliorates postmenopausal osteoporosis via regulation of bone metabolism and gut microbiota in ovariectomized rats

The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are limited.Herein,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorating postmenopausal osteoporosis in a rat model established using bilateral ovariectomy.After 3 months of FM(containing vitamin D,and casein phosphopeptides,1000 mg Ca/100 g)or control milk(110 mg Ca/100 g milk)supplementation,bone changes were assessed using dual-energy X-ray absorptiometry,microcomputed tomography,and bone biomechanical testing.The results revealed that FM can regulate bone metabolism and gut microbiota composition,which act on bone metabolism through pathways associated with steroid hormone biosynthesis,relaxin signaling,serotonergic synapse,and unsaturated fatty acid biosynthesis.Furthermore,FM administration significantly increased bone mineral content and density in the lumbar spine and femur,as well as femoral compressive strength,while improving femoral trabecular bone parameters and microarchitecture.Mechanistically,we found that the effects may be due to increased levels of estrogen,bone formation marker osteocalcin,and procollagen typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase 5b.Overall,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.

Understanding Osteoporosis: Pathophysiology, Risk Factors, Diagnosis, and Management

Osteoporosis is a systemic skeletal disease characterized by low bone mineral density (BMD) and deterioration of bone architecture, resulting in reduced bone strength and, consequently, increased susceptibility to fractures which poses a significant public health concern worldwide, particularly in aging populations [1]. The health-economic impact of vertebral and hip fractures has been extensively explored and it is well known that these fractures are associated with morbidity/disability and increased mortality;they also account for a substantial portion of the direct fracture costs. This review aims to provide a comprehensive overview of osteoporosis, including its pathophysiology, risk factors, diagnostic approaches, and management strategies. By elucidating the multifaceted nature of this condition, healthcare providers can better identify individuals at risk, implement preventive measures, and optimize treatment to reduce the burden of osteoporotic fractures.

Polycytosine RNA-binding protein 1 regulates osteoblast function via a ferroptosis pathway in type 2 diabetic osteoporosis

BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP.Polycytosine RNA-binding protein 1(PCBP1),an iron ion chaperone,is considered a protector of ferroptosis.AIM To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.METHODS A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose(HG)and/or ferroptosis inhibitors at different concentrations and times.Transmission electron microscopy was used to examine the morpho-logical changes in the mitochondria of osteoblasts under HG,and western blotting was used to detect the expression levels of PCBP1,ferritin,and the ferroptosis-related protein glutathione peroxidase 4(GPX4).A lentivirus silenced and overex-pressed PCBP1.Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin(OPG)and osteocalcin(OCN),whereas flow cytometry was used to detect changes in reactive oxygen species(ROS)levels in each group.RESULTS Under HG,the viability of osteoblasts was considerably decreased,the number of mitochondria undergoing atrophy was considerably increased,PCBP1 and ferritin expression levels were increased,and GPX4 expression was decreased.Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1,increased the expression levels of ferritin,GPX4,OPG,and OCN,compared with the HG group.Flow cytometry results showed a reduction in ROS,and an opposite result was obtained after silencing PCBP1.CONCLUSION PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment.Moreover,PCBP1 may be a potential therapeutic target for T2DOP.

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.

Integration of network pharmacology and bone marrow mesenchymal stem cells experimental research to reveal the molecular mechanisms for Hai Honghua medicinal liquor against osteoporosis

Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to promote fracture healing.However,the underlying mechanisms of HHML in the treatment of osteoporosis(OP)are still unclear.Methods:Firstly,Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and The Encyclopedia of Traditional Chinese Medicine were used to screen the targets of the active compounds of HHML.At the same time,OP targets were identified through GeneCards,Online Mendelian Inheritance in Man,DisGeNET,Therapeutic Target Database,Comparative Toxicogenomics Database and Human Phenotype Ontology databases.Next,protein-protein interaction and pathway networks were constructed for compound-disease common targets,and core targets and compounds were screened for molecular docking.Furthermore,rat bone marrow mesenchymal stem cells were extracted as model cells,and the osteogenic effects of HHML were verified via in vitro experiments.Results:Total of 343 common targets of HHML-OP and the top 10 target proteins in the protein-protein interaction network are TP53,AKT1,STAT3,HSP90AA1,ESR1,TNF,IL6,MAPK1,MAPK3 and MAPK8.Enrichment analysis yielded that the key molecular pathway was the PI3K/Akt signaling pathway.Molecular docking analysis showed that baicalein,erysodienone and naringenin docked with the target proteins AKT1,STAT3 and TP53,respectively,with low binding energy and high affinity.In addition,In vitro experiments demonstrated that HHML promoted the proliferation of bone marrow mesenchymal stem cells;compared with the control group,HHML-treated cells showed enhanced alkaline phosphatase staining,promoted the expression of OCN,RUNX2,BSP,and COL1 mRNAs as well as the expression of PI3K and AKT phosphorylated proteins.Secondly,the expression of target proteins revealed that HHML promoted the phosphorylation of STAT3 protein and inhibited the expression of P53.Conclusions:Our study investigated that HHML treatment with OP promotes bone formation possibly through activation of the PI3K/Akt signaling pathway and may involve STAT3 and TP53 target interactions.

Modulation of bone remodeling by the gut microbiota:a new therapy for osteoporosis

The gut microbiota(GM)plays a crucial role in maintaining the overall health and well-being of the host.Recent studies have demonstrated that the GM may significantly influence bone metabolism and degenerative skeletal diseases,such as osteoporosis(OP).Interventions targeting GM modification,including probiotics or antibiotics,have been found to affect bone remodeling.This review provides a comprehensive summary of recent research on the role of GM in regulating bone remodeling and seeks to elucidate the regulatory mechanism from various perspectives,such as the interaction with the immune system,interplay with estrogen or parathyroid hormone(PTH),the impact of GM metabolites,and the effect of extracellular vesicles(EVs).Moreover,this review explores the potential of probiotics as a therapeutic approach for OP.The insights presented may contribute to the development of innovative GM-targeted therapies for OP.

Super enhancers targeting ZBTB16 in osteogenesis protect against osteoporosis

As the major cell precursors in osteogenesis, mesenchymal stem cells(MSCs) are indispensable for bone homeostasis and development. However, the primary mechanisms regulating osteogenic differentiation are controversial. Composed of multiple constituent enhancers, super enhancers(SEs) are powerful cis-regulatory elements that identify genes that ensure sequential differentiation. The present study demonstrated that SEs were indispensable for MSC osteogenesis and involved in osteoporosis development. Through integrated analysis, we identified the most common SE-targeted and osteoporosis-related osteogenic gene,ZBTB16. ZBTB16, positively regulated by SEs, promoted MSC osteogenesis but was expressed at lower levels in osteoporosis.Mechanistically, SEs recruited bromodomain containing 4(BRD4) at the site of ZBTB16, which then bound to RNA polymerase IIassociated protein 2(RPAP2) that transported RNA polymerase Ⅱ(POL Ⅱ) into the nucleus. The subsequent synergistic regulation of POL Ⅱ carboxyterminal domain(CTD) phosphorylation by BRD4 and RPAP2 initiated ZBTB16 transcriptional elongation, which facilitated MSC osteogenesis via the key osteogenic transcription factor SP7. Bone-targeting ZBTB16 overexpression had a therapeutic effect on the decreased bone density and remodeling capacity of Brd4^(fl/fl)Prx1-cre mice and osteoporosis(OP) models.Therefore, our study shows that SEs orchestrate the osteogenesis of MSCs by targeting ZBTB16 expression, which provides an attractive focus and therapeutic target for osteoporosis.

Prevalence and risk factors of osteoporosis detected by dual-energy X-ray absorptiometry among Chinese patients with primary biliary cholangitis

BACKGROUND Osteoporosis is an extrahepatic complication of primary biliary cholangitis(PBC)that increases the risk of fractures and mortality.However,Epidemiological studies of osteoporosis in patients with PBC in China and the Asia-Pacific region is lack.AIM To assess the prevalence and clinical characteristics of osteoporosis in Chinese patients with PBC.METHODS This retrospective analysis included consecutive patients with PBC from a tertiary care center in China who underwent bone mineral density(BMD)assessment using dual-energy X-ray absorptiometry between January 2013 and December 2021.We defined subjects with T-scores≤-2.5 in any sites(L1 to L4,femoral neck,or total hip)as having osteoporosis.Demographic,serological,clinical,and histological data were collected.Independent risk factors for osteoporosis were identified by multivariate logistic regression analysis.RESULTS A total of 268 patients with PBC[236 women(88.1%);mean age,56.7±10.6 years;163 liver biopsies(60.8%)]were included.The overall prevalence of osteoporosis in patients with PBC was 45.5%(122/268),with the prevalence of osteoporosis in women and men being 47.0%and 34.4%,respectively.The prevalence of osteoporosis in postmenopausal women was significantly higher than that in premenopausal women(56.3%vs 21.0%,P<0.001).Osteoporosis in patients with PBC is associated with age,fatigue,menopausal status,previous steroid therapy,body mass index(BMI),splenomegaly,gastroesophageal varices,ascites,Mayo risk score,histological stage,alanine aminotransferase,albumin,bilirubin,platelet and prothrombin activity.Multivariate regression analysis identified that older age,lower BMI,previous steroid therapy,higher Mayo risk score,and advanced histological stage as the main independent risk factors for osteoporosis in PBC.CONCLUSION Osteoporosis is very common in Chinese patients with PBC,allowing for prior screening of BMD in those PBC patients with older age,lower BMI,previous steroid therapy and advanced liver disease.

Trim21 depletion alleviates bone loss in osteoporosis via activation of YAP1/β-catenin signaling

Despite the diverse roles of tripartite motif(Trim)-containing proteins in the regulation of autophagy,the innate immune response,and cell differentiation,their roles in skeletal diseases are largely unknown.We recently demonstrated that Trim21 plays a crucial role in regulating osteoblast(OB)differentiation in osteosarcoma.However,how Trim21 contributes to skeletal degenerative disorders,including osteoporosis,remains unknown.First,human and mouse bone specimens were evaluated,and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis patients.Next,we found that global knockout of the Trim21 gene(KO,Trim2^(1-/-))resulted in higher bone mass compared to that of the control littermates.We further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and elevating the activity of OBs;moreover,Trim21 depletion suppressed osteoclast(OC)formation of RAW264.7 cells.In addition,the differentiation of OCs from bone marrow-derived macrophages(BMMs)isolated from Trim21^(-/-)and Ctsk-cre;Trim21^(f/f)mice was largely compromised compared to that of the littermate control mice.Mechanistically,YAP1/β-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of BMSCs.More importantly,the loss of Trim21 prevented ovariectomy(OVX)-and lipopolysaccharide(LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 signaling.Our current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption,thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.

Postmenopausal Osteoporosis and Osteopenia Management with a Combination of Once-Monthly Oral Ibandronate and Cholecalciferol—A Systematic Review

Postmenopausal osteoporosis and osteopenia are chronic and uncurable conditions that invariably lead to an increased risk of vertebral, hip, and femoral neck fracture if left untreated. Clinical guidelines establish, in general, pharmacological combinations allied to lifestyle changes as the mainstay of their management, and also increasing bone marrow density, lowering fracture risk, and improving quality of life are their main therapeutic goals. The objective of this systematic review was to analyze the available data in the scientific medical literature regarding the role of the ibandronate and cholecalciferol combination in postmenopausal osteoporosis and osteopenia management. Based on our results, we concluded that the above combination is safe and feasible for the clinical control of both conditions.

PLAGL1 Is Identified as a Potential Diagnostic Marker for Co-Occurrence with Osteoporosis and Multiple Myeloma

Background: Osteoporosis (OP) is a common clinical manifestation of multiple myeloma (MM). The aim of this study was to investigate the possible molecular pathways and shared genes in the co-occurrence of OP and MM. Methods: The Gene Expression Omnibus database was used to retrieve gene expression information. Use WGCNA and differential analysis to screen out Hub genes. The GENEMANIA was used to build protein-protein interaction (PPI) networks. Enrichment analyses were performed to explore the functions. Validation datasets were selected to verify the diagnostic marker reliability of PLAGL1. The immune microenvironment of diseases was analyzed by immune infiltration analyses. Results: We confirmed a hub gene called PLAGL1, which is significantly under-expressed in both OP and MM. We found hub genes were associated with glucose and energy metabolism. Subsequently, the reliability of PLAGL1 for diagnosing OP and MM was verified using ROC curves, with all areas under the curve > 0.75. Moreover, PLAGL1 regulates t lymphocytes and may participate in the occurrence of OP in MM through immune pathways. Conclusions: PLAGL1 is a hub gene for the co-occurrence of OP and MM. It can regulate T-lymphocyte involvement in disease development. PLAGL1 may be a novel diagnostic marker for the co-occurrence of OP and MM.

The role of autophagy in the treatment of osteoporosis by Chinese medicines(natural)

Osteoporosis is one of the common orthopaedic diseases,characterised by increased bone fragility due to reduced bone mass and microstructural degeneration,posing a great threat to patients’quality of life and safety.In recent years,Chinese medicine(natural)has had a unique advantage in the treatment of osteoporosis and has shown good efficacy.Autophagy is an inherent cellular survival mechanism for the removal and recycling of damaged proteins and organelles and plays an important role in maintaining the stability of the intracellular environment and organ function.Therefore,this article aims to provide a comprehensive review of these Chinese medicines(natural)for the treatment of osteoporosis through autophagy.They have been intensively studied and reported to have effects such as promoting osteogenesis and anti-bone resorption.The Chinese medicines include plants such as Cistanche deserticola,Epimedium,Curculigo orchioides Gaertn,Achyranthes bidentata Blume,Leonurus japonicus Houtt,Ginseng,Chuanxiong Rhizome,Eucommia ulmoides,Morindae Officinalis Radix,Curcuma longa,Polygoni Cuspidati Rhizoma et Radix,Anemarrhena asphodeloides Bunge,Salvia miltiorrhiza Bge and Pueraria Lobata,thus providing evidence for the use of alternative herbal therapies for the effective treatment of osteoporosis.

To Explore the Relationship between Lower Extremity Vascular Sclerosis and Osteoporosis in Elderly Men with Type 2 Diabetes Mellitus

Objective: To investigate the correlation between lower extremity vascular sclerosis and osteoporosis in elderly men with type 2 diabetes mellitus. Methods: A total of 359 elderly male patients with type II diabetes hospitalized in the First Affiliated Hospital of Chongqing Medical University from January 2018 to June 2023 were retrospectively collected. According to the BMD (Bone Density Value), the patients were categorized into osteoporotic (T ≤ -2.5, n = 248) and non-osteoporotic groups (T > -2.5, n = 111). T test and Chi-square test were used to evaluate the differences in clinical data, biochemical markers and ABI between two groups. Multivariate logistic regression was used to analyze the risk factors of osteoporosis in elderly men with type 2 diabetes mellitus. Results: Compared with the non-osteoporotic group, the differences in diabetes course, systolic blood pressure, ABI, BMI, uric acid, triglyceride, and HDL in the osteoporotic group were statistically significant (P < 0.05). Logistic multivariate regression analysis showed that lower extremity vascular sclerosis was an independent risk factor for osteoporosis in elderly men with type 2 diabetes mellitus (P Conclusion: Atherosclerosis of the lower extremities in elderly men with T2DM is closely related to osteoporosis, and can lead to a decrease in bone mass, and an increase in osteoporosis.

Mesenchymal stem/stromal cells-derived exosomes for osteoporosis treatment

Osteoporosis is a systemic bone disease,which leads to decreased bone mass and an increased risk of fragility fractures.Currently,there are many anti-resorption drugs and osteosynthesis drugs,which are effective in the treatment of osteoporosis,but their usage is limited due to their contraindications and side effects.In regenerative medicine,the unique repair ability of mesenchymal stem cells(MSCs)has been favored by researchers.The exosomes secreted by MSCs have signal transduction and molecular delivery mechanisms,which may have therapeutic effects.In this review,we describe the regulatory effects of MSCs-derived exosomes on osteoclasts,osteoblasts,and bone immunity.We aim to summarize the preclinical studies of exosome therapy in osteoporosis.Furth-ermore,we speculate that exosome therapy can be a future direction to improve bone health.