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1.
Calciotropic and phosphotropic hormones in fetal and neonatal bone development.
Ryan, BA, Kovacs, CS
Seminars in fetal & neonatal medicine. 2020;(1):101062
Abstract
There are remarkable differences in bone and mineral metabolism between the fetus and adult. The fetal mineral supply is from active transport across the placenta. Calcium, phosphorus, and magnesium circulate at higher levels in the fetus compared to the mother. These high concentrations enable the skeleton to accrete required minerals before birth. Known key regulators in the adult include parathyroid hormone (PTH), calcitriol, fibroblast growth factor-23, calcitonin, and the sex steroids. But during fetal life, PTH plays a lesser role while the others appear to be unimportant. Instead, PTH-related protein (PTHrP) plays a critical role. After birth, serum calcium falls and phosphorus rises, which trigger an increase in PTH and a subsequent rise in calcitriol. The intestines become the main source of mineral supply while the kidneys reabsorb filtered minerals. This striking developmental switch is triggered by loss of the placenta, onset of breathing, and the drop in serum calcium.
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2.
Parathyroid Hormone: A Uremic Toxin.
Duque, EJ, Elias, RM, Moysés, RMA
Toxins. 2020;(3)
Abstract
Parathyroid hormone (PTH) has an important role in the maintenance of serum calcium levels. It activates renal 1α-hydroxylase and increases the synthesis of the active form of vitamin D (1,25[OH]2D3). PTH promotes calcium release from the bone and enhances tubular calcium resorption through direct action on these sites. Hallmarks of secondary hyperparathyroidism associated with chronic kidney disease (CKD) include increase in serum fibroblast growth factor 23 (FGF-23), reduction in renal 1,25[OH]2D3 production with a decline in its serum levels, decrease in intestinal calcium absorption, and, at later stages, hyperphosphatemia and high levels of PTH. In this paper, we aim to critically discuss severe CKD-related hyperparathyroidism, in which PTH, through calcium-dependent and -independent mechanisms, leads to harmful effects and manifestations of the uremic syndrome, such as bone loss, skin and soft tissue calcification, cardiomyopathy, immunodeficiency, impairment of erythropoiesis, increase of energy expenditure, and muscle weakness.
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3.
Investigation and management of hypocalcaemia.
Nadar, R, Shaw, N
Archives of disease in childhood. 2020;(4):399-405
Abstract
Hypocalcaemia is a common clinical scenario in children with a range of aetiological causes. It will often present with common symptoms but may occasionally be identified in an asymptomatic child. An understanding of the physiological regulation of plasma calcium is important in understanding the potential cause of hypocalcaemia and its appropriate management. The age of presentation will influence the likely differential diagnosis. We have presented a stepwise approach to the investigation of hypocalcaemia dependent on the circulating serum parathyroid hormone level at the time of presentation. The acute and long-term management of the underlying condition is also reviewed.
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4.
Calcium and Phosphate Hormones: Vitamin D, Parathyroid Hormone, and Fibroblast Growth Factor 23.
Underland, L, Markowitz, M, Gensure, R
Pediatrics in review. 2020;(1):3-11
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5.
Hypoparathyroidism.
Bilezikian, JP
The Journal of clinical endocrinology and metabolism. 2020;(6):1722-36
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Abstract
BACKGROUND Hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia and low or undetectable levels of parathyroid hormone. METHODS This review is an evidence-based summary of hypoparathyroidism in terms of relevant pathophysiological, clinical, and therapeutic concepts. RESULTS Many clinical manifestations of hypoparathyroidism are due to the lack of the physiological actions of parathyroid hormone on its 2 major target organs: the skeleton and the kidney. The skeleton is inactive, accruing bone without remodeling it. The kidneys lose the calcium-conserving actions of parathyroid hormone and, thus, excrete a greater fraction of calcium. Biochemical manifestations, besides hypocalcemia and low or undetectable levels of parathyroid hormone, include hyperphosphatemia and low levels of 1,25-dihydroxyvitamin D. Calcifications in the kidney, brain, and other soft tissues are common. Removal of, or damage to, the parathyroid glands at the time of anterior neck surgery is, by far, the most likely etiology. Autoimmune destruction of the parathyroid glands and other genetic causes represent most of the other etiologies. Conventional treatment with calcium and active vitamin D can maintain the serum calcium level but high doses may be required, adding to the risk of long-term soft tissue calcifications. The advent of replacement therapy with recombinant human PTH(1-84) represents a major step in the therapeutics of this disease. CONCLUSIONS Advances in our knowledge of hypoparathyroidism have led to greater understanding of the disease itself and our approach to it.
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6.
Vitamin D in chronic kidney disease: is there a role outside of PTH control?
Brogan, M, Astor, BC, Melamed, ML
Current opinion in nephrology and hypertension. 2020;(2):243-247
Abstract
PURPOSE OF REVIEW Vitamin D deficiency is common in patients with kidney disease and many patients receive vitamin D supplementation. Several large, well-designed clinical trials have been published in the last few years evaluating the effects of vitamin D supplementation on important outcomes for patients with kidney disease including effects on cardiovascular disease, secondary hyperparathyroidism, and kidney disease progression. RECENT FINDINGS Several negative trials have been published showing no effect of cholecalciferol supplementation on cardiovascular events, kidney disease progression, and albuminuria. Long-term supplementation does not appear to be associated with kidney stone disease. Vitamin D supplementation decreases parathyroid hormone (PTH) levels and high levels of 25-hydroxyvitamin D may be required for maximal suppression. SUMMARY There appear to be no effects of vitamin D supplementation on noncalcemic outcomes including progression of kidney disease, albuminuria, or cardiovascular disease. The primary reason to use vitamin D in kidney disease remains to lower PTH levels.
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7.
Calcium Levels in the Neonate.
Perino, JM
Neonatal network : NN. 2020;(1):35-39
Abstract
Calcium, the most abundant ion in the neonate, plays a role in bone formation, blood coagulation, muscle contractility, and nerve conduction. Calcium levels are regulated via a negative feedback loop by the parathyroid hormone, calcitonin, and vitamin D. Calcium levels in the neonate must be monitored carefully to avoid complications that affect the central nervous system as well as the cardiac and musculoskeletal systems.
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8.
Recombinant parathyroid hormone for hypoparathyroidism in children: a narrative review.
Dayal, D, Gupta, A, Gupta, S, Dutta, A
Pediatric endocrinology, diabetes, and metabolism. 2019;(4):194-201
Abstract
The conventional management of hypoparathyroidism in children involves the use of calcium and vitamin D analogs. This therapy effec-tively increases the serum calcium levels but worsens hypercalciuria and its consequences such as nephrocalcinosis and renal insuffi-ciency. Although replacement with the missing parathyroid hormone (PTH) is ideal and available for more than 2 decades, the reported concerns of osteosarcoma prohibited its use in children with open epiphyses. Nevertheless, the data accumulated over the past several years suggests that the fears of bone malignancies were probably overstated. With an aim to review the available data on recombinant PTH (rhPTH) use, we performed a literature search using international databases and identified 15 studies involving approximately 70 children with hypoparathyroidism due to various etiologies who received rhPTH1-34 for durations between 1 day and 13.5 years. All the studies appear to indicate that rhPTH1-34 therapy is an effective short and long-term strategy for treatment of hypoparathyroidism with better metabolic control, lesser effects on renal function and improved quality of life as compared to conventional therapy. A more significant conclusion is the safety of long-term use of rhPTH1-34 with no observed adverse skeletal effects so far. However, all studies mention the importance of a continued surveillance for adverse effects in the treated patients. This narrative review discusses the experi-ence of rhPTH1-34 use exclusively in children.
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9.
The effectiveness and safety of parathyroid hormone in fracture healing: A meta-analysis.
Hong, H, Song, T, Liu, Y, Li, J, Jiang, Q, Song, Q, Deng, Z
Clinics (Sao Paulo, Brazil). 2019;:e800
Abstract
The very large economic and social burdens of fracture-related complications make rapid fracture healing a major public health goal. The role of parathyroid hormone (PTH) in treating osteoporosis is generally accepted, but the effect of PTH on fracture healing is controversial. This meta-analysis was designed to investigate the efficacy and safety of PTH in fracture healing. The EMBASE, PubMed, and Cochrane Library databases were systematically searched from the inception dates to April 26, 2018. The primary randomized clinical trials comparing PTH treatment for fracture healing with placebo or no treatment were identified. We did not gain additional information by contacting the authors of the primary studies. Two reviewers independently extracted the data and evaluated study quality. This meta-analysis was executed to determine the odds ratio, mean difference, standardized mean difference, and 95% confidence intervals with random-effects models. In total, 8 randomized trials including 524 patients met the inclusion criteria. There were significant differences in fracture healing time, pain relief and function improvement. There were no significant differences in the fracture healing rate or adverse events, including light-headedness, hypercalcemia, nausea, sweating and headache, except for slight bruising at the injection site. We determined that the effectiveness and safety of PTH in fracture healing is reasonably well established and credible.
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10.
Secondary Hyperparathyroidism: Pathogenesis and Latest Treatment.
Mizobuchi, M, Ogata, H, Koiwa, F
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2019;(4):309-318
Abstract
The classic pathogenesis of secondary hyperparathyroidism (SHPT) began with the trade-off hypothesis based on parathyroid hormone hypersecretion brought about by renal failure resulting from a physiological response to correct metabolic disorder of calcium, phosphorus, and vitamin D. In dialysis patients with failed renal function, physiological mineral balance control by parathyroid hormone through the kidney fails and hyperparathyroidism progresses. In this process, many significant genetic findings have been established. Abnormalities of Ca-sensing receptor and vitamin D receptor are associated with the pathogenesis of SHPT, and fibroblast growth factor 23 has also been shown to be involved in the pathogenesis. Vitamin D receptor activators (VDRAs) are widely used for treatment of SHPT. However, VDRAs have calcemic and phosphatemic effects that limit their use to a subset of patients, and calcimimetics have been developed as alternative drugs for SHPT. Hyperphosphatemia also affects progression of SHPT, and control of hyperphosphatemia is, therefore, thought to be fundamental for control of SHPT. Currently, a combination of a VDRA and a calcimimetic is recognized as the optimal strategy for SHPT, and for other outcomes such as reduced cardiovascular disease and improved survival. The latest findings on the pathogenesis and treatment of SHPT are summarized in this review.