糖尿病骨质疏松与钙代谢调节激素的关系

目的分析糖尿病骨质疏松与钙代谢调节激素的关系，探讨其发生机理，方法应用双线X线吸收测定仪，观察92侧Ⅱ型糖尿病患骨密度变化，同时用化学和放射免疫法、测定血Ca、P、碱性磷酸酶(AKP)，甲状旁腺激素(PTH)，降钙素(CT)和骨钙素(OC)的含量。结果与对照组比较，糖尿病骨质疏松组血清Ca、P和AKP水平正常(P>0.05)；血PTH和OC升高(P<0.01)，CT降低(P<0．05)。结论糖尿病患这些激素变化是机体的一种代谢性调节机制，也是糖尿病骨质疏松的一个重要原因。     

IDDM儿童和青少年甲状旁腺和甲状腺功能测定及其临床价值

测定32例胰岛素依赖性糖尿病(IDDM)儿童和青少年血Ca、P、AKP、iPTH、CT、T_3和T_4浓度,与正常对照组相比,血Ca、AKP、iPTH和CT水平均明显升高,血T_3水平则明显降低。IDDM儿童和青少年患者钙磷代谢和骨代谢发生了明显异常变化,可以认为是糖尿病性骨质疏松发病的开始。作者认为,糖尿病性骨质疏松的发病可能有一个从继发性甲旁亢到甲旁低的连续变化过程。而IDDM儿童和青少年患者亚临床甲状腺功能减低对缓解钙磷代谢紊乱可能具有重要作用。     

糖尿病患者骨质改变的临床意义

我们测定了50例糖尿病患者桡骨的骨密度(BD).其中20例还测定血碱性磷酸酶(AKP),血Ca、P及24小时尿Ca、P的值.与正常对照组相比,64%糖尿病患者BD降低,AKP显著升高,血Ca、P正常,而24小时尿Ca排出明显增高.糖尿病BD降低与病程、病型无关,与血糖及AKP成负相关.BD测定是糖尿病骨病的一个重要的诊断指标.     

糖尿病肾病患者骨密度与钙调节激素和胱抑素C的变化和关系

用双能X线吸收测量法(DEXA)检测56例2型糖尿病肾病患者(简称为DN组)、43例单纯性2型糖尿病患者(简称为DM组)和50例正常对照组的骨密度(BMD),并测定各自的生化指标:血钙(Ca)、血磷(P)、碱性磷酸酶(ALP)、胱抑素C(Cys C)和钙调节激素指标:甲状旁腺素(PTH)、降钙素(CT)、骨钙素(BGP),做统计分析。结果 DN组BMD较DM组和对照组显著降低(P<0.01);P、ALP、PTH、BGP和CT显著升高(P<0.01),Ca降低(P<0.01)。BMD与Cys C、PTH和BGP呈负相关,r分别是-0.34、-0.41、-0.33,与血Ca、P、CT和ALP无相关性。Cys C与PTH和BGP呈正相关(r分别是0.41、0.32)。结论 DN患者BMD显著下降,可能与肾脏损伤程度和钙调节激素紊乱有关。     

2型糖尿病患者骨代谢生化指标观察

目的　探讨 2型糖尿病患者骨代谢生化指标变化。方法　测定 6 5例 2型糖尿病 (DM)患者及 5 9例年龄、性别相匹配健康对照者血 (Ca)、磷 (P)、骨钙素 (BGP)、甲状旁腺素 (PTH)、尿液中I型胶原降解产物 /肌酐(crosslaps/Cr)的水平。结果　 2型糖尿病病人组中BGP质量浓度显著低于对照组 (P <0 0 5 ) ,血PTH质量浓度显著高于对照组 (P <0 0 5 ) ,尿crosslaps/Cr高于对照组但差异无显著意义 (P >0 0 5 )。血Ca、P浓度与对照组无显著差异。结论　糖尿病可以引起骨代谢生化指标变化 ,及时测定血、尿中骨转换指标 ,对监测糖尿病骨代谢变化 ,防治骨质疏松具有重要意义。     

一氧化氮与2型糖尿病患者骨代谢变化的关系

目的　观察男性 2型糖尿病患者血清NO、骨代谢变化情况及NO与骨代谢的相互关系。方法　对 2 8例男性 2型糖尿病患者及 2 0例男性健康人群测量腰椎 (L2～L4)骨密度 ,并测定血清NO、BGP、PTH、CT、Ca、P、尿PYD ,观察两组各项指标的变化并进行比较。结果　 2型糖尿病患者血清NO较对照组明显升高 (P <0 0 1 ) ,骨密度低于对照组 (P <0 0 1 ) ,尿PYD高于对照组 (P <0 0 1 ) ;2型糖尿病患者NO水平与骨密度、血BGP呈负相关 ,与尿PYD排泄呈正相关。结论　 2型糖尿病患者存在骨密度的降低 ,升高的NO可能对骨密度降低、骨代谢变化起重要作用     

活性维生素D_3对糖尿病肾病维持性血液透析患者心脏功能的影响

目的探讨活性维生素D3对糖尿病肾病维持性血液透析患者心脏功能的影响。方法 54例糖尿病肾病维持性血液透析患者分为对照组和干预组,两组均接受常规透析治疗,干预组给予骨化三醇0.25μg/d治疗,观察24 w比较两组治疗前后血钙(Ca)、磷(P)、甲状旁腺激素(i PTH)、25(OH)D3等指标变化,同时观察脑钠肽(BNP)、左室舒张末期内径(LV)以及QT离散度(QTd)等指标的变化。结果与治疗前比较,治疗后干预组血Ca、25(OH)D3水平明显升高,i PTH明显下降,BNP和QTd明显下降(P<0.05);而对照组各指标无明显改变。结论活性维生素D3对糖尿病肾病维持性血液透析患者心脏具有保护作用,其作用机制可能通过升高Ca、25(OH)D3,降低i PTH和QTd发挥作用。     

糖尿病肾病患者血清甲状旁腺激素及骨密度测定的临床意义

目的探讨糖尿病肾病(DN)患者肾功能不同阶段的血清甲状旁腺激素(PTH)变化及与骨密度(BMD)、血钙、血磷的关系及其对骨代谢影响的临床特点。方法选择2009年3月至2011年3月就诊于吉林大学中日联谊医院内分泌科门诊或病房患者70例,根据DN诊断标准,对患者尿微量白蛋白、肾功能检测分组。分为无DN,亚临床DN,临床DN,终末期DN,并且选取无糖尿病、心脏、肝脏、肾脏及甲状旁腺疾病病史,未服用任何激素类药物的正常人28例,设为正常对照组。所有人空腹取静脉血,测定血PTH、血钙、血磷。采用Lexxos(Holland)双能X线BMD仪测量股骨颈、大转子区、Ward三角区骨密度。结果 (1)终末期DN患者血钙值明显低于正常对照组,血磷值明显高于正常对照组(P0.05);临床DN组及终末期DN组与对照组比较,血PTH明显升高(P0.05);临床DN组与亚临床DN组比较,血PTH明显升高(P0.05);终末期DN组与临床DN组比较,血PTH升高明显(P0.05)。(2)临床DN组及终末期DN组与对照组比较BMD值下降明显(P0.05);亚临床DN组与对照组比较以股骨颈处BMD下降为著(P0.05);终末期DN组与无DN组及亚临床DN组比较BMD值下降明显(P0.05);临床DN组与无DN组及亚临床DN组比较大转子区及Ward三角区BMD值有明显降低(P0.05)。(3)对终末期DN组做相关分析,PTH与血磷呈正相关,相关系数(r=0.62,P0.05);PTH与血钙呈负相关(r=-0.59,P0.05);PTH与BMD值呈负相关(r=-0.51,P0.05)。结论 (1)在临床DN组中,血尿素氮(BUN)、肌酐(CREA)、血磷、血钙等正常情况下,血PTH已升高,因此PTH亦可作为分析DN患者肾功能损害的一个参考指标。(2)在临床DN期,患者肾功能正常情况下,血PTH即可升高,BMD降低,提示应与原发性甲旁亢相鉴别,避免在临床工作误诊有重要意义。(3)随着DN患者肾脏损害加重,BMD可进行性下降,骨量丢失与DN程度有关,DN进展是糖尿病患者BMD下降的重要原因,其中血清PTH对BMD下降发挥了重要作用。     

泌尿系统疾病

2001046,纳米钙治疗恤性肾功能不全继发性甲旁亢的疗效/姚颖…刀中华肾脏病杂志一200。,16丈3)一142 100例患者治疗前血P、AKP、BGP和PTH显著高于正常对照组,而血Ca、BMD和1,25(OH):D。明显低于正常对照组。纳米钙治疗8周后.血P、AK只BGP和PTH显著下降。另外BUN和Scr治疗前后亦无明显变化。治疗前血清FTH与血P呈明显正相关,与1 .25(OH)。D3呈明显负相关,而与血Ca无关。治疗后血PTH与血Ca呈明显负相关与血P和1,25(OH妇3则无关。提示999纳米钙可为临床防治慢性肾功能不全继发性甲旁亢提供可行的治疗措施,且对肾功能没有影响…     

2型糖尿病患者骨密度与钙调节激素和性激素关系的研究

用双能X线吸收测量(DEXA)检测104例2型糖尿病患者(简称为DM组)和46例正常对照组BMD,并测定各自的生化指标、性激素和参与骨代谢有关的激素指标,做统计分析。结果DM组BMD较对照组降低(P0.01);PTH、CT升高(P0.01),ALP和BGP降低(P0.01);Ca和P无变化。男性T和女性E2显著降低(P0.01)。DM患者BMD与Glu、GHb、ALP、PTH呈负相关,与Ins呈正相关。结论DM患者BMD显著下降,可能与糖代谢改变致钙调节激素紊乱和性激素减少有关。     

不同药物对糖尿病骨质疏松的短期疗效比较

把糖尿病事并骨质疏松而血糖控制满意的患者分为单纯加用钙剂组（组１）、钙剂加维生素Ｄ２组（组２）、钙剂加钙全组（组３）、钙剂加密息组（组４）及单纯尿治疗组为对照组（组５），治疗三个月后进行疗效比较。结果组１、组５治疗前后骨密度、骨代谢指标（血钙、血磷、碱性磷酸酶（ＡＫＰ）、血甲主腺激素（ＰＴＨ）、尿羟脯氨酸（均无明显变化）（Ｐ〉０．０５）。组２治疗后ＰＴＨ明显降低（Ｐ〈０．０５）。组３、组４血ＰＴＨ     

Hypocalcemia with osteoblastic metastases in a patient with prostate carcinoma: A cause of secondary hyperparathyroidism

A 68 year old man with prostatic carcinoma and extensive painful osteoblastic metastases was discovered to have hypocalcemia (serum calcium 7.1 mg/dl) without evidence of hypoalbuminemia, renal failure or malabsorption. Baseline studies revealed hypocalciuria (24 hour urine calcium <5 mg/day), normal serum phosphate (3.4 mg/dl), low tubular reabsorption of phosphate (68 percent), undetectable serum calcitonin, normal serum 25-hydroxyvitamin D, slightly elevated serum parathyroid hormone level and increased urinary cyclic AMP (8.87 μmol/g creatinine). These studies were compatible with secondary hyperparathyroidism. The intravenous administration of parathyroid extract produced no further change in urinary phosphate but a 25-fold increase in nephrogenous cyclic AMP. Three days administration of intramuscular parathyroid extract slowly and temporarily restored serum calcium to normal levels while increasing urinary cyclic AMP and phosphate. Chemotherapy with cyclophosphamide and 5-fluorouracil rendered the patient free of pain while reducing serum acid and alkaline phosphatase levels and restoring serum total and ionized calcium and urinary cyclic AMP excretion to normal.     

SODIUM FLUORIDE STIMULATES OSTEOCALCIN IN NORMAL SUBJECTS

To test whether the administration of sodium fluoride in vivo results in an increase in osteocalcin concentration, we administered sodium fluoride to seven healthy male subjects for a period of 3 weeks. Fasting calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone and osteocalcin were measured prior to, during and 6 weeks after fluoride administration. Plasma calcium, phosphate and alkaline phosphatase and serum 25-hydroxyvitamin D and parathyroid hormone concentrations did not alter. Serum osteocalcin concentrations increased following fluoride administration, and the mean osteocalcin concentration at 3 weeks was significantly higher than the pretreatment mean. Plasma urea and creatinine concentrations did not alter. Six weeks after the cessation of fluoride treatment, the mean serum osteocalcin concentration had returned to the pretreatment baseline. We conclude that fluoride administration in normal subjects over a short period increases serum osteocalcin concentration and probably stimulates osteoblastic activity.     

Age-related changes in serum immunoreactive parathyroid hormone and its biological action in healthy men and women

Circulating levels of PTH and related parameters of calcium and phosphate metabolism were measured in healthy free-living elderly and young subjects residing in the Southwest to determine if parathyroid function changes with aging. Serum immunoreactive PTH (iPTH) was measured with two well characterized antisera; an amino (N)-terminal antiserum which cross-reacts with the biologically active domain (1-34) and recognizes intact hormone, and a midregion (44-68) antiserum which cross-reacts with intact hormone and biologically inactive midregion/C-terminal fragments. Serum iPTH in both RIAs was significantly increased in the elderly population. An age-related increase was also found for total urinary cAMP and serum alkaline phosphatase, whereas the tubular reabsorptive maximum for phosphate (TmP/GFR) decreased with age. No difference was found between men and women of the same age group for serum iPTH, urinary cAMP, or serum alkaline phosphatase. TmP/GFR declined with age in men, but not women. Correspondingly, serum phosphate was significantly lower in elderly men than in elderly women. Urinary calcium excretion was higher in elderly women than in men of the same age group. Neither serum total or ionized calcium decreased with age. In conclusion, the age-related increase in N-terminal PTH and alterations in associated parameters of phosphate and calcium metabolism are consistent with increased parathyroid function as men and women age. Factors other than PTH are responsible for the sex-related differences observed in TmP/GFR, calcium excretion, and serum phosphate. The cause of the increased circulating levels of apparently biologically active PTH is unclear, but extends beyond the age-related decrease in renal function.     

Is 2.5 mEq/L the Optimal Calcium Concentration of Dialysate in the Use of Sevelamer Hydrochloride? A Study of the Dialysate Calcium Concentration Recommended by K/DOQI Guidelines

We tested the effect of three different dialysate calcium concentrations on calcium-phosphorus metabolism during the use of sevelamer hydrochloride. After a calcium-containing phosphate binder was switched to sevelamer, the serum calcium, phosphorus, and intact parathyroid hormone levels and the markers of bone turnover were measured in the patients whose dialysate calcium concentrations were 2.5, 2.75, and 3.0 mEq/L. As a result, in the 2.75-mEq/L group, the serum calcium concentrations decreased and the intact parathyroid hormone level increased significantly. In the 2.5-mEq/L group, transient hypocalcemia occurred and the levels of both bone-alkaline phosphatase and osteocalcin increased. In the 3.0-mEq/L group, the serum calcium concentrations did not change significantly and only bone-alkaline phosphatase increased. If a calcium-containing phosphate binder is completely switched to sevelamer, dialysis using a dialysate calcium concentration below 3.0 mEq/L may result in hypocalcemia and acceleration of bone turnover.     

Sevelamer hydrochloride improves hyperphosphatemia in hemodialysis patients with low bone turnover rate and low intact parathyroid hormone levels

Sevelamer improves hyperphosphatemia without increasing the calcium load. However, it remains unknown whether sevelamer restores bone metabolism in hemodialysis patients with low bone turnover osteodystrophy and hypoparathyroidism. We investigated the changes in serum intact parathyroid hormone (iPTH) and bone metabolic marker levels after replacing calcium carbonate with sevelamer in these patients. We also conducted stratified analysis based on patient background and multivariate analysis to determine the factors affecting these parameters. During sevelamer replacement therapy, serum calcium and phosphate concentrations, and the calcium phosphate product were measured at 0, 1, 3, and 6 months. Serum iPTH, bone alkaline phosphatase and osteocalcin concentrations were measured at 0 and 6 months. In hemodialysis patients (71 men and 46 women, 63 +/- 12 years old) serum calcium levels and the calcium phosphate product decreased significantly at 1 month. Serum iPTH, bone alkaline phosphatase and osteocalcin levels increased significantly at 6 months. Increases in serum iPTH concentrations were observed in all stratified groups. Significant increases in serum bone alkaline phosphatase and osteocalcin concentrations were found only in the relative hypoparathyroidism group (iPTH levels > or =51.5 pg/mL, the median pretreatment level). Multivariate analysis showed that the factors affecting change in serum iPTH level are baseline serum iPTH, baseline calcium level (> or =9.5 mg/dL), and dialysis duration of 10 years or longer. Sevelamer appears useful for the treatment of hyperphosphatemia in these patients. Particularly, in the relative hypoparathyroidism group, the iPTH secretory response is probably enhanced and bone turnover may have been improved as a result of reducing the calcium load.     

Hypercalcemia and hyperphosphatemia in thyrotoxoicosis and the therapeutic effect of propranolol

Measured levels of serum calcium, phosphate, alkaline phosphatase, and urinary hydroxyproline were measured and calcium-phosphate product was calculated in 20 hyperthyroid patients and 20 normal controls. Eleven of the patients took propranolol 160 mg per day for 28 days. We found that the serum level of calcium was higher than that of normal controls. The incidence of hypercalcaemia in hyperthyroid patients was 10%. The serum level of phosphate and the calcium-phosphate product increased (P less than 0.01). Elevation of alkaline phosphatase and bone alkaline phosphatase were also observed (P less than 0.01). The urinary hydroxyproline was also elevated (P less than 0.01). After treatment with propranolol serum calcium and triiodothyronine decreased (P less than 0.05). It is suggested that the major mechanism of hypercalcaemia and hyperphosphatemia in hyperthyroidism was increase of bone absorption stimulated by triiodothyronine. Propranolol decreased the serum level of calcium through decreasing triiodothyronine level and through beta-receptor blocking effect as well as its direct effect on bone.     

Intravenous alfacalcidol once weekly suppresses parathyroid hormone in hemodialysis patients

Management of secondary hyperparathyroidism is difficult because of the interrelationship of parathyroid hormone, calcium and phosphorus. This study was carried out to assess the efficacy of intravenous administration of alfacalcidol once weekly versus twice weekly in patients with severe hyperparathyroidism. Twenty-one hemodialysis patients with intact parathyroid hormone >88 pmol/L were divided into two groups. Eleven patients (Group 1) were given a once-weekly alfacalcidol intravenously for 12 weeks. The starting dose was 4 microg which was increased or decreased by 1 microg per week. Ten patients (Group 2) were given twice-weekly alfacalcidol intravenously for 12 weeks. The starting dose was 2 microg twice weekly which was increased or decreased by 0.5 microg/dose. The dose was increased or decreased according to serum calcium and phosphorus levels. Serum calcium, phosphorus and alkaline phosphatase levels were measured weekly and intact parathyroid hormone every 4 weeks. Intact parathyroid hormone reduced significantly (P = 0.0001) from 128.12 +/- 35.42 pmol/L to 82.93 +/- 65.20 pmol/L and from 113.74 +/- 40.83 pmol/L to 64.24 +/- 35.17 pmol/L after 4 weeks in Groups 1 and 2, respectively. After 4 weeks alkaline phosphatase declined significantly (P = 0.0001) from 146.0 +/- 57.3 IU/L to 116.0 +/- 45.6 IU/L in Group 1 and from 139.0 +/- 45.1 IU/L to 116.6 +/- 38 IU/L in Group 2. There were no significant differences in serum levels of calcium, phosphorous or their product. Interestingly, an adenoma disappeared in one patient from Group 1, and out of two adenomas, one disappeared from another patient in the same group. These results indicate that intravenous alfacalcidol once weekly is safe and effective in suppressing high parathyroid hormone in hemodialysis patients.     

Serum osteocalcin and vitamin D metabolites in patients with ankylosing spondylitis.

OBJECTIVES--Osteocalcin is the major non-collagenous protein of bone and is regarded as a specific index of bone formation. The aim of this study was to examine the rate of bone formation measured by osteocalcin in 38 patients with ankylosing spondylitis (AS) and its dependence on various parameters of calcium and phosphate metabolism. METHODS--Serum osteocalcin, alkaline phosphatase, parathyroid hormone, and 1,25-dihydroxyvitamin D were measured in 38 patients with ankylosing spondylitis and in 52 controls. RESULTS--Mean serum osteocalcin was significantly reduced in patients with AS (men 1.7 (1.1) ng/ml; women 1.2 (1.1) ng/ml) compared with the corresponding control groups (men 3.2 (1.3) ng/ml; women 4.1 (1.7) ng/ml). In contrast, alkaline phosphatase was only slightly but significantly higher (135 (44) U/l) in patients with AS than in the corresponding controls (114 (35) U/l). Serum parathyroid hormone (AS 3.1 (0.7) v 2.7 (0.6) mE/ml) and 1,25-dihydroxyvitamin D (AS 64.0 (34.5) v 52.4 (6.7) pg/ml) were slightly but not significantly higher in patients with AS. Consequently, as both hormones are known to stimulate osteocalcin synthesis, they are not responsible for low osteocalcin levels in patients with AS. No significant correlation between alkaline phosphatase and osteocalcin was found. Low serum levels of osteocalcin in patients with AS reflect lower osteoblastic activity in AS. CONCLUSIONS--Bone turnover in patients with AS is characterised by low bone formation in the presence of normal levels of calcium regulating hormones.