原发性骨质疏松症中影响甲状旁腺素水平的因素分析

PTH主要影响钙、磷代谢及骨转换。在原发性骨质疏松患者中,甲状旁腺激素(PTH)轻度增高比较常见,影响PTH水平的因素及其机制尚不清楚,目前研究提示影响PTH水平的因素除血钙这一直接因素外,还包括维生素D水平、年龄、脂肪含量、血镁水平以及吸烟,此外可能与雌激素、雄激素及胰岛素样生长因子(IGF-1)等水平也有关系。这些因素在骨质疏松症发生发展中也发挥了一定的作用,综合分析影响PTH水平的多种因素对于骨质疏松症诊疗很重要。     

维持性血液透析患者甲状旁腺素与腰椎骨密度的关联

目的 探讨维持性血液透析(MHD)患者全段甲状旁腺素(iPTH)和定量计算机断层扫描(QCT)测定的腰椎体积骨密度(vBMD)的关联。方法 选取104例MHD患者,以QCT测定腰椎vBMD,收集人口学资料和实验室检测指标。采用多因素线性回归分析iPTH与vBMD的关联。使用平滑曲线拟合方法探索iPTH和vBMD的非线性关系。使用阈值效应分析计算拐点。结果 纳入人群骨质疏松发生率28.8%。多元线性回归分析结果显示,以iPTH作为连续性变量,iPTH与vBMD关联无统计学意义(P=0.094)。将iPTH按照三分位分低、中、高3组,以iPTH中间组作为参照,低iPTH组vBMD较参照组下降24.87 mg/cm³(P=0.010)。调整年龄、性别、透析龄、肾脏原发病、血钙、血磷、25-羟维生素D3[25-(OH)VD3]混杂因素,结果仍然稳健(P=0.002)。高iPTH组同参照组差异无统计学意义(P=0.657)。平滑曲线拟合结果显示iPTH与vBMD呈倒U形关系(非线性检验P=0.021)。阈值效应分析拐点iPTH为332 pg/ml。结论 过高、过低的iPTH...     

骨质疏松的研究方向

骨质疏松是发达国家日益受到重视的大众健康问题。美国国立卫生研究所和国家骨质疏松基金会最近召开专题讨论会,评价了骨质疏松研究现状,提出今后研究的方向。     

甲状旁腺素1-34对骨质疏松大鼠治疗作用的实验研究

目的探讨甲状旁腺素134(hPTH134)对骨质疏松的治疗作用以及与血钙、磷、维生素D代谢和生长因子的关系。方法用摘除大鼠双侧卵巢的方式制备骨质疏松模型(OVX),实验动物分为4个组:模型对照组(OVX组,摘除大鼠双侧卵巢不作任何处理);hPTH134治疗组(PTH组,摘除大鼠双侧卵巢12w后用hPTH134治疗8w);盐酸雷洛昔芬治疗组(摘除大鼠双侧卵巢12w后用雷洛昔芬治疗8w);假手术组(Sham组,仅切除卵巢周围的脂肪组织约3g,术后12w纳入实验)。应用HOLOGIC第4代双能X线4500W骨密度仪测大鼠腰椎、股骨上段骨密度值(BMD);以骨形态计量学测股骨骨小梁面积、矿化沉积率;用ELISA法测定血清IGF1水平和血清25OHVitD浓度以及血淋巴细胞VitD受体(VDR)含量。结果hPTH134治疗组、盐酸雷洛昔芬治疗组均较OVX组腰椎、股骨上段骨密度增高,组间比较差异有显著性(P<0.01)。hPTH134治疗组较盐酸雷洛昔芬治疗组股骨上段骨密度增高,两组之间差异有显著性(P<0.01)。hPTH134治疗组骨小梁面积明显增加、矿化沉积率增高。hPTH134治疗组、盐酸雷洛昔芬治疗组血清IGF1浓度值、血清25OHVitD浓度值升高,与OVX组比较差异有显著性(P<0.01)。各组血淋巴细胞VDR含量无明显变化,与OVX组比较差异无显著性(P>0.05)。结论hPTH134能够预防腰椎、股骨上段骨密度丢失,使骨小梁面积明显增加、矿化沉积率增高并且血清IGF1及血清25OHVitD浓度值升高,但对VDR含量无明显作用。     

甲状旁腺素的心血管效应

甲状旁腺素 (ＰＴＨ)是由甲状旁腺主细胞分泌的肽类激素 ,被认为是调节血钙水平的重要激素 ,目前认为甲状旁腺素可影响多种细胞功能 ,对心脏功能亦有影响 ,但作用机制还不清楚〔1 3〕。本研究运用Ｌａｎｇｅｎｄｒｏｆｆ灌注方法、微电极技术从不同水平来研究ＰＴＨ对心率、灌脉流量、心肌收缩力和自律性动作电位的影响 ,并初步探讨其作用机制。一、材料和方法1.兔窦房结标本的制备和自律性动作电位的记录 :成年家兔 ,击昏后迅速取出心脏置于 36℃台氏液中 ,制备窦房结标本并固定于恒温 (35 .5± 0 .5 )℃、恒流 (3ｍｌ/ｍｉｎ)标本槽中 ,灌…     

甲状旁腺激素相关蛋白治疗去卵巢大鼠骨质疏松的实验研究

目的观察人甲状旁腺激素相关蛋白(PTHrP)氨基端肽PTHrP1-34对去卵巢大鼠骨质疏松的治疗作用。方法 60只4个月龄Wistar健康雌性大鼠,其中40只行双侧卵巢摘除术,20只做假手术,6周后各处死10只证实骨质疏松造模成功。剩余卵巢摘除组30只随机分为3组,分别为:PTHrP治疗组、雌激素组、安慰剂组,每组10只,其他10只假手术组作对照。治疗3个月后,处死大鼠并测定股骨、腰椎骨密度(BMD),骨组织形态计量学参数,骨干重、灰重及血清钙、磷、碱性磷酸酶(ALP)水平。结果双侧卵巢摘除6周后,大鼠腰椎BMD明显低于假手术组(P<0．05)。3个月治疗后,PTHrP组大鼠股骨、腰椎BMD及骨灰重、干重比值明显高于安慰剂组,与雌二醇治疗组比较差异无统计学意义;小梁骨面积百分比、骨小梁厚度、成骨细胞表面及骨矿化沉积率也较安慰剂组明显升高。结论每日1次40μg／kg皮下注射人PTHrP1-34对去卵巢骨质疏松大鼠有明显治疗作用。     

甲状旁腺素联合骨髓间充质干细胞对骨质疏松大鼠股骨颈骨密度相关指标的影响

目的探索骨髓间充质干细胞(BMSCs)联合甲状旁腺激素(PTH)与二者单独使用对骨质疏松性大鼠骨密度相关指标的影响。方法将50只SD雌性大鼠分为A、B、C、D、E组,每组10只,B、C、D、E组切除双侧卵巢,A组大鼠仅切除卵巢周围同等大小的脂肪组织。术后12周各组抽取3只大鼠,检测大鼠的雌激素水平及骨密度相关指标骨小梁数量(Tb.N)、骨小梁厚度(Tb.Th)、骨小梁分离度(Tb.Sp)和骨体积分数(BV/TV)。脱颈法处死SD健康雄性大鼠取骨髓进行BMSCs细胞培养,流式细胞技术单标法检测BMSCs是否培养成功。术后12周,各组剩余7只大鼠。其中A和B组不做后期干预处理;C组按60μg/kg剂量背部皮下注射Rat PTH 1-34,隔日1次,连续12周;D组显露双侧股骨颈,注入浓度为5×108/ml的BMSCs;E组在D组的基础上在皮下注射PTH,注射浓度、频率与C组一致。所有大鼠均在干预12周后处死,Micro-CT测量5组大鼠股骨颈Tb.N、Tb.Th、Tb.Sp和BV/TV,观察成骨情况。使用SPSS 20.0软件进行统计分析。组间比较采用单因素方差分析,有统计学意义再进行LSD两两比较。结果术后12周,与A组比较,B、C、D及E组大鼠雌激素水平、Tb.N、Tb.Th及BV/TV显著下降,Tb.Sp明显升高,差异有统计学意义(P0.05),但B、C、D及E组各组间上述指标差异不明显(P0.05),可证明B、C、D及E组大鼠为骨质疏松模型。流式细胞技术单标法显示,P3代BMSCs表达CD29(99.86%)和CD90(99.73%),几乎不表达CD34(6.48%)和CD45(0.94%),证明BMSCs培养成功。干预12周后,Micro-CT数据显示,单独使用PTH或BMSCs及联合使用均可改善骨微观结构,但均未达到A组水平。与B组比较,C、D、E组的Tb.N、Tb.Th及BV/TV显著增加,Tb.Sp显著下降,差异有统计学意义(P0.05);与C或D组比较,E组Tb.N、Tb.Th及BV/TV显著增加,Tb.Sp显著下降,差异有统计学意义(P0.05)。结论 BMSCs联合PTH治疗局部骨质疏松的效果优于单独使用治疗的效果。     

甲状旁腺素在高血压发病中的作用

目的探讨甲状旁腺素(iPTH)及其与水盐代谢调节因素相互作用在高血压发病中的作用及机制。方法切除小鼠的甲状旁腺,检测小鼠24 h血压、白天血压和夜间血压的变化以及对小鼠血压节律和血压变异率的影响;给小鼠注射iPTH,检测小鼠体内醛固酮的含量以及血压的变化。结果敲除小鼠的甲状旁腺后,小鼠24 h、白天和夜间的收缩压和舒张压都显著低于对照组;iPTH敲除小鼠的血压变异率低于未敲除甲状旁腺的小鼠(P<0.05);甲状旁腺敲除小鼠的白天和夜间血压出现峰值的时间与对照组有所改变。对照组小鼠白天血压峰值出现在上午9点,夜间血压峰值为20点,夜间血压的峰值高于白天的峰值。甲状旁腺敲除小鼠的白天血压峰值出现在上午9点,夜间血压峰值时间为24点,夜间血压的峰值高于白天的峰值;给小鼠注射80μg/kg的iPTH后,醛固酮含量与对照组比较显著上升,血压比对照组显著升高(P<0.05)。结论 iPTH能降低血压,且能与醛固酮相互作用对血压进行调节。     

Parathyroid Hormone Levels May Predict Nonalcoholic Steatohepatitis in Morbidly Obese Patients

Background:

Obesity as a worldwide health problem is associated with nonalcoholic steatohepatitis (NASH). Since severe liver injury may be present in asymptomatic obese patients and a definite diagnosis of nonalcoholic steatohepatitis can only be made after an invasive procedure of liver biopsy, there is a need for noninvasive methods to predict the probability of NASH.

Objectives:

To investigate the role of vitamin D endocrine system in predicting the probability of presence of NASH in asymptomatic morbidly obese candidates of bariatric surgery.

Patients and Methods:

From December 09 to March 11, every patient undergoing bariatric surgery had a liver biopsy. Nonalcoholic steatohepatitis was diagnosed using the Lee’s criteria, the baseline labs obtained and the association between laboratory data and presence of NASH assessed.

Results:

Forty-six patients (34 women, aged 36.5 ± 10.6 years) were analyzed. The mean levels of liver enzymes were significantly higher in the group with NASH (P value < 0.01). In an unadjusted logistic model, PTH was the only variable in vitamin D endocrine system which was significantly associated with NASH (odds ratio (OR): 1.04, 95%CI: 1.01 - 1.07). After adjustment for possible confounding factors, age (OR: 1.22, 95%CI: 1.00 - 1.50) and PTH (OR: 1.08, 95%CI: 1.01 - 1.16) were predictive factors for NASH (P value < 0.05).

Conclusions:

Elevated serum PTH level was the predictive factor for NASH in morbidly obese patients. Also, we reported elevated serum liver enzymes, high serum PTH levels and older age as predictors of NASH in patients seeking obesity surgical treatments.     

甲状旁腺激素在心力衰竭中的作用及其机制探讨

心力衰竭(HF)是多种心血管疾病的终末阶段。研究发现,HF患者的甲状旁腺激素(PTH)水平明显增高;基础研究证实PTH、血管紧张素Ⅱ和醛固酮之间存在显著的交互作用,可能参与HF的发病。本文就PTH与HF的关系以及其参与HF发病的可能机制进行综述,以期将PTH作为HF的新标记物和临床干预靶点积累资料。     

Effect of Recent Alcohol Intake on Parathyroid Hormone and Mineral Metabolism in Men

The mechanisms by which alcohol intake, particularly moderate alcoho1 intake, effects bone metabolism are poorly defined. We have examined the relationship between mineral metabolism and recent self-reported alcohol intake (SRAI) across a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAI were obtained from each subject. SRAI was reported as between 0 and 45 oz/week. SRAI correlated positively with her function tests, including serum bilirubin (r= 0.30, p= 0.002), alkaline phosphatase (r= 0.30, p= 0.004), and aspartate aminotransferase (SGOT) (r= 0.29, p= 0.006). SRAI correlated with serum calcium corrected for albumin (r= -0.39, p < 0.001), estradiol (r= 0.43, p < 0.001), and immunoreactive parathyroid hormone (iPTH) (r= -0.51, p < 0.001), as well as urinary calcium (per 100 mg of creatinine) (r= 0.55, p < 0.001). We have arbitrarily divided the participants into two groups on the basis of their reported alcohol intake. Individuals in the first group had intakes ranging from none to moderate intake (drank 8.4 oz or less of ethanol per week, equivalent to an average of two drinks daily or less). Those in the second group had moderate or heavier intake, with >8.4 oz of ethanol intake/week. Mean serum iPTH was significantly greater in those in the first group (none to moderate), compared with the second group (moderate or heavier) (56.0 ± 3.4 and 39.9 ± 2.0 pM/liter, respectively). Calcium corrected for serum albumin was significantly greater in individuals in the first, compared with the second, group (9.23 ± 0.05 vs. 8.88 ± 0.07 mg/dl, respectively). In addition, urinary calcium (cod per 100 mg of creatinine) was significantly lower in the former, compared with the latter (3.1 ± 0.4 vs. 8.4 ± 1.1 mg/100 mg of creatinine, respectively). Similarly, urinary excretion of collagen crosslinks (corrected per 100 mg of creatinine) was significantly less in men in the second group, compared with the first group (316 ± 38 vs. 530 ± 78 nM/100 mg of creatinine, respectively). Not surprisingly, a series of correlations between iPTH and age, 250-hydroxyvitamin D, and testosterone were significant in individuals with none to moderate SRAI, but not moderate or heavier SRAI. Significant independent predictors of serum iPTH in the entire group of men were age (β= 0.215, p= 0.025), SRAI (β= -0.281, p= 0.003), 250-hydroxyvitamin D (β= -0.309, p= 0.002), and testosterone (β=?184, p= 0.048). We have concluded that, in free-living men, alcohol intake >8.4 oz/week was associated with decreased serum iPTH concentrations.     

Association between Parathyroid Hormone and Cardiovascular Disease

Although parathyroid hormone is known to be related with calcium and phosphate metabolism, it has been also reported to have several effects on the cardiovascular system including heart and vessels. However, the detailed pathophysiological mechanisms remain unclear. Clinical studies have indicated that parathyroid hormone is associated with cardiovascular events and mortality not only in patients with chronic kidney disease but also in those without chronic kidney disease. As a possible mechanism, it is thought that parathyroid hormone is associated with the renin-angiotensin-aldosterone system and has direct effects on the cardiovascular system. Therefore, we should pay attention to not only the control of serum phosphate and calcium levels but also the control of serum parathyroid hormone levels, especially in patients with chronic kidney disease.     

Emerging Association Between Parathyroid Hormone and Anemia in Hemodialysis Patients

Anemia is a common complication of chronic kidney disease (CKD). There are various causes of renal anemia such as decreased production of erythropoietin, resistance to erythropoietin, shortened survival of red blood cells, and bone marrow fibrosis. Secondary hyperparathyroidism (SHPT) is a less recognized, but potentially significant cause of renal anemia in CKD patients. Parathyroid hormone (PTH) has been regarded as a uremic toxin that has multiple adverse effects, and its elevated levels have been associated with renal anemia in hemodialysis patients. Moreover, recent clinical studies have shown that the treatment of SHPT using either vitamin D receptor activators, calcimimetics, or parathyroidectomy leads to improvement of anemia, supporting the role of PTH in renal anemia. Emerging data have also indicated the involvement of bone-derived fibroblast growth factor 23 in renal anemia. This review summarizes recent insights into the role of PTH in renal anemia and discusses the importance of treating SHPT in improving the control of renal anemia in hemodialysis patients.     

老年高血压患者动脉硬化与骨质疏松的相关性

目的　探讨老年高血压伴动脉硬化与骨质疏松的相关性。方法　收集我院年龄≥60岁住院患者149例，平均年龄72.7±10.1岁，其中109例原发性高血压患者为高血压组，40例非高血压患者为对照组，完善骨密度、四肢多普勒超声及相关生化检验等，将高血压组患者按照肱-踝脉搏波传导速度（BaPWV）以1900　cm/s为界分为高低两组，进行统计分析。结果　高血压组患者股骨颈、大转子、髋关节全部骨密度较对照组明显降低，差异有统计学意义（P<0.05）。左侧BaPWV≥1900　cm/s组患者股骨颈、大转子、粗隆间及髋关节全部骨密度较BaPWV＜1900　cm/s组下降明显，差异有统计学意义（P<0.05　）。偏相关性分析示：控制年龄因素后左侧BaPWV与左侧髋关节大转子及髋关节全部骨密度仍呈负相关（r－0.191和－0.199，P<0.05）。Logistic回归分析示年龄、载脂蛋白B是动脉硬化的危险因素。结论　老年高血压患者骨质疏松的危险增加，且其动脉硬化与髋部骨密度存在相关性，同侧动脉硬化程度增加的患者髋部骨密度下降的风险增加。     

Parathyroid Hormone,Its Fragments and Their Analogs for the Treatment of Osteoporosis

The susceptibility to traumatic fracturing of osteopenic bones, and the spontaneous fracturing of osteoporotic bones by normal body movements caused by the microstructural deterioration and loss of bone, are currently treated with antiresorptive drugs, such as the bisphosphonates, calcitonin, estrogens, and selective estrogen receptor modulators. These antiresorptive agents target osteoclasts and, as their name indicates, reduce or stop bone resorption. They cannot directly stimulate bone formation, increase bone mass above normal values in ovariectomized rat models, or improve microstructure. However, there is a family of agents - the parathyroid hormone (PTH) and some of its fragments and their analogs - which directly stimulate bone growth and improve microstructure independently from impairing osteoclasts. These drugs are about to make their clinical debut in treating patients with osteoporosis and, probably not too far in the future, for accelerating fracture healing. They stimulate osteoblast accumulation and bone formation in three ways via signals from the type 1 PTH/PTH-related protein (PTHR1) receptors on proliferatively inactive preosteoblasts, osteoblasts, osteocytes and bone-lining cells. The receptor signals shut down the proliferative machinery in preosteoblasts and push their maturation to osteoblasts, cause the osteoblastic cells to make and secrete several factors that stimulate the extensive proliferation of osteoprogenitors without PTHRI receptors, stimulate the reversion of bone-lining cells to osteoblasts, and extend osteoblast lifespan and productivity by preventing them from suicidally initiating apoptosis. The first of the PTHs to reach the clinic will be teriparatide [recombinant human (h)PTH-(1-34)], which was recommended for approval in 2001 by the US Food and Drug Administration Endocrinology and Metabolic Drugs Advisory Committee for the treatment of postmenopausal osteoporosis. Teriparatide has been shown to considerably increase cancellous and cortical bone mass, improve bone microstructure, prevent fractures and thus provide benefits that cannot be provided by current antiresorptive drugs, when administered subcutaneously at a daily dose of 20 microg for no longer than 2 years to patients with osteoporosis.     

Role of Parathyroid Hormone in Regulating Transporter and Metabolizing Enzyme Function

Recent studies demonstrate that parathyroid hormone (PTH) not only maintains mineral homeostasis through targeting the kidneys and bone, but also exerts its effects on other organs. For instance, PTH induces urate accumulation through inhibiting the expression of the ABCG2 in both the intestine and the kidney. In addition, PTH downregulates the expression of cytochrome P450 (CYP) 3A, a major enzyme for drug metabolism in both the intestine and liver, resulting in the increase of substrate drug exposure. These functions of PTH are mediated through the PTH receptor (PTHR) signaling. Since PTHR exists in various organs, PTH may regulate other, still unspecified transporters or enzymes in the organs that express PTHR.     

Intraoperative Parathyroid Hormone Monitoring Corroborates the Success of Parathyroidectomy in Children

Ob­jec­ti­ve: To assess the efficacy of intraoperative parathyroid hormone (PTH) monitoring in evaluating the outcome of parathyroidectomy in pediatric patients.Methods: Intraoperative PTH monitoring during parathyroidectomy was performed in five children (3M, 2F); three had parathyroid adenomas (single gland disease) and two had primary hyperplasia. One patient had undergone two previous surgical interventions to remove the parathyroid glands, but the PTH levels had remained high with persistence of symptoms. Immunoradiometric analysis was used for PTH measurements. Preoperative PTH values were obtained to monitor the baseline levels. Serum samples were collected 20 minutes after removal of the adenoma/parathyroid gland(s) and PTH levels were compared with preoperative values. Specimens were also confirmed by frozen sectional examination. Results: Mean age of the patients was 11 years (range: 3 months-16 years). Mean preoperative PTH values were 633.3±579 pg/mL (range: 143-1300 pg/mL). Intraoperative values decreased to 18.7±5.5 pg/mL (range: 8-27 pg/mL) following removal of the gland(s). Normal calcium levels were achieved with adequate management following surgery. One patient (with multiple surgeries and found to have an ectopic parathyroid gland) had hungry bone syndrome after the operation and was treated successfully. There were no major complications. All patients maintained normal calcium/phosphorus levels in the follow-up period, ranging from 2 to 5 years.Conclusion: An ectopic parathyroid gland or another undetected adenoma can be overlooked during surgery. Owing to the short life of the hormone, intraoperative PTH monitoring to determine PTH clearance proved to be a feasible marker for adequacy and safety of surgery and “cure”.     

Acute changes in serum calcium and parathyroid hormone circulating levels induced by the oral intake of five currently available calcium salts in healthy male volunteers

Summary Several calcium supplements are currently available and many of them are marketed without proper comparison of the bioavailability of the actual preparations. The aim of the present trial was to evaluate and compare the acute changes in serum calcium (Ca) and parathyroid hormone (PTH) levels following the oral administration of a vehicle and of five calcium salts currently prescribed in Western Europe. No significant changes in serum Ca or PTH levels were observed after administration of the vehicle. All calcium salts induced significant increases in serum Ca and decreases in serum PTH compared to baseline values. Comparison of the six response curves revealed a significantly greater increase in serum Ca and a greater decrease in serum PTH after each of the calcium salts than observed after the vehicle. However, no statistically significant differences were observed between the different calcium salts for serum Ca increments. The decrease in serum PTH observed after administration of an ossein-hydroxyapatite complex was significantly less important than after the four other calcium salts, even if statistically different than after vehicle. When assessing the area under the curve (AUC) of PTH values, we observed that calcium carbonate and citrate induce a significantly greater decrease in serum PTH than the other calcium salts which are, however, statistically more active than the vehicle. Serum PTH is decreased under the lower limit of the normal range (10 pg/ml), between t60 and t120 for calcium carbonate and citrate and between t60 and t90 for calcium gluconolactate while the mean PTH values remain within the normal range throughout the study with calcium pidolate, the ossein-hydroxyapatite complex and the vehicle. In conclusion, all calcium preparations significantly increase serum calcium and decrease serum parathormone, compared to what is observed after oral intake of a vehicle. However, significant differences in suppression of parathormone are observed between the different calcium preparations and might be of importance for their clinical use.