Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin D3 must be metabilically altered first in the liver to 25-hydroxyvitamin D3 (25 OH-D3) and subsequently in the kidney to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) before it can function. Because 1,25-(OH)2D3 is formed in the kidney and acts in intestine and bone to elevate serum calcium and phosphate concentrations, it can be considered a hormone. The production of 1,25-(OH)2D3 is feedback regulated either directly or indirectly by serum calcium and serum phosphate concentrations. The hypocalcemic regulation is mediated by the parathyroid glands. The hypophosphatemic stimulus, however, does not involve either the parathyroid or thyroid glands. Under conditions whereby the synthesis of 1,25-(OH)2D3 is repressed, 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3 is formed. This metabolite can be converted further to 1,24,25-trihydroxyvitamin D3 (1,24,25-(OH)3D3), which stimulate intestinal calcium transport but not bone calcium mobilization or phosphate transport reactions. A number of vitamin D-resistant bone diseases may be related to defective vitamin D metabolism. For example, bone disease related to choric renal failure likely results from defective formation of 1,25-(OH)2D3 in the kidney. Treatment of this disease with intravenously administered 1,25-(OH)2D3 is effective in correcting the bone lesions. 1Alpha-hydroxyvitamin D3 (1alpha-OH-D3), a new synthetic analog of 1,25-(OH)2D3 which is less expensive to produce than 1,25-(OH)2D3, is effective in anephric animals and may have several advantages over 1,25-(OH)2D3 in treating bone diseases.
 ...
PMID:The kidney as an endocrine organ involved in the function of vitamin D. 16 78

Bone histology and biochemical data indicate that hyperparathyroidism and abnormal metabolism of vitamin D are hallmarks of renal osteodystrophy. Early diagnosis is possible by means of bone biopsy. The clinical signs of renal bone disease include extraskeletal calcifications. Persistence of disease during hemodialysis treatment calls for treatment even of asymptomatic patients. Vitamin D3 and its metabolites or analogs play an important role in the suppression of hyperparathyreoidism and in combating osteomalacia.
 ...
PMID:[Renal osteopathy]. 121 56

Because of the high prevalence of metabolic bone disease in older persons, we investigated the possibility of impaired intestinal absorptive capacity for vitamin D3 in aging animals. Using a single-pass technique, we measured vitamin D absorption and mucosal accumulation in male rats 9 to 101 weeks of age. Intestinal length, water absorption, and vitamin D3 intestinal tissue concentration remained constant after 41 weeks of age. Vitamin D3 absorption increased from 1209 pmol/100 cm/hr at 9 weeks of age to 2114 pmol/100 cm/hr at 41 weeks of age and remained relatively constant thereafter. Because vitamin D3 absorption rate is partly regulated by the dimensions of the unstirred water layer, we assessed the dimensions of the UWL of our aging animals. As the animals aged, the surface area of the UWL increased from 197 to 316 cm2/100 cm, and its resistance decreased from 1.2 to 0.7 min/cm3/100 cm by 41 weeks of age and remained stable thereafter. Inasmuch as the UWL is a major regulatory step in the absorption of vitamin D, its constant dimensions after 41 weeks of age explain the normal absorption of vitamin D3 observed in our aging animals. If these findings are found to be true in humans as well, they would argue against the possibility of vitamin D3 malabsorption as a cause of metabolic bone disease seen in aging individuals.
 ...
PMID:Influence of aging on vitamin D absorption and unstirred water layer dimensions in the rat. 632 19

The bone histology of renal osteodystrophy is classified into osteitis fibrosa, osteomalacia, those of mixed, osteoporosis and low turnover bone. Osteitis fibrosa is the most frequent skeletal abnormality and is caused by various degrees of hyperparathyroidism. The main factors inducing hyperparathyroidism which is a well known complication in patients with renal failure include (a) phosphorus retention: 1) hypocalcemia and 2) decreased levels of 1 alpha, 25(OH)2 Vitamin D3, (b) reduced number of 1 alpha, 25(OH)2 Vitamin D3 receptors in parathyroid tissue, (c) skeletal resistance to set-point for calcium-regulated parathyroid hormone secretion. Serum or plasma levels of calcium, phosphorus, alkaline phosphatase, parathyroid hormone, calcitonin and tartrate resistant acid phosphatase are measured to evaluate hyperparathyroidism and metabolic bone disease. Dietary phosphorus restriction in chronic renal insufficiency prevents secondary hyperparathyroidism and renal osteodystrophy. Other treatment of phosphorus binders, Vitamin D metabolites or analogues, carcitonin and bisphosphonate are useful for the management of renal bone disease.
 ...
PMID:[Secondary hyperparathyroidism and tertiary hyperparathyroidism chronic renal failure, uremia]. 775 92

Vitamin D3 is modified by vitamin D3-25-hydroxylase in the liver, and 25-hydroxyvitamin D3-1alpha-hydroxylase in the kidney, to form the active metabolite, 1,25-dihydroxyvitamin D3. Chronic kidney disease (CKD) is characterized by reduced synthesis of 1,25-dibydroxyvitamin D3, inadequate renal phosphate clearance and calcium imbalance, secondary hyperparathyroidism (SHPT) and bone disease. CKD patients encounter a much higher risk of cardiovascular disease (CVD) than the general public. The cardiovascular risk factors for CKD patients include conventional factors such as age, gender, hypertension, diabetes, dyslipidemia and smoking, and non-conventional factors, such as anemia, uremia, reduced vascular compliance, inflammation and various hormonal factors. Several vitamin D analogs are currently available for the treatment of SHPT, and recent clinical data show that these analogs provide survival benefit for CKD patients in the order of paricalcitol > calcitriol > no vitamin D analog, independent of parathyroid hormone and calcium. Moreover, the survival benefit seems to be associated with cardiovascular causes. The observations made from these clinical studies raised intriguing questions about the involvement of the vitamin D receptor locus (VDR) in the cardiovascular system. This review discusses recent data regarding the role of vitamin D and its analogs in the CVD associated with CKD.
 ...
PMID:Cardiovascular disease in chronic kidney failure: is there a role for vitamin D analogs? 1581

Vitamin D3 is a fat-soluble secosteroid responsible for enhancing intestinal absorption of calcium, iron, and other materials. Vitamin D3 deficiency, therefore, can cause health problems such as metabolic diseases, and bone disorder. Female sex hormones including estrogen and progesterone are biosynthesized mainly in the granulosa cells of ovary. In this study, we isolated granulosa cells from porcine ovary and cultured for the experiments. In order to examine the effect of vitamin D3 on the ovarian granulosa cells, the mRNA and protein levels of genes were analyzed by real-time PCR and Western blot assay. The production of estrogen from the granulosa cells was also measured by the ELISA assay. Genes associated with follicle growth were not significantly altered by vitamin D3. However, it increases expression of genes involved in the estrogen-biosynthesis. Further, estrogen concentrations in porcine granulosa cell-cultured media increased in response to vitamin D3. These results showed that vitamin D3 is a powerful regulator of sex steroid hormone production in porcine granulosa cells, suggesting that vitamin D deficiency may result in inappropriate sexual development of industrial animals and eventually economic loss.
 ...
PMID:Effect of Vitamin D3 on Biosynthesis of Estrogen in Porcine Granulosa Cells via Modulation of Steroidogenic Enzymes. 2813 13