scholarly journals Critical Role of Calbindin-D28k in Calcium Homeostasis Revealed by Mice Lacking Both Vitamin D Receptor and Calbindin-D28k

2004 ◽  
Vol 279 (50) ◽  
pp. 52406-52413 ◽  
Author(s):  
Wei Zheng ◽  
Yixia Xie ◽  
Gang Li ◽  
Juan Kong ◽  
Jian Q. Feng ◽  
...  
Keyword(s):  
Vitamin D ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D Receptor ◽  
Calcium Homeostasis ◽  
Critical Role ◽  
Mineral Density ◽  
Genetic Ablation ◽  
High Calcium ◽  
Calbindin D28k

Calbindin (CaBP)-D28k and CaBP-D9k are cytosolic vitamin D-dependent calcium-binding proteins long thought to play an important role in transepithelial calcium transport. However, recent genetic studies suggest that CaBP-D28k is not essential for calcium metabolism. Genetic ablation of this gene in mice leads to no calcemic abnormalities. Genetic inactivation of the vitamin D receptor (VDR) gene leads to hypocalcemia, secondary hyperparathyroidism, rickets, and osteomalacia, accompanied by 90% reduction in renal CaBP-D9k expression but little change in CaBP-D28k. To address whether the role of CaBP-D28k in calcium homeostasis is compensated by CaBP-D9k, we generated VDR/CaBP-D28k double knockout (KO) mice, which expressed no CaBP-D28k and only 10% of CaBP-D9k in the kidney. On a regular diet, the double KO mice were more growth-retarded and 42% smaller in body weight than VDRKO mice and died prematurely at 2.5–3 months of age. Compared with VDRKO mice, the double KO mice had higher urinary calcium excretion and developed more severe secondary hyperparathyroidism and rachitic skeletal phenotype, which were manifested by larger parathyroid glands, higher serum parathyroid hormone levels, much lower bone mineral density, and more distorted growth plate with more osteoid formation in the trabecular region. On high calcium, high lactose diet, blood-ionized calcium levels were normalized in both VDRKO and the double KO mice; however, in contrast to VDRKO mice, the skeletal abnormalities were not completely corrected in the double KO mice. These results directly demonstrate that CaBP-D28k plays a critical role in maintaining calcium homeostasis and skeletal mineralization and suggest that its calcemic role can be mostly compensated by CaBP-D9k.

The role of vitamin D receptor gene polymorphisms in the bone mineral density of Greek postmenopausal women with low calcium intake

2011 ◽  
Vol 22 (8) ◽  
pp. 752-757 ◽  
Author(s):  
Maria G. Stathopoulou ◽  
George V.Z. Dedoussis ◽  
George Trovas ◽  
Eirini V. Theodoraki ◽  
Aikaterini Katsalira ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Calcium Intake ◽  
Gene Polymorphisms ◽  
Receptor Gene ◽  
Vitamin D Receptor Gene ◽  
Mineral Density ◽  
Receptor Gene Polymorphisms

scholarly journals Secondary hyperparathyroidism in patient with type 2 diabetes and stages 3–4 chronic kidney disease

2018 ◽  
Vol 21 (2) ◽  
pp. 128-134
Author(s):  
Lilit V. Egshatyan ◽  
Natalya G. Mokrisheva
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D Receptor ◽  
Receptor Activation ◽  
Mineral Density

Secondary hyperparathyroidism is an early complication of chronic kidney disease, with increasing severity as the glomerular filtration rate decreases and characterized by a progressive increase in parathyroid hormone and growth of the parathyroid glands. It is generally accepted that a deficiency in active form of vitamin D or calcitriol levels seems to play a relevant role in its development and progression of secondary hyperparathyroidism. A reduction in plasma calcitriol levels occurs early in renal disease. Major renal guidelines recommend use of vitamin D for secondary hyperparathyroidism in chronic kidney disease. In the treatment vitamin D receptor activation inhibit glandular hyperplasia; reduce parathyroid hormone levels impact on bone turnover and mineral density. Treatment with calcitriol can occasionally result in hypercalcemia and hyperphosphatemia in renal patients due promotes intestinal calcium and phosphorus absorption. This limits its suitability for the treatment. But next generation vitamin-D analogs such as paricalcitol have lower intestinal absorption of calcium, phosphorous and significantly lowers renin levels, albuminuria and blood pressure. In this article, we present the case of a Caucasian male with type 2 diabetes and secondary hyperparathyroidism in stages 34 chronic kidney disease. Our case study shows that in treating for secondary hyperparathyroidisms selective vitamin D receptor activation with paricalcitol reduction of levels parathyroid hormone, albuminuria, offering low chance hypercalcemia, hyperphosphatemia and other side effects.

Potential predictive marker of treatment effectiveness in patients with osteopenic syndrome after surgical menopause

GYNECOLOGY ◽  
2020 ◽  
Vol 22 (4) ◽  
pp. 39-42
Author(s):  
Yansiiat Z. Zaydieva ◽  
Elena V. Kruchinina ◽  
Olga S. Gorenkova ◽  
Elena Yu. Polyakova ◽  
Elena N. Kareva ◽  
...  
Keyword(s):  
Vitamin D ◽  
Combination Therapy ◽  
Vitamin D Receptor ◽  
Surrogate Marker ◽  
Predictive Marker ◽  
Expression Level ◽  
Mineral Density ◽  
Vitamin D Receptors ◽  
Surgical Menopause

Introduction. Patients with surgical menopause have a risk for osteopenic syndrome (OS). Menopausal hormone therapy (MHT) in combination with calcium and vitamin D promotes increase in bone mineral density (BMD). The expression level of vitamin D receptor in mononuclear fraction cells (MNFC) of blood can be considered as a predictive marker of effectiveness of OS therapy. Aim. To search a molecular predictive marker of the effectiveness of OS treatment. Materials and methods. The study included 100 women aged 4055 years with a duration of surgical menopause from 12 months to 6 years. The criterion for including patients in the study was the absence of contraindications to the use of MHT. The subject of the study was the determination of BMD by dual-energy X-ray absorptiometry, polymerase chain reaction diagnostics of the level of expression of vitamin D genes, estradiol and progesterone receptors, determination of 25-OH vitamin D in the blood. Results. Analysis of 12-month OS therapy effectiveness evaluated with a surrogate marker BMD. The increase in BMD up to 34% per year was treated as absence of negative dynamics, more than 4% per year as positive one. Significant effect of combination therapy compared with MHT on BMD in patients with surgical menopause with a low baseline level of BMD (due to hypovitaminosis D) is associated with the anti-inflammatory, bone-protective effect of vitamin D. In both groups of patients not responding; to the prescribed therapy we were able to conduct a comparative analysis of expression level of the target molecules in the MNFC before the start of treatment. The efficacy of MHT and combination therapy for BMD disorders is positively associated with the expression level of vitamin D receptors in MNFC before treatment. Therefore, the vitDR mRNA level is a potential predictive marker of the effectiveness of OS treatment. The expression levels of nuclear estradiol beta receptor and membrane receptor for progesterone in MNFC before treatment showed an upward trend in women responding to therapy. Conclusion. The expression level of the vitamin D receptor in MNFC of blood is significantly lower in the group of women with no/insufficient effect on 12-month combined therapy. This indicator can be considered as a predictive marker of the effectiveness of OS therapy.

Calcium and Vitamin D Supplementation. Myths and Realities with Regard to Cardiovascular Risk

2019 ◽  
Vol 17 (6) ◽  
pp. 610-617 ◽  
Author(s):  
Giovanna Muscogiuri ◽  
Luigi Barrea ◽  
Barbara Altieri ◽  
Carolina Di Somma ◽  
Harjit pal Bhattoa ◽  
...  
Keyword(s):  
Vitamin D ◽  
Side Effects ◽  
Secondary Hyperparathyroidism ◽  
Calcium Supplementation ◽  
Physiological Role ◽  
Bone Diseases ◽  
Current Evidence ◽  
Bone Homeostasis ◽  
Mineral Density ◽  
Muscle Health

Vitamin D and calcium are considered crucial for the treatment of bone diseases. Both vitamin D and calcium contribute to bone homeostasis but also preserve muscle health by reducing the risk of falls and fractures. Low vitamin D concentrations result in secondary hyperparathyroidism and contribute to bone loss, although the development of secondary hyperparathyroidism varies, even in patients with severe vitamin D deficiency. Findings from observational studies have shown controversial results regarding the association between bone mineral density and vitamin D/calcium status, thus sparking a debate regarding optimum concentrations of 25-hydroxyvitamin D and calcium for the best possible skeletal health. Although most of the intervention studies reported a positive effect of supplementation with calcium and vitamin D on bone in patients with osteoporosis, this therapeutic approach has been a matter of debate regarding potential side effects on the cardiovascular (CV) system. Thus, the aim of this review is to consider the current evidence on the physiological role of vitamin D and calcium on bone and muscle health. Moreover, we provide an overview on observational and interventional studies that investigate the effect of vitamin D and calcium supplementation on bone health, also taking into account the possible CV side-effects. We also provide molecular insights on the effect of calcium plus vitamin D on the CV system.

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