单次不同血液净化方式对慢性肾脏病-矿物质和骨异常患者钙磷及甲状旁腺素的影响

目的观察单次不同血液净化方式对慢性肾脏病-矿物质和骨异常患者血钙(Ca)、血磷(P)、甲状旁腺素(parathyroid hormone,PTH)的影响,为临床治疗提供依据。方法选择石河子大学医学院第一附属医院维持性血液透析并继发性甲状旁腺功能亢进(secondary hyperparathyroidism,SHPT)患者60例,随机分为低通量血液透析(hemodialysis,HD)组、血液透析滤过(hernodiafiltration,HDF)组、高通量血液透析(high--flux hemodialysis,HFHD)组,每组20例,采用血生化自动分析仪检测各组治疗前后血钙、血磷的水平,采用化学发光仪检测各组治疗前后PTH的水平,比较其治疗前、后的变化。结果单次HD、HDF、HFHD治疗后与治疗前相比,血钙水平均上升(P0.05),血磷水平均明显下降(P0.05),PTH水平无明显变化(P0.05),比较3组治疗前、后血钙、血磷变化程度无明显差异(P0.05)。结论单次HD、HDF、HFHD治疗均可达到降低血磷、升高血钙的效果,且效果无差异,但均不能有效清除PTH。因此,3种血液净化方式在纠正钙磷代谢紊乱方面效果相同,可依据各医院及患者具体情况开展。     

磷酸盐对PTH分泌和合成的直接调节作用及其机制

甲状旁腺激素(PTH)的分泌和合成受多种因素(如钙、磷酸盐和Vitamin D等)的调节.过去认为,磷酸盐是通过降低血钙和抑制1,25(OH)2D3的合成而间接影响PTH的分泌和合成.近年认为,除上述作用外,更重要的是磷酸盐可直接调节PTH的分泌和合成.磷酸盐对PTH调节作用位于PTH基因表达的转录后水平,并可能是通过蛋白质-RNA与PTH mRNA的3'-非翻译区的结合及甲状旁腺胞浆蛋白对PTH mRNA的降解机制完成的.     

磷酸盐对PTH分泌和合成的直接调节作用及其机制

甲状旁腺激素(PTH)的分泌和合成受多种因素(如钙、磷酸盐和Vitamin D等)的调节.过去认为,磷酸盐是通过降低血钙和抑制1,25(OH)2D3的合成而间接影响PTH的分泌和合成.近年认为,除上述作用外,更重要的是磷酸盐可直接调节PTH的分泌和合成.磷酸盐对PTH调节作用位于PTH基因表达的转录后水平,并可能是通过蛋白质-RNA与PTH mRNA的3'-非翻译区的结合及甲状旁腺胞浆蛋白对PTH mRNA的降解机制完成的.     

原发性甲状旁腺功能亢进症围手术期处理中国专家共识（2020版）

正甲状旁腺是人体重要的内分泌腺体之一,其分泌的甲状旁腺激素(parathyroid hormone,PTH)可直接或间接作用于骨、肾和小肠等组织器官,调节和维持血钙水平。甲状旁腺功能亢进症(hyperparathyroidism,HPT),简称甲状旁腺功能亢进,是由于甲状旁腺激素主动或被动分泌过多而导致的钙磷及骨代谢紊乱,从而引起的一组特殊临床综合     

甲状腺癌术后再发甲状旁腺癌1例诊治分析并文献复习

目的探讨甲状旁腺癌的临床诊疗经验。方法回顾性分析笔者所在医院收治的1例甲状腺癌术后再发甲状旁腺癌病例的临床资料和诊疗经过,并进行文献复习。结果患者第1次因甲状腺癌行手术治疗,术前甲状旁腺素(PTH)及血钙水平轻度升高,但未见甲状旁腺肿瘤,术后PTH及血钙降至正常水平。患者第2次以颈部肿物、甲状旁腺功能亢进症、高钙血症入院行手术治疗后,PTH及血钙再次降至正常水平,石蜡切片病理标本经专家会诊明确甲状旁腺癌的诊断。第2次术后1年患者的甲状旁腺癌复发,行微创消融治疗,术后PTH及血钙有所下降,但未达理想范围,现仍在随访中。结论甲状腺癌并发甲状旁腺癌临床罕见,其术前诊断困难,根据术后石蜡病理检查及免疫组化检查可以确诊。手术是其最有效的治疗方法,术后局部复发率较高,故术后应长期监测血钙和血PTH水平,尽早发现肿瘤复发或转移情况,尽早治疗,以求提高生存率和延长无瘤生存期。     

骨化三醇治疗对血液透析患者矿物质、骨代谢紊乱及FGF23的影响

目的:评价骨化三醇不同给药方案对血液透析患者矿物质及骨代谢紊乱(CKD-MBD)及FGF23的影响。方法:选取血甲状旁腺素(PTH)水平在300~621 pg/ml(正常的4~9倍)之间的血液透析患者,随机分成骨化三醇常规治疗组(常规组,22例)和间歇给药组(间歇组,26例),疗程16周,检测治疗前后血清FGF-23水平、钙磷代谢等指标变化。结果:(1)两组患者治疗终点与治疗前比较,血PTH均明显下降、血维生素D及FGF23均明显升高(P0.05)。间歇组在治疗终点,血钙明显升高、碱性磷酸酶明显下降(P0.05),而持续组,治疗前后血钙、碱性磷酸酶无明显变化。(2)在不同治疗时间点,持续组PTH明显下降(P0.05);间歇组PTH、碱性磷酸酶明显下降,血钙明显升高(P0.05)。治疗第4周、第8周,间歇组PTH下降较持续组明显(P0.05)。(3)治疗期间,持续组有6例患者血磷升高,间歇组无血磷升高患者。治疗期间无高钙血症发生。结论:骨化三醇不同给药方案能不同程度下降患者血PTH、升高FGF23,间歇组较持续组明显;间歇给药组血钙明显升高、碱性磷酸酶明显下降。两组治疗方案均能改善继发性甲状旁腺功能亢进,间歇给药组降PTH效果更佳。骨化三醇治疗轻中度继发性甲状旁腺功能亢进安全有效。     

原发性甲状旁腺功能亢进性骨质疏松症的中医病机及防治思路

原发性甲状旁腺功能亢进症是引起骨质疏松症的较常见病因,原发性甲状旁腺功能亢进症是由一个或多个甲状旁腺病理性(肿瘤或增生)过量分泌甲状旁腺激素所造成.随着血钙测定和甲状旁腺素测定在临床上的广泛运用,甲状旁腺功能亢进性骨质疏松的患病率也随之上升,目前我国原发性甲状旁腺功能亢进症多为骨型和肾型.治疗方面,主要以手术治疗和药物...     

药物促进骨形成——骨质疏松症治疗新举措

骨质疏松症是人体骨吸收与骨形成不平衡的结果,抑制骨吸收和促进骨形成均可治疗骨质疏松。特立帕肽是全长甲状旁腺素(PTH)的N末端第1~34个氨基酸片断,其重组形式复泰奥是迄今唯一被美国食品药品监督管理局(FDA)批准用于治疗骨质疏松症的促骨形成药物。众多随机对照试验显示,特立帕肽能升高血清骨形成标志物,增加骨密度,降低骨质疏松性骨折发生风险,其抑制骨吸收的效果优于双膦酸盐。美国推荐特立帕肽治疗高骨折风险的骨质疏松,加拿大则推荐特立帕肽为治疗严重骨质疏松的一线药物。     

甲状旁腺素促成骨作用的研究进展

甲状旁腺素(Parathyroid hormone,PTH)能够调节骨骼的合成代谢和分解代谢过程,通过影响包括成骨细胞、破骨细胞、骨骼内衬细胞、骨细胞等众多种类的细胞系,并激活多种信号途径,从而达到促进骨形成的作用.这取决于低剂量及间断性的给药方式.大量动物试验和临床研究,显示甲状旁腺素可有效的治疗骨质疏松.近年来动物实验发现甲状旁腺素也可有效的促进骨折愈合.甲状旁腺素作为骨形成促进剂,将广泛应用于临床治疗.     

重组人甲状旁腺素促骨合成研究进展

人甲状旁腺素(hPTH)的主要生理功能是调节钙磷代谢、促进维生素D代谢、激活骨细胞,是调节钙、磷代谢及骨转换的重要肽类激素之一,能精确调节骨的合成及分解代谢过程.hPTH片段目前已成为重要的骨形成促进剂,与受体结合后通过活化cAMP依赖的蛋白激酶A及钙离子依赖的蛋白激酶C信号传导途径发挥生物学作用.hPTH可使血清磷降低,间接影响骨的生长.大剂量hPTH可同时刺激和抑制骨胶原的合成,促进骨吸收,抑制骨形成;小剂量,特别是hPTH1～34片段可刺激骨胶原合成而促进骨形成.近年随着对成骨细胞与破骨细胞生物学的更深入了解,hPTH对骨的作用,尤其在骨质疏松症治疗上的研究有了很大进展,开发出特立帕肽(teriparatide)等新药用于预防和治疗原发性和继发性骨质疏松症.该文就hPTH的结构、作用机制及其促进骨形成、预防骨质疏松性骨折的研究进展作一综述.     

Skeletal Effects of Primary Hyperparathyroidism: Bone Mineral Density and Fracture Risk

Parathyroid hormone (PTH) is associated with anabolic and catabolic skeletal effects that vary according to the kinetics of serum levels and the type of bone. The anabolic effects are manifested in patients with a periodic rapid transient rise in serum PTH, as seen with daily subcutaneous injection of PTH(1–34) and PTH(1–84) in the treatment of osteoporosis. These patients have an increase in bone mineral density (BMD), particularly at skeletal sites with a high trabecular component, such as the lumbar spine, and a reduction in fracture risk. The catabolic effects are typified in patients with primary hyperparathyroidism (PHPT) who have chronic persistently elevated PTH levels. Patients with long-standing PHPT have a reduction in BMD, particularly at predominately cortical skeletal sites, such as the one-third radius, with relative preservation of BMD at the lumbar spine. Some but not all studies have reported an increase in fracture risk with PHPT. Because many patients with PHPT are postmenopausal women at risk for osteoporosis owing to estrogen deficiency, BMD and fracture risk may be a result of multiple factors with variable effects on bone remodeling. The skeletal effects of normocalcemic PHPT have not yet been fully characterized, but may not be the same as hypercalcemic PHPT.     

Present and future scope of recombinant parathyroid hormone therapy in orthopaedics

Parathyroid Hormone (PTH) has a significant role in calcium metabolism. Its intermittent administration has an anabolic effect on bone mineralization. Teriparatide (PTH 1-34), a recombinant form of parathyroid hormone, is useful in the treatment of osteoporosis, fracture healing, non-union, stress fracture, augmentation of implant fixation with bone, and chondroprotection in osteoarthritis. The present review article will elaborate on the potential approved uses of recombinant PTH in orthopedics and its evolving role in the management of fracture osteosynthesis and other common challenging bone pathologies.     

Parathyroid Hormone and Bone Healing

Fracture healing is a complex process, and a significant number of fractures are complicated by impaired healing and non-union. Impaired healing is prevalent in certain risk groups, such as the elderly, osteoporotics, people with malnutrition, and women after menopause. Currently, no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial in the treatment of fractures and could thus be a potentially new treatment option for induction of fracture healing in humans. Furthermore, fractures in animals with experimental conditions of impaired healing such as aging, estrogen withdrawal, and malnutrition can heal in an expedited manner after PTH treatment. Interestingly, fractures occurring at both cancellous and cortical sites can be treated successfully, indicating that both osteoporotic and nonosteoporotic fractures can be the target of PTH-induced healing. Finally, the data suggest that PTH partly prevents the delay in fracture healing caused by aging. Recently, the first randomized, controlled clinical trial investigating the effect of PTH on fracture healing was published, indicating a possible clinical benefit of PTH treatment in inducing fracture healing. The aim of this article is therefore to review the evidence for the potential of PTH in bone healing, including the underlying mechanisms for this, and to provide recommendations for the clinical testing and use of PTH in the treatment of impaired fracture healing in humans.     

Harnessing the parathyroids to create stronger bones

PURPOSE OF REVIEW: Parathyroid hormone is anabolic to bone but when secreted in excess it is catabolic. It is important, therefore, to understand the mechanisms that determine the normal circadian rhythm of parathyroid hormone secretion and whether the cellular response to it will be anabolic or catabolic. This may lead to new strategies for the treatment of osteoporosis and the low turnover bone disease of some dialysis patients. RECENT FINDINGS: The parathyroid plays a central role in normal mineral and bone homeostasis by acting on its receptor, the PTH/PTHrP receptor (PTH1R). In fact there is more than one receptor - the PTH2 receptor and a putative carboxy-terminal PTH receptor. The latter, in particular, may be particularly relevant to our understanding of the role of parathyroid hormone and its use in pharmacology. Parathyroid hormone in excess destroys bone, as in most patients with chronic renal failure, and when it is lacking this may result in low turnover bone disease. At a more subtle level, patients with postmenopausal osteoporosis may have a blunting of the normal circadian rhythm of parathyroid hormone, with its peak at night and nadir in the morning. Insights as to what determines whether parathyroid hormone will be anabolic or catabolic to bone are reviewed. SUMMARY: Attempting to correct the circadian rhythm in osteoporotic patients by calcilytic drugs or perhaps physiological equivalents may have a role in the future in treating osteoporosis. In the meantime, the administration of recombinant parathyroid hormone is an effective agent in the management of osteoporosis.     

Calcium homeostasis

Precise maintenance of the physiologic levels of both extracellular and intracellular ionized calcium is essential to life. Calcium and phosphate homeostasis is complex, yet three important hormones are responsible for modulating most of the extracellular control of these minerals. Parathyroid hormone acts directly on bone and kidney and indirectly on the intestine to maintain or restore the serum calcium level. The signal for increased PTH synthesis and secretion is a decrease in the serum ionized calcium concentration and a decrease in serum levels of 1,25(OH)2-D. Calcitonin is produced in parafollicular cells of the thyroid and inhibits bone resorption in pharmacologic doses. These cells recognize the calcium signal in a different way. A diminution in serum calcium decreases calcitonin production and release. The role of calcitonin in normal human physiology, however, remains in dispute. Finally, the biologically potent metabolite of vitamin D, 1,25(OH)2-D, stimulates intestinal absorption of calcium and phosphate. It also probably plays a role in the orderly mineralization and resorption of bone and has some influence on renal resorption of filtered calcium and phosphorus. A major stimulus to its production by proximal renal tubule cells is elevated PTH and decreased serum levels of calcium and phosphate. The absence of PTH as well as high serum calcium and phosphate levels can reduce its synthesis and secretion. These three hormones along with other mediators and messengers work in concert to maintain the normal calcium homeostasis. A disturbance at any level in this intricate regulatory network will result in a host of compensatory changes that may lead to clinical disease. A complete understanding of these normal mechanisms is a prerequisite to investigating the etiology and treatment of the various pathologic responses seen with many of the metabolic bone disorders.     

IL-33与绝经后骨质疏松女性骨密度和骨代谢指标相关性研究

目的 探索血清白细胞介素-33(IL-33)与绝经后骨质疏松女性骨密度和骨代谢指标相关性。方法 采用酶联免疫吸附法测定50例绝经后骨质疏松患者和50例正常绝经后妇女血清IL-33水平。采用双能X线骨密度仪(DXA)测量患者和对照组的骨密度(BMD)。检测维生素D、钙、碱性磷酸酶(ALP)、甲状旁腺激素(PTH)水平,以及1型胶原C末端肽(CTX)和1型前胶原N端前肽(P1NP)等骨转换指标。结果 在绝经后骨质疏松症女性中,IL-33水平显著低于健康对照组[(3.53±2.45) pg/mL vs (13.72±5.39) pg/mL,P=0.007];Spearman相关分析表明血清IL-33水平与年龄、BMI、PTH、CTX和P1NP水平呈负相关,与腰椎BMD和股骨颈BMD呈正相关。多元回归分析表明,年龄、BMI、腰椎BMD、PTH、股骨颈BMD和血清CTX和P1NP水平是骨质疏松症患者血清IL-33水平降低的独立预测因子。结论 血清IL-33降低是绝经后骨质疏松患者股骨颈和腰椎骨密度降低和骨转换增速的危险因素。     

甲状旁腺素相关肽治疗绝经后骨质疏松症的研究进展

甲状旁腺素相关肽(parathyroid hormone-related peptide,PTHrP)是人体内存在的一种分泌蛋白,它因与甲状旁素(parathyroid hormone,PTH)在分子结构和信号传导方面有很高的同源性,作为潜在的骨形成促进剂运用于治疗骨质疏松症。PTHrp通过各种信号传导通路调控骨代谢,发挥影响成骨细胞和破骨细胞的作用。并已在动物试验中被证实能有效地促进骨骼合成,改善骨微结构,提高骨量以及增加骨强度。相关药物Abaloparatide的临床研究证实其可显著增加骨密度,改善骨代谢,降低骨折风险,对绝经后骨质疏松有一定的治疗效果。     

Black bear parathyroid hormone has greater anabolic effects on trabecular bone in dystrophin-deficient mice than in wild type mice

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease that has deleterious consequences in muscle and bone, leading to decreased mobility, progressive osteoporosis, and premature death. Patients with DMD experience a higher-than-average fracture rate, particularly in the proximal and distal femur and proximal tibia. The dystrophin-deficient mdx mouse is a model of DMD that demonstrates muscle degeneration and fibrosis and osteoporosis. Parathyroid hormone, an effective anabolic agent for post-menopausal and glucocorticoid-induced osteoporosis, has not been explored for DMD. Black bear parathyroid hormone (bbPTH) has been implicated in the maintenance of bone properties during extended periods of disuse (hibernation). We cloned bbPTH and found 9 amino acid residue differences from human PTH. Apoptosis was mitigated and cAMP was activated by bbPTH in osteoblast cultures. We administered 28nmol/kg of bbPTH 1-84 to 4-week old male mdx and wild type mice via daily (5×/week) subcutaneous injection for 6 weeks. Vehicle-treated mdx mice had 44% lower trabecular bone volume fraction than wild type mice. No changes were found in femoral cortical bone geometry or mechanical properties with bbPTH treatment in wild type mice, and only medio-lateral moment of inertia changed with bbPTH treatment in mdx femurs. However, μCT analyses of the trabecular regions of the distal femur and proximal tibia showed marked increases in bone volume fraction with bbPTH treatment, with a greater anabolic response (7-fold increase) in mdx mice than wild type mice (2-fold increase). Trabecular number increased in mdx long bone, but not wild type bone. Additionally, greater osteoblast area and decreased osteoclast area were observed with bbPTH treatment in mdx mice. The heightened response to PTH in mdx bone compared to wild type suggests a link between dystrophin deficiency, altered calcium signaling, and bone. These findings support further investigation of PTH as an anabolic treatment for DMD-induced osteoporosis.     

Changes in serum levels of type I and III procollagen extension peptides during infusion of human parathyroid hormone fragment (1-34)

Parathyroid hormone (PTH) inhibits collagen synthesis in vitro, in organ or cell culture and cell-free translation systems. We have designed studies to measure the effects of PTH on collagen synthesis in vivo in humans, utilizing measurements of the serum levels of procollagen extension peptides during and after infusion of synthetic human PTH (hPTH) fragment (1-34). Radioimmunoassays for the carboxy-terminal peptide of type I procollagen (pColl-C) and the amino-terminal peptide of type III procollagen (pColl-III-N) were used to measure acute changes in serum during and after hPTH(1-34). In all six osteoporotic subjects and two normal individuals, serum levels of pColl-I-C were decreased by 16 hr of infusion and returned towards normal 14 hr after the infusion was discontinued; serum levels of pColl-III-N did not change significantly during the infusion, but were increased at 14 hr after the infusion was discontinued. The PTH-induced decrease in levels of pColl-I-C correlated with an increase in blood levels of ionized calcium. In all but two subjects the serum levels of 1,25-dihydroxy vitamin D [1,25(OH)2D] were also increased during the period when serum levels of pColl-I-C were decreased. These results are compatible with the conclusion that infusion of PTH acutely inhibits type I (bone) collagen synthesis, but not type III collagen synthesis. These effects could be direct or indirect, related in part to PTH-induced increased 1-alpha-hydroxylation of 25-(OH) vitamin D and the resultant increased serum levels of 1,25(OH)2D.     

Bone and hormones. Effects of parathyroid hormone on the bone

ACTION OF PTH: Parathyroid hormone (PTH) stimulates both bone formation and bone resorption. It also stimulates synthesis of 1,25-dihydroxyvitamin D3 which increases intestinal absorption of calcium and phosphorus and stimulates bone resorption. In bone tissue, PTH acts mainly on osteoblasts which, unlike osteoclasts, carry PTH receptors. PTH also exerts an indirect action on osteoclasts, increasing their number and activity. IMPACT OF INSUFFICIENT PTH: In the absence of PTH, bone remodeling is greatly reduced. Increased bone density has been observed in patients with hypoparathyroidism studied 10 years after total thyroidectomy. IMPACT OF EXCESS PTH: Chronic excess of PTH accelerates bone loss. In primary hyperparathyroidism, reduction of bone density to the order of 10% has been observed, which corresponds to one standard deviation compared with normal subjects of the same age and sex. The hypothesis of an increased risk of fractures remains unresolved. ADMINISTRATION OF PTH: Intermittent rather than continuous subcutaneous administration appears to be necessary to observe the anabolic effects of PTH on bone. The conjunction of favorable anabolic effects demonstrated in animal models, concerning both bone density and mechanical properties, and early studies in humans, provide converging arguments similar to those observed in preclinical investigations, suggest that PTH could be a promising treatment for osteoporosis.