Metabolism of 1,25-dihydroxyvitamin D3

1984 ◽  
Vol 64 (2) ◽  
pp. 478-504 ◽  
Author(s):  
R. Kumar
Keyword(s):  
Parathyroid Hormone ◽  
Serum Calcium ◽  
Biliary Excretion ◽  
Extracellular Fluid ◽  
Serum Phosphorus ◽  
General Terms ◽  
Wide Range ◽  
Calcium Phosphorus ◽  
Calcium And Phosphorus ◽  
Low Serum

Synthesis of 1,25(OH)2D3 is controlled by numerous factors. The major ones, however, are the circulating amounts of parathyroid hormone (the secretion of which is stimulated by low serum calcium), serum or extracellular fluid phosphorus concentrations, circulating levels of 1,25(OH)2D3 itself, and perhaps serum calcium directly. Many of the other factors noted have effects in vitro only or effects that are observed inconsistently or in one species only. Thus, in low-calcium states, 1,25(OH)2D3 synthesis increases because of increased parathyroid hormone activity. Parathyroid hormone may stimulate 1,25(OH)2D3 synthesis directly or via alterations (a decrease) in serum phosphorus or both. Low serum phosphorus will stimulate 1,25(OH)2D3 synthesis independent of parathyroid hormone levels. Low serum calcium may directly stimulate 25(OH)D3 1 alpha-hydroxylase activity independently of parathyroid hormone. In general terms the vitamin D-endocrine system tends to correct abnormalities in calcium and phosphorus homeostasis. The further metabolism of 1,25(OH)2D3 to other metabolites appears to be mainly a degradative or excretory process. Currently there is no evidence that 1,25(OH)2D3 must itself be altered to other metabolites prior to inducing intestinal calcium transport or bone mobilization. The processes involved in the excretion of 1,25(OH)2D3, such as side-chain oxidation and biliary excretion, are not regulated by serum calcium, phosphorus, or 1,25(OH)2D3 levels. The biliary excretion pathway is also unsaturable over a very wide range and not regulated by calcium, phosphorus, or vitamin D3. Therefore these processes, which account for a large part of the metabolism of 1,25(OH)2D3, are largely unregulated by factors that control the synthesis of 1,25(OH)2D3 and regulate the formation of other calcium-controlling hormones. Other processes involved in the metabolism of 1,25(OH)2D3, such as 24-hydroxylation and 26-hydroxylation, occur in normocalcemic and normophosphatemic states. 24-Hydroxylation is also induced by 1,25(OH)2D3, which benefits the organism, because excessive 1,25(OH)2D3 in various tissues can be altered to a less active metabolite, 1,24,25(OH)3D3. Although there is still no evidence concerning the regulation of C-24 oxidation by dietary calcium and phosphorus levels, the fact that this process is induced by 1,25(OH)2D3 suggests that the metabolic pathway functions in much the same manner as the 24-hydroxylation pathway. The formation of 1,25(OH)2D3-26,23-lactone occurs in normocalcemic states and in situations in which 1,25(OH)2D3 has been administered.

scholarly journals Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

2013 ◽  
Vol 304 (3) ◽  
pp. E310-E320 ◽  
Author(s):  
Stephen J. Quinn ◽  
Alex R. B. Thomsen ◽  
Jian L. Pang ◽  
Lakshmi Kantham ◽  
Hans Bräuner-Osborne ◽  
...  
Keyword(s):  
Serum Calcium ◽  
Fibroblast Growth Factor 23 ◽  
Threshold Level ◽  
Serum Levels ◽  
Serum Phosphorus ◽  
Dihydroxyvitamin D ◽  
Dietary Phosphorus ◽  
Calcium Phosphorus ◽  
Calcium And Phosphorus

Calcium and phosphorus homeostasis are highly interrelated and share common regulatory hormones, including FGF23. However, little is known about calcium's role in the regulation of FGF23. We sought to investigate the regulatory roles of calcium and phosphorus in FGF23 production using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR; PTH-CaSR DKO). In wild-type, PTH KO, and PTH-CaSR DKO mice, elevation of either serum calcium or phosphorus by intraperitoneal injection increased serum FGF23 levels. In PTH KO and PTH-CaSR DKO mice, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] despite no change in FGF23, suggesting direct regulation of 1,25(OH)2D3 synthesis by serum phosphorus. Calcium-mediated increases in serum FGF23 required a threshold level of serum phosphorus of about 5 mg/dl. Analogously, phosphorus-elicited increases in FGF23 were markedly blunted if serum calcium was less than 8 mg/dl. The best correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium × phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus appears to be fundamentally important in coordinating the serum levels of both mineral ions and ensuring that the calcium × phosphorus product remains within a physiological range.

DECREASED PARATHYROID FUNCTION IN HYPERTHYROIDISM: INTERRELATIONSHIPS BETWEEN SERUM PARATHYROID HORMONE, CALCIUM-PHOSPHORUS METABOLISM AND THYROID FUNCTION

1977 ◽  
Vol 84 (3) ◽  
pp. 566-575 ◽  
Author(s):  
Leif Mosekilde ◽  
Merete Sanvig Christensen
Keyword(s):  
Parathyroid Hormone ◽  
Urinary Excretion ◽  
Serum Calcium ◽  
Elevated Serum ◽  
Serum Levels ◽  
Urinary Calcium ◽  
Albumin Concentration ◽  
Parathyroid Function ◽  
Calcium Phosphorus ◽  
Calcium And Phosphorus

ABSTRACT Serum immunoreactive parathyroid hormone (S-iPTH) was measured together with serum and urinary calcium and phosphorus in 45 hyperthyroid patients in order to assess parathyroid function. Serum calcium and phosphorus were increased and positively correlated to the degree of hyperthyroidism. The prevalence of hypercalcaemia was 51.1 % using serum calcium values corrected for individual variations in serum albumin concentration compared to 15.6% using the uncorrected calcium values. S-iPTH was decreased and inversely correlated to serum calcium (corrected). Subnormal levels of S-iPTH were found in 28.9 % of the patients. The urinary excretion of calcium and phosphorus was increased and positively correlated to the degree of hyperthyroidism. The tubular reabsorption of calcium (TRCa %) was decreased, positively correlated to S-iPTH and inversely correlated to serum calcium. Increased mobilisation of bone mineral in hyperthyroidism is suggested mainly to be responsible for the elevated serum levels and increased urinary excretion of calcium and phosphorus and for the decreased parathyroid function.

Effects of serum calcium and phosphorus on skeletal mineralization in vitamin D-deficient rats

1986 ◽  
Vol 251 (2) ◽  
pp. E234-E240 ◽  
Author(s):  
M. E. Holtrop ◽  
K. A. Cox ◽  
D. L. Carnes ◽  
M. F. Holick
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Volume Density ◽  
Normal Serum ◽  
Serum Phosphorus ◽  
Deficient Diet ◽  
Hydroxyvitamin D ◽  
Normal Serum Calcium ◽  
Calcium And Phosphorus ◽  
Low Serum

In the present study, we have evaluated the role of calcium and phosphorus concentrations in serum on the mineralization of bone in the absence of vitamin D. This was accomplished by feeding mother rats and subsequently their pups vitamin D-deficient diets varying in calcium, phosphorus, and lactose content. After 5-7 wk on these diets, serum concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-hydroxyvitamin D [1,25(OH)2D] were undetectable. Rats fed a vitamin D-deficient diet containing 0.44% calcium and 0.3% phosphorus showed a serum calcium of 4.9-5.9 mg/dl and a serum phosphorus of 7.3-8.2 mg/dl; rickets (wide epiphysial plates) had developed as well as osteomalacia (wide osteoid seams). Rats maintained on a vitamin D-deficient diet containing 3% calcium and 0.65% phosphorus had normal serum calcium, low serum phosphorus, and severe rickets, but osteomalacia was not seen. Rats fed a diet containing 20% lactose, 4% calcium, and 1% phosphorus showed normal serum calcium, somewhat low serum phosphorus, normal serum PTH, normal width of the epiphysial plate, normal volume density of trabecular bone, and normal volume density of osteoid seams. These data confirm the findings of others, using a different experimental model, that serum calcium and phosphorus concentrations are the determining factors in mineralization defects and not the absence of 25(OH)D or 1,25(OH)2D. In these rats thyroparathyroidectomy is well tolerated, which makes for an ideal model for the study of the effects of calcium-regulating hormones on bone histology, cytology, and biochemistry.

Renal osteodystrophy

2013 ◽  
pp. 1274-1282
Author(s):  
Thomas Bardin ◽  
Tilman Drüeke
Keyword(s):  
Vitamin D ◽  
Bone Turnover ◽  
Serum Calcium ◽  
Renal Osteodystrophy ◽  
Serum Phosphorus ◽  
Osteitis Fibrosa ◽  
Alkaline Phosphatases ◽  
Calcium Phosphorus ◽  
Turnover Markers ◽  
25 Oh Vitamin D

Renal osteodystrophy (ROD) is a term that encompasses the various consequences of chronic kidney disease (CKD) for the bone. It has been divided into several entities based on bone histomorphometry observations. ROD is accompanied by several abnormalities of mineral metabolism: abnormal levels of serum calcium, phosphorus, parathyroid hormone (PTH), vitamin D metabolites, alkaline phosphatases, fibroblast growth factor-23 (FGF-23) and klotho, which all have been identified as cardiovascular risk factors in patients with CKD. ROD can presently be schematically divided into three main types by histology: (1) osteitis fibrosa as the bony expression of secondary hyperparathyroidism (sHP), which is a high bone turnover disease developing early in CKD; (2) adynamic bone disease (ABD), the most frequent type of ROD in dialysis patients, which is at present most often observed in the absence of aluminium intoxication and develops mainly as a result of excessive PTH suppression; and (3) mixed ROD, a combination of osteitis fibrosa and osteomalacia whose prevalence has decreased in the last decade. Laboratory features include increased serum levels of PTH and bone turnover markers such as total and bone alkaline phosphatases, osteocalcin, and several products of type I collagen metabolism products. Serum phosphorus is increased only in CKD stages 4-5. Serum calcium levels are variable. They may be low initially, but hypercalcaemia develops in case of severe sHP. Serum 25-OH-vitamin D (25OHD) levels are generally below 30 ng/mL, indicating vitamin D insufficiency or deficiency. The international KDIGO guideline recommends serum PTH levels to be maintained in the range of approximately 2-9 times the upper normal normal limit of the assay and to intervene only in case of significant changes in PTH levels. It is generally recommended that calcium intake should be up to 2 g per day including intake with food and administration of calcium supplements or calcium-containing phosphate binders. Reduction of serum phosphorus towards the normal range in patients with endstage kidney failure is a major objective. Once sHP has developed, active vitamin D derivatives such as alfacalcidol or calcitriol are indicated in order to halt its progression.

The effect of Cinacalcet on Serum Calcium, Phosphorus and Parathyroid Hormone in Hemodialysis Patients

2012 ◽  
Vol 1 (2) ◽  
pp. 55-60
Author(s):  
Erkan Sengul ◽  
Selma Satilmisoglu ◽  
Aysun Sengul ◽  
Sevim Dindar
Keyword(s):  
Parathyroid Hormone ◽  
Serum Calcium ◽  
Hemodialysis Patients ◽  
Calcium Phosphorus

scholarly journals Parathyroid Hormone Disturbances in Postmenopausal Women with Distal Forearm Fracture

2021 ◽  
Author(s):  
Axel Wihlborg ◽  
Karin Bergström ◽  
Paul Gerdhem ◽  
Ingrid Bergström
Keyword(s):  
Parathyroid Hormone ◽  
Adverse Effects ◽  
Postmenopausal Women ◽  
Serum Calcium ◽  
Forearm Fracture ◽  
Ionized Calcium ◽  
Distal Forearm ◽  
Distal Forearm Fracture ◽  
Population Prevalence ◽  
Wide Range

Abstract Background Primary hyperparathyroidism (PHPT) is a common endocrine disorder with a wide range of adverse effects, such as osteoporosis. Many women are not diagnosed due to asymptomatic disease or vague symptoms but are still at risk of severe adverse effects. Early identification of patients with PHPT is therefore of importance. The aim of this study was to determine PHPT prevalence among postmenopausal women with a distal forearm fracture. Methods Recruitment was conducted in conjunction with the occurrence of a distal forearm fracture at Karolinska University Hospital. In total, 161 postmenopausal women were included in a cross-sectional study with repeated evaluations. Analyzes of serum calcium, ionized calcium, phosphate, parathyroid hormone (PTH), and vitamin D were performed. Diagnosis of PHPT was based on clinical evaluations and biochemical definitions of serum calcium and PTH in coherence with previous population prevalence reports. Results Mean age was 64.7 (9.5) years, serum calcium 2.33 (0.10) mmol/L, ionized calcium 1.25 (0.05) mmol/L and PTH 54 (26) ng/L. PTH was elevated in 32 (20%) women. In total, 11 (6.8%) women were diagnosed with PHPT; 6 with classical PHPT and 5 with mild PHPT. The prevalence of PHPT was significantly increased compared to the population prevalence of 3.4% (p = 0.022). Conclusion Screening postmenopausal women in conjunction with low-energy distal forearm fracture revealed a large number of women with parathyroid disturbance. Evaluation of parathyroid hormone and calcium status in this group of patients seems beneficial.

scholarly journals Parathyroid Changes After RAI in Patients With Differentiated Thyroid Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Liu Xiao ◽  
Wenjie Zhang ◽  
Hongmei Zhu ◽  
Yueqi Wang ◽  
Bin Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Thyroid Carcinoma ◽  
Serum Calcium ◽  
Multivariate Regression Analysis ◽  
Differentiated Thyroid Carcinoma ◽  
Thyroid Imaging ◽  
Before And After ◽  
Calcium Phosphorus ◽  
The Mean ◽  
Calcium And Phosphorus

ObjectiveThe purpose of this study was to investigate parathyroid hormone (PTH), serum calcium, phosphorus, and 25-hydroxyvitamin D (25-OH-VD) changes before and after radioactive iodine (RAI) in differentiated thyroid carcinoma (DTC) patients at different time points.MethodsA total of 259 DTC patients who received RAI were prospectively enrolled. We evaluated PTH, serum calcium, phosphorus, and 25-OH-VD levels at baseline pre-RAI, five days, six weeks, and six months post-RAI, respectively. We analyzed the risk factors of hypocalcemia at five days post-RAI.ResultsThe mean PTH, serum calcium and phosphorus values decreased five days post-RAI compared with pre-RAI (PTH 4.18 ± 1.23 pmol/L vs. 3.95 ± 1.41 pmol/L; calcium 2.27 ± 0.09 mmol/L vs. 2.20 ± 0.11 mmol/L; phosphorus 1.25 ± 0.17 vs. 0.98 ± 0.20 mmol/L, P < 0.05), and the differences were statistically significant. The mean 25-OH-VD levels did not significantly decrease at five days post-RAI. 21.2% (55/259) of patients had hypocalcemia at five days post-RAI, and all of them were given oral calcium supplements. At six weeks post-RAI, all of the above parameters were higher than those at five days post-RAI. Multivariate regression analysis showed that baseline pre-RAI serum calcium < 2.27 mmol/L, PTH < 4.18 pmol/L and negative 99mTcO4- thyroid imaging were risk factors for hypocalcemia at five days post-RAI.ConclusionFor DTC patients with normal PTH and serum calcium levels at pre-RAI, their PTH, serum calcium, and phosphorus levels decreased at five days post-RAI. About one-fifth of patients could have hypocalcemia at five days post-RAI. Lower baseline pre-RAI serum calcium and PTH levels and negative 99mTcO4- thyroid imaging were risk factors for hypocalcemia five days post-RAI.

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