Effect of Osteoking on Inflammatory Injury and NF-κB/NFATc1 Signaling Pathway in Model Mice with Postmenopausal Osteoporosis / 中国实验方剂学杂志

ObjectiveTo explore the possible mechanism of Osteoking （OK） on postmenopausal osteoporosis （PMOP）. MethodForty adult female mice were randomly divided into a sham operation （Sham） group， osteoporosis model （OVX） group， estradiol intervention （E2） group， and OK group， with 10 mice in each group. The modeling was completed by conventional back double incision ovariectomy， and the corresponding drugs were given one week later. After 12 weeks， the body mass and uterine index of mice were measured， and the pathological changes of bone tissue and the number of osteoclasts （OCs） were determined by hematoxylin-eosin （HE） and tartrate-resistant acid phosphatase （TRAP） staining， respectively. Bone mineral density （BMD）， trabecular number （Tb.N）， trabecular separation （Tb.Sp）， and bone volume fraction （BV/TV） were measured by microcomputed tomography （Micro-CT）. The maximum load of the femur was detected by a three-point bending test. The contents of tumor necrosis factor-α （TNF-α） and bone resorption marker C-terminal telopeptide of type Ⅰ collagen （CTX-1） were measured by enzyme linked immunosorbent assay （ELISA）. The protein expression levels of nuclear factor-kappa B p65 （NF-κB p65）， phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65）， nuclear factor kappa B inhibitor alpha （IκBα）， phosphorylated nuclear factor kappa B alpha （p-IκBα）， nuclear factor of activated T cells 1 （NFATc1）， and proto-oncogene （c-Fos） were detected by Western blot. The mRNA expressions of OCs-related specific genes matrix metalloproteinase-9 （MMP-9）， NFATc1， TRAP， cathepsin K （CTSK）， and c-Fos were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the Sham group， the uterine index decreased significantly in the OVX group， and the body mass （BMI） increased significantly. The structure of bone trabeculae was completely damaged， and the number of OCs increased. BMD， Tb.N， BV/TV， and maximum load decreased， while Tb.Sp was up-regulated. The levels of TNF-α and CTX-1 in serum were up-regulated. The protein expressions of c-Fos， p-NF-κB p65/NF-κB p65， NFATc1， and p-IκBα/IκBα were increased. The mRNA expressions of NFATc1， c-Fos， CTSK， TRAP， and MMP-9 were up-regulated （P<0.05， P<0.01）. Compared with the OVX group， the body mass of the OK and E2 groups decreased， and the uterine index increased. The bone trabeculae increased， and the number of OCs decreased. BMD， Tb.N， BV/TV， and maximum load increased， while Tb.Sp decreased. The levels of TNF-α and CTX-1 in serum were decreased. The protein expressions of c-Fos， p-NF-κB p65/NF-κB p65， NFATc1， and p-IκBα/IκBα were decreased， and the mRNA expressions of NFATc1， c-Fos， CTSK， TRAP， and MMP-9 were decreased （P<0.05， P<0.01）. ConclusionOK can inhibit the NF-κB/NFATc1 signaling pathway and reduce bone mass loss by reducing the level of inflammatory injury factors in PMOP mice， which is one of the mechanisms for treating PMOP.

The Relationship between Bone Mineral Densitometry and Visceral Adiposity Index in Postmenopausal Women / A relação entre a densitometria mineral óssea e o índice de adiposidade visceral em mulheres na pós-menopausa

Abstract Objective It was aimed to compare visceral adiposity index (VAI) levels in patients with normal bone mineral density (BMD), osteopenia, and osteoporosis. Methods One hundred twenty postmenopausal women (40 with normal BMD, 40 with osteopenia, and 40 with osteoporosis) between the ages of 50 to 70 years were included in the study. For females, the VAI was calculated using the formula (waist circumference [WC]/[36.58 + (1.89 x body mass index (BMI))]) x (1.52/High-density lipoprotein [HDL]-cholesterol [mmol/L]) x (triglyceride [TG]/0.81 [mmol/L]). Results The time of menopause from the beginning was similar in all groups. Waist circumference was found to be higher in those with normal BMD than in the osteopenic and osteoporotic groups (p = 0.018 and p < 0.001, respectively), and it was also higher in the osteopenic group than in the osteoporotic group (p = 0.003). Height and body weight, BMI, blood pressure, insulin, glucose, HDL-cholesterol, and homeostasis model assessment-insulin resistance (HOMA-IR) levels were similar in all groups. Triglyceride levels were found to be higher in the normal BMD group, compared with the osteoporotic group (p = 0.005). The level of VAI was detected as higher in those with normal BMD, compared with the women with osteoporosis (p = 0.002). Additionally, the correlation analysis showed a positive correlation between dual-energy X-ray absorptiometry (DXA) spine T-scores, WC, VAI, and a negative correlation between DXA spine T-scores and age. Conclusion In our study, we found higher VAI levels in those with normal BMD, compared with women with osteoporosis. We consider that further studies with a larger sample size will be beneficial in elucidating the entity.

Resumo Objetivo O objetivo foi comparar os níveis de índice de adiposidade visceral (IVA) em pacientes com densidade mineral óssea (DMO) normal osteopenia e osteoporose. Métodos Cento e vinte mulheres na pós-menopausa (40 com DMO normal 40 com osteopenia e 40 com osteoporose) com idades entre 50 e 70 anos foram incluídas no estudo. Para o sexo feminino o VAI foi calculado pela fórmula (circunferência da cintura [CC]/[36 58 + (1 89 x índice de massa corporal (IMC))]) x (1 52/lipoproteína de alta densidade [HDL]-colesterol [mmol/L]) x (triglicerídeo [TG]/0 81 [mmol/L]). Resultados O tempo de menopausa desde o início foi semelhante em todos os grupos. A circunferência da cintura foi maior naqueles com DMO normal do que nos grupos osteopênicos e osteoporóticos (p = 0 018 e p < 0 001 respectivamente) e também foi maior no grupo osteopênico do que no grupo osteoporótico (p = 0 003) . Altura e peso corporal IMC pressão arterial insulina glicose HDL-colesterol e os níveis de avaliação do modelo de homeostase-resistência à insulina (HOMA-IR) foram semelhantes em todos os grupos. Os níveis de triglicerídeos foram maiores no grupo DMO normal em comparação com o grupo osteoporótico (p = 0 005). O nível de VAI foi detectado como maior naquelas com DMO normal em comparação com as mulheres com osteoporose (p = 0 002). Além disso a análise de correlação mostrou uma correlação positiva entre a absorciometria de raios-X de dupla energia (DXA) nas pontuações T da coluna CC VAI e uma correlação negativa entre as pontuações T da coluna DXA e a idade. Conclusão Em nosso estudo encontramos níveis mais elevados de VAI naquelas com DMO normal em comparação com mulheres com osteoporose. Consideramos que novos estudos com maior tamanho amostral serão benéficos na elucidação da entidade.

Effects of denosumab on bone mineral density around proximal femoral prosthesis after total hip replacement in postmenopausal osteoporotic patients / 中国骨伤

OBJECTIVE@#To evaluate the effect of denosumab on bone mineral density around proximal femoral prosthesis after total hip arthroplasty(THA) in the postmenopausal osteoporotic patients.@*METHODS@#Fifty-four consecutive patients underwent unilateral primary THA were included in this retrospective study. Twenty-five patients received denosumab for osteoporosis as the treatment group, and the twenty-nine without denosumab were the control group. At 1 week, 3month, 6 months, and 12 months after THA, bone turnover markers and proximal femoral periprosthetic bone mineral density (BMD) were measured.@*RESULTS@#At 3, 6 and 12 months after operation, the level of TRACP-5b in the control group was significantly higher than that in the treatment group (P<0.05);the level of bone-specific alkaline phosphatase (BALP) between two groups showed significant difference in 12 months after operation (control group was higher than treatment group, P<0.05). The BMD of Gruen 1 and Gruen 7 decreased at 3, 6 and 12 months after operation compared with 1 week after operation. Comparing the treatment group and the control group, the differences of the the decrease of BMD in Gruen 1 and Gruen 7 were no significant at 3 months after surgery. In Gruen 1, Gruen 7 at 6 months after operation and Gruen 1, Gruen 7 at 12 months after operation, the decrease of BMD in the control group was significantly higher than that in the treatment group(P<0.05). It is suggested that desudumab could inhibit the loss of BMD after 6 months, and continuously show a protective effect on bone mass at 12 months after operation.@*CONCLUSION@#After THA in postmenopausal patients with osteoporotic femoral neck fracture, Desuzumab can reduce the loss of BMD around the proximal femoral prosthesis and effectively inhibit bone resorption.

Association of serum sRANKL and Omentin-1 levels with bone mineral density and bone metabolism in postmenopausal osteoporosis patients / 中华内分泌外科杂志

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.

Iron accumulation and its impact on osteoporotic fractures in postmenopausal women / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Postmenopausal osteoporosis is a kind of degenerative disease, also described as "invisible killer." Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives. Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000 μg/L. It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause. In recent years, many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis, and a significant correlation has been found between iron accumulation and fragility fractures. In this review, we summarize and analyze the relevant literature including randomized controlled trials, systematic reviews, and meta-analyses between January 1996 and July 2022. We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation, osteoporosis, and postmenopausal fragility fractures, as well as the main clinical treatment strategies. We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation, in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.

Cost-utility analysis of denosumab and teriparatide in the treatment of postmenopausal osteoporosis in Chinese women / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of denosumab and teriparatide in the treatment of postmenopausal osteoporosis in Chinese women， and provide reference for relevant decision-making. METHODS From the perspective of health system in China， Excel 2003 was used to establish Markov model， and cost-utility analysis was used to evaluate the cost- effectiveness of denosumab or teriparatide combined with Calcium carbonate D3 tablets in the treatment of postmenopausal osteoporosis in Chinese women. Pharmacotherapy effects were obtained with network meta-analysis， and cost and health utility value data were obtained from published literature. The model cycle was 1 year， and the simulation time limit was the patient’s lifetime. Univariate sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the effects of model parameter changes on the robustness of the results. Through scenario analysis， the cost-effectiveness of domestic drug cost used as drug cost of terlipatide group was discussed； the influence of residual effects of teriparatide on the results and the cost-effectiveness of sequential use of desumamab after terlipatide withdrawal were also discussed. RESULTS The effect of denosumab regimen was better than that of terlipatide regimen [13.24 quality-adjusted life years （QALYs） vs. 12.96 QALYs]， with lower cost （51 224.64 yuan vs. 167 102.67 yuan）， denosumab regimen was the absolutely superior regimen. The results of single factor sensitivity analysis showed that the cost and discount rate of Terlipatide injection had greater impact on the results. The results of probability sensitivity analysis showed that when three times of China’s per capita gross domestic product （GDP） in 2021 was used as the threshold of willingness to pay， the probability of cost-effectiveness of denosumab regimen was 93.5%. The results of scenario analysis showed that， whether the drug cost of terlipatide regimen which was replaced by domestic drugs， or the residual effect of terlipatide was considered， or desulmonab was used sequentially after two years of terlipide treatment， denosumab regimen was always the absolute advantage regimen. CONCLUSIONS Denosumab combined with Calcium carbonate D3 tablets is more cost-effective than teriparatide combined with Calcium carbonate D3 tablets in the treatment of postmenopausal osteoporosis in Chinese women.

Mechanism of Zhibai Dihuang decotion in treating postmenopausal osteoporosis / 药学学报

In this study, the ovarian surgery (ovariectomy, OVX) was used to establish the osteoporosis mice model of primary menstruation, in order to evaluate the protective effects and mechanisms of Zhibai Dihuang decotion on postmenopausal osteoporosis (PMOP). The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University (number: 20210315-03), in compliance with the Institutional Animal Care Guidelines. C57BL/6 mice were divided into five groups, including Sham group, OVX group, low (32 g·kg-1·day-1) and high dose (64 g·kg-1·day-1) of Zhibai Dihuang decotion groups, positive drug group (alendronate, 9.9 mg·kg-1·q3d). After modeling, mice were given medication intervention for 8 weeks, and then femoral and tibial tissues were taken to detect indicators such as bone microstructure, bone resorption, and oxidative stress. The experimental results showed that after Zhibai Dihuang decotion administration, the bone microstructure damage caused by OVX surgery was alleviated, and the relevant parameters bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular number (Tb. N) and connectivity density (Conn. D) both significantly increased. At the same time, the number of TRAP positive osteoclasts decreased significantly, and the levels of proteins and genes related to osteoclast differentiation decreased, indicating that Zhibai Dihuang decoction could inhibit the increased activity of osteoclast caused by OVX. Afterwards, network pharmacology was used to construct the active compound action target network of Zhibai Dihuang decotion, and it was found that the target genes of its active ingredients were closely related to the oxidative stress pathway. Finally, the detection results of oxidative stress levels in bone tissues showed that after treatment with Zhibai Dihuang decotion, the levels of oxidative stress products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) in bone tissues of mice significantly decreased, while the levels of antioxidant stress substance L-glutathione (GSH) increased. These above results indicated that Zhibai Dihuang decotion can regulate the level of oxidative stress in the body and inhibit osteoclast activity, which played a therapeutic role in PMOP, as well as provided theoretical basis for the prevention and treatment of PMOP with traditional Chinese medicine.

Effect of Morinda officinalis on serum metabolic spectrum in ovariectomized osteoporosis rats / 中国药理学通报

Aim To study the effect of Morinda officinalis on serum metabolisms in ovariectomized osteoporosis rats based on metabonomics, and explore the mechanism of Morinda officinalis in the treatment of postmenopausal osteoporosis.Methods Forty-eight SD rats were randomly divided into sham operation group, model group and Morinda officinalis group.The Morinda officinalis group was given Morinda officinalis water extract by gavage.The model group and sham operation group were given normal saline by gavage.The bone mineral density(BMD)of the right femur was measured by dual energy X-ray absorptiometry; the maximum load of the tibia bending at three points and the lumbar compression was measured by universal material testing machine.The endogenous metabolites of ovariectomized osteoporosis rats were identified by serum metabonomics, and the potential differential metabolites were screened and identified..Results The BMD and maximum load of the model group decreased significantly, while the Morinda officinalis group increased significantly compared with the model group.The serum metabolic spectrum of the sham operation group was completely separated from that of the model group, and the Morinda officinalis group was close to the sham operation group, suggesting that the body had a tendency to return to normal after intervention of Morinda officinalis.28 metabolites and 5 metabolic pathways were identified to be related to ovariectomized osteoporosis.Morinda officinalis could regulate the contents of stearic acid, uracil and other metabolites, which were related to the biosynthesis of unsaturated fatty acids, the metabolism of pyrimidine and so on.Conclusion Morinda officinalis can prevent ovariectomized osteoporosis by regulating the lipid metabolism and nucleic acid metabolism.

Anogenital index and bone mineral density associations after natural and surgical menopause: a preliminary study

SUMMARY OBJECTIVE: The aim of this study was to evaluate postmenopausal women to determine whether an anogenital index (AGI) is associated with bone mineral density (BMD) based on the hypothesis that the effects of menopause are similar for both. METHODS: A total of 338 generally healthy postmenopausal women who were referred for a routine annual check and 140 women who met the inclusion criteria were enrolled in the study. Based on the menopausal status, the women were classified into natural menopause and surgical menopause. AGI was calculated by dividing anogenital distance by body mass index. The BMD of the femoral neck, body of the femur, and lumbar spine (L1 and L2) was measured using dual-energy x-ray absorptiometry. RESULTS: There was a statistically significant and same-directional correlation between age and AGI for all cases (r=0.234 and p=0.005). The AGI level decreased as the parity increased (r=-0.582 and p<0.001). The AGI level decreased significantly as the menopause duration was prolonged (r=0.288 and p<0.001). While there was no statistically significant correlation between L2-L4 BMD and AGI (p=0.128), as the femur and femoral neck BMD levels increased, the AGI level increased statistically significantly (r=0.330 and p<0.001, r=0.292 and p<0.001). CONCLUSION: The AGI levels in healthy postmenopausal women give preliminary information about their BMD status. A decrease in AGI levels may predict lower BMD in postmenopausal women. Further larger and well-controlled studies may be required to determine the relationship between AGI and BMD in the future.

Dexmedetomidine regulates angiogenesis of postmenopausal osteoporosis through miR-483-3p/CTNNB1 axis / 中华内分泌外科杂志

Objective:To determine the role and molecular mechanism of dexmedetomidine (DEX) in postmenopausal osteoporosis (PMOP) .Methods:Twenty-seven patients with PMOP admitted to Yantai Yantaishan Hospital from Jan. 2020 to Jan. 2021 were selected as PMOP group, and 20 healthy volunteers were selected as Normal group. The differentially expressed miRNAs in PMOP were screened, clinically, the expression of miR-483-3p and catenin beta 1 (CTNNB1) in serum samples of patients with PMOP was detected by qRT-PCR. In vitro experiment, Bone marrow mesenchymal stem cells (BMSCs) were induced into osteoblasts, Dex was used to treat BMSCs and intervene the expression of miR-483-3p, CTNNB1 in BMSCs, the expression level of osteogenesis related indexes (RUNX2、OCN、OPN) was detected. After coculturing Human umbilical vein endothelial cell (HUVECs) with BMSCs, angiogenesis experiment was utilized to detect the angiogenesis ability.Results:Compared with Normal group (1±0.46) (1.03±0.44) , the expression of miR-483-3p (3.23±1.61) was increased in serum of PMOP patients while expression of CTNNB1 (0.50±0.27) was inhibited ( t=5.99, P<0.001) ( t=5.14, P<0.001) . miR-483-3p has a good diagnostic effect on PMOP (AUC=0.86, P<0.001) . After Dex treatment, miR-483-3p level was decreased in BMSCs, CTNNB1 level was increased (all P<0.05) . Dex promoted the expression of RUNX2, OCN, OPN and number of angiogenesis, but this effect was partially reversed by miR-483-3p overexpression (all P<0.05) . CTNNB1 was confirmed as a target gene of miR-483-3p, the inhibition effects of miR-483-3p overexpression on osteogenic differentiation and angiogenesis of BMSCs induced by Dex was partially reversed by CTNNB1 overexpression (all P<0.05) . Conclusion:Dex enhanced CTNNB1 level in PMOP via inhibiting miR-483-3p, subsequently promoted osteogenic differentiation and angiogenesis of BMSCs and inhibited progression of PMOP.

Traditional Chinese and Western Medicine in Treatment of Postmenopausal Osteoporosis： A Review / 中国实验方剂学杂志

Postmenopausal osteoporosis （PMOP） is a systemic disease characterized by increased bone fragility caused by insufficient estrogen secretion in women after menopause，resulting in decreased bone mass and damage to the microstructure of bone tissues. The main clinical manifestations are low back pain，osteoporotic fractures，spinal deformities，and multiple organ dysfunction. PMOP directly leads to high morbidity， high mortality， and a decline in the quality of life. In addition to miss diagnosis， it is often not treated in time. In recent years， significant progress has been made in the research on factors related to the pathogenesis of PMOP. Based on the previous findings in recent years，this article described three major pathogenesis of PMOP， including intestinal flora imbalance，oxidative stress，and abnormal differentiation of bone marrow mesenchymal stem cells （BMMSCs）， and analyzed the current status of PMOP treatment， such as syndrome differentiation and treatment，acupuncture and moxibustion，exercise therapy， and external treatment in traditional Chinese medicine （TCM）， and basic measures，drug intervention，and physical therapy in western medicine. Among them，drug intervention in western medicine treatment is generally divided into bone resorption inhibitors，bone formation promoters，and other mechanism drugs according to the mechanism of action. This article summarized the specific methods and effects or mechanisms of TCM and western medicine in the clinical treatment of PMOP，which is expected to provide a reference for formulating reasonable health management models and drug treatments in the future.

Effect of Jingangwan on p38 MAPK，JNK，and IL-1 Content in Osteoporosis Model Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Jingangwan on the expression of osteoclast， c-Jun N-terminal kinase（JNK）， p38 mitogen-activated protein kinase（p38 MAPK）， and interleukin-1（IL-1） in the osteoporosis model rats， explore the mechanism of Jingangwan in the treatment of osteoporosis， and determine the optimal dosing concentration of Jingangwan. MethodFifty-six rats of SPF grade were randomized into a blank group，a sham operation group，a model group， model group，high-， medium-， and low-dose Jingangwan groups （0.72， 0.36， 0.18 g·kg-1·d-1， ig），and an estradiol valerate group （0.009 g·kg-1·d-1， ig）， with eight rats in each group. The rats in the model group， the blank group， and the sham operation group received 3 mL of normal saline， respectively. Samples were collected 12 weeks after drug administration. The number of osteoclasts was observed by tartrate-resistant acid phosphatase （TRAP） staining. Serum levels of JNK， p38 MAPK， and IL-1 were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of p38 MAPK and JNK were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultThe TRAP staining results showed that compared with the model group， the estradiol valerate group and the Jingangwan groups could inhibit the formation of osteoclasts to different degrees. As revealed by ELISA results， compared with the model group and the sham operation group， the model group showed increased serum levels of p38 MAPK， JNK， and IL-1 （P<0.01）， while compared with the model group， all the groups with drug intervention showed decreased levels of p38 MAPK， JNK， and IL-1 （P<0.01）. The serum levels of JNK and IL-1 in the high-dose Jingangwan group were lower than those in the estradiol valerate group （P<0.05）. Real-time PCR results showed that compared with the blank group， the model group showed increased relative mRNA expression of p38 MAPK and JNK in the thighbone （P<0.01）， while compared with the model group， all the groups with drug intervention showed decreased relative mRNA expression of p38 MAPK and JNK in the thighbone （P<0.01）. ConclusionJingangwan can inhibit the formation of osteoblasts，reduce the diameter of the bone marrow cavity，improve bone quality，suppress the production of inflammatory factors，affect the metabolism of the MAPK signaling pathway，and blunt p38 MAPK and JNK activities to inhibit the differentiation and proliferation of osteoblasts and regulate bone metabolism， thereby preventing osteoporosis. Therefore，Jingangwan may be of application value in maintaining bone health and treating osteoporosis.

Factors affecting postmenopausal osteoporosis in Dali Bai Autonomous Prefecture / 预防医学

Objective@#To investigate the prevalence of postmenopausal osteoporosis (PMOP) and analyze its influencing factors among women at ages of 50 to 59 years in Dali Bai Autonomous Prefecture, Yunnan Province, so as to provide insights into the prevention of PMOP among menopausal women.@*Methods@#Bai Ethnic menopausal women at ages of 50 to 59 years who received healthy examination at the Center of Healthy Examination, Dali Prefecture People's Hospital from June 2017 to May 2021 were selected as the study subjects, and subjects' demographic characteristics, living habits, history of diseases, family history of osteoporosis and history of parturition were collected using self-designed questionnaires. The height, body weight and bone density were measured, and fasting blood glucose, vitamin D3, blood lipids and liver functions were detected. The factors affecting the development of PMOP were identified using a multivariable logistic regression model.@*Results@#Totally 2 000 questionnaires were allocated, and 1 584 valid questionnaires were recovered, with an effective recovery rate of 79.20%. The respondents had a mean age of ( 56.22±2.61 ) years, and mean body mass index ( BMI ) of ( 24.62±2.35 ) kg/m2. There were 497 respondents ( 31.38% ) with a family history of osteoporosis, and the prevalence of PMOP was 20.64%. Multivariable logistic regression analysis identified age ( OR=1.135, 95%CI: 1.074-1.196 ), age of menarche ( OR=1.138, 95%CI: 1.059-1.217 ), duration of menopause (OR=1.425, 95%CI: 1.228-1.622), number of parturition ( >2, OR=5.036, 95%CI: 2.972-7.101 ), smoking ( OR=2.594, 95%CI: 1.767- 3.421 ), alcohol consumption ( OR=2.051, 95%CI: 1.503-2.598 ), family history of osteoporosis ( OR=2.540, 95%CI: 1.769-3.311 ), hypertension ( OR=1.492, 95%CI: 1.406-1.578 ), diabetes ( OR=1.774, 95%CI: 1.581-1.967 ), total cholesterol ( OR=1.483, 95%CI: 1.251-1.716 ), triacylglycerol ( OR=1.801, 95%CI: 1.576-2.026 ), low-density lipoprotein cholesterol ( OR=1.614, 95%CI: 1.498-1.731 ), fasting blood glucose ( OR=1.192, 95%CI: 1.077-1.307 ), BMI ( OR=0.934, 95%CI: 0.862-0.993 ), outdoor activity ( ≥1 time/week, OR: 0.413-0.549, 95%CI: 0.329-0.637 ), age of menopause ( OR=0.909, 95%CI: 0.841-0.977 ), daily intake of calcium ( ≥600 mg, OR: 0.493-0.644, 95%CI: 0.389-0.786 ), vitamin D3 level ( ≥20 ng/mL, OR: 0.604-0.719, 95%CI: 0.523-0.853 ) and high-density lipoprotein cholesterol ( OR=0.658, 95%CI: 0.550-0.767 ) as factors affecting the development of PMOP.@*Conclusions @#The prevalence of PMOP in Dali Bai Autonomous Prefecture is similar to the nationwide level in China, and old age, smoking, alcohol consumption, a family history of osteoporosis and high blood lipid levels may increase the risk of PMOP.

Mechanism of Bushen Huatan Prescription in Regulation of Osteogenesis and Adipogenic Differentiation and Improvement of Postmenopausal Bone Loss in Ovariectomized Rats with Osteoporosis / 中国实验方剂学杂志

ObjectiveTo explore the underlying mechanism of Bushen Huatan prescription in alleviating postmenopausal osteoporosis （PMOP） by maintaining the balance of osteogenesis and adipogenic differentiation in ovariectomized rats with osteoporosis. MethodSeventy-five 6-month-old non-pregnant female SD rats were randomly divided into sham-operation group， model group， atorvastatin group， liviol group， and Bushen Huatan prescription group. Bilateral ovaries were removed in the four groups except the sham-operation group， while only the same mass of adipose tissue around the ovaries was removed in the sham-operation group. On the 5th week after surgery， drugs were consecutively administrated for 8 weeks. Rats in the Bushen Huatan prescription group received 9.4 mg·kg-1 of the prescription， rats in the atorvastatin group received 0.92 mg·kg-1 of atorvastatin， rats in the Liviol group received 0.23 mg·kg-1 of liviol， and rats in the model group and the sham-operation group received saline once a day. Micro-computed tomography （Micro CT） was used to detect bone mineral density （BMD） of rat tibia in each group. Hematoxylin-eosin （HE） staining was used to detect the relative area of rat bone marrow adipose tissue （BMAT） in each group. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the relative expression levels of Runt-related transcription factor 2 （Runx2）， peroxisome proliferator-activated receptor （PPARγ）， leptin （LPN）， and leptin receptor （OBR） in bone tissues. ResultAs compared with the sham operation group， the BMD of rats in the model group decreased （P<0.05）， while the relative area of BMAT increased （P<0.05）. In addition， the expression levels of LPN， OBR， and Runx2 decreased in the model group （P<0.05）， while the level of PPARγ increased （P<0.05）. As compared with the model group， the BMD of rats in the atorvastatin group， the Livial group， and the Bushen Huatan prescription group increased （P<0.05）， and the relative area of BMAT decreased （P<0.05）. The expression levels of LPN， OBR， and Runx2 in these groups increased （P<0.05）， while the expression level of PPARγ decreased （P<0.05）. ConclusionBushen Huatan prescription plays the anti-osteoporosis role in the rat model of PMOP through up-regulating LPN and OBR in bone tissues and maintaining the balance of osteogenesis and adipogenic differentiation， thereby reducing postmenopausal bone loss and playing a role in the prevention and treatment of PMOP.

Profile and gene functional analysis of gut microbiota in women with postmenopausal osteoporosis / 中华微生物学和免疫学杂志

Objective:To explore the profile and gene functional changes of gut microbiota (GM) in women with postmenopausal osteoporosis (PMOP) in Northwest China, and the correlations between GM and bone mineral density (BMD).Methods:From November 2018 to October 2019, postmenopausal women were screened on their initial visits to our hospital, and 24 new osteoporosis (OP) patients, 30 new osteopenia patients and nine negative controls were recruited. Fecal samples were collected for GM DNA extraction, and Illumina platforms were used for high-throughput sequencing of 16S rRNA and metagenome. Species annotation, GM profile and gene functions were viewed and analyzed.Results:GM profiles were significatly different in different groups, and the LDA scores of Peptostreptococcaceae, Romboutsia, unidentified Clostridiales, Megamonas, Erysipelatoclostridium, Klebsiella and Erysipelatoclostridium ramosum were more than 3 in OP group. Metagenomic sequencing analysis indicated that gene numbers were positively correlated with BMD, and metabolism, carbohydrate metabolism, starch and sucrose metabolism and oxidative phosphorylation were negatively correlated with BMD. Receiver operating characteristic curve(ROC) showed that carbohydrate metabolism, starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, oxidative phosphorylation, respectively, could identify OP with preferable sensitivity and specificity (areas under curve were 0.70, 0.72, 0.73 and 0.75, respectively). Conclusions:High-throughput sequencing had great potential for GM analysis of postmenopausal women with OP, providing evidence of the correlations between GM and BMD.

Meta analysis of the relationship between C-reactive protein and postmenopausal osteoporosis / 中国综合临床

Objective:To systematically evaluate the correlation between C-reactive protein (CRP) and postmenopausal osteoporosis.Methods:PubMed, EMbase, Cochrane library, China biomedical literature database, China HowNet and Wanfang database were searched by computer to collect the clinical research literature related to CRP and postmenopausal osteoporosis. The retrieval period was from the establishment of the database to April 1, 2021. The two researchers screened the literature according to the inclusion and exclusion criteria, extracted the data and evaluated the quality, Revman5.3 software was used for meta-analysis.Results:A total of 12 studies were included, including 778 cases in postmenopausal osteoporosis group and 933 cases in non osteoporosis group. The results of combined analysis showed that the level of CRP in postmenopausal osteoporosis group was higher than that in non osteoporosis group, and the difference was statistically significant (standardized mean difference (SMD)=0.55, 95% CI (0.03, 1.07), P=0.04). Further subgroup analysis according to different grouping criteria and CRP detection methods showed that the level of CRP in patients with osteoporosis was higher than that in normal bone group ( SMD=0.88, 95% CI (0.07,1.69), P=0.03). There was no significant difference in CRP level between osteoporosis group and osteopenia Group (SMD=0.13, 95% CI (-0.05, 0.31), P=0.15). There was no correlation between CRP levels detected by automatic analyzer, chemiluminescence immunoassay and enzyme-linked immunosorbent assay and postmenopausal osteoporosis. The level of CRP in postmenopausal osteoporosis group detected by immunoturbidimetry was higher than that in non osteoporosis group (SMD=1.50, 95% CI (1.10,1.90), P<0.01). Conclusion:CRP level is related to postmenopausal osteoporosis. High CRP level may be a risk factor for postmenopausal osteoporosis.

LncRNA-NEF improves immune imbalance and PD-1/PD-1L-mediated Treg-Th17 cell balance in postmenopausal osteoporosis mice by miR-21 adsorption / 中华内分泌外科杂志

Objective:To investigate the regulatory mechanism of long non-coding RNA (lncRNA) NEF on T cell immune function in postmenopausal osteoporosis (PMOP) mice.Methods:Female Balb/c mice were used to construct OVX model ( n=46) and sham control group ( n=16) . Bone marrow mesenchymal stem cells (BM-SCs) from these two groups of mice were cultured. NEF recombinant expression vector (pIRSE2-NEF) was constructed and transfected into BMSCs. RT-qPCR was used to detect NEF and miR-21 levels in BMSCs cells in sham group, OVX group, and pIRSE2-NEF group. Luciferase gene report experiment was used to verify the binding effect of NEF and miR-21. The remaining 40 OVX mice were divided into 4 groups, including OVX group ( n=10) , pIRSE2-NEF injection group (pIRSE2-NEF group, n=10) , pIRSE2-NEF combined with PD-1 inhibitor group (pIRSE2-NEF+ PD-L1-IN-1 group, n=10) , and pIRSE2-NEF combined with miR-21 mimic (mimic) group (pIRSE2-NEF+ mimic group, n=10) . The remaining 10 mice in sham group were used as the control group. ELI-SA was used to detect the levels of IFN-γ, IL-2, IL-4, IL-13 and PD-1/PD-1L in peripheral blood. Flow cytometry was used to detect the shift of serum Treg-Th17 cell subsets. Results:Compared with the Sham group (1.01±0.04, 1.00±0.03) , the expression of NEF in BMSCs of OVX group was down-regulated (0.23±0.01) , and miR-21 was up-regulated (2.96±0.05) ( P<0.05) . Compared with OVX group (1.23±0.15, 5.20±0.31) , NEF in BMSCs cells of Pirse2-nef group was significantly up-regulated (6.83±0.35) ( P<0.05) , while miR-21 was down-regulated (0.29±0.11) ( P<0.05) .NEF has a direct binding base site with miR-21.The levels of IFN-γ (3.25±0.21) , IL-2 (2.44±0.06) and Th17/Treg ratio (3.18±0.65) in peripheral blood of mice in OVX group were significantly higher than those in Sham group (1.03±0.02, 1.00±0.01, 0.86±0.09) (all P<0.05) . The levels of IL-4 (0.45±0.02) , IL-13 (0.43±0.07) , PD-1 (0.24±0.03) and PD-1L (0.51±0.06) were significantly lower than those of Sham group (1.00±0.04, 1.00±0.02, 1.00±0.03, 1.00±0.00) ( P<0.05) ; Compared with OVX, IFN-γ (2.02±0.06) , IL-2 (0.88±0.01) and Th17/Treg ratio (1.43±0.22) in Pirse2-nef group were decreased. The levels of IL-4 (0.87±0.03) , IL-13 (0.84±0.07) , PD-1 (0.79±0.06) and PD-1L (0.77±0.06) were increased (all P<0.05) ; Compared with Pirse2-nef group, IFN-γ (2.89±0.06) , IL-2 (2.07±0.07) and Th17/Treg ratio (2.39±0.38) were increased in Pirse2-nef+ PD-L1-in-1 group. The levels of IL-4 (0.68±0.03) , IL-13 (0.76±0.08) , PD-1 (0.52±0.02) and PD-1L (0.83±0.04) were decreased (all P<0.05) . Moreover, the pIRSE2-NEF+ mimic group had the same adjustment effect as the pIRSE2-NEF+ PD-L1-IN-1 group. Conclusion:lncRNA-NEF improves immune imbalance and PD-1/PD-1L-mediated Treg-Th17 cell balance in postmenopausal osteoporosis mice by sponging miR-21.

Effect of Psoralen on Osteoporosis in Postmenopausal Rats and PI 3K/Akt/mTOR Signaling Pathway / 中国药房

OBJECTIVE：To stu dy the effect of psoralen on osteoporosis in postmenopausal rats and PI3K/Akt/mTOR signaling pathway. METHODS ：Totally 60 healthy female SD rats were randomly divided into normal group ，model group ，positive control group（0.09 mg/kg estradiol ），psoralen low-dose ，medium-dose and high-dose groups （22，44，88 mg/kg），with 10 rats in each group. Except for normal group ，the other groups were ovariectomized to establish Postmenopausal osteoporosis model. After 2 months of normal feeding after operation ，normal group and model group were given the constant volume of normal saline intragastrically，and administration groups were given the corresponding solution intragastrically ；the volume was 0.005 mL/g， once a day ，for consecutive 98 days. 24 h after last administration ，the BMD of femur and vertebra of right lower extremities in rats was determined. The contents of serum calcium ，osteocalcin and P1NP，the serum levels of BMP2 and VEGF were determined；mRNA and protein expression of PI3K，Akt and mTOR in femur tissue were detected.RESULTS ：Compared with normal group ，BMD of femur and vertebra ，serum contents of calcium ，osteocalcin，P1NP and serum levels of BMP 2，VEGF in model group were decreased significantly ，while the mRNA and protein expression of PI 3K，Akt and mTOR were increased significantly （P＜0.05 or P＜0.01）. Compared with model group ，BMD of femur and vertebra ，serum levels of calcium ， osteocalcin，P1NP and serum levels of BMP2（except for psoralen medium-dose group ），VEGF（except for psoralen medium-dose group）were increased significantly in psoralen medium-dose and high-dose groups ，positive control group ，while the mRNA expression（except for psoralen low-dose group ）and protein expression of PI 3K，Akt and mTOR in administration groups were decreased significantly （P＜0.05 or P＜0.01）；BMD of femur ，serum levels of calcium ，BMP2 and PI 3K protein expression in psoralen high-dose group were significantly higher than positive control group （P＜0.05），and mTOR mRNA expression in psoralen high-dose group was significantly lower than positive control group （P＜0.05）. CONCLUSIONS ：Psoralen can improve osteoporosis in postmenopausal rats ，the mechanism of which may b e associated with inhibiting PI 3K/Akt/mTOR signaling pathway.

Alcohol extract of morinda officinalis improves lipid metabolism and bone metabolism in ovariectomized obese rats / 中国组织工程研究

BACKGROUND: Previous studies have showed that the alcohol extract of Morinda officinalis can effectively improve the bone quality and body mass of obese rats after ovariectomy. However, the exact mechanism is unclear. In this study, leptin and leptin receptor were used as the breakthrough point to investigate the effect of alcohol extract of Morinda officinalis on lipid metabolism and bone metabolism in ovariectomized obese rats. OBJECTIVE: To investigate the effects of alcohol extract of Morinda officinalis lipid metabolism and bone metabolism in ovariectomized obese rats. METHODS: A total of 160 SPF female Sprague-Dawley rats were randomly divided into an osteoporosis group (n=120) and a sham operation group (n=40). A postmenopausal osteoporosis model was made in the osteoporosis group by removing both ovaries. After modeling, rats in the osteoporosis group were randomly subdivided into a normal diet group, a high-fat diet group and a high-fat diet + Morinda officinalis alcohol extract group, with 40 rats in each group. The sham operation group and the normal diet group were fed with ordinary diet, while the high-fat diet group and the high-fat diet + Morinda officinalis alcohol extract group were fed with high-fat diet. The high-fat diet + Morinda officinalis alcohol extract group was gavaged with 20 g/kg Morinda officinalis alcohol extract once a day, and the remaining three groups were gavaged with 2 mL of normal saline. The study protocol was approved by the Animal Ethic Committee of Fuzhou Second Hospital of Xiamen University in September 2018 with an approval No. 20180019. RESULTS AND CONCLUSION: Compared with the sham operation group, serum leptin, leptin receptor, osteoprotegerin and high-density lipoprotein cholesterol levels were significantly lower in ovariectomized rats (P < 0.05), whereas osteocalcin, RANKL, tartrate-resistant acid phosphatase 5b, cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels were significantly higher in ovariectomized rats (P < 0.05). Compared with the high-fat diet group, serum leptin, leptin receptor, osteoprotegerin and high-density lipoprotein cholesterol levels were significantly increased in the high-fat diet + Morinda officinalis alcohol extract group (P < 0.05), whereas osteocalcin, RANKL, tartrate-resistant acid phosphatase 5b, cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels were decreased to different extents in the high-fat diet + Morinda officinalis alcohol extract group (P < 0.05). To conclusion, the alcohol extract of Morindus officinalis can up-regulate the leptin and leptin receptor expression in serum of ovariectomized obese rats, so as to improve the abnormal bone metabolism and lipid metabolism in ovariectomized obese rats.

Randomized controlled trial outcome indicators of postmenopausal osteoporosis treated by traditional Chinese medicine / 中国中药杂志

This study evaluated the outcome indicators of the randomized controlled trials(RCTs) of traditional Chinese medicine(TCM) in the treatment of postmenopausal osteoporosis(PMOP) to provide a reference for the related research. Four Chinese databa-ses(CNKI, VIP, Wanfang and CBM) and three English databases(Cochrane Library, EMbase and PubMed) were searched syste-matically to screen RCTs of TCM in the treatment of PMOP according to the pre-set criteria, and the quality of the included trials was evaluated by the Cochrane risk-of-bias tool. A total of 29 627 articles were initially retrieved, and finally, 43 articles were included, including 34 in Chinese and 9 in English. As revealed by the results, the outcome indicators of 43 RCTs were mainly divided into six categories, with biochemical indicators accounting for 54.59%, bone mineral density(BMD) for 26.57%, quality of life for 6.28%, fracture for 1.94%, safety for 5.31%(including adverse reactions or events) and others for 5.31%. Biochemical indicators showed the maximum occurrence, followed by BMD. Many problems were found in the selection of outcome indicators of the TCM RCTs in the treatment of PMOP, such as the confusion of primary and secondary outcome indicators, the lack of endpoint criteria and vital clinical outcome indicators substituted by intermediate indicators, inconsistent evaluation standard of syndrome curative efficacy and neglected blinding in the measurement of subjective outcome indicators. The problems also included importance given to the efficacy indicators instead of the adverse outcome indicators, unnormalized indicator name, large quantitative range of the indicators, unconventional application of TCM efficacy criteria, seldom used confidence interval, relative effect indicator and absolute effect indicator.