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Anales de Pediatria Aug 2023Pseudohypoparathyroidism (PHP) is a spectrum of diseases characterized by insensitivity of target tissues to the action of parathyroid hormone and, consequently, by the...
Pseudohypoparathyroidism (PHP) is a spectrum of diseases characterized by insensitivity of target tissues to the action of parathyroid hormone and, consequently, by the presence of hyperphosphatemia and hypocalcaemia of varying severity. Early-onset obesity is a feature of PHP type 1A. This article discusses the need to establish uniform criteria to guide the nutritional management of patients with PHP. A decrease in energy expenditure calls for an adjustment of the energy content of the diet. Reducing the intake of foods rich in inorganic phosphorus helps to manage hyperphosphataemia. Targeted nutrition should be part of the treatment plan of children and adolescents with PHP, since it contributes to modulating the calcium and phosphorus metabolism imbalances characteristic of these patients.
Topics: Adolescent; Child; Humans; Pseudohypoparathyroidism; Parathyroid Hormone; Nutritional Status; Phosphorus
PubMed: 37481364
DOI: 10.1016/j.anpede.2023.05.007 -
FASEB Journal : Official Publication of... Aug 2023Little is known about the effect of the recently developed calcimimetic evocalcet (Evo) on parathyroid calcium-sensing receptor (CaSR) and vitamin D receptor (VDR)...
Little is known about the effect of the recently developed calcimimetic evocalcet (Evo) on parathyroid calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) expression. We examined the effects of Evo and cinacalcet (Cina) on CaSR and VDR expression in 5/6 nephrectomized Sprague-Dawley rats fed a high-phosphorus diet for 4 weeks to develop secondary hyperparathyroidism (SHPT). These uremic rats were divided into 4 groups-baseline control (Nx4W) and groups with additional treatment with either the Vehicle, Evo, or Cina for 2 weeks; normal rats were used as normal controls (NC). Blood parameters and parathyroid tissue were analyzed. CaSR and VDR expression levels were determined using immunohistochemistry. The degree of kidney injury and hyperphosphatemia was similar in the uremic groups (Nx4W, Vehicle, Cina, and Evo). Serum parathyroid hormone levels were significantly higher in the Nx4W and Vehicle groups than in the NC group. This increase was significantly suppressed in the Cina and Evo groups compared with that in the Vehicle group. Serum calcium levels were significantly and equally lower in the Cina and Evo groups relative to those in the Vehicle group. CaSR expression was significantly lower in the Nx4W and Vehicle groups than in the NC group. This downregulation was of an equally lesser magnitude in the Cina and Evo groups. A similar trend was observed for VDR expression. These results indicate that Evo and Cina treatment can increase parathyroid CaSR and VDR expression in uremic rats with SHPT, which could provide better control of mineral and bone disorder markers.
Topics: Rats; Animals; Receptors, Calcitriol; Receptors, Calcium-Sensing; Rats, Sprague-Dawley; Parathyroid Glands; Hyperparathyroidism, Secondary; Parathyroid Hormone; Cinacalcet
PubMed: 37462513
DOI: 10.1096/fj.202300209R -
Indian Journal of Pharmacology 2023Vitamin D deficiency (VDD) is highly prevalent across the globe. Cholecalciferol (Vitamin D3) fails to attain sufficient serum concentrations of 25-hydroxyvitamin D... (Clinical Trial)
Clinical Trial
Efficacy, safety, and dose-response effects of calcifediol supplementation on 25-hydroxyvitamin D, parathyroid hormone, and 1,25-dihydroxyvitamin D levels in healthy adults: An open-label, interventional pilot study.
BACKGROUND
Vitamin D deficiency (VDD) is highly prevalent across the globe. Cholecalciferol (Vitamin D3) fails to attain sufficient serum concentrations of 25-hydroxyvitamin D (25(OH)D) in a significant proportion of supplemented individuals. Calcifediol (25-hydroxyvitamin D3) is less studied in healthy adults and its effects on 25(OH)D, parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D (1,25(OH)2D) at higher doses are not well known.
MATERIALS AND METHODS
The study was an open-label, interventional trial recruiting consecutive participants with VDD who were allocated to receive either 2 capsules (50 μg-group) or 1 capsule (25 μg-group) daily doses of calcifediol. Baseline assessment included clinicodemographic parameters, dietary calcium, calcemic (calcium, inorganic phosphate, albumin, alkaline phosphatase, urine spot calcium/creatinine), and hormonal parameters (25(OH)D, PTH, and 1,25(OH)2D). Participants were followed up at 4 and 8 weeks with repeat assessments of calcemic and hormonal parameters.
RESULTS
There were 64 participants, 35 (50 μg-group) and 29 (25 μg-group), without any significant difference in any of the baseline parameters. 97.1% participants in the 50 μg-group (at 4 and 8 weeks) and 93.1% (at 4 weeks) and 96.5% (at 8 weeks) in the 25 μg-group attained 25(OH)D sufficiency (≥30 ng/ml) with calcifediol. The mean serum 25(OH)D was 84.0 ± 27.7 ng/ml in the 50 μg-group and 58.0 ± 23.6 ng/ml in the 25 μg-group group at 4 weeks, which later rose to 94.3 ± 21.8 ng/ml and 76.0 ± 16.4 ng/ml, respectively, at 8 weeks. PTH levels decreased in both groups at both time points. 1,25(OH)2D rose significantly in both groups at 4 and 8 weeks but was not significantly different between both groups. There was no case of incident hypercalcemia or symptomatic nephrolithiasis.
CONCLUSION
Calcifediol is a safe and efficacious alternative for oral Vitamin D supplementation in young adults. Increment in 25(OH)D levels is rapid and dose-dependent.
Topics: Humans; Young Adult; Calcifediol; Calcium; Cholecalciferol; Dietary Supplements; Parathyroid Hormone; Pilot Projects; Vitamin D; Vitamin D Deficiency
PubMed: 37929406
DOI: 10.4103/ijp.ijp_873_22 -
Clinical and Experimental Medicine Aug 2023In comparison to the regulation of calcium homeostasis, which has been widely studied over the last several decades, phosphate homeostasis is little understood. The... (Review)
Review
In comparison to the regulation of calcium homeostasis, which has been widely studied over the last several decades, phosphate homeostasis is little understood. The parathyroid hormone (PTH)/vitamin D axis has traditionally been used as a conceptual framework for understanding mineral metabolism. Recently, the fundamental regulator of phosphate homeostasis, fibroblast growth factor 23 (FGF23), which is produced by osteocytes and is involved in the hormonal bone-parathyroid-kidney axis, has attracted more attention. The secretion of FGF23 is controlled by diet, serum phosphate levels, PTH, and 1,25(OH)2 vitamin D. FGF-23, the FGF receptors and the obligate co-receptor α-Klotho work in concert to affect FGF-23 actions on targeted organs. Despite all efforts to investigate pleotropic effects of FGF23 in various endocrine organs, many aspects of the regulation and functions of FGF23 and the exact crosstalk among FGF23, serum phosphate, calcium, PTH, and vitamin D in the regulation of mineral homeostasis remain unclear; much efforts need to be established before it can be moved toward therapeutic applications. In this regard, we provide a brief overview of the novel findings in the regulation and function of FGF23 and refer to related questions and hypotheses not answered yet, which can be a window for future projects. We also focus on the current knowledge about the role of FGF23 obtained from our researches in recent years.
Topics: Humans; Calcium; Klotho Proteins; Glucuronidase; Phosphates; Fibroblast Growth Factors; Parathyroid Hormone; Vitamin D; Minerals
PubMed: 35708778
DOI: 10.1007/s10238-022-00844-x -
Physiological Research Dec 2023Multiglandular primary hyperparathyroidism (MGD) represents a rare form of primary hyperparathyroidism (PHPT). MGD is associated with hereditary PHPT, but the sporadic... (Review)
Review
Multiglandular primary hyperparathyroidism (MGD) represents a rare form of primary hyperparathyroidism (PHPT). MGD is associated with hereditary PHPT, but the sporadic MGD is more common and affects a similar patient profile as single gland parathyroid disease (SGD). The distinction between SGD and MGD is of great clinical importance, especially for the strategy of parathyroidectomy. Based on the limited knowledge available, MGD is likely to be a genetically heterogeneous disease resulting from the interaction of germline and somatic DNA mutations together with epigenetic alterations. Furthermore, these events may combine and occur independently in parathyroid tumors within the same individual with MGD. Gene expression profiling has shown that SGD and MGD may represent distinct entities in parathyroid tumorigenesis. We are waiting for studies to analyze exactly which genes are different in SGD and MGD in order to identify potential biomarkers that can distinguish between the two forms of the disease.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Hormone; Retrospective Studies; Parathyroid Glands; Molecular Biology
PubMed: 38116772
DOI: 10.33549/physiolres.935253 -
Biological Trace Element Research Feb 2024Cadmium exposure is associated with renal dysfunction and bone damage. Chronic kidney disease and bone loss are also related to parathyroid hormone (PTH). However,...
Cadmium exposure is associated with renal dysfunction and bone damage. Chronic kidney disease and bone loss are also related to parathyroid hormone (PTH). However, whether cadmium exposure affect PTH level is not completely understood. In this study, we observed the association between environmental cadmium exposure and PTH levels in a Chinese population. A ChinaCd study was performed in China in 1990s which included 790 subjects living in heavily, moderately and low cadmium polluted area. 354 of them (121 men and 233 women) also had the data of serum PTH. The cadmium levels in blood (BCd) and urine (UCd) were determined by flame atomic absorption spectrometry. Serum PTH was detected by immunoradiometric assay. Renal function was assessed based on urinary N-acetyl-β-d-glucosaminidase (UNAG), β-microglobulin (UBMG) and urinary albumin (UALB). The median BCd and UCd levels were 4.69 μg/L and 5.50 μg/g creatinine. The BCd, UCd, UNAG, UBMG and UALB levels in subjects with low PTH (< 5.0 ng/L) were significantly higher than those with PTH ≥ 5.0 ng/L (p < 0.05 or p < 0.01). Spearman correlation analysis also showed that UCd level was negatively correlated to PTH levels (r = -0.17, p = 0.008) in women. A weak correlation was also observed between PTH level and BCd in women (r = -0.11, p = 0.09) and UBMG in total population (r = -0.114, p = 0.07). Univariable and mutivariable logistic regression analysis both demonstrated that high BCd (> 10 μg/L) (odds ratio (OR) = 2.26, 95% confidence interval (CI):1.10-4.63; OR = 2.36, 95%CI: 1.11-5.05) and UCd level (> 20 μg/g cr) (OR = 2.84, 95% CI:1.32-6.10; OR = 2.97, 95%CI: 1.25-7.05) were associated with high risk of low PTH. Our data showed that environmental cadmium exposure was associated with low PTH level.
Topics: Female; Humans; Male; Cadmium; China; Environmental Exposure; Parathyroid Hormone
PubMed: 37140769
DOI: 10.1007/s12011-023-03689-x -
Minerva Medica Jun 2024Phosphate is a key component of mineralized tissues and is also part of many organic compounds. Phosphorus homeostasis depends especially upon intestinal absorption, and... (Review)
Review
Phosphate is a key component of mineralized tissues and is also part of many organic compounds. Phosphorus homeostasis depends especially upon intestinal absorption, and renal excretion, which are regulated by various hormones, such as PTH, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23. In this review we provide an update of several genetic disorders that affect phosphate transporters through cell membranes or the phosphate-regulating hormones, and, consequently, result in hypophosphatemia.
Topics: Humans; Hypophosphatemia; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Parathyroid Hormone; Phosphates; Vitamin D; Klotho Proteins; Phosphate Transport Proteins; PHEX Phosphate Regulating Neutral Endopeptidase; Intestinal Absorption; Glucuronidase; Phosphorus
PubMed: 38727708
DOI: 10.23736/S0026-4806.24.09198-5 -
Journal of Translational Medicine Dec 2023Osteoporosis is currently the most prevalent bone disorder worldwide and is characterized by low bone mineral density and an overall increased risk of fractures. To... (Review)
Review
Osteoporosis is currently the most prevalent bone disorder worldwide and is characterized by low bone mineral density and an overall increased risk of fractures. To treat osteoporosis, a range of drugs targeting bone homeostasis have emerged in clinical practice, including anti-osteoclast agents such as bisphosphonates and denosumab, bone formation stimulating agents such as teriparatide, and selective oestrogen receptor modulators. However, traditional clinical medicine still faces challenges related to side effects and high costs of these types of treatments. Nanomaterials (particularly gold nanoparticles [AuNPs]), which have unique optical properties and excellent biocompatibility, have gained attention in the field of osteoporosis research. AuNPs have been found to promote osteoblast differentiation, inhibit osteoclast formation, and block the differentiation of adipose-derived stem cells, which thus is believed to be a novel and promising candidate for osteoporosis treatment. This review summarizes the advances and drawbacks of AuNPs in their synthesis and the mechanisms in bone formation and resorption in vitro and in vivo, with a focus on their size, shape, and chemical composition as relevant parameters for the treatment of osteoporosis. Additionally, several important and promising directions for future studies are also discussed, which is of great significance for prevention and treatment of osteoporosis.
Topics: Humans; Gold; Bone Density Conservation Agents; Metal Nanoparticles; Osteoporosis; Teriparatide
PubMed: 38062495
DOI: 10.1186/s12967-023-04594-6 -
Journal of Bone and Mineral Research :... Nov 2023Active vitamin D is commonly used to control secondary hyperparathyroidism in dialysis patients, but it is unknown whether active vitamin D directly improves bone...
Active vitamin D is commonly used to control secondary hyperparathyroidism in dialysis patients, but it is unknown whether active vitamin D directly improves bone strength, independently of its ability to suppress parathyroid hormone (PTH). We analyzed the association between the prescription of active vitamin D and incidence of any fracture and hip fracture in 41,677 in-center hemodialysis patients from 21 countries in phases 3 to 6 (2005 to 2018) of the Dialysis Outcomes and Practice Patterns Study (DOPPS). We used Cox regression, adjusted for PTH and other potential confounders, and used a per-protocol approach to censor patients at treatment switch during follow-up. We also used a facility preference approach to minimize confounding by indication. Overall, 55% of patients were prescribed active vitamin D at study enrollment. Event rates (per patient-year) were 0.024 for any fracture and 0.010 for hip fracture. The adjusted hazard ratio (95% confidence interval) comparing patients prescribed versus not prescribed active vitamin D was 1.02 (0.90 to 1.17) for any fracture and 1.00 (0.81 to 1.23) for hip fracture. In the facility preference approach, there was no difference in fracture rate between facilities with higher versus lower active vitamin D prescriptions. Thus, our results do not suggest a PTH-independent benefit of active vitamin D in fracture prevention and support the current KDIGO guideline suggesting the use of active vitamin D only in subjects with elevated or rising PTH. Further research is needed to determine the role of active vitamin D beyond PTH control. © 2023 American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Vitamin D; Renal Dialysis; Parathyroid Hormone; Hyperparathyroidism, Secondary; Hip Fractures; Vitamin D Deficiency
PubMed: 37718534
DOI: 10.1002/jbmr.4913 -
Best Practice & Research. Clinical... Mar 2024Primary hyperparathyroidism (PHPT) is a systemic disease that affects all the systems of the body, specifically the bones and the kidneys. Its main action is on calcium... (Review)
Review
Primary hyperparathyroidism (PHPT) is a systemic disease that affects all the systems of the body, specifically the bones and the kidneys. Its main action is on calcium homeostasis. It tries to preserve the body's calcium level at the cost of phosphate. The criteria for surgery in asymptomatic PHPT patients revolve around raised serum calcium levels, renal dysfunction or nephrolithiasis, and bone health. It does not take into account the serum phosphate levels. Depending on the serum level, Hypophosphatemia is divided into mild, moderate, and severe categories. In PHPT, several studies have suggested that asymptomatic PHPT patients with moderate hypophosphatemia may warrant surgical intervention. Treatment of hypophosphatemia in PHPT is based upon the degree of hypophosphatemia, and treatment is given according to that oral or intravenous route; after surgical and medical treatment of PHPT, phosphate levels gradually normalized. But even after these considerations, phosphate levels in PHPT are not given much importance.
Topics: Humans; Calcium; Hyperparathyroidism, Primary; Phosphates; Parathyroid Hormone; Hypophosphatemia
PubMed: 37926613
DOI: 10.1016/j.beem.2023.101837