Increased circulating levels of γ-carboxyglutamic acid-containing protein and decreased bone mass in children on anticonvulsant therapy

Summary In order to investigate the pathophysiology of anticonvulsant-induced osteopenia, circulating levels of bone γ-carboxyglutamic acid-containing protein (Bone Gla Protein: BGP) and urinary excretion of BGP were measured in 16 chidren on chronic anticonvulsant therapy and in 12 control children. Using microdensitometry analysis, osteopenia was found in 25% of the anticonvulsant therapy group, but it was not observed in the control group. Serum BGP and A1-P levels were significantly increased in the anticonvulsant group compared with the control group (P<0.05 andP<0.01, respectively), and a positive correlation was found between serum BGP and A1-P levels (P<0.05). Urinary excretion of BGP and hydroxyproline showed an increase in the anticonvulsant group, but it was not statistically significant. On the other hand, there was no significant difference between the two groups in serum levels of vitamin D metabolites, PTH, calcitonin, Ca, or P or in urinary excretion of Ca or P. It is suggested, therefore, that the increased BGP level in children receiving anticonvulsant therapy is a reflection of high bone turnover due to anticonvulsant drug complications.     

原发性肾病综合征患者血清胰岛素样生长因子1的变化及其与骨代谢的关系

目的 探讨原发性肾病综合征（PNS）患者血清胰岛素样生长因子1（IGF-1）的变化及其与骨代谢指标之间的关系。评价IGF-1在PNS患者骨代谢异常机制中的临床价值。方法 随机选取2008年1月至2009年5月临床资料完整的慢性肾脏病（CKD）1、2期PNS患者30例为对象;健康体检者61例为健康对照组。测定血清IGF-1、钙、磷、PTH、25羟基维生素D3[25-（OH）D3]、骨钙素（BGP）、I型胶原吡啶交联C终端肽（CTx）及尿钙/尿肌酐（UCa/Cr）。双能X线骨密度仪检测患者骨密度（BMD）。 结果 与健康对照组比较,PNS组血Ca、25-（OH）D3及BGP水平显著降低;血CTx水平及UCa/Cr比值显著增高（均P < 0.05）;BMD水平降低[（1.078±0.090） g/cm2 比（1.090±0.062） g/cm2,P > 0.05],但差异无统计学意义。PNS组血清IGF-1水平显著低于健康对照组,差异有统计学意义[（155.75±17.48） μg/L比（223.17± 16.44） μg/L,P < 0.05],且与24 h尿蛋白量及CTx呈负相关（r = -0.757和r = -0.786,均 P < 0.05）;与血BGP和BMD呈正相关（r = 0.861和r = 0.584,均P < 0.05）。 结论 PNS患者（CKD 1、2期）存在骨代谢异常,表现为骨形成减少、骨吸收增加。血清IGF-1与血BGP、CTx及BMD相关,可作为反映PNS患者骨代谢改变的临床指标之一。     

慢性肾脏病患者骨代谢与尿蛋白量的关系

目的 研究慢性肾脏病（CKD）患者骨代谢状况与尿蛋白量的关系。 方法 随机挑选2008年1月至2009年5月在本院肾活检证实为原发性肾小球疾病的CKD患者71例为对象。按尿蛋白量分为3组：A组25例,尿蛋白量<1.0 g/24 h;B组16例,尿蛋白量 （1.0~<3.5） g/24 h;C组30例,尿蛋白量≥3.5 g/24 h。健康体检者58例为健康对照组。常规测定血清白蛋白、24 h尿蛋白量及血清钙、磷、PTH、25羟基维生素D3[25-(OH)D3]、骨钙素（BGP）、I型胶原吡啶交联C终端肽（CTx）及尿钙/肌酐（UCa/Cr）等骨代谢指标。双能X线骨密度仪检测患者骨密度（BMD）。对各因素间进行Pearson相关分析。 结果 与健康对照组比较,A、B、C组CKD患者血钙分别为（2.23±0.08）、（2.13±0.09）、（2.04±0.06）比 （2.37±0.12） mmol/L;血25-（OH）D3分别为（50.19±6.58）、（47.78±6.69）、（42.42±10.85）比（56.34±8.34） nmol/L（均P < 0.05）;而UCa/Cr显著升高,分别为0.25±0.11、0.34±0.13、0.41±0.05比0.14±0.06（均P < 0.05）。B、C组血BGP分别为（18.69±7.35）、（16.13±5.76） μg/L,显著低于健康对照组的（22.88±6.21） μg/L;血CTx分别为（413.59±114.93）、（516.21±314.25） ng/L,显著高于健康对照组的（304.53±234.15） ng/L（均P < 0.05）。A、B两组BMD与健康对照组差异无统计学意义;C组BMD显著低于健康对照组[（1.028±0.090）比（1.090±0.062） g/cm2,P < 0.05]。Pearson相关分析显示,24 h尿蛋白量与血钙、血 25-(OH)D3呈负相关,与UCa/Cr 呈正相关;UCa/Cr与血CTx 呈正相关,与血BGP呈负相关;25-(OH)D3与BGP呈正相关,与CTx呈负相关。 结论 原发性肾小球疾病CKD患者的骨代谢异常主要表现为骨形成降低,骨吸收增加,其变化与蛋白尿程度相关,而大量尿蛋白患者骨代谢显著异常。     

高转换型骨质疏松模型的生化特点

应用摘除卵巢的方法。建立大鼠高转换型骨质疏松模型。本模型有以下生化特征；血清骨钙素水平明显升高；血浆酸性磷酸酶活性增强：全尿钙、全尿羟脯氨酸和肌酐含量增高。提示血浆酸性磷酸酶活力可以作为此模型动物骨吸收的特异指标，血清骨钙素水平可用于评价骨转换率。用总尿钙和总尿羟脯氨酸指标评价骨量丢失，其敏感性高于尿钙/肌酐、羟脯氨酸/肌酐。     

Anticonvulsant drug-induced osteomalacia: Alterations in mineral metabolism and response to vitamin D3 administration

Summary Parameters of mineral metabolism were examined in 6 patients with moderately severe anticonvulsant drug-induced osteomalacia. Compared to 15 matched controls, the patients exhibited significantly reduced serum calcium, inorganic phosphate, and 25-hydroxyvitamin D concentration, elevated serum alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) concentration, reduced intestinal⁴⁷Ca absorption, reduced urinary calcium and increased urinary hydroxyproline excretion, and reduced forearm bone mass. Intestinal absorption of vitamin D₃ was normal. Following 4 months of treatment with vitamin D₃ (4000 units/day), serum 25-OHD concentration was increased to 3 times mean normal values and all parameters except serum iPTH, urinary calcium excretion, and forearm bone mass were returned to levels not significantly different from normal. Serum iPTH concentration was reduced by 39% (P<0.05); 24-h urinary calcium excretion rose by 98% (P<0.001), and forearm bone mass increased by 5.6% (P<0.05). It is concluded that moderate-dose vitamin D₃ supplementation is effective in normalizing parameters of mineral metabolism in this disorder, despite evidence of resistance to the biologic effects of vitamin D.     

顺铂对雌性大鼠骨密度影响的实验研究

目的本文通过对去势雌性大鼠的动物实验研究，观察顺铂对骨代谢、骨密度的影响，并探讨其可能机制。方法将三月龄雌性SD大鼠30只，随机分为对照组和化疗组，每组15只。各组大鼠均用1％戊巴比妥钠腹腔内麻醉，行双侧卵巢切除术。术后1W开始用药，每两周用药1次，共6次。对照组腹腔内注射生理盐水1ml；化疗组腹腔内注射顺铂2mg／kg溶于1ml生理盐水中。术后13W处死各组动物，处死前用代谢笼收集24h空腹尿标本，自动生化分析仪测定尿钙浓度并计算出24h排泌量。氯胺T氧化法测尿羟脯氨酸(HOP)浓度并计算出24h排泌量；麻醉动物，开腹后下腔静脉取血离心，放免法测骨钙素(BGP)、血尿素氮(BUN)；取腰椎L4-6椎体，双能X线骨密度测量仪测腰椎骨密度。结果化疗组与对照组相比，骨密度降低，24h尿HOP及24h尿Ca定量升高，均有显著意义，血BGP无差异。结论本实验表明顺铂对大鼠的骨代谢存在直接的不良影响，使骨吸收增加，表现为松质骨骨密度降低。     

Osteoprotegerin and bone mineral density in hemodiafiltration patients

A newly identified cytokine, osteoprotegerin (OPG) appears to be involved in the regulation of bone remodeling. In vitro studies suggest that OPG, a soluble member of the TNF receptor family of proteins, inhibits osteoclastogenesis by interrupting the intercellular signaling between osteoblastic stromal cells and osteoclast progenitors. As patients with chronic renal failure (CRF) often have renal osteodystrophy (ROD), we investigated the role of osteoprotegerin (OPG) in ROD, and investigated whether there was any relationship between serum OPG, intact parathyroid (PTH) (iPTH), vitamin D, and trabecular bone. Serum OPG combined with iPTH might be a useful tool in the noninvasive diagnosis of ROD, at least in cases in which the range of PTH values compromises reliable diagnosis. Thirty-six patients on maintenance hemodiafiltration (HDF) and a control group of 36 age and sex matched healthy subjects with no known metabolic bone disease were studied. The following assays were made on serum: iPTH, osteocalcin (BGP), bone alkaline phosphatase, 25(OH)-cholecalciferol, calcium, phosphate, OPG, IGF-1, estradiol, and free testosterone. Serum Ca++, P, B-ALP, BGP, IGF-1, iPTH, and OPG levels were significantly higher in HDF patients than in controls, while DXA measurements and quantitative ultrasound (QUS) parameters were significantly lower. On grouping patients according to their mean OPG levels, we observed significantly lower serum IGF-1, vitamin D3 concentrations, and lumbar spine and hip bone mineral density in the high OPG groups. No correlation was found between OPG and bone turnover markers, whereas a negative correlation was found between serum OPG and IGF-1 levels (r=-0.64, p=0.032). Serum iPTH concentrations were positively correlated with bone alkaline phosphatase (B-ALP) (r=0.69, p=0.038) and BGP (r=0.92, p<0.001). The findings made suggest that an increase in OPG levels may be a compensatory response to elevated bone loss. The low bone mineral density (BMD) levels found in the high OPG group might have been due to the significant decrease in serum IGF-1 and vitamin D3 observed. In conclusion, the findings made in the present study demonstrate that increased OPG in hemodiafiltration patients is only partly due to decreased renal clearance. As it may partly reflect a compensatory response to increased bone loss, this parameter might be helpful in the identification of patients with a marked reduction in trabecular BMD.     

扩张性心肌病患者骨代谢指标状况及其临床意义

目的探究扩张性心肌病(dilated cardiomyopathy,DCM)患者骨代谢指标水平状况及其临床意义。方法选取2016年3月至2018年3月在我院诊治的DCM患者48例作为研究对象并归入DCM组,选择同期在我院接受健康体检的成年人30名归入健康组,测定和比较两组的血清骨钙素(BGP)、钙(ICa)、骨特异性碱性磷酸酶(BALP)、甲状旁腺激素(PTH)、25羟基维生素D_3[25(OH) D_3]等骨代谢指标水平,以及大粗隆、股骨颈、腰椎等部位的骨密度(BMD),分析骨代谢指标BGP、ICa、BALP、PTH和25(OH) D_3分别与患者年龄、DCM病程、BMI、肌酸激酶同工酶、肌钙蛋白I和心功能分级等因素的相关性。结果(1) DCM组的BGP、ICa、25(OH) D_3等水平均低于健康组,BALP、PTH水平均高于健康组,差异均有统计学意义(P均0.05)。(2) DCM组大粗隆部位的BMD与健康组比较,差异无统计学意义(P0.05); DCM组的股骨颈及腰椎部位的BMD均低于健康组,差异均有统计学意义(P均0.05)。(3) BGP、ICa和25(OH) D_3分别与年龄、DCM病程及心功能分级呈负相关,BGP与肌酸激酶同工酶、肌钙蛋白Ⅰ呈负相关; BALP与年龄、DCM病程、肌酸激酶同工酶、肌钙蛋白Ⅰ及心功能分级呈正相关,PTH与心功能分级呈正相关(P均0.05)。结论 DCM患者的血清BGP、ICa、BALP、PTH、25(OH) D_3等骨代谢相关指标水平有明显波动,且骨代谢相关指标水平与DCM患者年龄、病程、肌酸激酶同工酶、肌钙蛋白Ⅰ及心功能分级等相关,DCM可能是造成骨代谢指标水平发生异常的重要原因。     

Comparison of vitamin D metabolism in early healthy and late osteoporotic postmenopausal women

Summary We studied 20 healthy premenopausal women aged 36.5±4.0 years (mean±1 SD), 123 healthy postmenopausal women aged 50.0±2.4 years, and 103 postmenopausal women aged 65.1±5.6 years with symptomatic osteoporosis (forearm and spinal fracture). Serum levels of vitamin D metabolites [25(OH)D, 24,25(OH)₂D₃, and 1,25(OH)₂D] were compared with (1) bone mass in the forearm (single photon absorptiometry) and in the spine (dual photon absorptiometry); (2) biochemical indices of bone formation (serum alkaline phosphatase, plasma bone Gla protien), and bone resorption (fasting urinary hydroxyproline); and (3) other biochemical estimates of calcium metabolism (serum calcium, serum phosphate, 24-hour urinary calcium, intestinal absorption of calcium). The present study revealed no difference in any of the vitamin D metabolites between the premenopausal women, the healthy postmenopausal women and the osteoporotic women as a group. The concentrations of 1,25(OH)₂D and 25(OH)D were significantly lower in patients with spinal fracture than in those with forearm fracture. In the early postmenopausal women, serum 1,25(OH)₂D was related to forearm bone mass (r=−0.20;P<0.05), intestinal calcium absorption (r=0.18;P<0.05), and 24-hour urinary calcium (r=0.21;P<0.05); serum 25(OH)D was related to spinal bone mass (r=0.23;P<0.01). In the osteoporotic women, serum vitamin D metabolites were not related to bone mass, but 1,25(OH)₂D was related to bone Gla protein (r=0.33;P<0.001), serum phosphate (r=−0.27;P<0.01), and 24-hour urinary calcium (r=0.43;P<0.001). The present study demonstrates that in a population that is apparently not deficient in vitamin D, a disturbance of the vitamin D metabolism is not likely to play a pathogenetic role in early postmenopausal bone loss. Patients with spinal fractures have low levels of vitamin D metabolites, which may aggravate their osteoporosis.     

Bone Mineral Changes in Acute Metabolic Acidosis due to Acute Gastroenteritis

We studied bone mineral metabolism changes complicated by acute gastroenteritis in a clinical acute metabolic acidosis milieu where we observed hypercalcemia, hypercalciuria, and elevated urinary hydroxyproline excretion. Serum magnesium and plasma osteocalcin, alkaline phosphatase, and IGF-1 levels were decreased. No significant changes in serum inorganic phosphate and plasma PTH, calcitonin, or 25-hydroxy vitamin D3 levels were detected. All abnormalities disappeared with the correction of acidosis. Observed hypercalcemia seems to be the result of increased calcium efflux from bone due to metabolic acidosis-induced catabolism of type 1 collagen and decreased osteoblastic activity. This study provides data regarding acute metabolic acidosis-induced changes in noninvasive parameters of bone modeling, assessed for the first time in humans.     

Serum bone gla protein (BGP) and other markers of bone mineral metabolism in postmenopausal osteoporosis

Summary Bone gla protein, the vitamin K-dependent protein synthesized by osteoblasts and measured in blood by radioimmunoassay, has been used as an index of the rate of bone turnover. The relationship of bone gla protein with other markers of bone mineral metabolism was determined in 31 untreated postmenopausal women with the osteoporotic syndrome. In addition to serum osteocalcin (BGP) we measured parathyroid hormone (PTH) (carboxyl and mid-molecule fragments), 25(OH)D, alkaline phosphatase, estradiol (E₂), estrone (E₁), dietary calcium intake, 24 hour urinary calcium excretion, and bone mineral density by CT scan of the lumbar vertebrae. Significant osteopenia was present on CT in untreated postmenopausal osteoporotic women (bone density in 18 out of 31 was below the critical value of 60 mg/cm³). Serum BGP correlated positively with CT scan (r+0.647,P<0.001). CT and age were negatively correlated (r−0.661,P<0.001) while CT and E₂ showed a positive correlation (r+0.554,P<0.01). Unexpectedly, BGP and age revealed a significant negative correlation (r−0.421,P<0.05). These findings suggest a state of low bone turnover in this group with untreated postmenopausal osteoporosis.     

新疆维吾尔族人群骨代谢特点研究

目的探讨新疆维吾尔族人的骨代谢特点。方法收集新疆库车地区维吾尔族人血清399例,分别按性别、年龄进行分组,比较各组血清25-羟基维生素D含量。另外,抽取60例50岁以下维吾尔族女性进行骨代谢指标测定,包括钙、磷、骨钙素及雌二醇。结果维吾尔族各年龄段女性血清25-羟基维生素D含量均低于同年龄段男性(P值均小于0.05)。男性及女性的血清25-羟基维生素D水平均与年龄呈负相关(r=-0.247,P=0.000;r=-0.181,P=0.018)。50岁以下女性血清钙含量分别与磷、骨钙素呈正相关,相关系数分别为r=0.344,P=0.007;r=0.288,P=0.026。血清钙含量与雌二醇呈负相关(r=-0.27,P=0.037)。结论年龄及性别可能是影响维吾尔族人血清维生素D含量的因素之一,维吾尔族人血清钙含量与磷、骨钙素以及雌激素有关。     

糖皮质激素诱导胰岛素样生长因子1降低对原发性肾病综合征患者骨代谢的影响

目的 观察糖皮质激素（GC）治疗的原发性肾病综合征（PNS）患者胰岛素样生长因子1（IGF-1）变化,探讨其水平改变对PNS患者骨代谢的影响及意义。 方法 以本院2008年1月至2009年8月临床资料完整的PNS患者39例为对象。口服泼尼松0.8~1.0 mg&#8226;kg-1&#8226;d-1,完全缓解2周后,以每2周减去原剂量的5％～10％的方式减量。最终每日或隔日5～10 mg维持（总疗程>24周）。测定应用激素前、治疗第4、8、12、24周末血白蛋白、24 h尿蛋白量、血清钙、磷、甲状旁腺激素（PTH）、25羟基维生素D3（25-（OH）D3）、骨钙素（BGP）、I型胶原吡啶交联C终端肽（CTx）及尿钙/肌酐;双能X线骨密度仪检测患者骨密度（BMD）;酶联免疫法测定血清IGF-1水平。使用Pearson 相关分析探讨IGF-1与骨代谢改变的关系。 结果 36例完成随访,并具备完整临床数据。治疗第4、8、12和24周与治疗前比较,患者血钙、25-（OH）D3水平均呈时间依赖性升高（P < 0.05）,相关分析提示,与尿蛋白量呈负相关 （r=-0.749,r=-0.831,P < 0.05）。骨形成指标血BGP、IGF-1水平呈时间依赖性降低（P < 0.05）,骨吸收指标CTx逐渐升高,至第12周起差异有统计学意义（P < 0.05）。第4周各部位BMD与治疗前差异均无统计学意义;第8周起腰椎（L1~L4）BMD值较治疗前显著下降（P < 0.05）;第 24 周,股骨颈和股骨干的BMD与治疗前差异有统计学意义（P < 0.05）。PNS患者经糖皮质激素治疗后,IGF-1与BMD和BGP呈正相关（r=0.495和r=0.896,均P < 0.05）,与血CTx呈负相关（r=-0.697,P < 0.05）。 结论 糖皮质激素呈时间依赖性导致PNS患者血清IGF-1水平降低。IGF-1下降与患者早期骨形成指标降低、骨吸收指标增高及后期骨密度下降相关。IGF-1途径可能参与GC 引起的PNS患者骨代谢改变。IGF-1有望成为反映或预测糖皮质激素诱导的骨质疏松的新型生化指标。     

老年男性2型糖尿病患者各种钙调激素与骨密度改变的关系

目的测定老年男性2型糖尿病患者各种钙调激素及骨密度,探讨老年男性2型糖尿病患者骨质疏松的发病机理,为其防治提供理论依据。方法用双能X线吸收法测定70例老年男性2型糖尿病患者及60例年龄、体重指数相匹配的对照者的腰椎及髋部骨密度,并采用放免法测定血清骨钙索(BGP)、抗酒石酸酸性磷酸酶(TRAP)、甲状旁腺素(PTH)、降钙素(CT)、1,25(OH)2D3、25(OH)D3、尿羟脯氨酸(HOP)等,两组进行比较。结果 老年男性2型糖尿病患者较对照组骨密度显著降低。血BGP、CT、1,25(OH)2D3浓度低于对照组(P<0.05).TRAP、PTH、尿HOP显著高于对照组(P<0.05)。结论老年男性2型糖尿病患者PTH、CT、1,25(OH)2D3等钙调激素分泌及代谢失常,影响骨代谢,出现糖尿病性骨质疏松,表现为骨吸收增加,骨形成减少与缓慢,骨吸收过程大于骨形成。     

慢性乙肝性肝硬化症男性患者血清性激素、钙调节激素和骨转换指标的变化

目的　慢性严重肝脏损害常合并肝性骨病。为了探讨终末期肝病患者的钙调节激素变化和骨转换率状态 ,我们回顾性分析了 17例乙肝后肝硬化失代偿的男性患者 ,并和年龄、身高、体重相匹配的健康男性进行对照研究。方法　肝硬化组和对照组均检测其血清性激素 [雄激素 (T)、雌激素 (E2 ) ],钙调节激素 [甲状旁腺素 (PTH)、降钙素 (CT)和 2 5羟维生素D3(2 5 -OHVD3) ]和骨转换指标 [血清骨钙素 (BGP)和尿脱氧吡啶啉 肌酐比值 (Dpd Cr) ]以及钙 (Ca2 + )、磷 (PO3- )和碱性磷酸酶 (ALP)。结果　显示与对照组相比 ,肝硬化组血清T明显降低、E2 水平和E2 T比值显著升高 ;血清PTH显著升高、2 5 -OHVD3明显降低 ,而CT差异不大。其中E2 升高和 2 5 -OHVD3降低有极显著意义。肝硬化组血清BGP和Ca2 + 水平明显降低、尿Dpd Cr比值和尿Ca2 + Cr比值明显升高。而血清CT和PO3- 差异不大。结论　我们认为慢性严重肝硬化患者骨量减低 ,呈现出骨形成降低、骨吸收增强之特征 ,与维生素D和性激素代谢异常有关 ,而PTH升高乃继发性改变     

Vitamin D in Paget's disease of bone

The role of vitamin D metabolism in Paget's disease of bone has not been well defined. Serum levels of the main, circulating vitamin D metabolites were measured in 23 patients with Paget's disease. Values of 25(OH)D3 and 24,25(OH)2D3 were within the normal range in most (more than 90%) of the subjects. 1,25(OH)2D3 was increased in 11 (48%) patients. Markedly elevated levels (93-298 pg/ml) were found in five patients. In a subgroup of patients with high 1,25(OH)2D3, the mean serum alkaline phosphatase activity was insignificantly higher, while serum calcium, phosphorous, and kidney function were the same as in a subgroup with normal 1,25(OH)2D3. 1,25(OH)2D3 levels were not affected by treatment with either calcitonin or etidronate disodium. Serum 1,25(OH)2D3 levels may be increased in a subset of patients with Paget's disease of bone.     

25 羟维生素D3与糖尿病骨质疏松患者的相关性研究

目的 观察 2 型糖尿病(T2DM)患者骨质疏松与25 羟维生素D3(25-OH-D3)的关系? 方法 测定186 例2 型糖尿病(T2DM)患者及65例年龄?性别相匹配健康对照者血(Ca) ?磷(P),采用酶联免疫法测定各组血清骨特异性碱性磷酸酶(ALP)?血清骨钙素(BGP)? (25-OH-D3)的浓度? 结果 2型糖尿病组BGP?25-OH-D3浓度低于对照组,差异显著(P<0.05),血清Ca?P?血浆ALP浓度与对照组之间无显著差异(P>0.05)? 女型糖尿病患者骨质疏松症的发病率高于男性,女性OP组BGP?25-OH-D3的浓度显著低于男性OP组(P<0.05)? 结论 2 型糖尿病患者 25-OH-D3的减少可影响钙?磷代谢,从而导致骨质疏松,因此对于 2 型糖尿病患者应早期适量补充钙剂及维生素D3?     

Calcium and vitamin D intake maintained from preovariectomy independently affect calcium metabolism and bone properties in Sprague Dawley rats

Summary

The interaction of habitual Ca and vitamin D intake from preovariectomy to 4 months postovariectomy on bone and Ca metabolism was assessed. Higher Ca intake suppressed net bone turnover, and both nutrients independently benefitted trabecular structure. Habitual intake of adequate Ca and ~50 nmol/L vitamin D status is most beneficial.

Introduction

Dietary strategies to benefit bone are typically tested prior to or after menopause but not through menopause transition. We investigated the interaction of Ca and vitamin D status on Ca absorption, bone remodeling, Ca kinetics, and bone strength as rats transitioned through estrogen deficiency.

Methods

Sprague Dawley rats were randomized at 8 weeks to 0.2 or 1.0 % Ca and 50, 100, or 1,000 IU (1.25, 2.5, or 25 μg) vitamin D/kg diet (2?×?3 factorial design) and ovariectomized at 12 weeks. Urinary ⁴⁵Ca excretion from deep-labeled bone was used to assess net bone turnover weekly. Ca kinetics was performed between 25 and 28 weeks. Rats were killed at 29 weeks. Femoral and tibiae structure (by μCT), dynamic histomorphometry, and bone Ca content were assessed.

Results

Mean 25(OH)D for rats on the 50, 100, 1,000 IU vitamin D/kg diet were 32, 54, and 175 nmol/L, respectively. Higher Ca intake ameliorated net bone turnover, reduced fractional Ca absorption and bone resorption, and increased net Ca absorption. Tibial and femoral trabecular structures were enhanced independently by higher Ca and vitamin D intake. Tibial bone width and fracture resistance were enhanced by higher vitamin D intake. Dynamic histomorphometry in the tibia was not affected by either nutrient. A Ca × vitamin D interaction existed in femur length, tibial Ca content, and mass of the soft tissue/extracellular fluid compartment.

Conclusions

Adequate Ca intake and serum 25(OH)D level of 50 nmol/L provided the most benefit for bone health, mostly through independent effects of Ca and vitamin D.     

In vivo bone metabolism and ex vivo bone marrow osteoprogenitors in vitamin D-deprived pigs

Vitamin D insufficiency is still a concern in countries where there is no routine food supplementation, such as France. A low vitamin D status is clearly associated with an increased risk of fracture in the elderly, but the long-term consequences of latent vitamin D insufficiency in young people and adults are not known. We fed 26 growing pigs a high calcium diet (1.1%) with a 1000 IU cholecalciferol/kg diet (controls), or without vitamin D (0D) for 4 months. We then analyzed the overall impact of low vitamin D status on osteotropic hormones (calcitriol and immunoreactive parathyroid hormone), plasma markers of bone remodeling (alkaline phosphatase [ALP] activity, carboxyterminal propeptide of type I procollagen [PICP], osteocalcin, hydroxyproline), whole bone parameters (ash content, bending moment), histomorphometry, and the populations of marrow osteoblastic and osteoclastic precursors by ex vivo cultures. The fall in plasma 25-dihydroxyvitamin [25(OH)D] in the 0D pigs indicated severe depletion of their vitamin D stores. However, they remained normocalcemic, were mildly hyperparathyroid after 2 months of vitamin D deprivation, and showed only a slight decrease in plasma calcitriol. The bone mineral content and bending moment of metatarsals decreased and they had increased osteoblastic (+59%, p < 0.05 0D vs. controls) and osteoclastic (+31%, p < 0.1 0D vs. controls) surfaces. This was not paralleled by increased bone turnover, because plasma hydroxyproline and ALP were unchanged and PICP and osteocalcin were decreased. The adherent fraction of bone marrow cells showed a great increase in the number of total stromal colony-forming units (CFU-F; +93%, p < 0.05 0D vs. controls) and in the percent of ALP(+) CFU-F (+58%, p < 0.01 0D vs. controls) in cultures from 0D pigs. More tartrate-resistant acid phosphatase-positive (TRAP(+)) multinucleated cells were generated in cultures of nonadherent marrow cells from 0D pigs, and the area of resorption was 345% greater than in controls. Thus, vitamin D deprivation caused only moderate hormonal changes in growing pigs fed a high-calcium diet, but affected their bone characteristics and greatly enhanced the pool of osteoblasts and osteoclasts by stimulating the commitment of their precursors in bone marrow.     

妊娠妇女性激素、骨密度、骨代谢生化指标的变化及相关性研究

目的：探讨妊振妇女骨密度和骨代谢的变化及其与性激素的关系。方法：随机选取63例健康脑力劳动孕妇和21例健康脑力劳动妇女分别测定骨密度,血清Ca、P、ALP、BGP和E2、P、FSH、LH、PRL以及尿HP/Cr、Ca/Cr比值。结果：孕期骨密度虽有下降但无显变化（P＞0.05),ALP和BGP在晚孕期有显变化（P＜0.05)且此变化与E2成正相关（r=0.61、0.36)。结论：妊娠期骨密度虽无明显变化,但晚孕期骨转换率明显增加且与E2呈正相关。提示可通过测定E2了解孕期骨代谢情况,并及时予以补钙等措施可能有益。