Bone mass and bone modelling markers in hypertensive postmenopausal women

Numerous phosphocalcium alterations associated with bone mineral density in hypertension have been described, but very few studies assess them. This study assesses bone mass in hypertensive postmenopausal women and the hypertension influence determining both calcium homeostasis and bone turnover markers. Blood and urine samples were analysed for calcium metabolism-related parameters. Densitometry studies were conducted in the lumbar spine (L2-L4). Hypertensive osteoporotic women--selected from 82 women, with 22% osteoporosis prevalence, similar to the rate for the same age in the Spanish population--had significantly higher levels of body mass index (29+/-4 vs 26+/-4, P=0.019), calciuria (293+/-146 vs 210+/-116 mg/24 h, P=0.023) and calcium/creatinine ratio (0.33+/-0.2 vs 0.22+/-0.1 P=0.003) vs hypertensive nonosteoporotic women. No relation was found between systolic and diastolic blood pressure with bone mass. However, there was a negative osteocalcin correlation (r=-0.386, P=0.0001, and r=-0.242, P=0.033). Calciuria is associated with bone mass decrease in hypertensive women, and there is no relation between bone mass and blood pressure.     

Alendronate in early postmenopausal women: effects on bone mass during long-term treatment and after withdrawal. Alendronate Osteoporosis Prevention Study Group

We studied the effect on bone mass of alendronate treatment for 5 yr and its withdrawal. Four hundred and forty-seven postmenopausal women with normal bone mass entered a 3-yr randomized trial followed by a 2-yr open label extension. Three hundred and eleven women completed the first 3 yr, and 263 consented to continue and completed the extension. We are reporting data from groups using the dose of alendronate currently approved for osteoporosis prevention (5 mg) or from the group in which alendronate treatment was withdrawn: 52 women received alendronate (5 mg) for 5 yr (group I), 56 received 3 yr of placebo followed by alendronate (5 mg) for 2 yr (group II), and 52 received alendronate (20 mg) for 2 yr followed by 3 yr off therapy (group III). In group I, alendronate (5 mg) increased bone mineral density (BMD) at the spine and trochanter by 2.5-3.2% (P < 0.001 vs. baseline) and stabilized total body and femoral neck BMD (change vs. baseline, P = NS) over 5 yr. By the end of 5 yr, BMD was comparable at the spine, hip, and total body in groups I and III. The 3-yr decrease in BMD after withdrawal of alendronate (20 mg) in group III was 1.8-5.7% (P < 0.01 vs. baseline) and similar to the 3-yr decrease in BMD in group II during the initial 3 yr. In conclusion, alendronate (5 mg) for 5 yr or alendronate (20 mg) for 2 yr followed by 3 yr off therapy prevented postmenopausal bone loss. After withdrawal of alendronate (20 mg), bone loss resumed at the normal early postmenopausal rate.     

Determinants of bone mass in postmenopausal women

Eighty white women, mean age 52 years, within one to six years postmenopausal, were studied to examine the relationship of various factors to bone mass. Forty-four of the women had annual measurements of bone mass, so that the rate of bone loss could be determined. Bone mass was measured by total body neutron activation analysis and photon absorptiometry of the distal radius (total body calcium [TBCa] and bone mineral content [BMC], respectively). Breast-feeding and pregnancy were noted to be associated with higher bone mass; those with lower BMC and/or TBCa tended to have higher serum alkaline phosphatase levels, lower testosterone levels, and more years since the cessation of menses. The rate of bone loss from the radius was greater in those with higher parathyroid hormone levels; those with reduced dietary intake of calcium and lower 25-hydroxyvitamin D levels had a greater rate of loss of TBCa.     

体重、体重指数与绝经后妇女骨丢失率的相关性研究

目的 评价体重、体重指数对绝经后妇女骨转换率的影响。方法 对1042名门诊体检的健康绝经后妇女测定身高、体重,计算体重指数（BMI）,DXA骨密度仪测定腰椎和股骨部位骨密度（BMD）,同时留取血液和尿液测定骨转换指标,如血清骨钙素（SM-BGP）、血清骨特异性碱性磷酸酶（S-BALP）、血Ⅰ型前胶原C端肽（S-PICP）,和骨吸收指标,如尿吡啶啉（U-PYD）、尿脱氧吡啶啉（U-DPD）、尿I型胶原羧基端肽（U-CTX）、尿Ⅰ型胶原氨基端肽（U-NTX）、尿钙（U-Ca）、尿肌酐（U-Cr）以及可以反映骨代谢的血完整甲状旁腺素（S-PTH）。结果 U-CTX/Cr（r=-0.233,P=0.000）、U-NTX/Cr（r=-0.110,P=0.016）和SM-BGP（r=-0.193,P=0.027）与BMI呈负相关。根据体重指数将受试对象分为三组：BMI≤24kg/m^2（正常组）,24kg/m^2〈BMI〈27kg／m^2（超重组）．27kg／m^2≤BMI（肥胖组）．U—CTX／Cr在三组的水平分别为：287．73±98．47;239．37±85．26;204．14±79．91,各组间差异均有统计学意义;U-NTX／Cr在三组的水平分别为：61．77±29．83;54．45±20．37;49．53±19．81,只在组1和组3间差异有统计学意义;SM—BGP在三组的水平分别为：26．16±12．75;24．57±10．98;20．82±7．99,组3与组1、组2间差异有统计学意义。多元逐步网归分析,BMI、腰椎BMD和年龄是影响绝经后妇女U—CTX／Cr、U—NTX／Cr、SM～BGP的主要因素。结论 BMI与骨转换率旱负相关,对于绝经后妇女,随着BMI的升高其骨形成（SM—BGP）或骨吸收（U—CTX、U—NTX）均有降低的趋势。     

Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Alendronate/Estrogen Study Group

The bisphosphonate alendronate and conjugated equine estrogens are both widely used for the treatment of postmenopausal osteoporosis. Acting by different mechanisms, these two agents decrease bone resorption and thereby increase or preserve bone mineral density (BMD). The comparative and combined effects of these medications have not been rigorously studied. This prospective, double blind, placebo-controlled, randomized clinical trial examined the effects of oral alendronate and conjugated estrogen, in combination and separately, on BMD, biochemical markers of bone turnover, safety, and tolerability in 425 hysterectomized postmenopausal women with low bone mass. In addition, bone biopsy with histomorphometry was performed in a subset of subjects. Treatment included placebo, alendronate (10 mg daily), conjugated equine estrogen (CEE; 0.625 mg daily), or alendronate (10 mg daily) plus CEE (0.625 mg daily) for 2 yr. All of the women received a supplement of 500 mg calcium daily. At 2 yr, placebo-treated patients showed a mean 0.6% loss in lumbar spine BMD, compared with mean increases in women receiving alendronate, CEE, and alendronate plus CEE of 6.0% (P < 0.001 vs. placebo), 6.0% (P < 0.001 vs. placebo), and 8.3% (P < 0.001 vs. placebo and CEE; P = 0.022 vs. alendronate), respectively. The corresponding changes in total proximal femur bone mineral density were +4.0%, +3.4%, +4.7%, and +0.3% for the alendronate, estrogen, alendronate plus estrogen, and placebo groups, respectively. Both alendronate and CEE significantly decreased biochemical markers of bone turnover, specifically urinary N-telopeptide of type I collagen and serum bone-specific alkaline phosphatase. The alendronate plus CEE combination produced slightly greater decreases in these markers than either treatment alone, but the mean absolute values remained within the normal premenopausal range. Alendronate, alone or in combination with CEE, was well tolerated. In the subset of patients who underwent bone biopsies, histomorphometry showed normal bone histology with the expected decrease in bone turnover, which was somewhat more pronounced in the combination group. Thus, alendronate and estrogen produced favorable effects on BMD. Combined use of alendronate and estrogen produced somewhat larger increases in BMD than either agent alone and was well tolerated.     

Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women

Statins are able to reduce cardiovascular morbility and mortality mainly through their hypocholesterolemic effect. Beyond the inhibition of cholesterol synthesis, the identification of "ancillary" mechanisms has motivated studies evaluating the relationship between the use of statins and the modification of bone mineral density (BMD). To date, clinical trials have provided discordant results. The aim of our study was to evaluate whether simvastatin treatment (40 mg/d) could modify BMD in hypercholesterolemic women (n = 40) after a 2-year treatment as compared with a control group treated only with diet (n = 20) and matched by gender, age, body mass index (BMI), lipids, menopausal age, and BMD and the number of osteopenic, osteoporotic, and normal women (on the basis of T-score value). Exclusion criteria were secondary hyperlipemias and osteoporosis and current or previous therapy with statins, bisphosphonates, and estrogens. The BMD was measured at the lumbar spine and hip by dual energy x-ray absorpiometry (DEXA). In the group treated by simvastatin, BMD, both on the spine and femoral hip, showed a significant increase after 8 and 24 months, respectively (0.878 +/- 0.133 v 0.893 +/- 0.130 and 0.907 +/- 0.132; 0.840 +/- 0.101 v 0.854 +/- 0.101; and 0.863 +/- 0.10, P <.001); there was a percentage increase of 1.7% after 8 months and 3.3% after 24 months at the spine; at the femoral hip, BMD increased 1.6% after 8 months and 2.7% after 24 months. The group treated only with hypolipidic diet demonstrated after 8 and 24 months a slight decrease in BMD both on the spine and femoral hip (respectively, 0.884 +/- 0.175 v 0.872 +/- 0.174 and 0.861 +/- 0.164; 0.860 +/- 0.110 v 0.853 +/- 0.096 and 0.847 +/- 0.095; P <.05). In conclusion, as partly suggested by retrospective or observational data, this longitudinal study indicates that simvastatin treatment exerts a beneficial effect on BMD.     

Hydroxyproline peptides and bone mass in postmenopausal and osteoporotic women.

Total and nondialyzable hydroxyproline excretion was measured in 59 postmenopausal women and 68 women with spinal osteoporosis. Hydroxyproline excretion was similar in both groups of women and the hypothesis that hydroxyproline excretion is normally distributed could not be rejected for either group. No relationship was found between hydroxyproline excretion (total and percentage of nondialyzable) and body weight, height, body surface area, or total body calcium or bone mineral content of the radius, or these latter values normalized for age, sex, and body size. There was no difference in hydroxyproline excretion in osteoporotic women who took supplemental calcium as compared to those that did not. These data fail to provide any evidence that bone turnover in osteoporotic women differs from that in younger postmenopausal women, or that osteoporosis arises from a subpopulation of women with rapid bone loss.     

替勃龙对绝经后骨质疏松症患者骨密度及骨代谢指标的影响

目的观察替勃龙(Livial)对绝经后女性骨质疏松症患者骨密度(BMD)和骨代谢指标的影响。方法对121名年龄51～62岁、自然绝经的女性进行骨密度测定,将89例骨质疏松女性患者随机分为替勃龙组(45例)和钙剂组(44例);32名绝经后骨密度正常的女性作为对照组。各组均于用药前、用药后12、24周采用酶联免疫吸附试验(ELISA)测定骨碱性磷酸酶(sBAP)、骨钙素(sOC)、Ⅰ型胶原交联C端肽(sCTx)和尿Ⅰ型胶原交联N端肽(uNTx),用双能X线吸收法(DEXA)测定腰椎正位,股骨颈,Ward’s三角和大粗隆的骨密度(BMD)。结果经治疗后,替勃龙组骨密度有所提高,而钙剂组和对照组骨密度均下降;替勃龙组的sBAP、sOC升高,sCTx、uNTx/Cr明显下降,钙剂组和对照组变化不明显。结论替勃龙治疗绝经后骨质疏松症疗效显著。单纯服用钙剂不能治疗绝经后骨质疏松症,且继续骨流失。     

Vitamin D receptor and aromatase gene interaction and bone mass in older African-American women

Aromatization of androgens by the CYP19 gene product, aromatase, is the major source of endogenous estrogen in postmenopausal women. We determined whether an Arg(264)Cys polymorphism in the CYP19 gene is associated with bone mineral density (BMD) and bone loss in older women. Because vitamin D regulates CYP19 gene expression, we also tested for an interaction with a translation start site polymorphism in the vitamin D receptor (VDR) gene. Hip BMD was measured twice, an average of 1.9 years apart, in 100 African-American women aged > or =65 years. Neither polymorphism alone was significantly associated with BMD or bone loss. BMD measurements in women with the less frequent allele at both loci were 0.5 to 1.3 SD lower than in women with neither or only a single rare allele (P <.001 for interaction). These women also experienced more rapid hip bone loss than other women (P <.05 for interaction). We conclude that VDR and CYP19 gene polymorphisms may jointly influence bone mass and the rate of bone loss in older African-American women.     

Effect of promethazine on lumbar vertebral bone mass in postmenopausal women

Abstract. Objectives. Work in mice suggests that the age-related loss of bone mineral noted in that species is caused by an intrinsic defect in a haematopoietic cell population which results directly or indirectly in increased bone resorption. This age-related loss of bone mineral is prevented or reversed by well-tolerated doses of promethazine HCL. The present study was undertaken to determine if promethazine would retard or reverse bone loss in postmenopausal women. Design. Postmenopausal women whose spine (L2 to L4) bone mineral content (BMC) was two standard deviations below young normal values were assigned randomly to receive calcium or promethazine and calcium daily. Subjects who had been taking oral oestrogen for more than 4 years also were assigned randomly but independently to the calcium or promethazine groups. Setting. All subjects were seen in the out-patient clinic of the Department of Medicine, School of Medicine, University of California, Los Angeles. Subjects. Healthy, ambulatory postmenopausal females were recruited by word of mouth and by advertisement from the local community. Fifty-four subjects completed the first 6 months of the study and 43 completed 30 months. Interventions. The subjects were assigned randomly to receive 1000 mg calcium daily or promethazine 50 mg and calcium 1000 mg daily throughout the period of the study. Main outcome measures. Bone mineral content of the lumbar vertebrae (L2 to L4) was determined by dual photon densitometry every 6 months. Dorsolumbar spine X-rays were obtained yearly and at the completion of the study to detect new compression fractures. Results. In the groups not taking oestrogen, BMC decreased at the rate of 1.53% year^?1 in the group given only calcium; in contrast, BMC increased at 3.22% year^?1 in the group given promethazine and calcium (P < 0.001). Among the women taking oestrogen, increases in mean BMC were noted in both groups, but those taking promethazine and calcium had a greater rate of increase than observed in the group taking only calcium (5.62% vs. 1.97% per year^?1, P < 0.001). Conclusions. These results suggest that promethazine can induce a modest increase in vertebral BMC in postmenopausal women who are not taking oestrogen and greater increases in those who are.     

Oral alendronate increases bone mineral density in postmenopausal women with primary hyperparathyroidism

The effect of biphosphonate therapy on bone mineral density (BMD) in patients with primary hyperparathyroidism (PHP) is unknown. Forty postmenopausal women (mean age, 70 yr) with PHP were randomized to receive alendronate 10 mg/d or placebo for 48 wk, followed by treatment withdrawal for 24 wk. The mean (+/-SD) changes in BMD at femoral neck (+4.17 +/- 6.01% vs. -0.25 +/- 3.3%; P = 0.011) and lumbar spine (+3.79 +/- 4.04% vs. 0.19 +/- 2.80%; P = 0.016) were significantly higher with alendronate at 48 wk. Serum calcium was reduced with alendronate but not placebo (-0.09 vs. +0.01 mmol/liter; P = 0.018). Serum bone-specific alkaline phosphatase activity was lower with alendronate from 12 wk onward and increased 24 wk after treatment withdrawal (21.1 +/- 12.8 to 7.3 +/- 4.9 IU/liter at 48 wk, and 15.0 +/- 14.8 IU/liter 24 wk after withdrawal; P = 0.002 for trend). Osteocalcin concentration decreased at 48 wk and increased 24 wk after alendronate withdrawal (P = 0.019 for trend of change over time) but not with placebo. Urinary N-telopeptide/creatinine ratio decreased with alendronate at 48 wk and increased 24 wk after treatment withdrawal (P = 0.008 for trend). N-telopeptide/creatinine ratio did not change with placebo. Alendronate improves BMD and reduces bone turnover markers in postmenopausal women with PHP.     

影响绝经后妇女骨量的相关因素分析

目的 探讨影响绝经后妇女骨量的相关因素。方法 记录142名健康绝经后妇女年龄、体重、身高、体重指数、初潮年龄、绝经年龄、初产年龄、分娩次数，采用放免法测定血清雌二醇（E2）、睾酮（T）、总三碘甲状腺原氨酸(TT3)、总甲状腺素（TT4）、甲状旁腺素全段（PTH－SP）、降钙素（CT）。双能X光骨密度仪测量腰椎、髋部、前臀骨密度值（BMD）。各项指标与骨密度值进行直线相关分析和逐步回归分析。结果 在一般状况的各项指标中，影响骨量的主要因素为年龄、绝经年龄和体重；骨量随E2、T、CT、TT3、TT4水平的下降而减少，随PTH水平的减少而增高，影响骨量的调钙激素为E2、TT4、PTH。结论 绝经后妇女随增龄和血PTH水平上调骨量丢失增加，血雌激素、甲状腺素水平及体重对维持骨量有重要作用。     

Influence of body composition on bone mass in postmenopausal osteoporotic women

We aimed at evaluating the relationship of lean and fat mass to bone mass in osteoporotic postmenopausal women. We invited 65 women who were being treated at the São Paulo Hospital osteoporosis outpatients’ clinic to participate. Body composition and bone mineral density (BMD) measurements were performed using Dual-energy X-ray absorptiometry methodology (DXA). The mean age and weight were 69.7 ± 6.4 years and 56.3 ± 7.6 kg, respectively. Accordingly to the body mass index (BMI), 52.8% were of normal weight and 47.1% of the patients were overweight. Overweight women had significantly higher bone mass. Similarly, skeletal muscle index (SMI) showed a positive effect on BMD measurements and women with sarcopenia had significantly lower BMD measurements in total femur and femoral neck. In multiple regression analysis only lean mass and age, after adjustments to fat mass and BMI, were able to predict total body bone mineral content (BMC) (R² = 28%). Also lean mass adjusted to age and BMI were able to predict femoral neck BMD (R² = 14%). On the other hand, none of the components of the body composition (lean mass or fat mass) contributed significantly to explaining total femur BMD and neither body composition measurements were associated with spine BMD. These findings suggest that lean mass has a relevant role in BMC and BMD measurements. In addition, lower BMI and lean mass loss (sarcopenia) is associated to lower BMC and BMD of femoral neck and total femur and possible higher risk of osteoporotic fracture.     

预防性服用阿仑膦酸钠降低绝经后妇女骨折风险的Meta分析

目的 系统评价阿仑膦酸钠对绝经后妇女骨质疏松性骨折的一级预防和二级预防的作用. 方法 按照Cochrane系统评价的方法,计算机检索美国国立生物医学信息中心Pubmed医学数据库、荷兰医学文摘Embase数据库、Cochrane图书馆临床对照试验数据库(2011年第2期)、中国生物医学文献数据库(CBM)、中文科技期刊全文数据库(CNKI)、万方及维普数据库,并检索所纳入文献的参考文献.收集所有相关随机对照试验,采用Cochrane协作网提供的软件RevMan 5.0进行Meta分析. 结果 共纳入11项随机对照试验进行评价.Meta分析结果显示,就二级预防而言,每天服用10 mg阿仑膦酸钠对减少脊椎、髋、腕部骨折发生率有统计学意义(RR=0.57,95％CI:0.49～0.67);但就一级预防而言,除减少椎体骨折的发生有统计学意义外(RR=0.55,95％CI:0.38～0.80),未发现减少其他骨折有统计学意义.与阿仑膦酸钠相关的不良反应无增加,敏感性分析结果无改变(RR=0.95,95％CI:0.83～1.09). 结论 阿仑膦酸钠的二级预防能减少绝经后妇女骨质疏松性骨折的发生,仍需对一级预防的疗效进行大样本研究.     

绝经后妇女膝骨关节炎与骨密度、骨代谢血清标志物的临床相关性

目的探讨绝经后妇女膝骨关节炎(KOA)与骨密度(BMD)、骨代谢血清标志物临床相关性。方法 180例绝经后妇女KOA患者分别进行体重、体重指数计算、绝经时间、腰1～4、股骨颈BMD测定及双膝关节X线拍片进行Kellgren-Lawrence(KL)分级,根据KOA KL分级比较BMD变化及酶联免疫吸附试验检测骨代谢血清标志物各项指标的变化。结果以KL结果分组,各组间绝经年龄无显著统计学差异(P>0.05),体重指数、年龄差异有统计学意义(P<0.05),随着KL级别增加,腰1～4和股骨颈BMD呈升高趋势,Ⅰ型胶原N端肽和Ⅰ膝胶原C端肽呈降低趋势。结论随着KL分级越高,BMD值越高,血清标志物水平越低。