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Objective To investigate the changes and predictive value of Omentin-1 levels in patients with type 2 diabetes mellitus(T2DM)under different bone metabolic status.Methods A total of 120 T2DM pa-tients admitted to a hospital from June 2021 to December 2022 were selected and divided into group A(normal bone mass,T-value-1.0,36 cases),Group B(bone loss,-2.5＜T-value＜-1.0,49 cases)and group C(osteoporosis,T-value-2.5,35 cases)according to different bone mineral density.Another 50 healthy sub-jects who underwent physical examination in a hospital during the same period were selected as the healthy control group.Basic data,serum Omentin-1 and bone metabolism levels of the 4 groups were compared,and the correlation between serum Omentin-1 and bone metabolism and blood glucose levels was analyzed by Pear-son correlation analysis.Multiple stepwise regression analysis was conducted to analyze the factors affecting bone mineral density in T2DM patients.Receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of serum Omentin-1 level in T2DM with osteoporosis.Results The fasting blood glucose(FBG)level of groups A,B and C was higher than that of healthy control group,and the hemoglobin A1c(HbA1c)and homeostasis model assessment of insulin resistance(HOMA-IR)of healthy control group,group A and group B were lower than that of group C,with statistical significance(P＜0.05).Omentin-1,type Ⅰ procollagen N-terminal propeptide(P Ⅰ NP)and osteocalcin(BGP)in healthy control group,group A and group B were higher than those in group C,while the β-CTX sequence of type Ⅰ collagen in healthy con-trol group,group A and group B was lower than that in group C,and the difference was statistically signifi-cant(P＜0.05).Pearson correlation analysis showed that the serum Omentin-1 level in T2DM patients was negatively correlated with the levels of HbA1c,HOMA-IR and β-CTX(r=-0.770,-0.807,-0.759,P＜0.05),and positively correlated with the levels of P Ⅰ NP and BGP(r=0.868,0.879,P＜0.05),but no sig-nificant correlation with FBG level(r=-0.085,P=0.152).Omentin-1,P Ⅰ NP,β-CTX,BGP,HbA1c and HOMA-IR were independent influencing factors of BMD in T2DM patients(P＜0.05).ROC curve analysis showed that the area under the curve of serum Omentin-1 level predicting T2DM with osteoporosis was 0.835(95％CI:0.764-0.906),and when the cut-off value was 50.325 ng/mL,the sensitivity was 0.854,the speci-ficity was 0.801,and the Youden index was 0.655.Conclusion Serum Omentin-1 expression is low in T2DM patients,and its expression is closely related to bone mineral density,bone metabolism and insulin resistance in T2DM patients,and can effectively predict the occurrence of T2DM with osteoporosis.
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BACKGROUND:Osteoporosis is a disease in which bone density and structure are destroyed and fractures are caused by increased bone fragility,leading to high clinical disability and mortality rates. OBJECTIVE:To review the research progress in the role of bone immunity in physiological and pathological processes related to bone metabolism,providing ideas for the research and clinical application of bone immunity in bone diseases. METHODS:The first author searched PubMed and CNKI databases in November 2022 for relevant literature using the keywords of"osteoimmunology,immuno-skeletal interface,bone metabolism,skeletal metabolism,lymphocyte,immune factor"in English and Chinese,respectively.The time range of retrieval was mainly from January 2010 to November 2022,and a small number of classical long-term literatures were included.After reading the topic and abstract for preliminary screening and excluding repetitive studies,low-quality journals and unrelated literature,81 documents were finally included for review. RESULTS AND CONCLUSION:Osteoimmunology refers to that bone and immune cells share the same microenvironment and interact with each other to jointly perform the"bone immune system,"which includes all cells in the bone marrow.Immuno-skeletal interface has protective effects on bone under physiological conditions,but it may lead to bone destruction under pathological conditions.Osteoprotegerin is mainly derived from B cells and can inhibit osteoclast metabolism.However,when the body is in an inflammatory state,T cells and B cells work together to promote bone resorption.In addition,interleukin-1,interleukin-6 and tumor necrosis factor-α regulate the expression of receptor activator of nuclear factor-κB ligand in vivo and affect bone metabolism.In most clinical diseases(such as rheumatoid arthritis,estrogen deficiency,HIV infection,and hyperparathyroidism),the immuno-skeletal interface interacts with the bone immune system,resulting in the regulation of bone metabolism.In terms of clinical prospect,the interaction between bone immunity and bone metabolism should be studied in order to propose new strategies for therapeutic intervention to reduce the risk of fracture.
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BACKGROUND:Currently,there is a lack of large sample studies to analyze the bone metabolism level of patients with femoral head necrosis of different etiologies and stages,which is not conducive to the development of better necrosis-promoting repair strategies. OBJECTIVE:To study the bone metabolism of patients with osteonecrosis of the femoral head with different etiologies and Association Research Circulation Osseous(ARCO)stages. METHODS:A retrospective study was performed on 401 patients diagnosed with osteonecrosis of the femoral head as the trial group,and 81 healthy subjects as the control group.The trial group could be divided into three groups according to different etiologies:steroid-induced osteonecrosis of the femoral head,alcoholic osteonecrosis of the femoral head and traumatic osteonecrosis of the femoral head,and were divided into stages Ⅱ/Ⅲ/Ⅳ according to different ARCO stages.Seven bone metabolism-related indicators of all subjects were collected,including bone metabolism-regulating hormone 25-hydroxyvitamin D and bone conversion markers:N-terminal propeptide of type Ⅰ procollagen,degradation product of type Ⅰ collagen,n-terminal middle molecular fragment of osteocalcin,general biochemical markers of bone metabolism:serum calcium,serum phosphorus,serum alkaline phosphatase.The bone metabolism levels of each group were compared and the independent factors associated with osteonecrosis of the femoral head were determined by binary Logistic regression analysis. RESULTS AND CONCLUSION:Compared with the control group,levels of degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen,n-terminal middle molecular fragment of osteocalcin,serum phosphorus and alkaline phosphatase in the trial group were significantly increased(all P＜0.05).Based on the presence or absence of the disease,according to binary Logistic regression analysis,degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen,and n-terminal middle molecular fragment of osteocalcin were independent factors associated with osteonecrosis of the femoral head.The levels of degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen in three groups of patients with different etiologies were higher than normal reference values.The bone metabolism-regulating hormone 25-hydroxyvitamin D and serum calcium in the alcoholic osteonecrosis of the femoral head group were higher than those in the other two groups(P＜0.05).The level of bone metabolism-regulating hormone 25-hydroxyvitamin D in steroid-induced and traumatic osteonecrosis of the femoral head groups was lower than the normal value.There were no significant differences in seven bone metabolism-related indicators in patients with ARCO stages Ⅱ,Ⅲ and Ⅳ osteonecrosis of the femoral head(all P＞0.05),but degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen in these three groups were higher than normal reference values.Bone metabolism-regulating hormone 25-hydroxyvitamin D in patients with ARCO stage Ⅱ and ARCO stage Ⅳ was lower than the normal reference value.It is concluded that the bone metabolism level of osteonecrosis of the femoral head patients was abnormal.The degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen of osteonecrosis of the femoral head patients with different etiologies and ARCO stages were all higher than the normal reference value,and they were in a state of high bone turnover.Degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen and n-terminal middle molecular fragment of osteocalcin may be risk factors for the pathogenesis of osteonecrosis of the femoral head.
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BACKGROUND:The mechanisms and targets of alendronate in the treatment of osteoporosis still need to be investigated in depth. OBJECTIVE:To investigate the mechanism by which alendronate regulates bone metabolism in rats with osteoporosis and to perform a bioinformatics analysis of differentially expressed proteins. METHODS:Female Sprague-Dawley rats were randomly divided into three groups(n=12 per group):model group,alendronate group and sham-operated group.Animal models of osteoporosis were prepared using ovariectomy in the model and alendronate groups.At 4 weeks after modeling,rats in the alendronate group were gavaged with alendronate;the other two groups were given the equal volume of normal saline.After 12 weeks of continuous gavage,the bone mineral density of the tibia was measured and the lumbar spine of the rats was taken for proteomic analysis using Tandem mass tag-liquid chromatography-tandem mass spectrometry technique to identify differentially expressed proteins for gene ontology,Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction analysis. RESULTS AND CONCLUSION:There were 32 up-regulated proteins and 51 down-regulated proteins identified between the alendronate group and model group.Gene ontology enrichment analysis showed that the differentially expressed proteins were mainly involved in molecular functions,such as binding and catalytic activity,and in biological processes,such as cellular process and metabolic process.Kyoto Encylopedia of Genes and Genomes enrichment analysis showed that the differentially expressed proteins in the alendronate group and model group were mainly involved in the biosynthesis of pantothenate and coenzyme A.Protein-protein interaction analysis indicated that among the differentially expressed proteins in the alendronate group and model group,Hspa1l,Enpp3,Unc45a,Myh9 and Cant1 were located at the nodes of the protein-protein interaction network and were closely related to bone metabolism.Overall,these findings indicate that alendronate may regulate bone metabolism in the rat model of osteoporosis by regulating the expression of differentially expressed proteins and biosynthesis of pantothenate and coenzyme A.
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BACKGROUND:Bone formation is the process by which osteoblasts synthesize and secrete osteoid and promote its mineralization,which generally involves mechanical signal transduction.Osteoblasts are primarily regulated by mechanical factors such as gravity,compressive stress,tensile stress,fluid shear stress,and hydrostatic pressure in vivo,and different mechanical stimuli modulate the proliferation,differentiation,and apoptosis of osteoblasts through various mechanisms,including hormones,cytoskeletal proteins,and microRNAs.By clarifying the effects of biomechanical forces on osteoblasts,it provides ideas and a reference basis for the treatment of osteometabolic diseases involving osteoblasts. OBJECTIVE:To review the effects of different biomechanical forces on the biological characteristics of osteoblasts. METHODS:We conducted a literature search using PubMed,Web of Science,FMRS,CNKI,and WanFang databases for relevant publications published from 2000 to 2023,covering basic research and tissue engineering studies related to the effects of biomechanical forces on osteoblasts.Ultimately,a total of 70 articles were reviewed. RESULTS AND CONCLUSION:Different biomechanical forces have an impact on the biological characteristics of osteoblasts,including proliferation,differentiation,and apoptosis,and these effects are dependent on the intensity and duration of the applied force.Specifically,the effects are as follows:(1)Under microgravity conditions,osteoblast proliferation and differentiation are inhibited,resulting in a decrease in bone density and the development of osteoporosis.(2)Compared to microgravity,hypergravity has a promoting effect on osteoblast proliferation.(3)The effects of compressive stress on osteoblasts are dependent on the loading intensity and time.Appropriate compressive stress can promote osteoblast proliferation and differentiation,which is beneficial for bone tissue formation and repair,while excessive compressive stress can cause osteoblast apoptosis and bone tissue destruction.(4)The biological effects of different types of tensile stress on osteoblasts differ.Studies have shown that a strain rate within the range of 0-12%has a promoting effect on osteoblast proliferation.(5)Fluid shear stress can promote osteoblast proliferation and differentiation and enhance the bone-inducing effect of biomaterials.(6)Static hydrostatic pressure can affect the biological behavior of osteoblasts,including proliferation,differentiation,and apoptosis,and these effects are closely related to the time and intensity of the pressure.Understanding the effects of different biomechanical forces on osteoblasts is of great significance for a deeper understanding of bone growth and maintenance mechanisms.
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BACKGROUND:Intestinal flora and its metabolites can participate in the pathological process of osteoporosis and play an important role in the diagnosis and treatment of osteoporosis.In addition,exercise can regulate the intestinal flora and thus affect the occurrence and development of osteoporosis. OBJECTIVE:To summarize the effects and mechanism of intestinal flora on osteoblasts,osteoclasts,and bone marrow mesenchymal stem cells,and the potential role of exercise-mediated intestinal flora in regulating osteoporosis. METHODS:"Intestinal flora,intestinal bacteria,metabolites of intestinal flora,bone metabolism,osteoporosis,exercise"were selected as keywords.Literatures from 1990 to 2023 were retrieved from PubMed and CNKI databases. RESULTS AND CONCLUSION:Changes in the abundance and diversity of intestinal flora and changes in the levels of intestinal flora metabolites such as trimethylamine oxide and bile acid can be used as biomarkers for the diagnosis of osteoporosis.The imbalance of intestinal flora can lead to intestinal barrier dysfunction and excessive production of lipopolysaccharides and trimethylamine oxide,induce the secretion of tumor necrosis factor-α and other inflammatory cytokines,activate the nuclear factor κB signaling pathway and aggravate oxidative stress,thus promoting osteoclast differentiation,inducing osteoblast apoptosis and affecting bone marrow mesenchymal cell migration.Remodeling intestinal flora homeostasis can inhibit inflammatory response,downregulate oxidative stress,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate the osteogenic migration of bone marrow mesenchymal cells to prevent and treat osteoporosis.Exercise can regulate intestinal flora homeostasis,improve intestinal barrier function,promote the secretion of short-chain fatty acids and bile acids,down-regulate serum lipopolysaccharide level,reduce oxidative stress,and then inhibit osteocyte apoptosis,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate osteocyte nutrient metabolism to exert the potential of preventing and treating osteoporosis.
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BACKGROUND:Oleanolic acid can promote osteoblast proliferation and inhibit osteoclast proliferation,thereby improving steroid-induced osteonecrosis of the femoral head,but its specific mechanism of action is not yet fully understood. OBJECTIVE:To explore the mechanism by which oleanolic acid alleviates steroid-induced osteonecrosis of the femoral head in rats by regulating the Wnt/β-catenin signaling pathway. METHODS:Forty Sprague-Dawley rats were randomized into control group,model group,oleanolic acid group and oleanolic acid+sFRP1 group.An animal model of steroid-induced osteonecrosis of the femoral head was established by injecting prednisolone acetate in the latter three groups.Rats in the oleanolic acid group were gavaged with 10 mg/kg/d oleanolic acid and intramuscularly injected with the corresponding saline;rats in the oleanolic acid+sFRP1 group were gavaged with 10 mg/kg/d oleanolic acid and intramuscularly injected with 1 mg/kg/d Wnt inhibitor-sFRP1;and rats in the control and model groups were administered by gavage and intramuscularly injected with equal volumes of saline for 6 weeks.The levels of serum calcium,phosphorus,transforming growth factor-β1,and alkaline phosphatase were detected.Micro-CT was applied to detect femoral morphology.The morphology of femoral tissue was detected by hematoxylin-eosin staining.Cell apoptosis was detected by TUNEL.The levels of Bcl-2,Bax,β-catenin,and Wnt proteins were determined by western blot. RESULTS AND CONCLUSION:Compared with the control group,the trabeculae bone and femoral head of the model group were seriously injured,the serum levels of calcium,phosphorus,and transforming growth factor-β1 were significantly decreased,the levels of Bcl-2,Wnt,and β-catenin proteins in bone tissue were significantly reduced,and the serum alkaline phosphatase level,cell apoptosis rate,and Bax protein level were significantly increased(P<0.05).Compared with the model group,the degree of trabecular thinning in the oleanolic acid group was significantly improved,and the degree of femoral head damage was significantly reduced,serum alkaline phosphatase level,cell apoptosis rate,and Bax protein level were significantly reduced,serum levels of calcium,phosphorus,and transforming growth factor-β1,and levels of Bcl-2,Wnt,and β-catenin proteins in bone tissue were significantly increased(P<0.05).Compared with the oleanolic acid group,the oleanolic acid+sFRP1 group showed opposite changes in the above-mentioned indicators(P<0.05).To conclude,oleanolic acid can improve bone metabolism indicators and trabecular structure and attenuate femoral head necrosis in rats with steroid-induced osteonecrosis of the femoral head,which can be achieved by activating the Wnt/β-catenin signaling pathway.
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BACKGROUND:The pathogenesis of osteoporosis is complex,and its essence is the weakening of bone formation and the enhancement of bone absorption caused by various reasons,resulting in the imbalance of bone metabolism.In recent years,N6-methyladenosine has been found(N6-methyladenosine,m6A)methylation can prevent and treat osteoporosis by regulating bone metabolism. OBJECTIVE:Taking the regulation of bone metabolism by m6A methylation as an entry point,to systematically sort out and summarize the research progress of m6A methylation in osteoporosis,so as to provide certain theoretical reference bases for the search of new therapeutic targets for osteoporosis. METHODS:CNKI,WanFang,VIP,PubMed,MEDLINE,Nature,and Cochrane databases were retrieved for relevant literature published from database inception to 2023.The keywords were"osteoporosis,m6A methylation,bone metabolism,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts"in Chinese and English.Duplicates and obsolete non-referenced documents were excluded,and a total of 73 standard papers were included for further review. RESULTS AND CONCLUSION:m6A methylation can affect the activity and differentiation of bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts through various pathways to regulate bone metabolism and prevent osteoporosis.The regulatory process of m6A methylation is extremely complex,and its related proteins play different roles in different cells.Even in the same kind of cells,the same type of proteins may have radically different roles,regulating different physiological and pathological processes.
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AIM:To investigate the effect of Bushen formulae(BHF)on bone metabolism and its possible mechanism in ovariectomized rats with high salt intake.METHODS:According to the random number table method,80 SPF-grade Sprague-Dawley rats were divided into sham group,ovariectomy(OVX)group,medium-high-salt diet(MSD)group,high-salt diet(HSD)group,BHF group,BHF with normal saline(BHF+NS)group,BHF+MSD group,and BHF+ HSD group,with 10 rats in each group.After modeling,different diets and BHF formula interventions were administered,and the concentrations of sodium chloride added to MSD group and HSD group were 2%(w/w)and 8%(w/w),respective-ly.The dose of BHF was 7.8 g·kg-1·d-1,once a day,and the treatment lasted for 12 weeks.Bone density,bone microar-chitecture,bone parameters,bone metabolism biomarkers,bone histopathological changes,the expression of epithelial sodium channel α(ENaCα),Na-Cl cotransporter(NCC),and voltage-gated chloride channel 3(ClC-3)proteins in bone tissue were detected in each group.RESULTS:Compared with sham group,the rats in OVX group had reduced bone density and destroyed bone microstructure.Compared with OVX group,the bone microstructure in MSD and HSD groups was more significantly damaged,while the levels of bone formation markers,bone glycoprotein(BGP)and type Ⅰ procolla-gen N-terminal peptide(PINP),were significantly increased in HSD group(P<0.05).Moreover,the levels of bone re-sorption markers,such as amino-terminal cross-linked telopeptides of type Ⅰ collagen(NTX),carboxy-terminal cross-linked telopeptides of type Ⅰ collagen(CTX)and tartrate-resistant acid phosphatase(TRACP),were significantly in-creased(P<0.05),indicating that bone metabolism was in high-conversion state.High-salt diet accelerated the structural destruction of bone trabeculae,and Western blot results showed that high-salt diet caused decreases in the protein expres-sion levels of ENaCα and ClC-3 and an increase in the protein expression level of NCC in femoral tissues(P<0.05).After BHF intervention,the expression of relevant ion channels caused by high salt could be regulated to different degrees.CONCLUSION:Bushen formulae could differentially regulate the expression of relevant ion channels ENaCα,ClC-3,and NCC induced by high salt to different degrees,which has certain ameliorative and therapeutic effects on the imbalance of bone metabolism.
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Bone is a dynamic tissue undergoing continuous regeneration and reconstruction， and its metabolic activities are mainly regulated by bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. In addition， a variety of cells such as adipocytes， inflammatory cells， endothelial cells， and nerve cells can affect bone metabolism by changing the bone marrow microenvironment. The incidence of bone metabolic diseases caused by bone metabolism disorders is increasing with aging of the population. At present， the clinical treatment of bone metabolic diseases has the disadvantages of long cycle， high cost and many side effects. Therefore， there is an urgent need for safe and effective prevention and treatment drugs. Corylin is an isoflavonoid extracted from Psoraleae Fructus， which has a variety of pharmacological effects such as anti-inflammatory， anti-oxidation， anti-tumor， anti-atherosclerosis， attenuating obesity and improving insulin resistance. Studies have shown that corylin not only exerts osteoprotective effects by promoting osteoblast differentiation and inhibiting osteoclast differentiation， but also plays a positive role in bone metabolism by regulating lipid metabolism， inflammatory response， angiogenesis and anti-aging. The current review overviews the effects and mechanisms of corylin on regulating bone metabolism directly or indirectly， hoping to open up a new perspective for the prevention and treatment of osteoporosis， fracture， osteoarthritis and other related diseases.
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ObjectiveTo explore the therapeutic mechanism of Bushen Huoxue prescription from the perspective of bone metabolism by observing the clinical efficacy of this prescription in treating femoral head necrosis （ONFH， syndrome of liver and kidney deficiency） and its influences on bone metabolism indexes： N-terminal propeptide （PINP） and β-collagen degradation product （β-CTX）. MethodSixty-six ONFH patients with the syndrome of liver and kidney deficiency in Zhengzhou Traditional Chinese Medicine Hospital of Orthopedics from December 2021 to September 2022 were selected. The patients were randomized into an experimental group and a control group by the parallel control method， with 33 patients in each group. The experimental group received Bushen Huoxue prescription orally， while the control group received Xianlinggubao Capsules orally， with a treatment cycle of 6 months. The visual analogue scale （VAS） score， Harris score， Association Research Circulation Osseous （ARCO） staging， imaging changes， quantitative scores of TCM symptoms， and serum levels of PINP and β-CTX were determined before and after treatment. The occurrence of adverse events and reactions was recorded. ResultThe total response rate in the experimental group was 83.87% （26/31）， which was higher than that （68.75%， 22/32） in the control group （Z=-2.096， P<0.05）. After treatment， the single and total scores of TCM symptoms， VAS score， and β-CTX level decreased in the two groups （P<0.05）. Moreover， the decreases in the scores of hip pain， lower limb mobility， soreness of waist and knees， and lower limb flaccidity， total score of TCM symptoms， VAS score， and β-CTX level in the experimental were larger than those in the control group （P<0.05）. After treatment， the imaging results showed no significant improvement in the two groups. The Harris score and PINP level in both groups increased after treatment （P<0.05）， and the increases were more obvious in the experimental group than in the control group （P<0.05）. No serious adverse event or adverse reaction appeared during the observation period. ConclusionBushen Huoxue prescription can relieve pain and TCM symptoms and improve the hip joint function in treating ONFH patients with the syndrome of liver and kidney deficiency. It can inhibit the development of ONFH， increase PINP， and decrease β-CTX. No obvious side effect appears during the clinical observation period， which shows that Bushen Huoxue prescription has good safety.
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Bone metabolism refers to the decomposition and anabolism occurring during bone remodeling， and its balance is regulated by bone resorption and bone formation. A slight deviation of this balance causes various skeletal diseases， such as osteoporosis and renal osteodystrophy. Traditional Chinese medicine （TCM） monomers and compounds have certain advantages in treating bone metabolism diseases. The Wnt signaling pathway includes the canonical Wnt signaling pathway， dependent on β-catenin， and the non-canonical Wnt signaling pathway， independent of β-catenin. Both types of pathways can maintain bone metabolism balance by regulating bone formation and bone resorption and are essential for bone development， bone mass maintenance， and bone remodeling. A variety of TCM monomers （albiflorin， catalpol and icariin） and formulas （Zuogui pill， Yishen gugu prescription， Duzhong jiangu prescription， etc.） have been confirmed to promote differentiation of bone marrow mesenchymal stem cells， proliferation and differentiation of osteoblasts， bone injury repair， and osteoporosis improvement by activating the Wnt signaling pathway in recent years. Here， this article summarizes the research progress in the Wnt signaling pathway regulation of bone metabolism by TCM monomers and compounds to provide ideas for the clinical application of TCM and the research and development of new drugs for the prevention and treatment of bone metabolism diseases.
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Senile osteoporosis (SOP) is a systemic bone disease characterized by increased susceptibility to fractures. The pathogenesis of SOP is complex and not well understood. Currently, the rapid aging model mouse, senescence accelerated mouse prone 6 (SAMP6), is an ideal model for studying the mechanisms of SOP development and exploring its prevention and treatment. This model exhibits characteristics including increased bone fragility, degradation of bone microstructure, loss of bone matrix, and abnormal metabolism and dysfunction of bone cells, faithfully replicating the process of SOP occurrence and progression at both macroscopic and microscopic levels.
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Objective:To analyze the bone turnover markers in systemic lupus erythematosus (SLE) patients with different disease activity and the risk factors of osteoporosis.Methods:In this retrospective study, a total of 417 SLE inpatients were enrolled from the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi′an Jiaotong University, from March 2019 to June 2020. According to SLEDAI score, the patients were divided into 3 groups: 281 patients disease with inactive disease group; 99 patients with mild active disease group; and 37 patients with moderate/severe active disease. ANOVA test was used to compare the differences in serum bone turnover markers (PTH, NOST, VITDT, β-crossl, TP1NP, Ca and P) and bone density (Spine L 1~4 and left femur) among the three groups, and Tukey's method was used for the two groups comparison. Logistic regression analysis was used to investigate the risk factors of osteoporosis. Results:Serum VITDT, β-crossl and Ca levels were significantly different among the 3 groups ( F=11.66, P<0.001; F=7.22, P<0.001; F=29.38, P<0.001). Compared with patients in the inactive group, patients with both the mild disease group (VITDT: t=3.94, P<0.001; Ca: t=5.10, P<0.001) and the moderate/severe disease group (VITDT: t=3.33, P<0.001; Ca: t=7.19, P<0.001) had lower VITDT levels [(20.3±9.7) ng/ml vs. (15.9±9.3) ng/ml vs. (14.8±7.4) ng/ml] and serum Ca levels [(2.19±0.15)mmol/L vs. (2.09±0.21)mmol/L vs. (2.00±0.16)mmol/L]. Moreover, the moderate/severe disease group patients had much lower serum Ca levels ( t=2.36, P<0.05), compared with patients with the mild disease group. Compared with the patients with inactive group, both the mild activey group ( t=3.06, P<0.01) and the moderate/severe activie group ( t=2.99, P<0.01) patients had higher serum β-crossl levels [(419±316) pg/ml vs. (543±424) pg/ml vs. (586±343) pg/ml]. Compared with patients with the inactive disease group both patienes with the mild active group and the moderate/severe disease group patients had significantly decreased spine BMD ( t=2.75, P<0.01; t=2.71, P<0.01), Z-score ( t=5.65, P<0.001; t=4.70, P<0.001), T-score ( t=3.02, P<0.01; t=3.37, P<0.001), whereas, no difference was found between the mild disease group and moderate/severe disease group. Compared with the inactive group patients, both the mild active group and moderate/severe disease group patients had lower left femur BMD levels ( t=2.83, P<0.001; t=2.65, P<0.001) and T-score ( t=2.24, P<0.05; t=1.977, P<0.05) and no difference was found between the mild disease group and the moderate/severe disease group. Logistic regression analysis showed that age [ HR (95% CI)=1.080 (1.052, 1.109), P<0.001], BMI [ HR (95% CI)=0.801 (0.704, 0.911), P<0.001], SLEDAI score [ HR (95% CI)=1.047 (1.025, 1.076), P<0.05] and cumulative glucocorticoids dose [1.046 (1.006, 1.087), P<0.05] were associated with osteoporosis of SLE patients. Conclusion:Abnormal bone metabolism and decreased bone density are associated with SLE disease activity in SLE patients, especially in those with advanced age, low BMI and receiving high cumulative dose of glucocorticoids. Osteoporosis should be proactively prevented in the SLE patients.
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Objective To investigate the changes and clinical significance of serum 25-hydroxyvitamin D3[25(OH)D3],blood calcium and bone metabolism indexes in menopausal women with benign paroxysmal positional vertigo(BPPV).Methods A total of 103 menopausal BPPV patients from Hangzhou Ninth People's Hospital from August 2020 to August 2021 were enrolled into BPPV group.According to the one-year recurrence situation,they were divided into recurrence group(n=18)and non-recurrence group(n=85).A total of 50 healthy menopausal women during the same period were enrolled as control group.The clinical data,serum 25(OH)D3,calcium and bone metabolism indexes[procollagen typeⅠN-terminal propeptide(PINP),N-terminal midfragment of osteocalcin(N-MID),β-isomerised C-terminal telopeptide of collagen typeⅠ(β-CTX),bone alkaline phosphatase(BALP)]were collected.Logistic regression model was constructed to analyze the risk factors of BPPV in menopausal women.The predictive value of related indexes for BPPV recurrence was analyzed by receiver operating characteristic curves.Results The serum 25(OH)D3 level in BPPV group was significantly lower than that in control group(P<0.05),and the proportion of long-term irregular diet,PINP,N-MID and BALP levels were significantly higher than those in control group(P<0.05).Multivariate Logistic regression analysis showed that low 25(OH)D3,high PINP,high N-MID and high BALP were all risk factors for BPPV in menopausal women(P<0.05).The 25(OH)D3 level in recurrence group was significantly lower than that in non-recurrence group(P<0.05),and the PINP,N-MID and BALP levels were significantly higher than those in non-recurrence group(P<0.05).The area under the curve(AUC)of 25(OH)D3,PINP,N-MID,BALP and the four combined predictions for BPPV recurrence were 0.833,0.654,0.697,0.782 and 0.910,respectively,and the AUC of the four combined predictions was the largest.The sensitivity and specificity were 98.97%and 70.62%,respectively.Conclusion There is no significant change in level of serum calcium in menopausal women with BPPV.Decreased serum 25(OH)D3 and increased PINP,N-MID and BALP are risk factors of BPPV,which can be applied to predict BPPV recurrence.
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Objective: To analyze correlation of occupational hydrogen fluoride exposure to low doses of bone metabolism index through occupational epidemiological investigation and benchmark dose calculation. Methods: In May 2021, using cluster sampling method, 237 workers exposed to hydrogen fluoride in a company were selected as the contact group, and 83 workers not exposed to hydrogen fluoride in an electronics production company were selected as the control group. The external exposure dose and urinary fluoride concentration, blood and urine biochemical indicators of the workers was measured.The relationship between external dose and internal dose of hydrogen fluoride was analyzed. The external dose, urinary fluoride was used as exposure biomarkers, while serum osteocalcin (BGP), serum alkaline phosphatase (AKP) and urinary hydroxyproline (HYP) were used as effect biomarkers for bone metabolism of hydrogen fluoride exposure. The benchmark dose calculation software (BMDS1.3.2) was used to calculate benchmark dose (BMD) . Results: Urine fluoride concentration in the contact group was correlated with creatinine-adjusted urine fluoride concentration (r=0.69, P=0.001). There was no significant correlation between the external dose of hydrogen fluoride and urine fluoride in the contact group (r=0.03, P=0.132). The concentrations of urine fluoride in the contact group and the control group were (0.81±0.61) and (0.45±0.14) mg/L, respectively, and the difference between the two groups was statistically significant (t=5.01, P=0.025). Using BGP, AKP and HYP as effect indexes, the urinary BMDL-05 values were 1.28, 1.47 and 1.08 mg/L, respectively. Conclusion: Urinary fluoride can sensitively reflect the changes in the effect indexes of biochemical indexes of bone metabolism. BGP and HYP can be used as early sensitive effect indexes of occupational hydrogen fluoride exposure.
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Humanos , Fluoruros/efectos adversos , Ácido Fluorhídrico , Benchmarking , Biomarcadores , Exposición Profesional/efectos adversosRESUMEN
Objective:To investigate the effect of bone marrow derived mesenchymal stem cells (BMSC) transplantation on bone metabolism and its mechanism in ovariectomized osteoporosis rats.Methods:Forty clean SD female rats aged 7 weeks were divided into 4 groups according to the random number table method: sham operation group, model group, the transplantation group, positive control group, in addition to control the rest of the group were performed bilateral oophorectomy build osteoporosis rats model, after 2 months of model establishment, rats in transplantation group were injected with 80 μl/kg PBS solution containing bone marrow mesenchymal stem cells through tail vein, rats in sham operation group and model group were injected with the same amount of PBS solution through tail vein, and rats in positive control group were given Xianlinggubao (0.5 g/100 g) by gavage every day. Serum and femur were collected 14 days after treatment. Hematoxylin and eosin staining (HE) was used to observe the histopathological changes of femur. Micro-CT was used to measure bone mineral density and bone parameters. The expression levels of osteocalcin, osteoprotegerin, alkaline phosphatase and insulin-like growth factor 1 were detected by enzyme-linked immunosorbent assay (ELISA) kit. The serum levels of calcium, phosphorus and magnesium were measured by spectrophotometer. The protein expressions of RANKL, OPG, TRAF6 and NF-KB1 in femur of each group were detected by Western blot.Results:Compared with the sham operation group, the bone mineral density (BMD) of the model group was decreased by (0.28±0.01) g/cm 3, bone volume fraction (BMD) was decreased by (0.28±0.01) g/cm 3. BV/TV) decreased by (19.73±2.02) %, trabecular thickness (Tb.Th) decreased by (0.082±0.008) mm, trabecular number (Tb.N) decreased by (1.60±0.17) mm -1 and trabecular separation/spacing (Tb.Sp) increased (0.273±0.024) mm, osteoprotegerin (489.49±55.29) ng/L, alkaline phosphatase (229.13±15.05) U/L, insulin-like growth factor-1 (236.64±14.32) μg/L, and osteocalcin were decreased (1.866±0.109) μg/L, calcium (11.98±1.09) mg/dl, phosphorus (6.85±0.68) mg/dl, and magnesium decreased (0.62±0.04) mg/dl) , the relative expression level of RANKL increased (1.05±0.09) , the relative expression level of OPG decreased (0.58±0.08) , the relative expression level of RANKL increased (0.74±0.10) , and the relative expression level of NF-kB1 increased (1.01±0.11) ( P<0.05) ; bone mineral density, bone mineral density, bone mineral density BMD (0.38±0.04 g/cm 3, BV/TV (26.73±2.74) %, Tb.Th (0.094±0.006) mm, Tb.N (2.67±0.09) mm-1 and Tb.Sp were decreased (0.241±0.026) mm) , osteoprotegerin (720.09±67.41) ng/L, alkaline phosphatase (269.48±14.15) U/L, insulin-like growth factor 1 (IGF-1) decreased (335.95±24.13) μg/L, and osteocalcin increased (1.392±0.153) μg/L, calcium (7.12±0.53) mg/dl, phosphorus (4.54±0.32) mg/dl, magnesium (0.87±0.08) mg/dl. RANKL relative expression level increased (0.59±0.05) , OPG relative expression level decreased (0.97±0.10) , RANKL relative expression level increased (0.45±0.06) , NF-kB1 relative expression level increased (0.72±0.06) ( P<0.05) ;bone mineral density, bone mineral density, bone mineral density BMD (0.36±0.05) g/cm 3, BV/TV (28.72±3.20) %, Tb.Th (0.096±0.011) mm, Tb.N (2.85±0.24) mm -1 Tb.Sp was basically unchanged (0.241±0.027) mm, osteoprotegerin was decreased (716.78±36.90) ng/L, alkaline phosphatase was basically unchanged (270.65±18.59) U/L, and insulin-like growth factor 1 was decreased (336.94±17.50) μg/L, osteocalcin (1.377±0.101) μg/L, calcium (7.13±0.80) mg/dl, phosphorus (4.58±0.71) mg/dl, and magnesium (0.89±0.04) remained unchanged mg/dl, the relative expression level of RANKL increased (0.55±0.08) , the relative expression level of OPG decreased (0.98±0.13) , the relative expression level of RANKL was basically unchanged (0.40±0.05) , and the relative expression level of NF-kB1 increased (0.65±0.09) ( P<0.05) . Conclusion:Bone marrow mesenchymal stem cell transplantation can improve osteoporosis in ovariectomized rats by regulating bone metabolism and serum levels of calcium, phosphorus and magnesium, which may be related to RANKL/OPG/TRAF6 pathway.
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Objective:To investigate the correlation between serum recombinant sclerostin (SOST) and dickkopf-related protein 1 (DKK-1) levels and bone metabolism indexes in patients with osteoporosis after differentiated thyroid cancer surgery.Methods:A total of 110 patients diagnosed with osteoporosis after differentiated thyroid cancer surgery were recruited as the study group, and another 110 patients without osteoporosis diagnosed after differentiated thyroid cancer surgery were recruited as the control group. The general data, bone mineral density, serum SOST, DKK-1 levels and bone metabolism indicators N-terminal propeptide of type I procollagen (PINP), bone alkaline phosphatase (BALP), beta-isomerized C-telopeptide (β-CTX), 25-hydroxyvitamin D3 [25- (OH) D3] levels were compared between the two groups. The correlation between serum SOST, DKK-1 levels and bone metabolism indexes was analyzed, and the risk factors affecting the formation of osteoporosis were explored.Results:The T value of bone mineral density in the study group (-3.27±0.92) was significantly lower than that in the control group (-1.23±0.27, t=22.32, P<0.001). The serum SOST (15.84±1.34, t=32.53, P<0.001) and DKK-1 (5.96±1.40, t=4.82, P<0.001) levels in the study group were significantly higher than those in the control group (SOST: 10.24±1.21, DKK-1: 5.05±1.40). The serum PINP (40.95±9.84, t=7.59, P<0.001), BALP (23.14±5.26, t=5.06, P<0.001) and β-CTX (1.07±0.54, t=4.96, P<0.001) in the study group were significantly higher than those in the control group (31.48±8.64, 19.64±4.99, 0.78±0.29), and the 25- (OH) D3 level (13.68±4.49) was significantly lower than that of the control group (18.31±5.72, t=6.68, P<0.001). Serum SOST was positively correlated with PINP ( r=0.33, P=0.001), BALP ( r=0.23, P=0.016) and β-CTX ( r=0.19, P=0.046), but not with 25- (OH) D3 ( r=-0.09, P=0.349). Serum DKK-1 was positively correlated with PINP ( r=0.19, P=0.044), BALP ( r=0.26, P=0.007) and β-CTX ( r=0.21, P=0.028), but not with 25- (OH) D3 ( r=-0.16, P=0.088). Serum SOST and DKK-1 levels were independent risk factors for osteoporosis (all P<0.05) . Conclusion:Serum SOST and DKK-1 levels are independent risk factors for the formation of osteoporosis, which are significantly positively correlated with bone metabolism indexes PINP, BALP, and β-CTX in patients with osteoporosis after differentiated thyroid cancer surgery.
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Objective:To investigate the relationship between serum soluble receptor activator of nuclear factor-κB ligand (sRANKL), Omentin-1 levels and postmenopausal osteoporosis (PMOP) .Methods:A total of 310 menopausal patients admitted to Qingdao Municipal Hospital from Jun. 2017 to Jul. 2021 were selected, including 165 patients with PMOP and 145 women with simple menopause as the control group. Serum sRANKL and Omentin-1 levels were detected by ELISA. Bone mineral density and bone metabolism indexes [N-terminal propeptide of typeⅠprecollagen (PINP), bone alkaline phosphatase (BALP), β isomer of the C-terminal telopeptide of type Ⅰ collagen (β-CTX) and osteocalcin (OC) ] were compared between the two groups. The correlation between serum sRANKL and Omentin-1 levels and bone mineral density and bone metabolism indexes in PMOP patients was analyzed by Pearson. The predictive value of sRANKL and Omentin-1 to PMOP was analyzed by ROC curve. Logistic regression analysis of the influence of multiple factors on PMOP.Results:Compared with the control group (15.62±4.41) (42.56±8.53), the serum sRANKL level (26.63±8.12) was increased and Omentin-1 level (32.32±5.52) was decreased in PMOP group ( t=14.55, P<0.001; t=12.69, P<0.001). The serum sRANKL in PMOP group was positively correlated with PINP, β-CTX and OC, while the serum Omentin-1 level was negatively correlated with the above indexes by Pearson analysis. ROC curve showed that serum sRANKL and Omentin-1 had important reference significance in predicting PMOP. Logistic regression suggested that increased sRANKL and decreased Omentin-1 were risk factors for PMOP. Conclusion:Serum sRANKL and Omentin-1 in patients with PMOP are correlated with bone mineral density and bone metabolism, and have potential as diagnostic targets of PMOP.
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Objective:To study the correlation of bone metabolism biomarkers between newborn twins and their mothers during pregnancy.Methods:From January 1, 2018 to June 30, 2022, newborn twins with mild symptoms admitted to the neonatal department of our hospital were retrospectively reviewed. The clinical data of the twins and their mothers were collected, including bone metabolism biomarkers of the twins within 3 d after birth and their mothers within last month during pregnancy. The twins were assigned into different groups according to gestational age(GA), birth weight(BW), the relationship between BW and GA(appropriate for GA(AGA),small for GA(SGA) and large for GA(LGA), birth season, gender, and the mothers' age, ethnicity, pre-delivery body mass index (BMI), gestational BMI increase, number of births and chorionic properties. The correlations of bone metabolism biomarkers between the twins and their mothers were analyzed.Results:A total of 302 pairs of twins were included. The incidence of insufficient or deficient serum 25-(OH)D 3 was 97.4% among the mothers, and 87.7% among the twins. The levels of blood phosphorus ( r=0.262, P<0.001) and 25-(OH)D 3 ( r=0.239, P=0.002) in mothers were positively correlated with the twin with larger BW. No significant differences existed in 25-(OH)D 3 between genders, AGA,SGA and LGA, birth season, and mothers' age, ethnicity, pre-delivery BMI, gestational BMI increase and chorionic properties( P>0.05). 25-(OH)D 3 in the twins were positively correlated with BW and 25-(OH)D 3 of mothers before delivery ( P<0.05) and negatively correlated with number of births ( P<0.05). Conclusions:In most mothers and their newborn twins, 25-(OH)D 3 are insufficient or deficient. The levels of blood phosphorus and 25-(OH) D 3 are correlated between the newborns and their mothers. The lower the BW of the newborn, the more times the mother give birth and the lower the mother's pre-delivery 25-(OH)D 3 level, the lower the newborn's 25-(OH)D 3 level.