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Jornal Brasileiro de Nefrologia 2021
Topics: Bone Diseases; Humans; Parathyroid Hormone
PubMed: 34910800
DOI: 10.1590/2175-8239-JBN-2021-S108 -
Clinical Chemistry and Laboratory... Apr 2023Parathyroid hormone (PTH) determination is of paramount importance for the exploration of diseases related with calcium metabolism and for the follow-up of patients... (Review)
Review
Parathyroid hormone (PTH) determination is of paramount importance for the exploration of diseases related with calcium metabolism and for the follow-up of patients suffering from bone and mineral disorders associated with chronic kidney diseases (CKD-MBD). Unfortunately, the biologically active form of PTH, i.e. 1-84 PTH, circulates in the blood stream with many fragments and post-translationally modified forms, which decreases the specificity of immunoassays. The assays used to measure PTH, either from 2nd or 3rd generation, are not standardised, which may lead to interpretation errors and clinical consequences. Reference ranges for PTH have neither been always correctly established and the stability of the peptide is also a matter of concern. Fortunately, these last years, newer techniques using mass spectrometry (either high resolution or triple quadripole) coupled with liquid chromatography have been developed, which will help to standardise the different assays. Indeed, PTH assays standardisation is one of the task of the IFCC Committee for Bone Metabolism. Such standardisation will allow a better consistency in the interpretation of the results and will promote studies aiming at the establishment of correct reference ranges.
Topics: Humans; Parathyroid Hormone; Radioimmunoassay; Peptides; Chromatography, Liquid; Mass Spectrometry
PubMed: 36640443
DOI: 10.1515/cclm-2022-0942 -
Frontiers in Endocrinology 2024Magnesium (Mg), a nutritional element which is essential for bone development and mineralization, has a role in the progression of osteoporosis. Osteoporosis is a... (Review)
Review
Magnesium (Mg), a nutritional element which is essential for bone development and mineralization, has a role in the progression of osteoporosis. Osteoporosis is a multifactorial disease characterized by significant deterioration of bone microstructure and bone loss. Mg deficiency can affect bone structure in an indirect way through the two main regulators of calcium homeostasis (parathyroid hormone and vitamin D). In human osteoblasts (OBs), parathyroid hormone regulates the expression of receptor activator of nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) to affect osteoclast (OC) formation. In addition, Mg may also affect the vitamin D3 -mediated bone remodeling activity. vitamin D3 usually coordinates the activation of the OB and OC. The unbalanced activation OC leads to bone resorption. The RANK/RANKL/OPG axis is considered to be a key factor in the molecular mechanism of osteoporosis. Mg participates in the pathogenesis of osteoporosis by affecting the regulation of parathyroid hormone and vitamin D levels to affect the RANK/RANKL/OPG axis. Different factors affecting the axis and enhancing OC function led to bone loss and bone tissue microstructure damage, which leads to the occurrence of osteoporosis. Clinical research has shown that Mg supplementation can alleviate the symptoms of osteoporosis to some extent.
Topics: Humans; Osteoporosis; Magnesium; Animals; Parathyroid Hormone; RANK Ligand; Osteoblasts; Bone Remodeling; Vitamin D; Magnesium Deficiency; Osteoclasts; Osteoprotegerin
PubMed: 38904051
DOI: 10.3389/fendo.2024.1406248 -
Pflugers Archiv : European Journal of... Mar 2022Fibroblast growth factor 23 (FGF23) is an important bone hormone that regulates phosphate homeostasis in the kidney along with active vitamin D (1,25(OH)D) and... (Review)
Review
Fibroblast growth factor 23 (FGF23) is an important bone hormone that regulates phosphate homeostasis in the kidney along with active vitamin D (1,25(OH)D) and parathyroid hormone (PTH). Endocrine effects of FGF23 depend, at least in part, on αKlotho functioning as a co-receptor whereas further paracrine effects in other tissues are αKlotho-independent. Regulation of FGF23 production is complex under both, physiological and pathophysiological conditions. Physiological regulators of FGF23 include, but are not limited to, 1,25(OH)D, PTH, dietary phosphorus intake, and further intracellular and extracellular factors, kinases, cytokines, and hormones. Moreover, several acute and chronic diseases including chronic kidney disease (CKD) or further cardiovascular disorders are characterized by early rises in the plasma FGF23 level pointing to further mechanisms effective in the regulation of FGF23 under pathophysiological conditions. Therefore, FGF23 also serves as a prognostic marker in several diseases. Our review aims to comprehensively summarize the regulation of FGF23 in health and disease.
Topics: Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucuronidase; Humans; Kidney; Parathyroid Hormone; Phosphates; Renal Insufficiency, Chronic
PubMed: 35084563
DOI: 10.1007/s00424-022-02668-w -
Journal of Neuroendocrinology Sep 2022Tuberoinfundibular peptide of 39 residues (TIP39) acts via its endogenous class B G-protein coupled receptorthe parathyroid hormone 2 receptor (PTH2R). Hence, it is also... (Review)
Review
Tuberoinfundibular peptide of 39 residues (TIP39) acts via its endogenous class B G-protein coupled receptorthe parathyroid hormone 2 receptor (PTH2R). Hence, it is also known as parathyroid hormone 2. The peptide is expressed in the brain by a small number of neurons with a highly restricted distribution, which in turn project to a large number of brain regions that contain PTH2R. This peptide neuromodulator system has been extensively investigated over the past 20 years including its behavioural actions, such as its role in the control of nociception, fear and fear incubation, anxiety and depression-like behaviours, and maternal and social behaviours. It also influences thermoregulation and potentially auditory responses. TIP39 probably exerts direct effect on the neuronal networks controlling these behaviours based on the localization of PTH2R and local TIP39 actions. In addition, TIP39 also affects the secretion of several hypothalamic hormones providing the basis for indirect behavioural actions. Recently developed experimental tools have stimulated further behavioural investigations, and novel results obtained are discussed in this review.
Topics: Neuropeptides; Neurotransmitter Agents; Parathyroid Hormone; Receptor, Parathyroid Hormone, Type 2
PubMed: 35499975
DOI: 10.1111/jne.13130 -
Clinical and Experimental Nephrology May 2023Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease-mineral and bone disorder... (Review)
Review
Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease-mineral and bone disorder (CKD-MBD). Both hormones increase as kidney function declines, presumably as a response to maintain normal phosphate balance, but when patients reach kidney failure, PTH and FGF23 fail to exert their phosphaturic effects, leading to hyperphosphatemia and further elevations in PTH and FGF23. In patients with kidney failure, the major target organ for PTH is the bone, but elevated PTH is also associated with mortality presumably through skeletal and nonskeletal mechanisms. Indeed, accumulated evidence suggests improved survival with PTH-lowering therapies, and a more recent study comparing parathyroidectomy and calcimimetic treatment further suggests a notion of "the lower, the better" for PTH control. Emerging data suggest that the link between SHPT and mortality could in part be explained by the action of PTH to induce adipose tissue browning and wasting. In the absence of a functioning kidney, the classical target organ for FGF23 is the parathyroid gland, but FGF23 loses its hormonal effect to suppress PTH secretion owing to the depressed expression of parathyroid Klotho. In this setting, experimental data suggest that FGF23 exerts adverse nontarget effects, but it remains to be confirmed whether FGF23 directly contributes to multiple organ injury in patients with kidney failure and whether targeting FGF23 can improve patient outcomes. Further efforts should be made to determine whether intensive control of SHPT improves clinical outcomes and whether nephrologists should aim at controlling FGF23 levels just as with PTH levels.
Topics: Humans; Bone and Bones; Fibroblast Growth Factors; Parathyroid Glands; Parathyroid Hormone; Renal Insufficiency
PubMed: 36977891
DOI: 10.1007/s10157-023-02336-y -
Physiological Research Nov 2021Parathyroid hormone (PTH) increases the release of serum calcium through osteoclasts, which leads to bone resorption. Primary, PTH stimulates osteoblasts leading to...
Parathyroid hormone (PTH) increases the release of serum calcium through osteoclasts, which leads to bone resorption. Primary, PTH stimulates osteoblasts leading to increase RANKL (receptor activator for nuclear factor kappa-B ligand) expression and thus differentiation of osteoclasts. In kidneys, PTH increases calcium and decrease phosphate reabsorption. In kidneys, PTH stimulates 1alpha-hydroxylase to synthesize active vitamin D. Primary hyperparathyroidism (PHPT) is characterized by skeletal or renal complications. Nowadays, the classical form of PHPT is less seen and asymptomatic or subclinical (oligo symptomatic) forms are more frequent. Previously, it was thought that cortical bone is preferably affected by PHPT and that predispose bones to fracture at sites with a higher amount of cortical bone. However, an increased risk of vertebral fractures has been found by most of the studies showing that also trabecular bone is affected. Bone Mass measurement (BMD) at all skeletal sites is advised, but another specific tool for fracture assessment is needed. Trabecular bone score (TBS), an indirect measure of trabecular bone, maybe a useful method to estimate fracture risk. TBS is associated with vertebral fractures in PHPT regardless of BMD, age, BMI and gender. Furthermore, there is an association between TBS and high resolution peripheral quantitative computed tomography (HR-pQCT) parameters in the trabecular and cortical compartment. However, studies considering the effect of PHPT treatment on TBS are more conflicting. Secondary hyperparathyroidism caused by vitamin D deficiency was associated with impaired bone microarchitecture in all age categories, as measured by TBS and Hr-pQCT with further improvement after treatment with vitamin D.
Topics: Absorptiometry, Photon; Bone Density; Bone and Bones; Calcium; Parathyroid Hormone; Vitamin D
PubMed: 35503045
DOI: No ID Found -
International Journal of Molecular... Aug 2022Vitamin D belongs to the group of liposoluble steroids mainly involved in bone metabolism by modulating calcium and phosphorus absorption or reabsorption at various... (Review)
Review
Vitamin D belongs to the group of liposoluble steroids mainly involved in bone metabolism by modulating calcium and phosphorus absorption or reabsorption at various levels, as well as parathyroid hormone production. Recent evidence has shown the extra-bone effects of vitamin D, including glucose homeostasis, cardiovascular protection, and anti-inflammatory and antiproliferative effects. This narrative review provides an overall view of vitamin D's role in different settings, with a special focus on chronic kidney disease and kidney transplant.
Topics: Calcium; Humans; Kidney; Parathyroid Hormone; Phosphorus; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 36012412
DOI: 10.3390/ijms23169135 -
Experimental Biology and Medicine... Nov 2022Delivering the parathyroid hormone (PTH) gene has been attempted preclinically in a handful of studies, but delivering full-length PTH (1-84) using adeno-associated...
Delivering the parathyroid hormone (PTH) gene has been attempted preclinically in a handful of studies, but delivering full-length PTH (1-84) using adeno-associated viral (AAV) vectors has not. Given the difficulty in achieving therapeutic levels of secreted proteins using gene therapy, this study seeks to determine the feasibility of doing so with PTH. An AAV vector was used to deliver human PTH driven by a strong promoter. We demonstrate the ability to secrete full-length PTH from various cell types . PTH secretion from hepatocytes was measured over time and a fluorescent marker was used to compare the secretion rate of PTH in various cell types. Potency was measured by the ability of PTH to act on the PTH receptors of osteosarcoma cells and induced proliferation. PTH showed potency by inducing proliferation in two osteosarcoma cell lines. , AAV was administered systemically in immunocompromised mice which received xenografts of osteosarcoma cells. Animals that received the highest dose of AAV-PTH had higher liver and plasma concentrations of PTH. All dosing groups achieved measurable plasma concentrations of human PTH that were above the normal range. The high-dose group also had significantly larger tumors compared to control groups on the final day of the study. The tumors also showed dose-dependent differences in morphology. When looking at endocrine signaling and endogenous bone turnover, we observed a significant difference in tibial growth plate width in animals that received the high-dose AAV as well as dose-dependent changes in blood biomarkers related to PTH. This proof-of-concept study shows promise for further exploration of an AAV gene therapy to deliver full-length PTH for hypoparathyroidism. Additional investigation will determine efficacy in a disease model, but data shown establish bioactivity in well-established models of osteosarcoma.
Topics: Humans; Animals; Mice; Parathyroid Hormone
PubMed: 35666091
DOI: 10.1177/15353702221097087 -
Endocrinology and Metabolism (Seoul,... Dec 2019Intraoperative parathyroid hormone monitoring (IPM) has been shown to be a useful adjunct during parathyroidectomy to ensure operative success at many specialized... (Review)
Review
Intraoperative parathyroid hormone monitoring (IPM) has been shown to be a useful adjunct during parathyroidectomy to ensure operative success at many specialized medical centers worldwide. Using the Miami or ">50% intraoperative PTH drop" criterion, IPM confirms the complete excision of all hyperfunctioning parathyroid tissue before the operation is finished, and helps guide the surgeon to identify additional hyperfunctioning parathyroid glands that may necessitate further extensive neck exploration when intraoperative parathyroid hormone (PTH) levels do not drop sufficiently. The intraoperative PTH assay is also used to differentiate parathyroid from non-parathyroid tissues during operations using fine needle aspiration samples and to lateralize the side of the neck harboring the hypersecreting parathyroid through differential jugular venous sampling when preoperative localization studies are negative or equivocal. The use of IPM underscores the recognition and understanding of sporadic primary hyperparathyroidism (SPHPT) as a disease of function rather than form, where the surgeon is better equipped to treat such patients with quantitative instead of qualitative information for durable long-term operative success. There has been a significant paradigm shift over the last 2 decades from conventional to focused parathyroidectomy guided by IPM. This approach has proven to be a safe and rapid operation requiring minimal dissection performed in an ambulatory setting for the treatment of SPHPT.
Topics: Humans; Hyperparathyroidism, Primary; Monitoring, Intraoperative; Parathyroid Hormone; Parathyroidectomy; Point-of-Care Systems
PubMed: 31884732
DOI: 10.3803/EnM.2019.34.4.327