The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly, leading to an Omicron outbreak in Shanghai in mid-December after adjustments to the Coronavirus Disease 2019 (COVID-19) control strategy. To investigate the impact of COVID-19 infection among hypothyroid patients, we gathered data on the hypothyroid outpatients with COVID-19 infection during this time at the Thyroid Disease Center (TDC) of Shanghai Central Hospital. Patients were divided into two groups based on whether their hypothyroidism was caused by Hashimoto’s Thyroiditis (HT): the HT and the non-HT group. We assessed the differences between pre-infection and clinical follow-up at one month (day (D) 30) and three months (D90) after COVID-19 infection. In HT group, thyroid-stimulating hormone (TSH) levels decreased significantly compared to pre-infection levels (p = 0.013), while free triiodothyronine (FT3) levels increased at D90 compared to both D30 post-infection and pre-infection levels (p < 0.001 and p = 0.005). Hemoglobin levels also increased after COVID-19 infection (p = 0.033). For non-HT patients, FT3 levels increased at D30 compared to pre-infection levels (p = 0.017). Moreover, inactivated SARS-CoV-2 vaccination can preserve thyroid function stability in patients with hypothyroidism.

BACKGROUND:Osteoporosis is a chronic disease of bone metabolism with high incidence rates. Recently, exosome therapy has emerged as a promising avenue for the treatment of osteoporosis. However, the role of autophagy-induced osteoblast-derived exosomes (Auto-exo) in osteoporosis has yet to be elucidated. METHODS:The effect of Auto-exo on bone formation was assessed in vivo. The composition of gut microbiota was determined through 16S rDNA sequencing, and metabolite profiles were analyzed using liquid chromatography-mass spectrometry (LC-MS). Cell experiments were conducted to explore the role of bilirubin in bone formation. RESULTS:Auto-exo were successfully isolated and identified. Auto-exo promoted bone formation and alleviated osteoporosis progression in a mouse model of osteoporosis. 16S rDNA sequencing revealed that Auto-exo changed diversity and composition of gut microbiota in osteoporotic mice, with a notable increase in Lactobacillus and a decrease in Dubosiella and Faecalibaculum. LC-MS analysis indicated that Auto-exo treatment reduced the elevated levels of bilirubin in osteoporotic mice. Cell experiments uncovered that bilirubin remarkably inhibited osteoblast differentiation. Furthermore, Auto-exo promoted osteoblast differentiation via inhibiting bilirubin production. CONCLUSIONS:Our findings demonstrated that Auto-exo promoted bone formation by modulating the gut microbiota-metabolite bilirubin axis, thereby alleviating osteoporosis progression. This discovery provides a novel perspective on the mechanism underlying the therapeutic effects of Auto-exo on osteoporosis.

OBJECTIVE:This study aimed to analyze the correlation between bone mineral density (BMD) and bone resorption markers in postmenopausal women with osteoporosis fractures and identify risk factors for second fractures.METHODS:This retrospective analysis of 1,239 older women with fractures with a median age of 70 years who attended Shanghai General Hospital from January 2007 to December 2016, included a first fracture group (1,008 cases) and a second fractures group (231 cases). The risk factors for fractures were analyzed by comparing these groups on clinical characteristics, BMD, and bone metabolism markers stratified by quartiles of serum C-terminal telopeptide of type 1 collagen (CTX). Binary logistic regression analysis was used to identify risk factors for second fractures.RESULTS:In the whole sample, BMD was negatively correlated with age and serum osteocalcin and positively correlated with body mass index (BMI). In women with first fractures, those in the highest quartile of serum CTX had the lowest spine and hip BMD. Second fractures were significantly associated with BMI, lower spine and hip BMD, and higher serum osteocalcin but not CTX. Binary logistic regression analysis showed that high BMI (odds ratio [OR], 1.08 [95% CI, 1.03-1.14]; P = 0.001), low lumbar BMD (OR, 0.24 [95% CI, 0.07-0.82]; P = 0.023), low total hip BMD (OR, 0.05 [95% CI, 0.00-0.88]; P = 0.041), and lack of antiosteoporosis treatment (OR, 2.71 [95% CI, 2.71-4.08]; P < 0.001) were independent risk factors for second fractures.CONCLUSIONS:In older women with fractures, BMD was significantly lower in women with second fractures than in those with first fractures. Higher levels of serum CTX and osteocalcin, which indicates increased bone resorption, were negatively correlated with BMD. In women with a first fracture, serum CTX higher than 605 pg/mL was negatively correlated with BMD, whereas no correlation was found between different CTX and BMD in women with second fractures. High BMI and low BMD as well as not receiving antiosteoporosis treatment were independent risk factors for second fractures.

目的 了解骨转换指标(bone turnover markers,BTMs)以及其他骨代谢指标水平与女性原发性骨质疏松症(primary osteoporosis,POP)患者初次脆性骨折发生的相关性.方法 2005年7月至2016年12月在上海市第一人民医院骨质疏松症专病门诊初次就诊且已确诊POP、资料齐全并符合骨折史由初诊时患者自述及影像学检查显示为初次新发骨折,为主要部位脆性骨折等纳入标准的女性患者,共117例,按骨折后1年内就诊患者及未发生骨折患者分为骨折组和未骨折组,记录所有研究对象的一般资料、血清生化及BTMs、骨密度(bone mineral density,BMD)检测结果、骨折史等临床资料进行回顾性分析研究.结果 与未骨折组相比,骨折组血清Ca显著下降,差异有统计学意义(P<0.05);且骨折组BMD L1-4显著降低,差异有统计学意义(P<0.05).按年龄进行亚组分析发现:骨折组血清Ca均低于未骨折组,其中≤70岁两组差异有统计学意义(P<0.05);骨折组BMD较未骨折组均下降,>70岁组BMD L1-4差异有统计学意义(P<0.05).Spearman相关分析显示:BMD L1-4(r=-0.188,P=0.043)、血清骨钙素(bone Gla protein,BGP)(r=-0.217,P=0.019)、血清Ca(r=-0.302,P=0.001)、血清25羟维生素D(25 hydroxyvitamin D,25OHD)(r=-0.189,P=0.041)与骨折发生呈负相关;二元Logistic回归分析表明:BMDL1-4(OR=0.042,P=0.039)、血清BGP(OR=0.948,P=0.049)、Ca(OR=0.042,P=0.039)、25OHD(OR=0.975,P=0.015)均为骨折的保护因素.结论 腰椎BMD、血清BGP、Ca、25OHD与脆性骨折发生相关.

Background As postmenopausal osteoporotic fractures can cause higher rates of disability and mortality in women; it is essential to analyze the factors associated with primary and recurrent fractures in postmenopausal osteoporosis (PMOP) patients. Methods Retrospective analysis of 2478 PMOP patients aged ≥ 50 years who attended the Shanghai General Hospital from January 2007 to December 2016, including 1239 patients with no fractures and 1239 patients with histories of fractures (1008 in the primary fracture group and 231 in the re-fracture group). All patients' basic clinical data, serum biochemical and bone metabolic markers, bone mineral density (BMD), and other indicators were recorded uniformly. Comparing the differences between the clinical characteristics of patients with primary and recurrent fractures, as well as the differences in the clinical characteristics of patients with primary and recurrent fractures in combination with different diseases, further analyses the risk factors for primary and recurrent fractures in PMOP patients. SPSS.26 was used for statistical analysis. Results Compared to the unfractured group, the fractured group was older and had lower height and bone mineral density (all P < 0.01), with the re-fractured group having lower BMD at each key site than the primary fracture group (all P < 0.01). Analysis of the combined disease subgroups showed that serum BGP levels were lower in the primary and re-fracture patients with diabetes than in the non-diabetic subgroup ( P < 0.05), and serum CTX levels were lower in the re-fracture group with diabetes than in the primary fracture group with diabetes ( P < 0.05). Patients with recurrent fractures with cardio-vascular diseases had lower BMD than the subgroup without cardio-vascular diseases ( P < 0.05) and also had lower BMD than the group with primary fractures with cardio-vascular diseases ( P < 0.05). Multiple logistic regression analysis showed that advanced age, overweight, low lumbar spine and total hip BMD were risk factors for primary and recurrent fractures; and comorbid chronic liver and kidney diseases were risk factors for primary fractures. Conclusion PMOP patients with advanced age, overweight, low bone mineral density, and comorbid chronic liver and kidney diseases are at greater risk of fractures and require early intervention to reduce fractures occurrence. Moreover, those who are elderly, overweight, and have low bone density should also be aware of the risk of re-fractures.

Sarcopenia is characterized by a progressive reduction in muscle mass or muscle physiological function associated with aging, but the relevant molecular mechanisms are not clear. Here, we identify the role of the myogenesis modifier CPNE1 in sarcopenia. CPNE1 is upregulated in aged skeletal muscles and young skeletal muscle satellite cells with palmitate-induced atrophy. The overexpression of CPNE1 hinders proliferation and differentiation and increases muscle atrophy characteristics in young skeletal muscle-derived satellite cells. In addition, CPNE1 overexpression disrupts the balance of mitochondrial fusion and division and causes endoplasmic reticulum stress. We found that the effects of CPNE1 on mitochondrial function are dependent on the PERK/eIF2α/ATF4 pathway. The overexpression of CPNE1 in young muscles alters membrane lipid composition, reduces skeletal muscle fibrosis regeneration, and exercise capacity in mice. These effects were reversed by PERK inhibitor GSK2606414. Moreover, immunoprecipitation indicates that CPNE1 overexpression greatly increased the acetylation of PERK. Therefore, CPNE1 is an important modifier that drives mitochondrial homeostasis to regulate myogenic cell proliferation and differentiation via the PERK-eIF2α pathway, which could be a valuable target for age-related sarcopenia.

目的 了解合并不同疾病的男性骨量异常患者骨代谢指标、骨密度(bone mineral density,BMD)及骨折的情况.方法对2006年1月至2017年12月在上海市第一人民医院内分泌科骨质疏松亚专科就诊的928例男性骨量异常患者进行回顾性研究.根据研究目的不同,将患者分为有或无糖尿病组、有或无慢性肝病组、有或无慢性肾病组、有或无慢性胃病组、有或无心血管疾病组及骨量减低组和骨质疏松组.分别观察各组各项指标的差异.结果单因素回归分析提示受试者年龄、体重、L1～4 BMD、股骨颈BMD、全髋BMD、β-CTX、慢性胃病、骨质疏松症是骨折史的影响因素,差异具有统计学意义(P<0.05);骨折史与受试者年龄、β-CTX、慢性胃病、骨质疏松症因素成正相关,与体重、L1～4 BMD、股骨颈BMD、全髋BMD成负相关;多因素回归分析提示年龄、BALP、2型糖尿病、骨质疏松是骨折的危险因素,而25OHD水平是骨折的保护性因素.结论对于男性骨量异常患者,需要重点关注年龄较大、β-CTX和BALP水平较高、合并慢性胃病以及2型糖尿病的患者,对这类患者应积极进行抗骨质疏松干预及治疗,以减少此类患者骨折的发生率.

OBJECTIVE:The association of the gut microbiome with bone turnover markers (BTMs) in postmenopausal women is poorly understood.METHODS:Fecal samples were collected from 97 Chinese postmenopausal women, and the serum CTX and P1NP were determined. Individuals with serum CTX lower or higher than the median value were divided into LCTX and P1NP groups; and individuals with serum P1NP lower or higher than the median value were grouped into LP1NP and HP1NP groups. Microbiota profiles were determined by high-throughput 16S rRNA gene sequencing.RESULTS:In postmenopausal women, only Faecalibacterium showed significant alteration in the HCTX group compared with the LCTX group (P=0.004, q=0.143). Linear discriminant analysis effect size (LEfSe) analysis revealed that Clostridiaceae (P=0.015, LDA=2.89), Faecalibacterium (P=0.017, LDA=4.60), Prevotella (P=0.040, LDA=3.61) and Clostridium (P=0.007, LDA=2.79) were abundant in the LCTX group, and Facklamia (P=0.044, LDA=3.10) was enriched in the HCTX group. Peptostreptococcaceae (P=0.048, LDA=2.83) and the SMB53 (P=0.028, LDA=2.05) genus were enriched in the LPINP group, and Veillonellaceae (P=0.025, LDA=4.43) and the S24_7 (P=0.023, LDA=3.08) family were enriched in the HPINP group. Six taxa correlated with BTMs in all subjects, including Clostridium (Clostridiaceae) that was negatively correlated with serum CTX amounts significantly (r=-0.34, P<0.001).CONCLUSION:This study identified taxa-specific differences in the intestinal microflora associated with BTMs, notably CTX. These findings may help in uncovering the roles of gut microbiota on bone metabolism.

目的 了解不同体质量指数(body mass index,BMI)2型糖尿病(type 2 diabetes mellitus,T2DM)患者的骨转换指标、 骨密度及骨折情况.方法 回顾2006-2018年在上海市第一人民医院骨质疏松专病门诊初次就诊且已确诊T2DM,同时资料齐全、 符合纳入标准的患者,共1422例(其中男性199例,女性1223例).据世界卫生组织(World Health Organization,WHO)推荐中国成年人肥胖诊断标准,根据BMI分为4组:BMI<18.5 kg/m2为消瘦组,18.5 kg/m2≤BMI<24 kg/m2为正常组,24 kg/m2≤BMI<28 kg/m2为超重组,BMI≥28 kg/m2为肥胖组.采用回顾性分析记录所有研究对象的一般资料、 血清生化及骨转换指标(bone turnover marker,BTM)、 骨密度(bone mineral density,BMD)、 骨折史等临床资料.结果 与正常组相比,消瘦组Ⅰ型胶原羧基端肽(type 1 collagen carboxy terminal peptide,β-CTX)增高,超重组及肥胖组均降低,差异有统计学意义(均P<0.05);消瘦组血清骨钙素(bone gla protein,BGP)增高,肥胖组降低(均P<0.05);消瘦组L1-4、 股骨颈、 全髋BMD降低(均P<0.05),而超重组和肥胖组增高(均P<0.05).与消瘦组相比,正常组、 超重组及肥胖组β-CTX、BGP明显降低,L1-4、 股骨颈、 全髋BMD显著增高,差异有统计学意义(均P<0.05).BMI与β-CTX(r=-0.120,P=0.000)、BGP(r=-0.104,P=0.000)呈负相关,与P(r=0.061,P=0.023)呈正相关;与L1-4BMD(r=0.283,P=0.000)、 股骨颈BMD(r=0.249,P=0.000)、全髋BMD(r=0.337,P=0.000)呈正相关.T2DM患者中女性(OR=1.869,P=0.009)、 年龄(OR=1.018,P=0.014)、BMI(OR=1.084,P=0.000)均是骨折发生的危险因素,而L1-4 BMD(OR=0.361,P=0.027)及全髋BMD(OR=0.085,P=0.012)是骨折的保护性因素.结论 在肥胖T2DM患者中BMD可能会低估其骨折风险,因此在预测T2DM患者骨折风险方面不仅要参考骨密度情况,还需全面考虑其他影响因素,如性别、 年龄、BMI等,以便对患者进行综合的评估及管理.

目的 从细胞水平探索氯沙坦钾对骨骼肌损伤的保护作用及其机制.方法 用2％马血清诱导分化L6成肌细胞;CCK-8试剂盒及Western Blot确定合适的氯沙坦细胞处理浓度.实验分为4组:对照组,二甲基亚砜组,棕榈酸(1 mmol/L)组以及棕榈酸(1 mmol/L)+氯沙坦钾(50μmol/L)组.Western Blot检测凋亡相关蛋白(cleaved caspase-3、cleaved PARP、Bcl-2、Bax)、自噬相关蛋白(LC3、Beclin 1),实时荧光定量PCR(quantitative real-time PCR,qPCR)检测P53和P21 mRNA表达水平.结果 显微镜下观察及Western Blot检测myogenin蛋白表达增加,证明骨骼肌细胞诱导分化成功.CCK-8试剂盒检测示氯沙坦钾浓度为50、100、200、400μmol/L时L6成肌细胞活力分别为0.87±0.087、1.11±0.037、1.21±0.099、1.30±0.068,其中50μmol/L时细胞活力最大,且对cleaved caspase-3蛋白表达抑制最明显.与未作处理的对照组比较,qPCR显示棕榈酸处理组骨骼肌细胞P53、P21 mRNA表达量分别从0.36±0.03、0.50±0.05上调至0.68±0.08、1.07±0.02(P<0.05),cleaved caspase3、cleaved PARP蛋白表达均增加,LC3Ⅱ/LC3Ⅰ及Beclin 1蛋白表达减低;与棕榈酸单独处理组比较,氯沙坦钾与棕榈酸共处理组P53、P21 mRNA表达量分别从0.68±0.08、1.07±0.02下调至0.44±0.01、0.67±0.03(P<0.05),cleaved caspase-3、cleaved PARP蛋白表达减低,LC3Ⅱ/LC3Ⅰ及Beclin1蛋白无显著改变.结论 氯沙坦钾通过抑制cleaved caspase3及其底物cleaved PARP表达抑制细胞凋亡,但这种保护效应并不是通过自噬途径实现的.

Background/Aims: Postmenopausal osteoporosis is considered to be an autoimmune and inflammatory process, and IL-17 plays important roles in the loss of bone mass. Sclerostin (SOST) acts as a negative regulator of bone formation by inhibiting the Wnt signaling pathway. It also is a mediator of the crosstalk between the skeletal and immune systems. However, few studies have examined the role of SOST gene in the differentiation of T helper 17 (Th17) cells. Methods: Adipose-derived stem cells (ADSCs) were isolated and transfected with pcDNA3-SOST or shSOST, and then co-cultured with CD4+ T cells isolated from peripheral blood mononuclear cells. The differentiation, adipogenesis, and osteogenesis of Th17 and regulatory T (Treg) cells were examined by western blot, intracellular and intranuclear staining, ELISA, and real-time quantitative PCR in this co-culture model. Results: The SOST gene promoted the secretion of IL-6 and TGF-β in ADSCs. After co-culture of ADSCs with CD4+ T cells, the SOST gene increased the number of CD4+IL-17+ cells and the levels of IL-17 and RORγ. However, the number of CD4+CD25+Foxp3+ cells was decreased, which was accompanied with a reduction of IL-10 and Foxp3 expression. In the meantime, the SOST gene inhibited the expression of COL1, OCN, and OPN, reduced the activity of alkaline phosphatase, and increased the expression of LPL and PPARγ. Furthermore, IL-17 promoted SOST gene-induced adipogenesis and increased the inhibition of osteogenesis. Conclusions: SOST promoted the differentiation of Th17 cells and reduced the differentiation of Treg cells, which exacerbated the SOST gene-induced inhibition of osteogenesis from ADSCs.

Objective To observe the clinical characteristics of idiopathic osteoporosis among premenopausal women. Methods 28 idiopathic osteoporosis patients, 15 secondary osteoporosis patients and 56 normal cases were selected from 1043 premenopausal women according to the inclusion criteria in Shanghai First People's hospital between September 2005 and December 2016. Subjects were divided into three groups: idiopathic osteoporosis group, secondary osteoporosis group and control group. Retrospective statistical analyses were performed for basic clinical characteristics, bone turnover markers, bone mineral density ( BMD) and fracture data. Results BMD of the lumbar spine, femoral neck and hip in the idiopathic osteoporosis group were significantly lower than that of the control group (t＝ -3. 794, P＜0. 01; t＝ -4. 080, P＜0. 01; t＝ -5. 632, P＜0. 01). There were no significant differences in the levels of calcium, phosphorus and vitamin D between the idiopathic osteoporosis group and the control group (t＝0. 120, P＞0. 05; t＝0. 121, P＞0. 05; t＝0. 004, P＞0. 05). There was a trend of lower levels of OC and β-CTX in the idiopathic osteoporosis group than that of the control group, but the differences were not statistically significant (t＝1. 605, P＞0. 05; t＝1. 543, P＞0. 05). BMD of the lumbar spine in the secondary osteoporosis group was significantly lower than that in the idiopathic osteoporosis group ( P＝0. 035). However, there were no significant differences in BMD of the femoral neck and hip between the secondary osteoporosis group and the idiopathic osteoporosis group (P＝0. 298, 0. 223). The levels of OC and β-CTX in the secondary osteoporosis group were higher than that in control group (P ＝0. 020, P ＜0. 01). There was no significant difference in the level of OC between the secondary osteoporosis group and the idiopathic osteoporosis group (P＞0. 05). The level of β-CTX in the secondary osteoporosis group was higher than that in the idiopathic osteoporosis group (P＜0. 01). Conclusion The pathogenesis of idiopathic osteoporosis in premenopausal women may not be related to the levels of Ca, P and 25OHD, and the high turnover of bone metabolism might be the main cause of the disease.

Objective To evaluate the value of Short Physical Performance Battery( SPPB)and timed up and go (TUG)test in the measurement of muscle function,strength and mass in the elderly. Methods One hundred and six elderly women whose medical records were complied and maintained in Shanghai Hongkou District Ouyang Street Community Health&nbsp;Service Center from July to October in 2015 and met the inclusion criteria were enrolled in this study. SPPB( tandem standing test,2. 44 - meter walking speed test and 5 times of sitting and standing test)and TUG test were performed in them. The muscle function was assessed by usual gait speed,muscle strength was measured by handgrip strength,and muscle mass was evaluated by calculating relative appendicular skeletal muscle mass( RASM) by dual - energy X - ray absorptiometry( DXA). The correlation between SPPB,TUG and usual gait speed,handgrip strength,RASM were analyzed. Results The mean value of usual gait speed,handgrip strength,and RASM of the 106 elderly women was respectively(1. 32 ± 0. 28) m/ s, (19. 46 ± 3. 91)kg,(5. 94 ± 0. 82) kg/ m2 . Results of SPPB and TUG test showed that the mean time that the women needed to complete the tandem standing test,2. 44 - meter walking speed test,5 times of sitting and standing test,and TUG test was (7. 81 ± 3. 13)s,(1. 83 ± 0. 44)s,(9. 91 ± 3. 06)s,and(8. 96 ± 2. 34)s,respectively. Usual gait speed was negatively correlated with age,BMI,time needed to complete the 2. 44 - meter walking speed test,5 times of sitting and standing test, and TUG test(P < 0. 05). The time needed to complete the tandem standing test had no relation with usual gait speed(P >0. 05). Level of handgrip strength was negatively correlated with age,and the time required to complete the 2. 44 - meter walking speed test(P < 0. 05),but it had no relation with BMI,time required to complete the tandem standing test,5 times of sitting and standing test and TUG test( P > 0. 05). Result of RASM was positively correlated with BMI,time required to complete 5 times of sitting and standing test,and TUG test(P < 0. 05),but it had no correlation with age,time required to complete the tandem standing test,and 2. 44 - meter walking speed test(P > 0. 05). After adjusting age and BMI,the results of correlation analysis demonstrated that usual gait speed was negatively correlated with the time required to complete the 2. 44 -meter walking speed test,5 times of sitting and standing test,and TUG test(P < 0. 05),while it had no relation with the time needed to complete the tandem standing test( P > 0. 05). Level of handgrip strength was negatively correlated with the time required to complete the 2. 44 - meter walking speed test(P < 0. 05),but it had no relation with the time required to complete the tandem standing test,5 times of sitting and standing test,and TUG test( P > 0. 05). The time required to complete the tandem standing test,2. 44 - meter walking speed test,5 times of sitting and standing test,and TUG test had no correlation with the result of RASM(P > 0. 05). Multiple linear regression analysis showed that factors influencing the usual gait speed were the time needed to complete the 2. 44 - meter walking speed test(β = - 0. 658,SE = 0. 024,t = - 27. 529,P < 0. 001),and that needed to complete the TUG test(β = - 0. 015,SE = 0. 005,t = 3. 254,P = 0. 002). And the time required to complete the 2. 44 - meter walking speed test was the influencing factor for level of handgrip strength( β = - 2. 422,SE = 0. 835,t= - 2. 628,P = 0. 005). Conclusion Muscle function can be measured by both 2. 44 - meter walking speed test and TUG test. Muscle strength can be evaluated by 2. 44 - meter walking speed test. SPPB and TUG test are of no value in measuring muscle mass,but they can be used as the tools for the measurement of muscle function and strength.

To evaluate several tests of physical performance for sarcopenia screening and assessment, by investigating physical performance and function in older women. 106 community-dwelling older women from a community in Shanghai were enrolled in this study. Physical function assessed by short physical performance battery (SPPB), timed get-up-and-go (TUG), handgrip strength, and usual gait speed were asked to perform. Total lean mass was determined by Dual energy X-ray absorptiometry, the relative appendicular skeletal muscle mass ( RASM) was defined as appendicular skeletal muscle mass/height2 . 13 individuals were diagnosed as sarcopenia according to a consensus diagnostic criteria for sarcopenia, as developed by the Asian Working Group for Sarcopenia ( AWGS) in 2014. Body mass index and handgrip strength in the sarcopenia group were significantly lower than those in the non-sarcopenia group (P=0. 026, P=0. 004 respectively), and there was no significant differences in the age, SPPB score, TUG, and usual gait speed. Linear regression analysis showed RASM was significantly positively correlated with body mass index (r=0. 842, P<0. 01), time to rise from a chair and return to the seated position five times (r=0. 203, P=0. 036),TUG(r=0. 258, P=0. 008)and grip strength (r=0. 217, P=0. 025), meanwhile, both body mass index and grip strength entered Logistic regression analysis. Low weight and low handgrip strength are independent predictive factors of sarcopenia in older women. Sarcopenia screening for older women with low body-weight and weak handgrip strength is more urgently required

microRNAs是一类内源性表达的、长度约为22个核苷酸的非蛋白编码的单链RNA分子,是重要的转录后基因表达调控因子.在多种生理和病理过程中发挥重要作用,到目前为止,在动植物以及病毒中已经发现有24521个miRNA分子,miR-378是其中的一种,miR-378通过多种机制与众多疾病的发生发展密切相关.miR-378在不同肿瘤组织中起到不同作用,在胃癌,肝癌,结直肠癌等肿瘤中起到抑癌基因的作用,在白血病,胰腺癌,卵巢癌等肿瘤中起到癌基因的作用.在心血管方面,miR-378可以通过多种机制起到保护血管,延缓心血管疾病的发展.在骨代谢方面,miR-378可通过不同机制抑制或促进成骨细胞的分化.本文就其与肿瘤、心血管、骨代谢以及其他方面的研究进行介绍,为这些疾病的治疗和预防提供一种新的思路.

目的 探讨老年人群脆性骨折的临床特点及与骨密度(BMD)、骨代谢标记物的关系,为老年人脆性骨折的防治提供依据.方法 选取2009年1月至2013年12月在我院骨质疏松门诊初诊的老年脆性骨折患者(年龄≥65岁),记录骨折部位、次数,同时测定患者体质量指数(BMI)、BMD、尿钙/尿肌酐比(uCa/Cr)、血钙、血磷、骨碱性磷酸酶(BAP)、骨钙素(OC)、I型胶原羧端末肽(β-CTX)和25-羟维生素D[25-(OH) D]等指标.按骨折部位分为椎体骨折组、髋部骨折组及其他部位骨折组,按骨折次数分为单次骨折组和多次骨折组.采用SPSS 19.0软件进行统计学分析.结果 共有1072例患者发生1241例次脆性骨折,椎体骨折439例次,髋部骨折112例次,其他部位骨折690例次,其中162例患者有多次多部位骨折.所有患者骨量减少检出率达95.0％,其中骨质疏松检出率为55.1％.不同部位骨折各组患者的年龄、BMI、BMD差异均具有统计学意义(P＜ 0.05或P＜0.01),而uCa/Cr、血钙、血磷、OC、β-CTX和25-(OH)D差异均无统计学意义(P＞0.05).单次骨折组和多次骨折组比较,两组年龄和BMD差异均具有统计学意义(P＜0.05或P＜0.01),而BMI、血钙、血磷、BAP、OC、β-CTX、25-(OH)D和uCa/Cr组间比较差异无统计学意义(P＞0.05).结论 老年人群的脆性骨折与年龄和BMD密切相关,改善BMD有助于减少再次脆性骨折的发生,对高龄患者尤其重要.

BACKGROUND/AIMS:Osteoporosis is a progressive bone disease characterized by a decrease in bone mass and density, which results in an increased risk of fractures. Mesenchymal stem cells (MSCs) are progenitor cells that can differentiate into osteoblasts, osteocytes and adipocytes in bone and fat formation. A reduction in the differentiation of MSCs into osteoblasts contributes to the impaired bone formation observed in osteoporosis. MicroRNAs (miRNAs) play a regulatory role in osteogenesis and MSC differentiation. MiR-27a has been reported to be down-regulated in the development of osteoporosis and during adipogenic differentiation.METHODS:In this study, a miRNA microarray analysis was used to investigate expression profiles of miRNA in the serum of osteoporotic patients and healthy controls and this data was validated by quantitative real-time PCR (qRT-PCR). MSCs isolated from human and mice with miR-27a inhibition or overexpression were induced to differentiate into osteoblasts or adipocytes. TargetScan and PicTar were used to predict the target gene of miR-27a. The mRNA or protein levels of several specific proteins in MSCs were detected using qRT-PCR or western blot analysis. Ovariectomized mice were used as in vivo model of human postmenopausal osteoporosis for bone mineral density measurement, micro-CT analysis and histomorphometric analysis.RESULTS:Here, we analyzed the role of miR-27a in bone metabolism. Microarray analysis indicated that miR-27a expression was significantly reduced in osteoporotic patients. Analysis on MSCs derived from patients with osteoporosis indicated that osteoblastogenesis was reduced, whereas adipogenesis was increased. MSCs that had undergone osteoblast induction showed a significant increase in miR-27a expression, whereas cells that had undergone adipocyte induction showed a significant decrease in miR-27a expression, indicating that miR-27a was essential for MSC differentiation. We demonstrated that myocyte enhancer factor 2 c (Mef2c), a transcription factor, was the direct target of miR-27a using a dual luciferase assay. An inverse relationship between miR-27a expression and Mef2c expression in osteoporotic patients was shown. Silencing of miR-27a decreased bone formation, confirming the role of miR-27a in bone formation in vivo.CONCLUSION:In summary, miR-27a was essential for the shift of MSCs from osteogenic differentiation to adipogenic differentiation in osteoporosis by targeting Mef2c.

目的 通过分析骨质疏松症患者使用抗骨质疏松药物治疗好转停药后骨密度和骨转换指标的变化,探讨骨质疏松症患者停药后的最佳评估时间.方法 收集2008年8月至201 1年10月134例在上海市第一人民医院骨质疏松门诊初诊为骨质疏松症(T值≤-2.5),并使用双膦酸盐药物治疗(疗程≥3年)好转停药后的患者,根据评估时间将患者分为3组:A组停药6个月评估(n =62例);B组停药12个月评估(n=55例);C组停药6个月和12个月均评估(n=17例).回顾性分析所有被纳入者的年龄、体质量指数(body mass index,BMI)、用药时间、治疗终点和停药后不同时间的骨密度(bone mineral density,BMD)、血钙、血磷、血清25羟维生素D(25 hydroxy-vitamin D,25OHD)、骨钙素(bone gamma-carboxyglutamic-acid-containing proteins,BGP)和Ⅰ型胶原交联羧基末端肽(cross-linked carboxv-terminal telopeptide of type Ⅰ collagen,CTX)等临床资料.结果 62例停药6个月评估患者,腰椎、股骨颈和全髋骨密度[分别为(1.063±0.13)、(0.817±0.08)和(0.896±0.080)g/cm2]较治疗终点的基线骨密度均有降低趋势,其中腰椎和全髋骨密度变化,差异有统计学意义(P＜0.05),但变化值小于骨密度仪的最小有意义变化值(least significant change,LSC),则无临床意义.55例停药12个月评估患者,腰椎、股骨颈、全髋骨密度[分别为(1.071±0.09)、(0.815±0.08)和(0.887±0.07) g/cm2]较治疗终点的基线骨密度降低更为明显,其中腰椎、全髋骨密度变化差异有统计学意义(P＜0.05);股骨颈骨密度有明显的降低(P=0.085).17例停药6个月和12个月均评估的患者,停药6个月时腰椎、股骨颈、全髋骨密度有降低趋势,停药12个月的骨密度相对于停药6个月的骨密度进一步降低.各组患者的骨转换指标(bone turnover marker,BTM)较治疗终点的基线骨转换指标均有明显的上升,且差异均有统计学意义(P＜0.05).结论 骨质疏松患者治疗好转停药1年时评估骨密度及骨转换指标可早期预测及评估转归.

Objective To observe the efficacy of sequential therapy of raloxifene in postmenopausal women with osteoporosisafter3to5yearstreatmentofalendronate.Methods 240eligiblecasesofpostmenopausalwomenwithoste-oporosis from 11 538 patients selected according to the inclusion criteria in Shanghai first people’s hospital between Octo-ber 2005 and October 2013 were collected.Subjects were divided into two groups (A and B).A group (155 cases):All patients newly initiated treatment with raloxifene.B group (85 cases): Patients with 3 to 5 years failure of alendronate treatment previously were switch to raloxifene.All patients received supplemental calcium and active vitamin D.A retro-spective statistical analysis was performed for basic clinical characteristics, duration of treatment, BTM, BMD and fracture data.Results BMD at lumbar spine, femoral neck and hip in the A group were significantly higher after raloxifene treat-ment for 12 months than that before treatment (t=10.778, P<0.000 1;t=3.587, P<0.000 1;t=7.998, P<0.000 1). The percent changes in BMD at the lumbar spine and femoral neck were 3.3% and 1.5% and 1.4 % ( P<0.05 ) . There was a significant difference in the percent decrease in BGP andβ-CTX at 12 months (t=6.392, P<0.000 1;t=13.078, P<0.000 1).B group switched to raloxifene after 3-5 years of alendronate treatment.BMD at lumbar spine, femoral neck and hip in the sequential therapy group were trend to be higher than that before treatment, but the difference was not statistically significant (t=1.093, P=0.277; t=1.896, P=0.061; t=1.045, P=0.299).No statistically significant difference of annual change rate of BGP andβ-CTX was found after raloxifene treatment than before.However, the percentage changes in the BMD at lumbar spine and femoral neck were significantly higher after raloxifene treatment for 12 months than that before treatment ( t=3.729, P<0.000 1;t=2.191, P=0.031; t=2.929, P<0.01) .The per-centage changes in BMD at lumbar spine and femoral neck were significantly higher in A group than in B group ( t =5.756, P<0.000 1; t=0.713, P<0.000 1; t =0.736, P<0.000 1).Conclusion Raloxifene significantly in-creased bone mineral density and reduce bone turnover in postmenopausal patients with osteoporosis.If alendronate treat-ment was secondary failure, we could switch to raloxifene treatment to reduce the bone loss.

Objective To investigate the clinical characteristics of bone metabolism in elderly women patients with osteoporosis( over 80 years) and the effect of bisphosphonate. Methods Back from August 2005 to August 2013 in Shanghai First People's Hospital out-patient,treatment with bisphosphonates more than 12 months,there were 232 elderly women patients with osteoporosis at the age of over 80( the elder group) and 454 non old postmenopausal women patients with osteoporosis at the age of 47- 65( the control group),who have been measured the bone mineral density and bone metabolism before and after treatment. Record their ages,heights,weights,treatment period,bone mineral density( BMD),serum osteocalcin,serum phosphorus,25-hydroxy-vitamin D( 25OHD),bone metabolism markers,and other clinical datas before and after treatment. Results There was no significant difference in body mass index,serum calcium,phosphorus,and lumbar spine BMD between two groups before treatment. The level of 25 OHD,body tarnover marker,femoral neck BMD and total hip BMD in the elder group were significantly lower than those in the control group before treatment( P 0. 05). BMD and 25 OHD increased after bisphosphonate treatment for 12 months. The percentage changes in the lumbar spine,femoral neck,and total hip were 3. 29%,1. 24%,and 1. 00 %( P 0. 05) in elder group,3. 51%,1. 18%,and 1. 58 %( P 0. 01) in the control group. There was a significant difference in the percentage decrease in bone gamma-carboxyglutamic-acid-containing proteins and Ⅰtype collagen pyridine cross-linked final peptide in the two groups( P 0. 05). There was no significant difference in the percentage changes in the serum calcium and phosphorus after bisphosphonate treatment for 12 months. Conclusion Senile patients with osteoporosis was in a relatively low bone turnover state. Bisphosphonate had the similar effects for different levels of bone turnover. Bisphosphonate might be used in the elderly patients( ≥80) with osteoporosis.