住院老年男性26例骨密度与雄性激素关系分析

目的:观察老年骨质疏松症与雄激素水平是否有关。方法:住院>60岁的老年男性病人26例,用酶联免疫方法测定性激素,包括睾酮(T)、促性腺激素(FSH、LH)泌乳素(PLT),雌激素(E2)。应用NOLAND双能X线骨密度仪测定骨密度,并进行相关分析。结果:显示睾酮(T)与Ward三角区骨密度(BMD)密切相关,r=0.4075,P<0.025;促黄体生成素(LH)与L2～4BMD密切相关,r=0.4649,P<0.01。结论:雄激素减低是造成老年男性骨质疏松的重要因素之一。     

Association of genetic variations in aromatase gene with serum estrogen and estrogen/testosterone ratio in Chinese elderly men

BackgroundSingle nucleotide polymorphism (SNP) rs2470152 of the gene CYP19A1 is associated with serum estradiol (E2) levels in Caucasian men. However, it remains to be verified if rs2470152 is the sole determinant accounting for the association. We determined whether 2 CYP19A1 SNPs tagging different haploblocks (rs2470152 and rs2899470) are associated with sex steroid levels in Chinese men.MethodSerum sex steroid level including E2, estrone (E1) and testosterone (T), of 1402 Chinese men aged ≥ 65 years were analyzed. Genotyping of the two CYP19A1 SNPs was performed using T_m-shift allele-specific PCR.ResultsSNP rs2899470 was significantly associated with serum E2, E1 levels and E2/T ratio (p < 0.001). However, SNP rs2470152 was only modestly associated with E2/T ratio (p = 0.023). Analysis of haplotype showed a significant association between C-G, T-T haplotype with serum E2/T ratio (p = 0.019 and p = 1 × 10^? 5, respectively). Similarly, E2 levels was also associated the T-T and T-G haplotypes (p = 1 × 10^? 5).ConclusionThe genetic variation of CYP19A1 was associated with circulating estrogen levels in Chinese elderly men. In addition, it revealed that haplotype of rs2899470 and rs2470152, rather than rs2899470 alone, was a better indicator for the serum E2/T ratio and E2 levels.     

雌激素对骨代谢的调节作用

雌激素对于维持骨吸收与骨形成的平衡具有极其重要的作用。雌激素对骨代谢具有直接作用。雌激素通过破骨细胞和成骨细胞受体,限制骨转换,抑制骨吸收,提高骨密度。雌激素通过骨代谢调节因子、甲状旁腺激素等发挥其间接调节作用。植物雌激素及其衍生物分子结构与雌激素类似,可以与雌激素受体结合发挥雌激素作用。植物雌激素已成为当前雌激素替代疗法的研究热点。     

Mitochondrial function in bone resorption and formation

Mitochondria are involved in diverse biological processes through energy production, ROS generation and apoptosis, and mitochondrial dysfunction causes metabolic disorders, neurodegenerative disease, cancer and aging. Recent evidence links mitochondrial function to bone cell activity, especially bone-resorbing ostroclasts. Mitochondria of bone cells may provide a clue to the understanding of the pathogenesis of bone disease and also for development of new treatment options.     

骨吸收与骨形成

骨吸收通常与破骨细胞相伴随。破骨细胞性骨吸收是在骨的微环境内进行的复杂分子生物学反应过程。自从20世纪80年代初明确了破骨细胞来源于骨髓干细胞以后,方有可能对骨的破坏机理进行深入研究。成骨细胞是骨形成过程中的重要功能细胞,其主要功能是分泌骨基质(包括胶原及糖蛋白)及进行合成。成骨细胞还参与破骨细胞性骨吸收的调节,两者是骨代谢过程中的重要核心细胞。本文对骨吸收与骨形成过程及其相互关联做了较为全面的阐述。     

Amitriptyline disposition in young and elderly normal men

The disposition of a single parenteral or single oral dose of amitriptyline was followed in seven young (mean age 22 yr, range 21 to 23) and five elderly (mean age 71 yr, range 62 to 81) healthy men. The mean systemic clearance did not change with age (10.8 +/- 2.1 ml/min/kg in elderly and 12.5 +/- 2.3 ml/min/kg in young subjects). Mean t 1/2 was longer in the older (21.7 +/- 2.9 hr) than in the younger group (16.2 +/- 6.1 hr) as a result of an increase in the volume of distribution (17.1 +/- 2.4 and 14.1 +/- 2.0 l/kg). The bioavailability and the fraction of the drug bound to plasma proteins did not change with age. Single doses of amitriptyline were not well tolerated clinically by either elderly or young subjects, which confirms the need for a gradual buildup in the therapeutic regimen and for close clinical surveillance of elderly depressed patients treated with amitriptyline.     

中老年男性血清睾酮与代谢综合征的关系

目的 探讨中老年男性代谢综合征(MS)患者血清睾酮下降的原因.方法 选取45～ 83岁的中老年男性56例为研究对象,分别测量其血压、身高、体质量,计算体质量指数(BMI),检测空腹状态下生化指标[血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]、空腹胰岛素(FIN)及血清睾酮,并用稳态公式(HOMA)计算胰岛素抵抗指数(HOMA-IR).根据CDS建议的MS诊断标准,将研究对象分为MS组及非MS组,分析睾酮浓度与各指标的关系.结果 中老年男性MS组血清睾酮浓度明显低于非MS组[(9.97±3.87)nmol/L与(13.73±3.93)nmol/L,t=3.337,P＜0.01],多因素回归分析显示,血清睾酮浓度与年龄、腰围、HOMA-IR呈负相关(回归系数分别为-0.214、-0.329、-0.317,标准回归系数分别为-0.730、-0.597、-0.313,t值分别为-5.833、-4.681、-2.686,P均＜0.01).结论 中老年男性MS患者血清睾酮浓度下降,血清睾酮浓度与年龄、腰围、胰岛素抵抗密切相关.     

Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formation

Bone remodeling is characterized by the sequential, local tethering of osteoclasts and osteoblasts and is key to the maintenance of bone integrity. While bone matrix–mobilized growth factors, such as TGF-β, are proposed to regulate remodeling, no in vivo evidence exists that an osteoclast-produced molecule serves as a coupling factor for bone resorption to formation. We found that CTHRC1, a protein secreted by mature bone-resorbing osteoclasts, targets stromal cells to stimulate osteogenesis. Cthrc1 expression was robustly induced when mature osteoclasts were placed on dentin or hydroxyapatite, and also by increasing extracellular calcium. Cthrc1 expression in bone increased in a high-turnover state (such as that induced by RANKL injections in vivo), but decreased in conditions associated with suppressed bone turnover (such as with aging and after alendronate treatment). Targeted deletion of Cthrc1 in mice eliminated Cthrc1 expression in bone, whereas its deficiency in osteoblasts did not exert any significant effect. Osteoclast-specific deletion of Cthrc1 resulted in osteopenia due to reduced bone formation and impaired the coupling process after resorption induced by RANKL injections, impairing bone mass recovery. These data demonstrate that CTHRC1 is an osteoclast-secreted coupling factor that regulates bone remodeling.     

中药骨康对去势大鼠骨吸收与骨形成影响的实验研究

目的探讨中药骨康治疗绝经后骨质疏松大鼠模型的作用机制.方法采用雌性SD大鼠,随机分为正常对照组、模型组、中药骨康组及尼尔雌醇组,去双侧卵巢后造绝经后骨质疏松大鼠模型,造模3个月后,分别采用生理盐水、中药骨康及尼尔雌醇灌胃,灌胃3个月后采用摘眼球取血,测定其血清骨钙素、降钙素含量.结果中药骨康组大鼠血清骨钙素、降钙素水平明显高于模型组,两者相比有显著性差异,P<0.05.结论中药骨康具有抑制去势大鼠骨质吸收,促进骨形成的作用.     

The association between serum testosterone and mortality among elderly men on hemodialysis

Objectives

This study examines the associations between total testosterone levels and dialysis mortality.

Methods

Elderly men who initiate hemodialysis in Taoyuan General Hospital from January 2012 to June 2017 were enrolled. We reviewed clinical characteristics and biochemical data from start of dialysis and followed over a 5‐year period after dialysis. Body composition parameters were assessed 3‐6 months after dialysis. Skeletal muscle mass index (SMMI) was defined by skeletal muscle mass divided by squared height. We defined those with lowest tertile of testosterone values as low testosterone group. Adjusted hazard ratios (aHRs) and 95% confidence interval (95% CI) for mortality and cumulative survival curves were evaluated by Cox hazards model and Kaplan‐Meier method. The discriminative power of SMMI and testosterone levels was calculated according to the area under the curve and the receiver operating characteristic curve (AUROC).

Results

From a total of 137 elderly hemodialysis patients, the range of lowest, middle, and highest tertile of testosterone values was <6.25 nmol/L, 6.25‐10.5 nmol/L, and >10.5 nmol/L. After multivariate adjustment other than SMMI, total testosterone levels at baseline were a significant predictor for mortality aHR(95% CI): 0.79 (0.70‐0.91). The unadjusted and adjusted c‐statistics of SMMI vs testosterone values to predict overall were 770 (0.688‐0.852) vs 0.779 (0.691‐0.866) and 855 (0.812‐0.886) vs 0.812 (0.744‐0.856) (Ps < .05), whereas the capacity of c‐statistics was similar (χ² = 0.143 and 2.709, Ps > .05).

Conclusions

Total testosterone value was a predictor for mortality. It was noninferior to SMMI in predicting dialysis mortality.

     

体外诱导大鼠破骨样细胞形成及促进骨吸收的实验

目的:通过大鼠四肢长骨骨髓细胞的体外诱导培养,观察1.25-(OH)2D3对破骨样细胞形成的影响。方法:4周龄SD大鼠长骨骨髓细胞悬液接种于预置盖玻片或牙本质片的24孔培养板内,试验组加入诱导剂1.25-(OH)2D3(1×10-8mol/L)而对照组不加,每3d换液1次,培养2周。结果:培养1周左右光镜下可见有多核破骨样细胞形成,胞体大,抗酒石酸酸性磷酸酶(TRAP)染色阳性,牙本质片上有骨吸收陷窝形成。证明所形成多核细胞为破骨样细胞。结论:1.25-(OH)2D3(1×10-8mol/L)可诱导大鼠骨髓破骨样细胞的形成。     

Early effects of ethinyloestradiol and norethisterone treatment in post-menopausal women on bone resorption and calcium regulating hormones

The early effects of sex steroid therapy were assessed in 28 normal post-menopausal women, 18 treated with ethinyloestradiol and 10 with norethisterone. There was a reduction in the fasting urinary excretion of both calcium and hydroxyproline with both treatments, indicating reduced bone resorption. This was apparent after 1 week of therapy but became more marked after 3 weeks. These changes were not accompanied by any changes in plasma levels of calcitonin or parathyroid hormone. Patients receiving ethinyloestradiol showed a marked increase in plasma 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentration but this was explicable entirely in terms of increased plasma levels of vitamin D binding protein. There was no change in the free plasma level of 1,25(OH)2D. Patients treated with norethisterone showed no increase in plasma concentrations of 1,25(OH)2D. We conclude that both ethinyloestradiol and norethisterone have a rapid and similar effect in reducing bone resorption. This is not mediated via the plasma levels of the calcium regulating hormones.     

一氧化氮介导雌激素的骨形成增加作用

背景雌激素的具体骨保护机制目前尚不清楚,一氧化氮可能在雌激素促进骨形成增加中起到一定的作用.目的探讨雌激素治疗对卵巢切除大鼠血浆硝酸盐/亚硝酸盐水平的影响.设计随机对照的试验.单位上海市杨浦区中心医院骨科和同济医院大学附属协和医院骨科.材料实验在同济医科大学动物实验中心完成,选用3个月龄清洁级健康雌性SD大鼠36只,体质量220～245 g,由同济医科大学动物实验中心提供.干预12只SD大鼠完整切除双侧卵巢,设为卵巢切除组;另12只暴露双侧卵巢而不予以切除,设为对照组;雌激素治疗组12只切除双侧卵巢后即刻及后每隔2周皮下注射苯甲酸雌二醇125 μg.主要观察指标通过免疫组织化学染色方法检测一氧化氮合成酶在骨组织中的表达,双能X射线测定骨矿密度值,图象分析系统进行骨形态学计量学测量,光密度法测定血浆硝酸盐/亚硝酸盐水平.结果卵巢切除导致血浆硝酸盐/亚硝酸盐水平及骨矿密度值、小梁骨体积等骨形态学计量学参数显著下降.手术后6周,对照组和卵巢切除组平均血浆硝酸盐/亚硝酸盐水平分别为(22.4±1.7),(16.2±3.7)μmol/L;骨矿密度值分别是(0.245±0.030)g/cm2和(0.189±0.030)g/cm2;小梁骨体积分别为(31.97±3.50)%和(17.14±4.20)%,两组之间差异均有显著性意义(P＜0.01).雌激素治疗抑制了卵巢切除导致的这些变化,雌激素治疗组平均血浆硝酸盐/亚硝酸盐水平为(21.9±3.5)μmol/L,骨矿密度值为(0.234±0.020)g/cm2,小梁骨体积为(26.53±1.63)%,与卵巢切除组比较,均有显著性升高(P＜0.01);与对照组比较,差异均无显著性意义(P＞0.05).一氧化氮合成酶免疫活性信号在成骨细胞内测得,雌激素治疗组一氧化氮合成酶信号较卵巢切除组也显著性增强(P＜0.01).结论雌激素通过诱导一氧化氮的产生而刺激骨形成,一氧化氮是雌激素诱导骨形成增加的介导剂.     

雌激素受体基因多态性与老年妇女的骨密度

背景:雌激素受体α基因多态性与骨质疏松的发生相关有一定的关系,但是对于危险基因型的研究还存在商榷余地。目的:分析雌激素受体基因多态性与老年妇女骨密度的相关性。方法:选择检查的老年健康妇女120例,提取全血基因组DNA,选择限制性内切酶PvuⅡ和XbaⅠ进行酶切,分析基因型的分布与频率。同时选择双能X射线骨密度仪测股骨颈、大转子及Ward三角处的骨密度值。结果与结论:XbaⅠ酶切基因型XX 6例,Xx 78例,xx 36例;PvuⅡ酶切PP 32例,Pp 50例,pp 38例。不同基因型老年妇女的年龄、绝经年龄与体质量指数值对比差异无显著性意义(P>0.05)。PvuⅡ酶切PP基因型妇女的大转子与ward三角处的骨密度值明显大于Pp及pp妇女(P<0.05);而XbaⅠ酶切基因多态性在老年妇女中股骨颈、大转子与Ward三角的骨密度均无显著差异(P>0.05)。说明雌激素受体基因多态性与老年妇女骨密度有一定的相关性,P等位基因对老年妇女大转子与Ward三角处的骨密度的维持有一定作用。