Effects of long-term treatment with loop diuretics on bone mineral density, calcitropic hormones and bone turnover

BACKGROUND: Loop diuretics (LD) are widely used in the treatment of cardiovascular diseases and disorders with fluid accumulation. LD are known to increase renal calcium losses and may thereby affect calcium homeostasis and bone metabolism. OBJECTIVE: We studied to what extent long-term treatment with LD affects calcium homeostasis and bone metabolism. DESIGN AND SUBJECTS: In a cross-sectional design we compared 140 postmenopausal women treated with a LD for more than 2 years with 140 age-matched women not in diuretic therapy. RESULTS: Treatment with LD was associated with significantly increased urinary calcium, plasma parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D levels. Per 40 mg day(-1) of furosemide, urinary calcium was increased by 17% (P < 0.05) and plasma PTH levels were increased by 28% (P = 0.04). Users of LD had a 17% higher body weight (P < 0.001) compared with nonusers. This was due to a 32% higher fat mass (P < 0.001) and a 6% higher lean tissue mass (P < 0.001). Moreover, users of LD had a higher bone mineral density (BMD) at the spine (+7.5%, P < 0.001), hip (+4.8%, P = 0.004), forearm (+3.7%, P = 0.01) and whole body (+2.5%, P = 0.06). However, after adjustment for body weight differences, BMD did not differ between groups. Nevertheless, duration of LD treatment was positively associated with BMD at the spine (P = 0.03) and whole body (P < 0.05). BMD at the spine increases by 0.3% per 1 year of treatment. CONCLUSIONS: The increased renal calcium losses in users of LD are compensated for by a PTH-dependent increase in 1,25(OH)(2)D levels. Thereby calcium balance remains neutral without major effects on bone metabolism.     

Effect of venesection on bone mineral density in an eugonadal woman with haemochromatosis

BACKGROUND: A 41-year-old premenopausal woman with newly diagnosed haemochromatosis was found to have osteopenia on screening bone mineral densitometry. METHODS AND RESULTS: Liver biopsy showed grade 3 haemochromatosis with an hepatic iron index of 4. Investigation for secondary factors for osteopenia revealed no cause. The patient was clinically and biochemically eugonadal. Following venesection of 8 L blood (4 g iron) over 17 months and calcium supplementation, her bone density rose significantly. Neck of femur bone density increased by 6.0% over 13 months and lumbar vertebral bone density increased by 7.2%. There are no previous reports of response of bone density to venesection in eugonadal patients or in women with haemochromatosis.     

Normative bone mineral density values in Filipino women

Objective: To obtain reference values of bone mineral density (BMD) for Filipino women in order to make a population‐specific diagnosis of osteoporosis. Method: Sudy design: Cross‐sectional. Setting: Osteoporosis Unit, Joint and Bone Center, Section of Rheumatology and Clinical Immunology, Department of Medicine, University of Santo Tomas Hospital, Manila, Philippines. Participants: 442 healthy Filipino women volunteers recruited from the outpatient department, Rheumatology and Clinical Immunology Clinic of the University of Santo Tomas Hospital and from within the University of Santo Tomas campus. Subjects with known underlying illness or conditions or intake of drugs that predispose to osteoporosis were excluded from the study. Intervention: Bone mineral density (BMD) measurements, expressed in grams per square centimenter of the lumbar spine, non‐dominant femur and non‐dominant forearm were done in 442 consecutive healthy Filipino women using the LUNAR DPX‐IQ machine. Results: Means and standard deviations of BMD measurements at each site were calculated using Kwikstat software Version 3.6, Release 7. Results were grouped in decades to serve as reference per decade. Conclusion: Bone mineral density measurements of these 442 healthy Filipino women may serve as an initial reference guide for the diagnosis of osteoporosis in Filipino women.     

HOXD4基因多态性与老年男女性低骨量的关系

目的同源异形盒（homeobox,HOX）基因在调节软骨分化和成骨细胞中扮演了很重要的角色。本研究目的是探讨HOXD4基因多态性与老年男性和女性低骨量的关系。方法筛选711名（年龄61．8±6．9岁）老年男性（其中419例健康男性、276例骨量减少患者和16例骨质疏松患者）和617名（年龄58．9±6．4岁）绝经后妇女（其中272例健康女性、291例骨量减少患者和54例骨质疏松患者）共1328个研究对象,所有对象均为居住在上海30年以上的汉族人。双能X线吸收仪（GE Lunar Prodigy和Hologie QDR2000）检测左侧股骨颈BMD（bone mineral density,BMD）。骨量减少和骨质疏松的诊断分别按照股骨颈BMD为同性别正常峰值BMD的-1和-2．5个标准差,同时排除继发性低骨量的存在。使用Taqman荧光探针法检测HOXD4的3个标签位点：rs1867863、sr13418078和rs4972504的单核苷酸多态性（single nucleotide polymor-phisms,SNPs）。结果与其他人群不同,在我们的研究中rs13418078只发现CC基因型。在711例老年男性中,rs1867863的基因型频率依次为AA（40．5％）、AC（45．7％）、CC（13．8％）,rs4972504的基因型频率依次为CC（51．6％）、CT（40．5％）、TT（7．9％）;在617例老年女性中,~1867863的基因型频率依次为AA（42．3％）、AC（43．1％）、CC（14．6％）,rs4972504的基因型频率依次为CC（53．5％）、CT（38．7％）、TT（7．8％）;等位基因频率分布均符合Hardy—Weinberg定律。未发现此两位点SNP在骨质疏松组、骨量减少组和骨量正常组之间频率分布的差异（P均〉0．05）。结论本研究第一次提示了HOXD4的rs1867863和rs4972504位点多态性可能不是中国汉族老年男性和女性低骨量的风险因子。     

雷奈酸锶对绝经后骨质疏松症妇女骨密度的影响

目的观察雷奈酸锶(SR)对绝经后骨质疏松症妇女骨密度的影响。方法采用随机、双盲、安慰剂对照研究,对36例绝经后妇女分为试验组(n=18)和安慰剂组(n=18),分别给予SR 2g/d及安慰剂,共12个月。分别在用药前、用药6个月、用药12个月测定受试者的骨密度。结果与安慰剂组相比,使用SR 6个月后,SR组腰椎的骨密度增加1.98%,安慰剂组增加1.15%,两组比较差异无显著性(P0.05),SR组总髋部的骨密度增加2.22%,安慰剂组增加0.20%,两组比较差异具有显著性(P0.05);使用SR 12个月后,SR组腰椎的骨密度增加4.08%,安慰剂组降低0.53%,两组比较差异具有极显著性(P0.01),SR组总髋部的骨密度增加3.17%,安慰剂组降低0.46%,两组比较差异具有极显著性(P0.01)。共有4例提前终止研究(SR组2例,安慰剂组2例)。结论 SR能增加绝经后骨质疏松症妇女骨密度,服用顺应性好,安全。     

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人的一生不断进行着骨的新陈代谢。这是通过旧骨吸收和新骨形成来完成。在正常人两者紧密偶联,假如两者失偶联会引起骨量、骨结构和骨强度的改变。但体内骨结构和骨强度很难被检测。近代通过测定骨转换生化标志物了解是否存在骨代谢的失衡。文章介绍骨形成和骨吸收的生化标志物及其临床应用,由于无创伤,价较廉,正被推广应用。     

Depressive symptoms and rates of bone loss at the hip in older women

OBJECTIVES: To ascertain whether depressive symptoms are associated with increased rates of bone loss at the hip. DESIGN: Population-based prospective cohort study. SETTING: Four clinical centers in the United States. PARTICIPANTS: Four thousand one hundred seventy-seven community-dwelling women, aged 69 and older, enrolled in the Study of Osteoporotic Fractures. MEASUREMENTS: Depressive symptoms were assessed using the Geriatric Depression Scale (GDS). Subjects were categorized as depressed if their GDS score was 6 or greater at the fourth examination. Bone mineral density (BMD) at the hip was measured using dual-energy x-ray absorptiometry at the fourth and sixth examinations (average 4.4 years between examinations). Use of antidepressant medications was assessed by interview and verified from medication containers at the fourth and sixth examinations of the Study of Osteoporotic Fractures. A computerized dictionary was used to categorize type of medication. RESULTS: In age-adjusted models, mean total hip BMD decreased 0.69%/year in 3,977 women with a GDS score of less than 6, compared with 0.96%/year in 200 women with a GDS score of 6 or greater (P<.01). Results were not substantially altered when adjusted for potential confounders and when users of antidepressants were excluded from the analysis. CONCLUSION: Depression, as defined by a GDS score of 6 or greater, was associated with an increased rate of bone loss at the hip in this cohort of older women. Clinicians should be aware of a possible increased rate of bone loss in older, depressed women.     

铁调素对去卵巢大鼠骨代谢的影响

目的观察铁调素对去卵巢大鼠骨代谢的影响。方法将30只10周龄雌性Wistar大鼠分为假手术(sham)组、铁调素(hepc)组和生理盐水对照(OVX)组,每组10只。Hepc和OVX组行双侧卵巢摘除术后,分别经腹腔注射750μg/kg铁调素(hepcidin)溶液和等量生理盐水。9周后经颈静脉取血、处死后留股骨。检测股骨骨密度(BMD)、骨生物力学、血清骨代谢标志物及血清铁水平。结果与sham组相比,OVX组BMD及骨最大载荷、弯曲应力、弹性载荷、弹性模量均降低,差异均有统计学意义(P0.05),同时血清骨形成蛋白-2水平下降,而骨吸收指标Ⅰ型胶原交联C端肽(CTX-1)水平上升,血清铁浓度升高,差异均有统计学意义(P0.05);经铁调素干预的hepc组骨密度较OVX组增加了21.7%,上述骨生物力学指标也有明显改善,差异均有统计学意义(P0.05),虽然血清骨形成蛋白-2水平无明显升高,差异无统计学意义,但血清CTX-1水平下降33.5%,血清铁浓度降低17.2%,差异均有统计学意义(P0.05)。结论铁调素能改善绝经后骨质疏松大鼠模型骨代谢和力学特性,该作用可能通过改善体内铁超载、降低骨吸收实现。     

河北地区健康女性不同年龄不同部位骨密度调查分析

目的分析河北地区不同年龄不同部位健康女性的骨密度变化。方法将河北地区923名健康女性,年龄20～80岁,每10岁为1组,分为6组,所有受试对象均记录年龄、身高、体重、体重指数（BMI）、女性绝经年限,同时测定腰椎2_4、股骨颈、ward＇s三角、大转子、转子间的骨密度（BMD）;计算各组骨质疏松发生情况,找出各部位骨峰值,分析年龄、BMI与各部位骨密度的关系,同时分析50岁以上女性年龄、BMI、绝经年限与骨密度的相关性。结果40～49岁骨质疏松（OP）发现率为11．72％,50～59岁为31．54％,60～69岁为63．42％,70～79岁为79．84％,骨峰值出现在30—39岁,30—39岁不同部位骨密度均明显高于其他年龄组（P〈0．05）;20～29岁与40～49岁各部位BMD无明显差别（P〉0．05）;其他各年龄组股骨颈、ward＇s三角、大转子、转子间骨密度两两比较均有显著差别（P〈0．05）;肥胖组的L2-4,ward＇s三角区BMD均明显高于正常体重组与超重组（P〈0．05）,但后两组无明显差别（P〉0．05）;肥胖组的股骨颈、大转子、转子间BMD均明显高于正常体重组（P〈0．05）,但肥胖组与超重组,正常体重组与超重组相比以上部位BMD无明显差别（P〉0．05）,相关分析表明：各部位骨密度与年龄呈负相关,与BMI呈正相关,50岁以上女性同时发现绝经年限与各部位骨密度呈负相关,但相关性以年龄最好。结论建立了河北地区健康女性不同年龄不同部位骨密度的数据库,为骨质疏松预防、诊治提供参考数据。     

阿伦膦酸钠对老年女性2型糖尿病骨质疏松患者骨代谢标志物的影响

目的观察老年女性2型糖尿病（T2DM）骨质疏松患者应用阿伦膦酸钠（ALN）联合钙尔奇D治疗后骨密度（BMD）和骨代谢指标的变化。方法采用双能X线骨密度仪（DEXA）对34例老年女性糖尿病骨质疏松患者给予ALN联合钙尔奇D治疗6个月,对比治疗前后腰椎和髋部BMD及骨代谢标志物的变化。结果 ALN联合钙尔奇D治疗6个月后腰椎和髋部T值和BMD均增加,尤其L1、L3、L4及L总部位增加显著;血清抗酒石酸酸性磷酸酶5b、尿羟脯氨酸/肌酐比值和骨碱性磷酸酶水平较治疗前降低,血清降钙素水平较治疗前升高（P均〈0.05）。结论 ALN联合钙尔奇D治疗老年女性T2DM患者骨质疏松疗效明显,短时间内可显著改善骨代谢指标和提高腰椎BMD。     

Bone Mineral Density Screening and the Frequency of Osteopenia/Osteoporosis in Turkish Adult Patients With Celiac Disease

Background: The aim of this study was to evaluate the prevalence of osteopenia and osteoporosis in adult patients with celiac disease (CD) at diagnosis and/or in the follow-up after a gluten-free diet (GFD).MethodsAdult patients diagnosed with CD were retrospectively screened through follow-up records and computer databases. Patients assessed by dual-energy X-ray absorptiometry (DEXA) at diagnosis and/or in the follow-up after a GFD were included in the study.Results: One hundred patients who underwent a DEXA scan at least once after diagnosis or after being on a GFD were included in the study. The mean age of the patients at diagnosis was 34.61 ± 10.3 years, and 84% of the patients (n = 84) were female. At the time of diagnosis (n = 46), the prevalence of osteopenia and osteoporosis was 67.3% and 15.2%, respectively, at the lumbar spine, and 43.4% and 10.8%, respectively, at the femur. After a GFD (n = 78), the prevalence of osteopenia and osteoporosis was 61.5% and 8.9%, respectively, at the lumbar spine, and 37.1% and 2.5%, respectively, at the femur. ConclusionThe prevalence of CD patients with low bone mineral density (BMD) is high after diagnosis and in the follow-up after a GFD. It is important for all patients with CD to undergo a DEXA scan to determine the follow-up and/or treatment characteristics.     

The clinical utility of bone turnover markers in the evaluation of bone disease in patients with haemophilia A and B

Haemophilia A and B have been associated with increased prevalence of low bone mineral density (BMD). However, the utility of bone turnover markers (BTM) remains unknown. The aim of this study was to evaluate bone metabolism in men with haemophilia and to investigate associations between BTM and bone disease. Serum N‐ (NTX‐I), C‐terminal telopeptide of type I collagen (CTX‐I) and tartrate‐resistant acid phosphatase band‐5b (TRAP‐5b), as bone resorption markers, and osteocalcin (OC) and bone‐specific alkaline phosphatase (b‐ALP), as bone formation markers, were assessed. Seventy men with haemophilia A (n = 59) or B (n = 11) were studied. Patients with low BMD had significantly higher b‐ALP concentrations compared with those with normal BMD (12.8 ± 1.60 vs. 9.72 ± 0.58 μg/L, P = 0.009), without any differences in the other BTM. NTX‐I and CTX‐I concentrations were negatively associated with oestradiol levels and hip BMD and positively with human immunodeficiency virus infection, number of affected joints and arthropathy scores. B‐ALP and OC concentrations were negatively associated with hip BMD, severity of haemophilia and fracture history, and positively with the number of affected joints and testosterone concentrations. After multivariate analysis, NTX‐I levels remained negatively associated with oestradiol levels, whereas b‐ALP concentrations negatively correlated with the level of physical activity and positively with the number of affected joints. Increased bone metabolism exists in men with haemophilia and low BMD. Increased b‐ALP levels may identify patients at high risk for fracture. Increased number of target joints, low physical activity and low oestradiol concentrations are independently associated with increased bone metabolism.     

维生素D受体基因和雌激素受体基因多态性与老年人低骨量的关系

目的探讨维生素D受体基因(VDR)和雌激素受体基因(ESR1)多态性与老年男性、女性低骨量的关系。方法 378名老年男性[平均年龄(61.1±7.0)岁,其中260名健康男性、110例骨量减少和8例骨质疏松患者]和334名绝经后妇女[平均年龄(58.4±6.3)岁,其中148名健康女性、153例骨量减少和33例骨质疏松患者]共712人,均为居住在上海30年以上汉族人。用双能X线测量仪检测上述受试者左侧股骨颈骨密度(bone mineral density,BMD)。按照股骨颈BMD低于同性别正常峰值BMD的-1～-2.5和-2.5标准差为标准诊断骨量减少和骨质疏松,排除继发性低骨量。检测VDR基因FokⅠ、ApaⅠ、CDX 2位点ESR 1基因的PvuⅡ和XbaⅠ位点单核苷酸多态性(single nucleotide polymorphisms,SNPs)。结果 378名老年男性中,FokⅠ的基因型频率为FF(28.0%)、Ff(50.0%)和ff(22.0%),ApaⅠ的基因型频率为AA(9.5%)、Aa(43.4%)和aa(47.1%);CDX 2的基因型频率为AA(22.2%)、AG(45.8%)和GG(32.0%);PvuⅡ的基因型频率为PP(14.1%)、Pp(46.0%)和pp(39.9%);XbaⅠ的基因型频率为XX(5.0%)、Xx(36.8%)和xx(58.2%)。334名老年女性中,FokⅠ的基因型频率为FF(25.7%)、Ff(55.1%)和ff(19.2%),ApaⅠ的基因型频率为AA(10.2%)、Aa(44.0%)和aa(45.8%);CDX 2的基因型频率为AA(22.8%)、AG(47.9%)和GG(29.3%);PvuⅡ的基因型频率为PP(9.9%)、Pp(45.2%)和pp(44.9%);XbaⅠ的基因型频率为XX(2.1%)、Xx(36.8%)和xx(61.1%)。等位基因频率分布均符合Hardy-Weinberg定律。老年男性和女性的骨质疏松组、骨量减少组和骨量正常组之间上述基因SNP频率分布未见差异(P均0.05)。结论 VDR的FokⅠ、ApaⅠ及CDX 2位点和ESR 1的PvuⅡ及XbaⅠ位点多态性可能不是纳入本研究汉族老年男性和女性低骨量的风险因子,尚需更大样本量的实验予以证实。     

435名女性体检者血清铁蛋白与骨密度的相关性

目的了解正常女性随年龄增长体内铁含量与骨密度变化的关系,分析铁含量与骨密度的相关性。方法收集2011年1月至2012年12月在苏州大学附属第二医院435名22~80岁体检女性血清铁蛋白和骨密度数据。采用电化学发光法检测血清铁蛋白,采用双能X线吸收仪测定骨密度。按每5岁为1个年龄段分组,分别统计各组受试者血清铁蛋白和不同部位骨密度的平均值,观察血清铁蛋白、骨密度随年龄变化的情况。将血清铁蛋白按5等分法分类,运用非条件Logistic回归法,分析随血清铁蛋白升高,发生骨量减少风险的变化。采用多元逐步回归分析、偏相关分析法,了解正常女性血清铁蛋白变化与骨密度的相关性。结果女性血清铁蛋白随年龄增加而增加,骨密度随年龄增加而下降,两者变化趋势在围绝经期、绝经期变化显著。骨量减少组(-2.5T值-1.0)血清铁蛋白平均值显著高于骨量正常组(P0.001),骨质疏松组(T值≤-2.5)血清铁蛋白平均值显著高于骨量减少组(P0.01)和骨量正常组(P0.001)。校正混杂因素后,血清铁蛋白按5等分法分组,非条件Logistic回归显示血清铁蛋白最高组与最低组相比,股骨颈和腰椎发生骨量减少的OR值(95%CI)分别为2.82(1.25~6.38)和2.04(0.92~4.51),提示随血清铁蛋白增加,骨量减少发生的风险增加。多元逐步回归分析显示,与骨密度变化相关指标为年龄、体重、血清铁蛋白和体重指数(BMI),校正年龄、体重、BMI、C反应蛋白(CRP)等混杂因素后,血清铁蛋白与不同部位骨密度均呈显著负相关(P0.05)。结论随着年龄增长,女性血清铁蛋白逐渐升高、骨密度逐渐下降,二者呈显著负相关。血清铁蛋白增高时,骨量减少、骨质疏松发生率升高。     

中老年妇女骨转换生化指标和骨密度的变化

目的 探讨中老年妇女骨转换生化指标与骨密度随绝经的变化.方法 408名符合条件40 ～80岁的女性志愿者,同一时间段留取血清和晨尿,统一用酶免方法 测定血清骨碱性磷酸酶(BAP)、骨钙素和尿I型胶原氨基末端肽(uNTX);用舣能X线骨密度仪测定前后位腰椎1-4(L1-4)、左侧股骨颈的骨密度.结果 (1)BAP、骨钙素和uNTX与年龄、孕次、生育次数和绝经年限呈正相关(均P相似文献