Vitamin D, Parathyroid Hormone, Insulin Sensitivity and Islet β-Cell Secretory Function in Diabetic Patients from South Kivu in the Democratic Republic of Congo: Cross-Sectional Study

Background: The role of vitamin D and parathyroid hormone in the metabolic profile of type 2 diabetes mellitus in sub-Saharan Africa has not been adequately assessed. The aim of this study was to determine the prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin sensitivity and β-cell secretory function among Congolese type 2 diabetics. Methodology: Fasting glycaemia, fasting insulin, 25OH D3 and human parathyroid hormone (hPTH) were measured in one hundred and eighty-four type 2 diabetic patients followed as outpatients in South Kivu. Levels of 25OH D3 65 pg/ml defined low vitamin D and elevated parathyroid hormone levels, respectively. The HOMA model was used to measure insulin sensitivity and β-cell secretory function. Results: Medians (IQR) were 25.3 (20.4 - 32.4) ng/ml for 25OH D3 and 53.7 (38.4 - 115.7) pg/ml for hPTH. 58.7% of diabetics had insulin resistance, 126 (68.5%) had low vitamin D and 80 (43.5%) had hyperparathyroidism. In multivariate analysis, hPTH (partial r = −0.28;p = 0.0002) and 25OH D3 (partial r = 0.16;p = 0.03) showed an independent association with insulin sensitivity after adjustment for body mass index and waist circumference. Finally, hPTH (partial r = 0.27;p = 0.0002) was the sole determinant of β-cell secretory function. Conclusions: This study confirms the high prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin resistance and impaired islet β-cell secretory function among Congolese with type 2 diabetes mellitus. Vitamin D and calcium supplementation should be envisaged for cases of deficiency in this region.

Post Thyroidectomy Assessment of Intact Parathyroid Hormone for Early Prediction of Hypocalcaemia

Background: As the half-life of intact parathyroid hormone (iPTH) is very low, it reflects parathyroid insufficiency within minutes to hours after total thyroidectomy. Therefore, iPTH level assessment in the postoperative period can be used to predict the development of hypocalcaemia. The optimal time point to measure serum iPTH is important for the accurate prediction of hypocalcaemia. Aim: This paper aims to evaluate the ability of iPTH as an early predictive marker of hypocalcaemia and determine which time iPTH is more able to predict postoperative hypocalcaemia. Method: This prospective observational study was conducted in the Department of Otolaryngology-Head & Neck Surgery, BSMMU, Dhaka, from July 2020 to December 2021, with 67 patients who underwent total thyroidectomy. iPTH levels were measured on the day before the operation and at 1 hour, 4 hours, and 24 hours after the operation. S.calcium levels were measured on the day before the operation and 1st postoperative day. All the data were compiled and sorted properly and were analyzed statistically. Results: Postoperative hypocalcaemia developed in 18 cases, with an incidence of 26.9%. Pearson correlation showed a significant correlation between postoperative iPTH at 1 hr, 4 h, and 24 hr with 1st postoperative calcium value. The Receiver operating characteristic (ROC) curve was processed for the postoperative iPTH at 1 hr, 4 h, and 24 hr. The sensitivity, specificity, cut-off value, and mean AUC found 93.9%, 94.4%, ≤14.0, 0.988;95.9%, 94.4%, ≤09.5, 0.993 and 91.8%, 94.4%, ≤11.0, 0.993 respectively. Conclusion: iPTH can be used as an early predictor of post-thy-roidectomy hypocalcaemia. 4 hr iPTH showed more sensitivity and specificity for a cut-off value near the laboratory reference range.

PTHrP促进RANKL诱导巨噬细胞分化为破骨细胞参与中耳胆脂瘤骨破坏

目的:骨质进行性吸收破坏是中耳胆脂瘤最重要的临床特征之一,可导致一系列颅内外并发症,而目前中耳胆脂瘤骨破坏的机制尚未明确。本研究旨在探究甲状旁腺激素相关蛋白(parathyroid hormone-related protein,PTHrP)参与中耳胆脂瘤骨破坏的机制。方法:收集后天性中耳胆脂瘤患者的25例胆脂瘤标本和13例外耳道正常皮肤组织标本。采用免疫组织化学染色方法检测PTHrP、核因子κB受体活化因子配体(receptor activator for nuclear factor-kappa B ligand,RANKL)和骨保护素(osteoprotegerin,OPG)在中耳胆脂瘤和外耳道正常皮肤组织中的表达,抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)染色法检测中耳胆脂瘤和外耳道正常皮肤组织中是否存在TRAP阳性多核巨噬细胞。选取小鼠单核巨噬细胞RAW264.7细胞进行干预,分为RANKL干预组和PTHrP+RANKL共同干预组,采用TRAP染色法检测2组破骨细胞的生成情况,实时聚合酶链反应(real-time polymerase chain reaction,real-time PCR)检测干预后2组破骨细胞相关基因TRAP、组织蛋白酶K(cathepsin K,CTSK)和活化T细胞核因子1(nuclear factor of activated T cell cytoplasmic 1,NFATc1)的mRNA表达水平,骨吸收陷窝实验检测2组破骨细胞的骨吸收功能。结果:免疫组织化学染色结果显示,PTHrP和RANKL在中耳胆脂瘤组织中的表达均显著增高,OPG表达降低(均P<0.05),且PTHrP的表达与RANKL、RANKL/OPG比值均呈显著正相关,与OPG表达呈显著负相关(分别r=0.385、r=0.417、r=-0.316,均P<0.05)。同时,PTHrP、RANKL的表达水平与中耳胆脂瘤的骨破坏程度均呈显著正相关(分别r=0.413、r=0.505,均P<0.05)。TRAP染色结果显示中耳胆脂瘤上皮周围基质中有大量TRAP阳性细胞,并存在细胞核数量为3个或3个以上的TRAP阳性破骨细胞。RANKL或PTHrP+RANKL联合干预5 d后,与RANKL干预组相比,PTHrP+RANKL联合干预组的破骨细胞数量显著增加(P<0.05),且破骨细胞相关基因TRAP、CTSK和NFATc1的mRNA表达水平均升高(均P<0.05)。骨吸收陷窝扫描电镜结果显示RANKL干预组、PTHrP+RANKL联合干预组的骨片表面均形成骨吸收陷窝;与RANKL干预组相比,PTHrP+RANKL联合干预组的骨片表面骨吸收陷窝数量显著增加(P<0.05),面积也更大。结论:PTHrP可能通过促进RANKL诱导胆脂瘤组织周围基质中的巨噬细胞分化为破骨细胞,参与中耳胆脂瘤骨破坏。

阿仑磷酸钠辅助PVP治疗对老年骨质疏松性压缩性骨折BALP、PTH及N-MID-OT水平的影响

目的分析阿仑磷酸钠辅助经皮椎体成形术(PVP)治疗对老年骨质疏松性压缩性骨折骨碱性磷酸酶(BALP)、甲状旁腺激素(PTH)及N端中段骨钙素(N-MID-OT)水平的影响。方法选取2019年1月至2022年2月唐山市丰润区人民医院收治的老年骨质疏松性压缩性骨折患者107例,按照治疗方式不同分为观察组和对照组,对照组采取PVP治疗(n=52),观察组采取阿仑磷酸钠辅助PVP治疗(n=55)。对比两组Oswestry功能障碍指数问卷表(ODI)、视觉模拟量表(VAS)、骨代谢指标(BALP、PTH、N-MID-OT水平)、不良反应及再骨折发生率。结果两组术后2个月、6个月、12个月ODI评分均下降,且观察组术后各时间段ODI评分均低于对照组,差异有统计学意义(P<0.05)。两组术后2个月、6个月、12个月VAS评分均下降,且观察组术后各时间段VAS评分均低于对照组,差异有统计学意义(P<0.05)。两组术后BALP、PTH及N-MID-OT水平均下降,且观察组术后BALP、PTH及N-MID-OT水平均低于对照组,差异有统计学意义(P<0.05)。两组不良反应总发生率对比,差异无统计学意义(P>0.05),但观察组再骨折发生率(7.28%)明显低于对照组(25.00%),差异有统计学意义(P<0.05)。结论阿仑磷酸钠辅助PVP治疗可有效改善老年骨质疏松性压缩性骨折患者椎体功能,减轻其疼痛程度,改善患者体内BALP、PTH及N-MID-OT水平,促进其术后恢复。

^(131)I治疗对分化型甲状腺癌患者术后血清iPTH、IGF-1水平的影响

目的探讨^(131)I治疗对分化型甲状腺癌患者术后血清全段甲状旁腺激素(iPTH)、胰岛素样生长因子1(IGF-1)水平的影响。方法回顾性分析河南科技大学第一附属医院2020年1月至2022年9月收治的73例分化型甲状腺癌患者,均接受甲状腺全切除并于术后2个月采用^(131)I治疗,随访1个月根据治疗情况将患者分为有效组(51例)和无效组(22例)。比较两组患者治疗前及治疗7 d iPTH和IGF-1水平,以及有效组治疗后各时间点血清iPTH、IGF-1水平。结果两组患者治疗后7 d血清iPTH、IGF-1水平均低于治疗前,且有效组低于无效组(P<0.05);有效组治疗后不同时间点血清iPTH、IGF-1水平差异有统计学意义(P<0.05)。结论分化型甲状腺癌患者^(131)I治疗后血清iPTH、IGF-1水平变化可用于判断甲状旁腺功能恢复情况,血清iPTH还可预示术后低钙血症的发生。

急性缺血性脑卒中患者PTH、IL-6表达水平及其与神经功能和近期预后的关系

目的探讨急性缺血性脑卒中(AIS)患者甲状旁腺素(PTH)、白介素6(IL-6)表达水平及其与神经功能和近期预后的关系。方法选取2020年3月至2022年10月宝鸡市康复医院收治的104例AIS患者作为观察组,另选取60例健康体检者作为对照组,所有受检者均采用酶联免疫法检测PTH、IL-6水平,观察组患者均行影像学检查,依照Adams分类法将患者梗死灶面积分为轻度40例,中度35例,重度29例;依照多伦多临床评分系统(CSS)将患者神经功能缺损分为轻型47例,中型35例,重型22例;发病1个月后随访,采用改良Rankin量表(mRs)评分将患者分为预后良好者77例,预后不良者27例,比较两组受检者的血清PTH、IL-6水平,并比较不同梗死面积、不同神经功能缺损程度、不同预后状态患者的血清PTH、IL-6水平,绘制受试者工作特征曲线(ROC)评估PTH、IL-6表达水平对疾病诊断的评估价值,并比较不同预后状态患者基础资料、既往病史及颈部大动脉狭窄程度、牛津社区卒中研究分型(OSCP)分型、溶栓前美国国立卫生院卒中量表(NIHSS)评分、发病至溶栓(OTT)时间差异,采用多因素Logistic回归分析AIS患者预后影响因素,采用Spearman相关性分析血清指标与梗死灶面积、神经功能缺损程度及预后的关系。结果观察组患者入院时的PTH、IL-6表达水平分别为(12.29±2.16)pg/mL、(11.58±3.17)ng/L,明显高于对照组的(10.03±1.29)pg/mL、(6.71±1.70)ng/L,差异均有统计学意义(P<0.05);血清PTH、IL-6表达水平联合评估AIS疾病状态的ROC曲线下面积(AUC)为0.906(敏感度为94.23%、特异度为83.33%),大于PTH、IL-6单独检测[AUC分别为0.799(敏感度为88.46%、特异度为51.67%)、0.827(敏感度为86.54%、特异度为66.67%)],且联合检测特异度高于PTH、IL-6单独检测,差异均有统计学意义(P<0.05);不同梗死面积患者比较,随着梗死灶面积的增加,血清PTH、IL-6表达水平也随之升高,差异均有统计学意义(P<0.05);不同神经功能缺损程度患者比较,随着临床神经功能缺损程度的增加,血清PTH、IL-6表达水平也随之升高,差异均具有统计学意义(P<0.05);预后不良者的PTH、IL-6表达水平分别为(14.89±1.40)pg/mL、(13.17±2.88)ng/L,明显高于预后良好者的(11.48±1.73)pg/mL、(10.99±2.03)ng/L,差异均有统计学意义(P<0.05);经多因素Logistic回归分析结果显示,颈部大血管狭窄程度、OSCP分型、溶栓前NIHSS评分、OTT时间、PTH含量、IL-6含量均是AIS患者预后影响因素(P<0.05);经Spearman相关性分析结果显示,PTH、IL-6表达水平与梗死灶面积、神经功能缺损、mRs预后均呈正相关(P<0.05)。结论PTH、IL-6与AIS发病相关,在一定程度上反映AIS患者病情严重程度及预后,有助于AIS的临床诊断与评估。

Safety,Tolerability and Pharmacokinetic Study of Recombinant Human Parathyroid Hormone [rhPTH(1-84)] in Chinese Healthy Volunteers

The current study was designed to determine the safety, tolerability and pharmacokinetic parameters of recombinant human parathyroid hormone [rhPTH （1-84）] used for the treatment of osteoporosis. In the single-dose format pharmacokinetic study, thirty-six healthy male volunteers received three dose levels of rhPTH （1-84） subcutaneously： 1, 2, and 4 μg/kg. The blood was timing drawn and the serum concentration of rhPTH （1-84） was determined by enzyme linked immunosorbent assay （ELISA）. Serum concentration-time curves of PTH （1-84） exhibited a double-peak pattern, the first peak appearing about 10 to 30 min after administration and the second peak occurring about 1.5 to2 h after administration. Serum terminal half-time of PTH （1-84） was approximately 2 h. The parameters indicated the serum levels were directly proportional to the administered dose, with the mean Cmax and AUC0_24 ranging from approximately 543.47 to 1845 pg/mL and 2358.6 to 9232.12 pg.h.mL^-1 over the dose range. The drug was well tolerated, the clinical symptoms were generally mild and of short duration.

CKD患者PTH水平与心功能、血钙、血磷水平的关系分析

目的:探究PTH与CKD患者的心功能、血钙和血磷水平的关系。方法:选取120例CKD患者和同期30例肾小球滤过率正常患者,收集心功能、PTH、血钙、血磷水平数据并分析各指标相关性。结果:CKD各期与对照组年龄、BMI、血钙和LVEF无显著差异(P>0.05),且血压、PTH、血磷、钙磷乘积和LVMI均高于对照组(P<0.05);PTH与LVMI、磷和钙磷乘积有显著正相关(P<0.05);多因素分析显示,PTH与LVMI、钙磷乘积、血压有明显正相关关系(P<0.05)。结论:CKD患者的PTH水平升高与血压、血磷、钙磷乘积及左心室重量相关。

血清Ca、P、iPTH、HbA1c表达水平与糖尿病肾病血透患者预后的相关性

目的:分析血清钙(Ca)、磷(P)、全段甲状旁腺激素(iPTH)、糖化血红蛋白(HbA1c)表达水平与糖尿病肾病(DKD)血透患者预后的相关性。方法:回顾性分析2020年1月—2021年12月在首都医科大学石景山教学医院进行血液透析治疗的83例糖尿病肾病患者的临床资料。根据患者随访1年内非计划再入院情况分为预后较差组(n=21)与预后良好组(n=62)。比较两组透析治疗前血清Ca、P、iPTH、HbA1c表达水平。分析DKD血透患者血清Ca、P、iPTH、HbA1c水平与预后的关系。以受试者工作特征(ROC)曲线评估血清P、iPTH、HbA1c水平对DKD预后的预测价值。结果:预后良好组血清P、iPTH水平均高于预后较差组,HbA1c水平低于预后较差组,差异有统计学意义(P<0.05)。多因素logistic回归分析显示血清P、iPTH及HbA1c均是DKD血透患者预后的影响因素(P<0.05)。ROC结果显示,血清P、iPTH、HbA1c水平对DKD血透患者预后预测的AUC分别为0.659、0.871、0.855,具有较高的预测价值。结论:DKD血透患者预后与血清P、iPTH及HbA1c表达有关,临床可通过检测DKD血透者血清P、iPTH、HbA1c水平预测预后,并对预后较差者积极干预,以期改善患者预后。

外周血PTH、CRP表达水平对缺血性脑卒中患者预后的评估价值

目的 探究外周血甲状旁腺激素(PTH)、C反应蛋白(CRP)表达水平对缺血性脑卒中患者预后的评估价值。方法 以2018年6月至2021年12月秦皇岛市工人医院116例缺血性脑卒中患者为研究对象,根据脑梗死面积将其分为腔隙梗死(49例)、小梗死(44例)及大梗死(23例),比较不同梗死面积患者外周血PTH、CRP水平,分析其与梗死面积的相关性;根据发病3个月后的改良Rankin量表(mRS)评分将患者分为预后良好组(≤2分)及预后不良组(>2分),分析外周血PTH、CRP水平对患者预后的预测价值及与不良预后发生的关系。结果 三组患者PTH、CRP水平比较,大梗死组患者>小梗死组患者>腔隙梗死组患者,差异有统计学意义(P<0.05);外周血PTH、CRP水平与缺血性脑卒中患者梗死面积呈正相关(P<0.05);预后不良组外周血PTH、CRP水平高于预后良好组,差异有统计学意义(P<0.05);外周血PTH、CRP水平联合检测预测患者预后的AUC大于PTH单独检测(P<0.05);PTH≥12.82 ng/L、CRP≥8.16 mg/L提示缺血性脑卒中患者预后不良(P<0.05)。结论 缺血性脑卒中患者外周血PTH、CRP水平与梗死面积相关,两者联合检测对患者预后具有评估价值。

外周血PTH、CRP表达水平对缺血性脑卒中患者预后的评估价值

目的:探究外周血甲状旁腺激素(PTH)、C反应蛋白(CRP)表达水平对缺血性脑卒中患者预后的评估价值。方法:选取2018年6月—2021年12月北京市丰台中西医结合医院收治的116例缺血性脑卒中患者为研究对象,根据脑梗死面积将其分为轻度组(n=49)、中度组(n=44)及重度组(n=23),比较不同严重程度患者的外周血PTH、CRP水平,分析其与梗死面积的相关性;根据发病3个月后的改良Rankin量表(mRS)评分将患者分为预后较好组(n=91)及预后不良组(n=25),分析外周血PTH、CRP水平对患者预后的预测价值及与不良预后发生的关系。结果:中度组、重度组PHT、CRP水平均高于轻度组,且重度组PHT、CRP水平高于中度组,差异有统计学意义(P<0.05)。外周血PTH、CRP水平与缺血性脑卒中患者梗死面积呈正相关(P<0.05)。预后不良组外周血PTH、CRP水平高于预后较好组,差异有统计学意义(P<0.05)。外周血PTH、CRP水平联合检测预测患者预后的曲线下面积(AUC)大于PTH、CRP单独检测,差异有统计学意义(P<0.05)。PTH≥12.82 ng/L、CRP≥8.16 mg/L是导致缺血性脑卒中患者出现不良预后的影响因素(P<0.05)。结论:缺血性脑卒中患者外周血PTH、CRP水平与梗死面积相关,且两者联合检测对患者预后具有评估价值。

术中及围手术期血清iPTH监测对501例继发性甲状旁腺功能亢进患者手术效果的精准诊断研究——“Diagnostic Accuracy Study of Intraoperative and Perioperative Serum Intact PTH Level for Successful Parathyroidectomy in 501 Secondary Hyperparathyroidism Patients”的二

目的甲状旁腺切除术(parathyroidectomy,PTX)是继发性甲状旁腺功能亢进患者(secondary hyperparathyroidism,SHPT)的有效治疗方式,然而由于甲状旁腺位置和数目异常的存在,部分患者术后SHPT仍持续存在。本研究探讨PTX患者术中及围手术期血清全段甲状旁腺激素(intact parathyroid hormone,iPTH)监测对手术效果精准诊断的意义。方法记录501例行甲状旁腺全切+自体前臂移植术(不伴胸腺切除)的慢性肾脏病患者的术中及围手术期血清iPTH值。术后一周内患者血清iPTH≤50 pg/ml为手术成功;若>50 pg/ml则在6月内进行随访,随访血清iPTH<300 pg/mL即为手术成功,否则为SHPT持续存在。结果 433例(86.4%)患者手术成功,49例(9.8%)患者SHPT持续存在,19例(3.8%)患者缺乏有效随访归为手术效果未知组。肝炎(n=204)与非肝炎(n=297)患者比较,基线血清iPTH水平及术中血清iPTH下降百分比无显著统计学差异(P>0.05)。受试者工作特征(receiver operating characteristic,ROC)曲线结果表明术后20分钟血清iPTH下降≥88.9%提示手术成功(曲线下面积0.909,敏感度78.6%,特异度88.5%)。术后4天血清iPTH≥147.4 pg/ml提示SHPT持续存在(曲线下面积0.998,敏感度100%,特异度99.5%)。结论甲状旁腺切除术中血清iPTH监测能提示甲状旁腺切除是否彻底,避免对患者不必要的探查,降低手术并发症的发生率。围手术期血清iPTH监测提示SHPT是否持续存在,对此类患者需密切随访、及时开始药物治疗或必要时再次手术。

血液灌流联合血液透析对尿毒症皮肤瘙痒临床疗效、β_(2)-MG及PTH的影响

目的 分析血液灌流联合血液透析对尿毒症皮肤瘙痒临床疗效、β_(2)-微球蛋白(β_(2)-MG)及甲状旁腺激素(PTH)的影响。方法 选取2021年12月—2022年10月收治的尿毒症皮肤瘙痒201例,根据治疗方案不同分为对照组98例和研究组103例。对照组采用血液透析治疗,研究组采用血液灌流联合血液透析治疗。比较2组临床疗效、炎性因子[白细胞介素-1(IL-1)、IL-6、降钙素原(PCT)]、肾功能指标[血尿素(BUN)、血清肌酐(Scr)、β_(2)-MG]、钙磷代谢指标[血清磷、钙、PTH]及复发率。结果 研究组总有效率为91.26%(94/103)高于对照组的79.59%(78/98)(P<0.05)。治疗后,2组IL-1、IL-6、PCT、BUN、Scr、β_(2)-MG、PTH及血清磷水平均较治疗前下降,且研究组低于对照组(P<0.05)。治疗后,2组血清钙水平较治疗前上升,且研究组高于对照组(P<0.05)。研究组复发率为5.83%(6/103)低于对照组的43.88%(43/98)(P<0.05)。结论 血液灌流联合血液透析治疗尿毒症皮肤瘙痒的效果显著,可改善炎症状态,降低PTH、β_(2)-MG水平,有效清除患者体内大中分子代谢物质。

Comparison between recombinant human parathyroid hormone(1-34) and elcatonin in treatment of primary osteoporosis

Objective:To evaluate the efficacy and safety of rhPTH(1-34) vs.elcatonin.Methods:Sixty palients with primary OP were randomly divided into two groups according to the ratio of 3:1.rhPTH(1-34) group(PTH group) was treated with subcutaneous injection of rhPTH(1-34) 20 μg daily for 18 months,and the elcalonin group(CT group) was treated with intramuscular injection of elcatonin 20 U weekly for 12 months.Bone mineral density(BMD) of the lumbar spine 2-4(L_(2-4))and femoral neck,serum calcium and phosphorus,urinary calcium,serum hone specific alkaline phosphatase(BSAP).and urinary c-terminal telopeptides of type Ⅰ collagen/creatinine(uCTX-Ⅰ /Cn were tested at baseline,and 6.12.and 18 months after treatment.Results:In PTH group.HMD of L_(2-4),at 6,12.and 18 months,BDM of Femoral neck at 18 month,BSAP at 6 and 12 months and uCTX- Ⅰ /Cr at 6.12 and 18 months were all significantly raised.In CT group.HMD of L_(2-4) at12 month and that of femoral neck at 12 and 18 months were significantly elevated,while HSAP was significantly decreased at 12 and 18 months,and no significant difference on CTX- Ⅰ /Cr was observed.When BMD growth and growth rate between two groups were compared.PTH group had better improvement in L_(2-4) BMD and growth rate than CT group at 6.12.and 18 months.BMD growth and growth rale of femoral neck al 12 month and its growth at 18 month in CT group were higher than in PTH group,hut there was no significant difference between two groups regarding the growth rates at 18 month.Besides,there were no significant differences regarding the rales ol adverse reactions between two groups.Conclusions:rhPTH(1—34),is safe and effective in the treatment of primary OP.It is superior to elcatonin in improving vertebral HMD at onset time,growth rate and growth range,but inferior to elcatonin at HMD of femoral neck.

Osteoporotic fracture and parathyroid hormone

Osteoporosis and age-related bone loss is associated with changes in bone remodeling characterized by decreased bone formation relative to bone resorption,resulting in bone fragility and increased risk of fractures.Stimulating the function of bone-forming osteoblasts,is the preferred pharmacological intervention for osteoporosis.Recombinant parathyroid hormone(PTH),PTH(1-34),is an anabolic agent with proven benefits to bone strength and has been characterized as a potential therapy for skeletal repair.In spite of PTH’s clinical use,safety is a major consideration for long-term treatment.Studies have demonstrated that intermittent PTH treatment enhances and accelerates the skeletal repair process via a number of mechanisms.Recent research into the molecular mechanism of PTH action on bone tissue has led to the development of PTH analogs to control osteoporotic fractures.This review summarizes a number of advances made in the field of PTH and bone fracture to combat these injuries in humans and in animal models.The ultimate goal of providing an alternative to PTH,currently the sole anabolic therapy in clinical use,to promote bone formation and improve bone strength in the aging population is yet to be achieved.

Impact of parathyroid hormone on bone marrow-derived stem cell mobilization and migration

Parathyroid hormone(PTH) is well-known as the principal regulator of calcium homeostasis in the human body and controls bone metabolism via actions on the survival and activation of osteoblasts. The intermittent administration of PTH has been shown to stimulate bone production in mice and men and therefore PTH administration has been recently approved for the treatment of osteoporosis. Besides to its physiological role in bone remodelling PTH has been demonstrated to influence and expand the bone marrow stem cell niche where hematopoietic stem cells, capable of both self-renewal and differentiation, reside. Moreover, intermittent PTH treatment is capable to induce mobilization of progenitor cells from the bone marrow into the bloodstream. This novel function of PTH on modulating the activity of the stem cell niche in the bone marrow as well as on mobilization and regeneration of bone marrow-derived stem cells offers new therapeutic options in bone marrow and stem cell transplantation as well as in the field of ischemic disorders.

Hypoxia-inducible factor-1a restricts the anabolic actions of parathyroid hormone

The hypoxia inducible factors （Hifs） are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1a in osteoanabolic signaling, we assessed the effect of Hif-1a loss-of-function on bone formation in response to intermittent parathyroid hormone （PTH）. Mice lacking Hif-1a in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. Consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1a protein levels via a post-transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1a-mediated suppression of β-catenin transcriptional activity. Together, these data indicate that Hif-1a functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1a function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH.

Effect of parathyroid hormone on apoptosis of human medullary thyroid carcinoma cells

Objective The aim of the study was to investigate the effect of parathyroid hormone(PTH) on the apoptosis of human medullary thyroid carcinoma(MTC) cells.Methods In vitro cultured medullary thyroid carcinoma cell lines were treated with parathyroid hormone and parathyroid hormone receptor-monoclonal antibody,and the apoptosis of cells was detected by flow cytometry.Results The cell morphology changed significantly after treatment based on the observation using the inverted phase-contrast microscope.Various concentrations of parathyroid hormone and parathyroid hormone receptor-monoclonal antibody effectively induced apoptosis in a time-and concentrationdependent manner.When the concentration of parathyroid hormone was 2.0 μmol/L and that of parathyroid hormone receptor-monoclonal antibody was 1.0 μmol/L,the apoptotic rate was 13.24% and 20.78%,respectively,representing a statistically significant difference from that of the control cells(P < 0.05).Conclusion PTH plays a role in inducing apoptosis of human MTC cells.

Development and validation of RP-HPLC and RP-UPLC methods for quantification of parathyroid hormones (1-34) in medicinal product formulated with meta-cresol

Rapid and sensitive reversed phase high performance liquid chromatography (RP-HPLC) and ultra performance liquid chromatography (RP-UPLC) method with UV detection has been developed and validated for quantification of parathyroid hormone (PTH) in presence of meta-cresol as a stabilizer in a pharmaceutical formulation.Chromatography was performed with mobile phase containing 0.1% Trifluoroacetic acid (TFA) in MilliQ water and 0.1% TFA in acetonitrile with gradient program and flow rate at 0.3 mL/min for HPLC and 0.4 mL/min for UPLC.Quantification was accomplished with internal reference standard (qualified against innovator product and National Institute for Biological Standards and Control (NIBSC) standard).The methods were validated for linearity (correlation coefficient 0.99),range,accuracy,precision and robustness.Robustness was confirmed by considering three factors;mobile phase composition,column temperature and flow rate/age of mobile phase.Intermediate precision was confirmed on different equipments,different columns and on different days.The relative standard deviation (RSD) (<2% for RP-HPLC and <1% for UPLC,n=30) indicated a good precision.Retention time was found about 17 min and 2 min by HPLC and UPLC methods,respectively.Both methods are simple,highly sensitive,precise and accurate and have the potential of being useful for routine quality control.

Parathyroid hormone pulsatility: physiological and clinical aspects

Parathyroid hormone （PTH） secretion is characterized by an ultradian rhythm with tonic and pulsatile components. In healthy subjects, the majority of PTH is secreted in tonic fashion, whereas approximately 30% is secreted in low-amplitude and high-frequency bursts occurring every 10-20 min, superimposed on tonic secretion. Changes in the ultradian PTH secretion were shown to occur in patients with primary and secondary osteoporosis, with skeletal effects depending on the reciprocal modifications of pulsatile and tonic components. Indeed, pathophysiology of spontaneous PTH secretion remains an area potentially suitable to be explored, particularly in those conditions such as secondary forms of osteoporosis, in which conventional biochemical and densitometric parameters may not always give reliable diagnostic and therapeutic indications. This review will highlight the literature data supporting the hypothesis that changes of ultradian PTH secretion may be correlated with skeletal fragility in primary and secondary osteoporosis.