血清镁浓度与绝经后妇女骨质疏松症的关系探讨

目的探讨绝经后妇女血清镁浓度与骨密度的关系。方法随机选取在2005年9月至2006年8月骨质疏松门诊绝经后妇女患者379例,检测患者的血清镁、钙、磷浓度及甲状旁腺激素(PTH),测身高、体重、计算体重指数(BMI=体重/身高2)。双能X线吸收法分别测定患者腰椎L1~L4骨密度,按WHO标准,根据骨密度分为骨质疏松组、骨量减少组和骨量正常组。统计分析采用SPSS 13.0for Windows软件。结果进入本数据统计者,骨质疏松组113例,骨量减少组190例,骨量正常组76例。3组血清镁浓度分别为0.740±0.122 mmol.L-1、0.738±0.121 mmol.L-1和0.744±0.099mmol.L-1,组间差异无显著性(P=0.97)。3组间血清钙、磷浓度及PTH值差异均无显著性。协方差分析仍显示各组间血清镁差异无显著性,年龄和BMI对组间血清镁差异无影响,而血清钙对血清镁有影响(F=8.352,P=0.004)。Pearson相关分析显示血清镁浓度与钙浓度呈正相关(r=0.283,P<0.01);与PTH值呈负相关(r=-0.177,P=0.029);与磷浓度也呈负相关(r=-0.194,P=0.018);但与绝经后妇女骨密度无相关性(r=-0.020,P=0.794)。结论绝经后妇女血清镁浓度在骨质疏松组与非骨质疏松组之间无差异。PTH在维持绝经后妇女血清镁、钙、磷浓度稳定中可能起重要作用。对绝经后妇女补镁的必要性及如何评估机体缺镁有待进一步研究。     

雌激素受体α基因甲基化与骨质疏松关系的研究进展

妇女绝经后体内雌激素水平显著下降,发生骨质疏松和骨折的风险显著增加。DNA甲基化作为表观遗传作用机制之一,与骨质疏松的发生有着重要关系。雌激素受体α基因甲基化水平升高会抑制雌激素受体α基因的表达,进而影响骨的新陈代谢,但具体作用机制有待于进一步研究。这种甲基化的状态是可以逆转的,通过干预基因甲基化,可以影响骨形成和骨重吸收的过程,进而为诊断和治疗骨质疏松提供新的思路。研究显示血清同型半胱氨酸(Hcy)会影响雌激素受体α基因甲基化水平,绝经后妇女平均血清Hcy浓度显著高于绝经前妇女,提示血清Hcy浓度可以作为早期筛查骨质疏松的指标之一;葛根素达到合适浓度后可抑制成骨细胞雌激素受体α基因甲基化,增强细胞ERαmRNA表达,进而促使成骨细胞增殖分化,从而用于骨质疏松的治疗。通过分析阐明雌激素受体α基因甲基化与骨质疏松的关系,可以早期筛选骨质疏松的高危人群,更简便快捷地诊断骨质疏松,为临床进行基因诊断提供理论依据;可以选择性地开发调节雌激素受体α基因甲基化药物,从而使治疗骨质疏松的靶向性更强,为骨质疏松的基因治疗提供理论依据。     

绝经后骨质疏松骨代谢标志物研究进展

骨代谢标志物包括骨吸收标志物和骨形成标志物,可及时反映骨转换状态,灵敏度高、特异性强,可用于骨质疏松分型诊断、骨折风险预测、抗骨质疏松疗效评价及代谢性骨病鉴别诊断。女性绝经后雌激素水平下降,骨形成与骨吸收失偶联,骨重建失衡,易导致骨质疏松发生。该文就绝经后骨质疏松骨代谢标志物研究进展作一综述。     

绝经前卵巢切除妇女骨代谢变化初探

目的：观察绝经前去势妇女雌激素与骨代谢的变化，对绝经后骨质丢失的类型及机制进行初步探讨。方法：采用术前及术后自身对照方法，对１５例因非恶性妇科疾患于绝经前行全子宫加双侧附件切除术的妇女进行了为期半年的随访，观察血清雌二醇及有关骨代谢指标的动态变化。结果：术后半年，血清雌二醇水平持续下降，骨合成指标及骨分解指标均明显升高，且与雌二醇水平呈显著性负相关。非优势侧前臂中远１／３交界尺桡骨平均骨密度下降２％。结论：术后发生了快速骨质丢失，其骨转换类型是高转换型，雌激素水平下降是直接主要原因。人工绝经对骨代谢影响短期内高于自然绝经，长期影响有待观察。     

绝经后女性铁蓄积与骨代谢及机体炎症反应的相关性研究

目的研究绝经后女性铁蓄积与骨代谢及机体炎症反应的相关性。方法将117名绝经后女性体检者按照骨密度(bone mineral density,BMD)值分成3组:骨量正常组(T≥-1)、骨量减少组(-2.5T-1)和骨质疏松组(T≤-2.5)。所有体检者均测定:血清生化指标[钙、磷、25(OH)D、血红蛋白、CRP、白细胞、肌酐、尿酸、丙氨酸氨基转移酶、谷草转氨酶、空腹血糖]、铁代谢指标[血清铁蛋白(Fer)、转铁蛋白(TRF)]、骨代谢指标[Ⅰ型胶原代谢产物(β-CTX、PINP)]。结果绝经后女性随着年龄增大,体内血清铁蛋白升高,铁蓄积增加,患骨质疏松症的风险增加,同时伴随β-CTX、PINP、CRP升高。其中血清铁蛋白与骨密度呈负相关,与β-CTX、PINP、CRP呈正相关。结论绝经后女性体内存在铁蓄积,同时伴有慢性炎症反应,铁蓄积可促进I型胶原蛋白降解,加速骨质疏松的进程。     

绝经后骨质疏松症对股骨近端的生物学影响

骨质疏松症是一种以系统骨量、骨强度及骨微结构损害为特征常导致骨折风险增加的疾病,是绝经后妇女常见且严重的情况。骨质疏松症在骨折发生前大多是一种隐性疾病,存在着检测和治疗不足的情况。而骨质疏松性骨折的发生常导致疼痛、畸形、活动障碍,对患者的生活质量造成严重影响。绝经后骨质疏松症是一种好发于中老年女性的全身性骨骼系统疾病。众所周知,雌激素是一种维持正常骨量的重要保护因素。绝经后妇女体内雌激素水平的降低与骨量的迅速流失密切相关。在妇女绝经之后,骨重建增加,内在的不平衡加速了骨质流失,最终导致骨质疏松症的形成。干预绝经后骨质疏松症的最主要的目的是防止骨折。最常发生骨质疏松性骨折的部位是椎体(脊柱)、股骨近端(髋部)及前臂远端(腕部)。其中,髋部骨折是骨质疏松症最严重的后果,往往导致重大残疾和过早死亡。鉴于绝经后骨质疏松症的特殊性及髋部骨折的严重性,系统全面地了解绝经后骨质疏松症对股骨近端的影响显得尤为重要。     

血清催产素浓度与绝经后女性骨密度相关性研究

目的探讨催产素与绝经后妇女骨代谢指标以及腰椎和髋部骨密度之间相关性。方法检测185例骨密度正常和132例患骨质疏松症女性的血清催产素、瘦素、雌激素和骨代谢指标浓度。腰椎和股骨颈的BMD通过双能X线吸收法测量。结果患骨质疏松症女性的血清催产素浓度低于骨密度正常的女性(P0.05)。骨质疏松症组中血清催产素浓度与年龄、绝经年限、体质量指数(body mass index,BMI)和血清PINP、BLAP和CTX浓度呈负相关;与瘦素和雌激素具有明显正相关性;在正常骨密度组中,血清催产素浓度和各种指标未发现明显的相关性。调整年龄和BMI后,腰椎和股骨颈骨密度仍然与绝经年限以及血清PINP、BLAP和CTX浓度呈负相关,与雌激素、瘦素和催产素浓度呈正相关。对年龄和BMI进行调整后,进行多元回归分析显示绝经年限、血清催产素、PINP和CTX是腰椎和股骨颈骨密度的显著预测因子。结论绝经后女性患者较高的血清催产素水平与较高的腰椎和股骨颈骨密度有关。     

绝经后骨质疏松性腰椎骨折骨代谢指标的变化

目的了解雌二醇和白细胞介素-6等骨代谢指标在骨质疏松症发病中的作用。方法选择女性腰椎骨折患者120例,绝经后有骨质疏松者60例(OP组),绝经后无骨质疏松者30例(NOP组),另外选择绝经前妇女30例为对照组。对120名妇女雌二醇、骨密度、白细胞介素-6、血清总碱性磷酸酶、骨钙素、尿羟脯氨酸肌酐比值、尿钙肌酐比值等指标进行了测定。结果绝经后妇女骨形成指标骨钙素及碱性磷酸酶明显高于对照组妇女,其中碱性磷酸酶在OP组和NOP组间有差异,而骨钙素在OP组和NOP组间无差异;绝经后妇女骨吸收指标尿羟脯氨酸肌酐比值及尿钙肌酐比值明显高于对照组妇女,OP组又明显高于NOP组;绝经后妇女的血清雌二醇的含量明显低于对照组(绝经前妇女),OP组又明显低于NOP组;绝经后妇女血清白细胞介素-6的含量明显高于对照组妇女,而OP组又明显高于NOP组。结论雌二醇、白细胞介素-6等骨代谢指标与骨质疏松关系密切。这充分说明雌激素水平的下降,IL-6分泌增多,导致骨吸收加速。     

载脂蛋白E对绝经后妇女骨质疏松影响的研究进展

载脂蛋白E(Apolipoprotein E,Apo E)在脂代谢中起核心作用,载脂蛋白E不仅作为重要角色参与脂代谢,也同时会影响骨代谢。现阶段多种研究表明,骨质疏松与脂代谢异常是受各种原因影响的代谢性疾病,二者关系紧密,绝经后妇女由于雌激素水平变化,常导致骨代谢与脂代谢紊乱,同时雌激素水平也被证实对Apo E有较大影响。国内外学者多将绝经后妇女骨质疏松与脂代谢异常的着重点放于Apo E,集中研究Apo E对骨代谢与脂代谢的调节作用。骨代谢与脂代谢的异常在我国中老年妇女人群中出现率极高,且往往伴随发生。骨质疏松对中老年妇女的日常生活,甚至生命安全皆有重要影响。本文通过整理载脂蛋白E对骨代谢以及绝经后妇女骨质疏松影响的现阶段研究,进一步对其相关性制作综述。     

绝经后骨质疏松症发病机制研究进展

绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)是指女性绝经后卵巢内分泌功能失调衰退,导致雌激素水平下降,从而导致破骨细胞的骨吸收大于成骨细胞的骨形成的一种代谢性疾病。骨质疏松症没有特异性的临床表现,直到轻微的创伤诱发骨折时才会引起重视,所以预防骨质疏松症是临床工作的重中之重。目前有很多研究报道了骨质疏松症发生发展的机制,在机体内雌激素的缺乏引起炎症因子与MicroRNA激活,从而引起RANKL-RANK-OPG轴的紊乱,引起骨质流失。同时雌激素充当抗氧化剂来保护骨,抵抗氧化应激。本文就绝经后骨质疏松症的发生机制做一综述。     

年龄和雌激素对绝经后妇女骨转换生化指标的影响

目的调查骨转换生化指标的差异,并评估激素和年龄相关因素与绝经前和绝经后妇女生化指标的关系。方法选取在2016年1月至2018年1月期间在我院就诊的女性患者作为研究对象。根据问卷调查,共选出496名健康女性,其中绝经前244例,绝经后女性252例。根据试剂制造商提供的指南评估不同的骨标志物,并且采用化学发光免疫测定法进行激素测定,特别是雌二醇水平评估。结果与绝经前妇女相比,绝经后妇女血清钙水平和雌二醇水平显著降低,而绝经后妇女血清磷和碱性磷酸酶(ALP)水平显著升高(P0.05)。年龄与绝经后骨标志物(ALP和钙)显著相关(P 0.05),而绝经前组无显著相关性。绝经后妇女钙与雌二醇之间呈显著正相关,而ALP与雌二醇之间呈显著负相关。此外,在体质指数和年龄校正偏相关分析中,绝经后妇女雌二醇和骨标志物之间没有显著相关性。结论绝经后女性雌激素水平和骨代谢异常对骨质疏松症的预测有积极的意义。     

雌激素受体α及β亚型与绝经后骨质疏松的关系

绝经后雌激素水平下降是绝经后骨质疏松症发病的主要原因,随着年龄增长和绝经后体内雌激素水平降低,骨细胞上的ER的数量和功能均降低,可以部分解释绝经后妇女骨质疏松症发生率骤升的现象,骨细胞上的ER与绝经后骨质疏松症发生有重要的关系。ERα和ERβ在不同部位的骨骼及不同的骨细胞中分布有所差异,二者在骨代谢中可能行使着不同的功能,本文就此进行了详细的综述。     

Evidence that type I osteoporosis results from enhanced responsiveness of bone to estrogen deficiency

Type I osteoporosis occurs within 20 years after menopause and is associated with excessive cancellous bone loss and fractures of the vertebrae and distal radius. We have suggested that it may be caused by estrogen deficiency plus some additional factor predisposing to excessive bone loss. One such factor might be a greater degree of sex steroid deficiency, a possibility that could not be previously excluded because assays of sufficient sensitivity have only recently become available. Thus, we studied 36 women with vertebral fractures due to typical high turnover type I postmenopausal osteoporosis and 36 normal postmenopausal women using new ultrasensitive assays with detection limits of 1 pg/ml for estradiol, 5 pg/ml for estrone and 5 ng/dl for testosterone to test if type I osteoporosis results from enhanced responsiveness of bone to estrogen deficiency. Mean levels of serum sex steroids were identical in both groups, but bone turnover was increased by up to 55% in the women with type I osteoporosis. Moreover, compared with controls, the osteoporotic women had a 51% higher (P<0.01) serum osteoprotegerin level, which was likely a compensatory response to the increased bone turnover. In the osteoporotic women, 1-year treatment with transdermal estrogen in 14 women reduced total deoxypyridinoline, an index of bone resorption, by 58% as compared with placebo treatment in 17 women (P<0.001). Thus, as compared to controls, postmenopausal osteoporotic women had comparable sex steroid levels but higher bone turnover levels that were responsive to estrogen therapy. This is consistent with the hypothesis that the greater bone loss in type I osteoporosis is the result of impaired responsiveness of bone to low postmenopausal levels of sex steroids.     

Alteration of the circadian rhythm of intact parathyroid hormone and serum phosphate in women with established postmenopausal osteoporosis

Several studies have established that the circulating concentration of intact parathyroid hormone, PTH (1–84), over 24 h follows a circadian rhythm. The importance of this circadian rhythm is not known although some authors have detected alterations in the rhythm in metabolic bone disease and following dietary manipulation. We have studied the circadian rhythm of PTH (1–84) in 8 premenopausal women, 8 postmenopausal women with established osteoporosis and 8 postmenopausal women with no evidence of osteoporosis. Blood samples were obtained at 30-min intervals over a 24-h period and significant differences were found in the profiles of PTH (1–84) and serum phosphate in the three groups studied. Premenopausal women possessed a nocturnal/early morning increase in PTH (1–84) and phosphate (between 2200 and 0700 hours), as did postmenopausal women without osteoporosis. In postmenopausal women with osteoporosis the nocturnal increase in PTH (1–84) and serum phosphate was absent and PTH (1–84) decreased during the period 2200-0700 hours. A shift in acrophase is observed between premenopausal and postmenopausal women without osteoporosis. No acrophase was found in postmenopausal women with osteoporosis for either PTH (1–84) or serum phosphate. No circadian rhythm, acrophase or significant amplitude was observed in serum adjusted calcium or ionized calcium in any group studied. Alterations in the circadian rhythms for PTH (1–84) and serum phosphate occur in patients with postmenopausal osteoporosis that suggest the normal dynamics of PTH (1–84) secretion may play a role in both calcium and phosphate metabolism and the bone remodelling process. Whether these changes are causative or a response to the pathology will require further investigation.     

尼尔雌醇防治绝经后及老年妇女骨质疏松的临床观察

对 2 0例绝经后妇女和老年妇女分别给予尼尔雌醇用药 3个月 ,并于给药前后分别测定空腹尿钙与肌酐 (Ca/Cr) ,羟脯氨酸与肌酐 (OHPr/Cr)比值以及血清碱性磷酸酶 (AKP)、雌二醇 (E2 )、降钙素 (CT)的值。以探讨尼尔雌醇减缓不同绝经年限妇女骨量丢失的作用机制。结果显示尼尔雌醇给药前后两组妇女血清E2 的水平未见明显变化 ,但其血清CT的水平均较给药前有程度不同的升高。空腹尿Ca/Cr、OHPr/Cr比值以及血清AKP水平均较给药前显著下降 (P <0 0 0 5及P <0 0 1)。故此提示 ,尼尔雌醇可能通过刺激甲状腺C细胞而增加CT的分泌或直接作用于骨组织等多种途径抑制骨质的吸收 ,维持其骨矿含量的相对稳定。因此 ,本研究在国内首次为尼尔雌醇用于减缓老年妇女骨质的丢失提供了一定的理论依据。     

Treatment of Postmenopausal Women with Osteoporosis or Low Bone Density with Raloxifene

Raloxifene, a selective estrogen receptor modulator (SERM), has been shown to improved bone mineral density (BMD) and serum lipid profiles in healthy postmenopausal women. The objective of this study was to examine the effects of raloxifene on BMD, biochemical markers of bone metabolism and serum lipids in postmenopausal women with low bone density or osteoporosis. This Phase II, multicenter, 24-month, double-masked study assessed the efficacy and safety of raloxifene in 129 postmenopausal women (mean age ± SD: 60.2 ± 6.7 years) with osteoporosis or low bone density (baseline mean lumbar spine BMD T-score: −2.8). Women were randomly assigned to one of three treatment groups: placebo, 60 mg/day raloxifene-HCl (RLX 60) or 150 mg/day raloxifene-HCl (RLX 150) and concomitantly received 1000 mg/day calcium and 300 U/day vitamin D₃. At 24 months, BMD was significantly increased in the lumbar spine (+3.2%), femoral neck (+2.1%), trochanter (+2.7%) and total hip (+1.6%) in the RLX 60 group compared with the placebo group (p<0.05). The RLX 150 group had increases in BMD similar to those observed with RLX 60. A greater percentage of raloxifene-treated patients, compared with those receiving placebo, had increased BMD (p<0.05). Serum bone-specific alkaline phosphatase activity, serum osteocalcin, and urinary type I collagen:creatinine ratio were significantly decreased in the RLX-treated groups, compared with the placebo group (p<0.01). RLX 60 treatment significantly decreased serum levels of triglycerides, and total- and LDL-cholesterol levels (p<0.01). The rates of patient discontinuation and adverse events were not significantly different among groups. In this study, raloxifene increased bone density, decreased bone turnover, and improved the serum lipid profile with minimal adverse events, and may be a safe and effective treatment for postmenopausal women with osteoporosis or low bone density. Received: 26 December 1998 / Accepted: 31 March 1999     

中药龟丝补骨片对绝经后早期妇女性激素和钙调节激素的影响

目的 观察中药龟丝补骨片对绝经后早期妇女性激素和钙调节激素的影响。以中医“肾虚”理论探讨其防治绝经后骨质心松症的作用机制，方法 将63例40岁以上的自然绝经1年以上但不超过5年的健康妇女，根据骨密度值T-Score低于-2.0为标准分为绝经后骨质疏松症组以上但不超过5年的健康妇女，根据骨密度值T-Score低于-2.0为标准分为绝经后骨质疏松症组（OP）和非骨质疏松症组（NO），并依就诊次序按1：2比率序贯进入尼尔雌醇组（n)和龟丝补骨片组（g)，单盲观察尼尔雌醉和龟丝补骨片的治疗作用6个月，治疗前和后第3、6个月分别完成中医肾虚证症状量化表调查，并检测血清性激素，促性腺激素和钙调节激素，成功随访率达93.65%。结果 龟丝补骨片对肾阴虚证和肾气虚证均有较好的改善作用，且似乎对减轻肾阴虚证更有效，同时发现龟丝补骨片具有类似雌激素样作用，同尼尔雌醇相似，可显提高E2/T比值；此外，龟丝补骨片对血清PTH和CT水平均有增加趋势，PTH/CT比值于治疗后第6个月时显下降；血清25-OH-VD3和钙水平明显增加，ALP水平明显下降，结论 龟丝补骨片具有促进钙代谢，调整钙调节激素的作用，可能是其发挥抗骨质疏松症的作用机制之一。     

Fuller Albright. His concept of postmenopausal osteoporosis and what came of it

Fifty years ago Albright contributed the following to understanding osteoporosis: (1) He recognized it as a deficiency of formation, not of mineralization of bone matrix; (2) he observed that 40 of 42 patients with osteoporosis before age 65 were women past menopause or young women postoophorectomy; (3) he concluded that estrogen stimulates osteoblasts (a conclusion later challenged); (4) he demonstrated by metabolic balance studies that estrogen causes a positive calcium balance in postmenopausal osteoporosis; (5) he introduced periodic progesterone to prevent or treat endometrial hyperplasia from prolonged estrogen therapy; and (6) he showed that long-term therapy arrested vertebral damage and height loss in postmenopausal osteoporosis and prevented them if started early. Since Albright's time, more sensitive methods of assessing bone density have replaced conventional roentgenograms. Some large scale trials of estrogen have indicated increased bone density and fewer fractures. Unopposed estrogen increases risk of endometrial cancer and decreases mortality from other cancers, myocardial infarction, stroke, and osteoporosis. Trials of calcitonin, diphosphonates, fluoride, vitamin D, and high calcium intake have not proved more effective than estrogen.     

Postmenopausal osteoporosis. Digital Rx radiogrammetry in the diagnosis and follow-up of treatment with alfacalcidol

Postmenopausal osteoporosis is characterised by an increased resorption of trabecular bone, a consequence of estrogen deficit. Changes in vitamin D metabolism are also an important contributors to the development of osteoporosis in postmenopausal women. Vitamin D and its active metabolites (Alfacalcidol, Calcitriol) perform important functions in regulation of the calcium balance and the bone metabolism. Aim of our study was to determine the efficacy of Alfacalcidol (Alpha D3) in reducing the loss of bone mass. 391 postmenopausal women with osteopenia and 165 postmenopausal women with osteoporosis were treated 24 months with Alfacalcidol. The bone mineral density (BMD) was measured by Digital Rx Radiogrammetry (DXR). In osteopenic women treated with 0.5 mg Alfacalcidol, bone mineral density increased after 12 and 24 months with 3.4% and 2.3%. In osteoporotic women the increase of BMD was 1.8% and 2.4% after 12 and respectively 24 months. On the control group BMD decreased with 3.4% after 24 months. In our study Alfacalcidol confirmed the abolishment of the loss of bone mass.