老年男性骨质疏松与相关影响因素的关系

目的 测定老年男性不同年龄组骨密度及有关的影响因素,以探讨老年男性骨质疏松的发生与有关影响因素的关系,为防治老年男性骨质疏松症提供依据。方法 双能量X线骨密度测定仪测定前臂骨密度;全自动生化分析法测定血清钙（Ca)、磷（P）;放免法测定甲状旁腺素（PTH）、降钙素（CT）、1,25（OH）2D3、25（OH）D3、白介素－6（IL－6）。97例老年男性分为骨质疏松组与非骨质疏松组,并与60岁以下男性 进行比较。结果 老年男性骨密度、CT,1,25（OH2）D3、25（OH）D3随年龄增长而降低,PTH、IL－6随着年龄增长而升高（P＜0．05）。骨质疏松组与非骨质疏松组比较,PTH、IL－6二明显升高,CT、25（OH）D3、1,25（OH）2D33明显下降（P＜0．05－0．001）。结论 骨质疏松有关影响因素的改变使骨吸收增加,骨形成降低,导致骨丢失,引发骨质疏松症。     

慢性肝病患者血清VitD3水平与骨代谢的关系

检测了部分慢性乙型肝炎(下简称慢乙肝)及肝硬化患者的血清1,25(OH)2D3、骨钙素(BGP)、甲状旁腺素(PTH)、钙、磷及尺桡平均密度(BMD),并与对照组比较.结果两组患者血清1,25(OH)2D3、BGP及BMD值均明显下降,肝硬化组下降尤为显著.肝硬化组血清PTH显著升高.两组患者血钙明显降低,而血磷三组间无差异.1,25(OH)2D3水平与BGP、BMD呈显著正相关;PTH与血钙、BMD无相关性.提示慢性肝病患者存在以骨形成减少为主的骨代谢紊乱,其中血清1,25(OH)2D3减少为关键因素,PTH虽升高,但与肝病患者骨密度变化无相关.     

Effects of donkey-hide glue reinforcing bone oral solution on serum 25-OH-VD3、1，25-(OH )2-VD3 concentration and the expression of VDR in rats

目的 研究阿胶强骨口服液(donkey-hide glue reinforcing bone oral solution, DGRBOS) 对SD大鼠血液25-羟基维生素D3 (25-OH-VD3)、1,25-羟基维生素D3(1,25-(OH)2-VD3)和肝脏VDR基因表达的影响,探讨DGRBOS治疗骨质疏松的疗效机制.方法 6月龄SD大鼠36只, 随机分为A组(假手术组),B组(卵巢切除+生理盐水组),C组(卵巢切除+阿胶强骨口服液组),每组12只.6个月后取材检测.采用ELISA法对去势大鼠血清25-OH-VD3和1,25-(OH)2-VD3进行研究,用荧光定量PCR对肝脏VDR基因进行定量分析.结果 C组(卵巢切除+阿胶强骨口服液组)血液中25-羟基维他命D3浓度和1,25-羟基维他命D3浓度与B组(卵巢切除+生理盐水组)比较明显增高,其中对25-羟基维他命D3浓度增高尤为明显,已接近A组(假手术组),P=0.002(P＜0.01),差异有明显的统计学意义.荧光定量PCR(FQ-PCR)结果B 组与C组相比,P=0.004(P＜0.01),说明扩增效率的差异有明显的统计学意义.结论 阿胶强骨口服液增加去势大鼠血液中25-OH-VD3、1,25-(OH)2-VD3的浓度,同时上调肝脏中VDR的表达水平,是阿胶强骨口服液治疗骨质疏松的机制之一.     

老年骨质疏松症患者躯体功能与血清1,25-二羟维生素D_3的相关性及对骨骼肌的影响

目的探讨老年骨质疏松症患者躯体功能与血清1,25-二羟维生素D-3[1,25-(OH)_2D_3]的相关性及对骨骼肌的影响。方法选取2016年5月-2017年5月收治的老年骨质疏松症患者90例,根据患者是否合并有骨骼肌减少症进行分组。研究组患者皆合并骨骼肌减少症(n=58),对照组无骨骼肌减少症(n=32)。所有患者皆行常规体格及骨密度检查,并分析老年骨质疏松症患者躯体功能与血清1,25-(OH)_2D_3的相关性。结果研究组患者体内1,25-(OH)_2D_3水平明显高于对照组,差异有统计学意义(P0.05);Spearman秩相关分析显示,骨质疏松症患者血清1,25-(OH)_2D_3与骨骼肌减少评价指标中的步速、握力呈正相关(P0.05),而与四肢骨骼肌量指数无明显关系(P0.05);将患者体内1,25-(OH)_2D_3水平与骨骼肌减少影响因素间进行Spearman秩相关分析显示,血清1,25-(OH)_2D_3与与BMI、HOMA-IR、hs-CRP水平无明显关系(P0.05),而与体内IGF-1、IL-10呈正相关,与ROS、i PTH、TNF-α、IL-6水平呈负相关(P0.05)。结论血清1,25-(OH)_2D_3水平的降低会导致骨质疏松患者躯体功能低下,包括握力减少以及步行速度减慢,与此同时,血清1,25-(OH)_2D_3受骨骼肌减少指标及相关因素的影响,可将其作为判断是否会发生骨骼肌减少的指标之一。     

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。     

护骨胶囊对去卵巢大鼠钙相关激素和性腺激素影响的研究

目的观察护骨胶囊(Hugu capsules,HG)对去卵巢大鼠血清中与钙代谢直接相关的激素和性激素及子宫的影响。方法将60只SD雌性大鼠随机分为假手术组(Sham)、去卵巢组(OVX)、仙灵骨葆胶囊组(Pos)和护骨胶囊低、中、高剂量组(HG-L、HG-M和HG-H)。大鼠卵巢切除后,隔天开始,连续灌胃3个月。处死大鼠,取大鼠子宫与血清,观察HG对子宫重量,血清1,25双羟维生素D3(1,25(OH)2D3)、甲状旁腺激素(PTH)、雌二醇(E2)、孕酮(P)、睾酮(T)变化及子宫内膜组织的影响。结果与Sham组比:OVX组的PTH(P0.01)和T(P0.05)升高,E2(P0.01)和P(P0.05)降低;子宫重量显著减少,子宫内膜萎缩。与OVX组比:PTH在HG各个剂量组都降低,在Pos组无变化;E2在HG-L和HG-M组显著增加,在Pos组无变化;P在HG-L组降低,在Pos组显著升高;T在HG-L和HG-H组无变化,HG-M组降低,而Pos组显著升高;HG各个剂量组和Pos组的子宫重量和子宫内膜较OVX组均无明显差异。结论护骨胶囊对OVX大鼠的作用是调节PTH和E2水平,此调节作用与仙灵骨葆胶囊的作用机制不一样。护骨胶囊在补充雌激素的同时对子宫的影响不大,为推广护骨胶囊临床防治绝经后骨质疏松提供了实验依据。     

刺老苞根皮对糖皮质激素诱导的大鼠骨质疏松症的干预影响

目的本研究拟在验证刺老苞根皮提取物对糖皮质激素诱发的大鼠骨质疏松症的干预作用。方法 90只SD大鼠(雌雄各半)随机分成6组,即(雌/雄)对照组、(雌/雄)模型组、(雌/雄)治疗组(刺老苞根皮提取物组),每组15只。其中模型组与治疗组采用连续注射地塞米松磷酸钠(DXM)造成继发性骨质疏松,而后直接灌胃刺老苞根皮提取物(20 mg/kg),观察其治疗作用。8周后,检测脂代谢指标[血清胆固醇(TC)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)含量]、骨代谢指标[骨钙素(BGP)、1,25-(OH_2D_3)、骨矿物含量、骨密度值、骨力学参数]、激素指标[甲状旁腺(PTH)、睾酮(T)、雌二醇(E2)、生长激素(GH)、黄体生长素(LH)、卵泡生成素(FSH)、孕酮(P)、泌乳素(PRL)含量]以及卵巢、子宫湿重的变化情况。结果与对照组相比,模型组雌性大鼠脂代谢指标[血清高密度脂蛋白-胆固醇(HDL-C)]、骨代谢指标[骨钙素(BGP)、1,25-(OH_2D_3)、骨矿物含量、骨密度值、骨力学参数]、激素指标[雌二醇(E2)、生长激素(GH)、黄体生长素(LH)、卵泡生成素(FSH)、孕酮(P)、泌乳素(PRL)含量]以及卵巢、子宫湿重均有所下降(P0.01);雄性大鼠脂代谢指标[血清高密度脂蛋白-胆固醇(HDL-C)]、骨代谢指标[骨钙素(BGP)、1,25-(OH_2D_3)、骨矿物含量、骨密度值、骨力学参数]、激素指标[睾酮(T)]均也有所下降(P0.01),而雌/雄脂代谢指标[胆固醇(TC)、低密度脂蛋白-胆固醇(LDL-C)]及雄性大鼠激素指标[甲状旁腺(PTH)]则有所升高(P0.01)。与模型组相比,治疗组雌性大鼠脂代谢指标[血清高密度脂蛋白-胆固醇(HDLC)]、骨代谢指标[骨钙素(BGP)、1,25-(OH_2D_3)、骨矿物含量、骨密度值、骨力学参数]、激素指标[雌二醇(E2)、生长激素(GH)、黄体生长素(LH)、卵泡生成素(FSH)、孕酮(P)、泌乳素(PRL)含量]以及卵巢、子宫湿重均有所升高(P0.05);雄性大鼠脂代谢指标[血清高密度脂蛋白-胆固醇(HDL-C)]、骨代谢指标[骨钙素(BGP)、1,25-(OH_2D_3)、骨矿物含量、骨密度值、骨力学参数]、激素指标[睾酮(T)]均也有所升高(P0.05),而雌/雄脂代谢指标[胆固醇(TC)、低密度脂蛋白-胆固醇(LDLC)]和雄性大鼠激素指标[甲状旁腺(PTH)]则有所下降(P0.05)。结论刺老苞根皮提取物可以有效治疗糖皮质激素诱发的继发性骨质疏松症。     

应用microCT技术对中药干预去卵巢小鼠骨组织微结构的分析

目的应用micro CT技术观察健骨颗粒对C57小鼠去卵巢骨质疏松模型骨组织骨量、骨微结构及生物力学的影响。方法将4周龄清洁级C57小鼠30只随机分为三组(假手术组10只、卵巢切除小鼠两组各10只),两组卵巢切除小鼠术后1周开始,分别用健骨颗粒和生理盐水进行灌胃,假手术组用生理盐水灌胃。2个月后,小鼠左胫骨行micro CT检测及图像分析、右胫骨行生物力学三点抗压最大载荷检测。结果与假手术组比较,去卵巢组BMC、BMD、Mean、BV、BS显著下降(P0.01),TMC下降(0.01P0.05);与去卵巢组比较,去卵巢中药组BMC、BMD、Mean指标显著提高(P0.01);图像分析结果显示去卵巢组较假手术组骨皮质薄,骨小梁数量少,形态细小、不连续呈扭曲或断裂状等明显骨质疏松病理特征,去卵巢中药组介于两者之间。生物力学结果显示三组胫骨三点抗压最大载荷均具有明显差异(P0.01)。结论去卵巢2月成功建立小鼠绝经后骨质疏松症模型;健骨颗粒抗骨质疏松作用明显,主要通过增加骨量和改善骨小梁微结构来最终提高骨强度;micro CT对骨质疏松参数分析简洁、高效,图像多维、全面,与传统的检测方法相比,具有一定的优势。     

1,25 - 二羟维生素 D3 及其类似物与慢性肾脏疾病

1,25 - 二羟维牛素 D3 即活性维生素 D3(1,25 - dihydroxyvitamin D3,1,25 - (OH)2D3)属于第二甾体类激素,其生物学作用主要包括调节钙磷代谢和骨的再建,调节细胞增生与分化以及免疫调节等.慢性肾脏疾病(chronic kidney disease,CKD)患者中广泛存在维生素D缺乏和继发性甲状旁腺机能亢进(secondary hyperparathyroidism,SHPT),1,25 - (OH)2D3 及其类似物可以抑制甲状旁腺激素(parathyroid hor - mone,PTH)分泌,降低血PTH,改善心血管病变,增加CKD患者生存率.     

1,25 - 二羟维生素 D3 及其类似物与慢性肾脏疾病

1,25 - 二羟维牛素 D3 即活性维生素 D3(1,25 - dihydroxyvitamin D3,1,25 - (OH)2D3)属于第二甾体类激素,其生物学作用主要包括调节钙磷代谢和骨的再建,调节细胞增生与分化以及免疫调节等.慢性肾脏疾病(chronic kidney disease,CKD)患者中广泛存在维生素D缺乏和继发性甲状旁腺机能亢进(secondary hyperparathyroidism,SHPT),1,25 - (OH)2D3 及其类似物可以抑制甲状旁腺激素(parathyroid hor - mone,PTH)分泌,降低血PTH,改善心血管病变,增加CKD患者生存率.     

健脾方对去势大鼠维生素D代谢的影响

目的采用放射免疫方法与分子生物学方法从VitD代谢的角度探讨健脾方防治原发性骨质疏松症的机制。方法建立卵巢切除致骨质疏松大鼠模型,运用骨组织病理学、血液生物化学等方法综合观察健脾方对模型大鼠骨密度、尿吡啶酚（PYD）和血清骨钙素（BGP）的影响;同时应用放射免疫方法与逆转录聚合酶链式反应观察健脾方对模型大鼠血清1,25（OH）2D3和小肠、肾脏组织维生素D受体基因（VDR mRNA）表达的影响。结果健脾方能升高模型大鼠的骨密度,降低模型大鼠血清1,25（OH）2D3的含量（P〈0.05）,同时能上调模型大鼠小肠、肾脏VDR mRNA的表达。结论健脾方能增强机体对血清1,25（OH）2D3反应敏感性,上调小肠与肾脏VDR mRNA的表达,调节VitD代谢。     

1,25二羟维生素D3与5-氟尿嘧啶对乳腺癌细胞生长及凋亡的影响

目的研究1，25二羟维生素D3[1，25(OH)2D3]与5-氟尿嘧啶(5-Fu)对人乳腺癌细胞株MCF-7生长及凋亡的影响。方法采用噻唑蓝(MTT)比色法分析细胞生长抑制作用，流式细胞术测定细胞周期和凋亡率，免疫组织化学法检测bcl-2蛋白表达。结果1，25(OH)2D3与5-Fu均可抑制MCF-7细胞生长、1，25(OH)2D3阻滞细胞周期于G0／G1期，5-Fu阻滞细胞周期于S期，并可诱导细胞凋亡；当两药联合应用时，上述作用得到显著加强，凋亡率明显上升。两药均可下调bcl-2蛋白表达，当两药联合应用时，bcl-2蛋白几乎不表达。结论1，25(OH)2D3与5-Fu联合应用对乳腺癌细胞具有协同抑制生长和诱导凋亡作用。     

1，25（OH）2D3对脂多糖作用下大鼠腹膜间皮细胞维生素D受体及肿瘤坏死因子α、转化生长因子β1表达的影响

目的 研究脂多糖（LPS）对大鼠腹膜间皮细胞（RPMC）维生素D受体(VDR)及肿瘤坏死因子α（TNF-α）、转化生长因子β1（TGF-β1）表达的影响,从而为1,25（OH）2D3在腹膜透析相关腹膜炎中的应用提供理论依据。 方法 胰蛋白酶消化法原代培养腹膜间皮细胞、传代、经鉴定后分组：(1)正常对照组;(2)脂多糖组：不同浓度的脂多糖（1、10、100 mg/L）分别作用6 h;10 mg/L脂多糖分别作用2、6、12 h;(3)1,25（OH）2D3作用组：10 mg/L脂多糖预孵育2 h后,加1,25（OH）2D3(10－8 mol/L、10－7 mol/L、10－6 mol/L)再作用6 h。RT-PCR法检测VDR mRNA的表达;Western印迹法检测VDR蛋白表达;ELISA法检测上清液TNF-α、TGF-β1的表达。 结果 与对照组相比,LPS组RPMC VDR mRNA和蛋白表达均显著下调（均P < 0.05）。与LPS组相比,1,25（OH）2D3组VDR mRNA和蛋白表达均显著上调（均P < 0.01）。LPS组上清液中TNF-α、TGF-β1浓度均显著高于对照组（均P < 0.01）;1,25（OH）2D3组上清液中TNF-α、TGF-β1浓度均显著低于LPS组（均P < 0.01）。 结论 LPS能下调RPMC VDR mRNA和蛋白的表达,上调TNF-α、TGF-β1表达。1,25（OH）2D3可逆转LPS的作用,上调RPMC VDR mRNA和蛋白的表达,并下调TNF-α、TGF-β1表达。VDR对腹膜透析相关腹膜炎具有一定的保护作用,并具有抑制腹膜纤维化的作用。     

Regulation of calcium absorption by 1,25,dihydroxy-vitamin D--studies of the effects of a bisphosphonate treatment

In 10 patients with Paget's disease of bone and 2 patients with osteoporosis, we studied the effects of hypocalcemia and hypophosphatemia induced by disodium-(3-amino-1-hydroxypropylidene)-1,-bisphosphonate (APD) treatment on the serum concentration of PTH and 1,25-dihydroxy-vitamin D [1,25(OH)2D3] and on calcium absorption and balance. The fall in serum calcium and phosphate was associated with a rise in the serum concentration of PTH and 1,25(OH)2D3, coupled with increases in net calcium absorption and calcium balance. The concentration of 1,25(OH)2D3 was significantly related (P less than 0.001) to the serum calcium (r = 0.66), the serum phosphate (r = 0.78), and the serum PTH (r = 0.71), confirming the interrelated control of these parameters on 1,25(OH)2D3 production. Moreover the rise in 1,25(OH)2D3 caused an appropriate rise in calcium absorption (r = 0.74) and calcium balance (r = 0.86), showing that this vitamin D metabolite contributes as a hormone to calcium homeostasis.     

High ratio of 1,25-dihydroxyvitamin D3 to parathyroid hormone in serum of tuberculous patients with end-stage renal disease

AIM: Diagnosis of tuberculosis is sometimes difficult because of the low specificity of diagnostic procedures especially in patients on end-stage renal disease (ESRD). As abnormal vitamin D metabolism has been reported in tuberculosis, the aim of the present study was to determine whether serum concentration of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) may be a useful diagnostic indicator of tuberculosis in patients with ESRD. PATIENTS AND METHODS: Serum concentrations of 1,25-(OH)2D3, parathyroid hormone (PTH), and calcium were compared in 6 patients with ESRD and active tuberculosis (ESRD-TB group) and 110 patients with ESRD and no tuberculosis (ESRD group). These parameters were compared before and after treatment for tuberculosis in patients of ESRD-TB group. RESULTS: Hypercalcemia was observed in all 6 patients in the ESRD-TB group. Both higher serum concentration of 1,25-(OH)2D3 and lower serum concentration of PTH were observed in the ESRD-TB group relative to the ESRD group, suggesting enhanced extrarenal production of 1,25-(OH)2D3 and suppressed secretion of PTH by hypercalcemia in the ESRD-TB group. However, these parameters could not be used to distinguish the ESRD-TB group from the ESRD group. The ratio of 1,25-(OH)2D3 to PTH in serum was above 0.9 in the ESRD-TB group and below 0.9 in the ESRD group. Antituberculous treatment reduced this ratio to the range observed in the ESRD group. CONCLUSION: High ratio of 1,25-(OH)2D3 to PTH in serum is noted in active tuberculous patients with ESRD because of enhanced extrarenal production of 1,25-(OH)2D3.     

胎肾细胞悬液对维甲酸所致骨质疏松大鼠部分钙调节激素的影响

目的探讨胎肾细胞悬液改善维甲酸所致大鼠骨质疏松的机理,为临床用药提供客观依据.方法通过静脉输注胎肾细胞悬液,采用放免分析法测定维甲酸所致骨质疏松大鼠血清雌二醇、降钙素、甲状旁腺素、骨钙素等钙调节激素含量,观察胎肾对上述指标和骨形态的影响.结果与维甲酸造模组比较,胎肾细胞悬液组大鼠血清雌二醇、降钙素、骨钙素水平升高,甲状旁腺素降低（P＜0.05）,胫骨骨重、灰重和骨基质均增加（P＜0.01）,胫骨骨长变化不大（P＞0.05）.骨病理形态计量中,胎肾细胞组大鼠骨小梁厚度、面积及密度均高于模型组,而骨小梁间隙明显缩小（P＜0.05）.结论胎肾细胞改善维甲酸所致大鼠骨质疏松机制与部分钙调节激素的变化有关.     

Lack of relationship between parathyroid hormone and 1,25-dihydroxyvitamin D in chronic renal failure

In the present study, concentrations of parathyroid hormone (PTH), determined by an intact PTH assay and a midregion/C-terminal PTH assay, 1,25-dihydroxyvitamin D [1,25(OH)2D3], ionized calcium and phosphate were measured in 15 patients with a stable creatinine clearance (Ccr) of 21.2 +/- 14.4 ml/min (mean +/- SD; group 1) and in 10 patients with a Ccr regularly undergoing hemodialysis (group 2, Ccr not measured). In group 1, the mean concentration of 1,25(OH)2D3 was significantly increased compared with the level in group 2, whereas no differences were found concerning the concentrations of intact PTH, midregion/C-terminal PTH, ionized calcium and phosphate. In group 1, the PTH concentration correlated inversely with ionized calcium concentration and Ccr, which in turn, was directly correlated. The concentration of 1,25(OH)2D3 correlated inversely with phosphate concentration, but did not correlate with either PTH or ionized calcium concentrations. In group 2 no correlation was found between any of the biochemical variables. The data demonstrate that in patients with stable renal failure, the concentration of ionized calcium still regulates PTH secretion but other variables such as parathyroid cell mass and setpoint may interfere with the interrelation. The elevated concentration of phosphate in renal failure may override PTH as a regulator of the renal 1,25(OH)2D3 formation. The lack of correlation in the hemodialyzed patients may be attributed to extrarenal production of 1,25(OH)2D3, reduced binding of 1,25(OH)2D3 to parathyroid tissue or the major changes in calcium homeostasis caused by the hemodialysis.     

Combined treatment with cyclosporin A and cortisone acetate minimizes the adverse bone effects of either agent alone

Although cyclosporin A (CsA) and cortisone acetate (CRT) adversely affect bone, their combined effect on bone is unknown. Sprague Dawley rats were therefore administered either vehicle or CsA (7.5 mg/kg/day) by gavage and saline or CRT (2 mg/100 mg/day) by s.c. injection for 28 days. Group A received vehicle plus saline, group B CsA plus saline, group C vehicle plus CRT, and group D CsA/CRT. Serial bloods were sampled over a 28-day period for ionized calcium (Ca), PTH, 1,25 dihydroxyvitamin D (1,25(OH)2D), and bone gla protein (BGP osteocalcin) and tibia were examined on day 28 for histomorphometry. Results were compared with group A. Ca and PTH levels in groups B, C, and D were similar to those in group A during the study period. Group B had lower body weights, elevated levels of BGP, and an increase in 1,25(OH)2D. Group C developed weight loss and a decrease in BGP and 1,25(OH)2D. Group D had weight loss, BGP levels between those of group A and group C, and 1,25(OH)2D values similar to group A. Bone histomorphometry revealed high turnover osteopenia in group B and hyperostosis in group C with a decrease in bone formation and osteoclastlike cells. Combination therapy returned these to control values. In conclusion, the adverse effects of either CsA or CRT on bone in rats are minimized by combined therapy.     

Regulation of 1,25-dihydroxyvitamin D3 by calcium in the parathyroidectomized, parathyroid hormone-replete rat

Parathyroid hormone (PTH) is a major stimulus for the renal production of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Elevated arterial blood ionized calcium ([Ca2+]) depresses serum 1,25-(OH)2D3 in nonparathyroidectomized rats even when serum PTH is maintained at high levels by infusion. However, suppression by [Ca2+] of endogenous PTH, causing the fall in 1,25-(OH)2D, cannot be excluded. To determine whether [Ca2+] regulates 1,25-(OH)2D3 in the absence of a variation in PTH, we parathyroidectomized (PTX) rats (post-PTX calcium levels less than 7.0 mg/dl), inserted arterial and venous catheters, and then replaced PTH using an osmotic pump. We varied [Ca2+] by infusing either 75 mM sodium chloride (control), 0.61 mumol/min of EGTA (EGTA), or calcium chloride at 0.61 mumol/min (low calcium) or 1.22 mumol/min (high calcium) for 24 h 5 days after surgery. Blood was then drawn from the rat through the arterial catheter. Compared with the control, [Ca2+] fell with EGTA, remained constant with the low-calcium infusion, and rose with the high-calcium infusion. 1,25-(OH)2D3 was correlated inversely with [Ca2+] in all four groups together (r = -0.635, n = 34, p less than 0.001), within the control group alone (r = -0.769, n = 11, p less than 0.002), and within the EGTA group alone (r = -0.774, n = 10, p less than 0.003). Serum phosphorus, PTH, and arterial blood pH were not different in any group, and none correlated with serum 1,25-(OH)2D3. We conclude that 1,25-(OH)2D3 levels are regulated by [Ca2+] independently of serum PTH, phosphorus, and acid-base status, all of which support the hypothesis that [Ca2+] is a principal regulator of serum 1,25-(OH)2D3 in the rat.