calcitriol and Calcinosis

Hyperphosphatemic familial tumoral calcinosis (hFTC) is a rare disorder of phosphate metabolism defined by hyperphosphatemia and ectopic calcifications in various locations. To date, recessive mutations have been described in three genes involving phosphate metabolism: FGF23, GALNT3, and α-Klotho, all of which result in the phenotypic presentation of hFTC. These mutations result in either inadequate intact fibroblast growth factor-23 (FGF23) secretion (FGF23 or GALNT3) or resistance to FGF23 activity at the fibroblast growth factor receptor/α-Klotho complex (α-Klotho). The biochemical consequence of limitations in FGF23 activity includes increased renal tubular reabsorption of phosphate, hyperphosphatemia, and increased production of 1,25-dihydroxyvitamin D. The resultant ectopic calcifications can be painful and debilitating. Medical treatments are targeted toward decreasing intestinal phosphate absorption or increasing phosphate excretion; however, results have been variable and generally limited. Treatments that would increase FGF23 levels or signaling would more appropriately target the genetic etiologies of this disease and perhaps be more effective.

Topics: Calcinosis; Diet Therapy; Diphosphonates; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucuronidase; Humans; Hyperostosis, Cortical, Congenital; Hyperphosphatemia; Klotho Proteins; Models, Genetic; Mutation; N-Acetylgalactosaminyltransferases; Phosphates; Polypeptide N-acetylgalactosaminyltransferase; Vitamin D

FGF23 is an endocrine FGF produced by osteocytes, which increases excretion of phosphate and suppresses the production of 1,25 (OH) 2D. Excessive action of FGF23 causes various forms of hypophosphatemic rickets/osteomalacia, while the loss of function of FGF23 results in the condition called familial hyperphosphatemic tumoral calcinosis. 1,25 (OH) 2D stimulates the production of FGF23, and the interaction between FGF23 and 1,25 (OH) 2D plays a central role in mineral homeostasis. In addition to the its roles in mineral homeostasis, recent studies have suggested the direct action of FGF23 on osteoblasts and chondrocytes.

Topics: Animals; Bone and Bones; Calcification, Physiologic; Calcinosis; Cartilage; Chondrocytes; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Homeostasis; Humans; Hyperostosis, Cortical, Congenital; Hyperphosphatemia; Osteoblasts; Osteocytes; Osteomalacia; Phosphates; Rickets, Hypophosphatemic; Vitamin D

Vascular calcification or mineralization is a major complication seen in patients with advanced stages of chronic kidney disease (CKD), and it is associated with markedly increased morbidity and mortality. Most of the CKD-related vascular mineralization is attributable to abnormal mineral ion metabolism. Elevated serum calcium and phosphate levels, along with increased calcium-phosphorus byproduct, and the use of active vitamin D metabolites are thought to be the predisposing factors for developing vascular mineralization in patients with CKD. Recent experimental studies have shown that vascular mineralization can be suppressed by reducing serum phosphate levels, even in the presence of extremely high serum calcium and 1,25-dihydroxyvitamin D levels, indicating that reducing 'phosphate toxicity' should be the important therapeutic priority in CKD patients for minimizing the risk of developing vascular mineralization and the disease progression.

Topics: Animals; Calcinosis; Coronary Disease; Disease Models, Animal; Disease Progression; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucuronidase; Humans; Hydroxyapatites; Hypercalcemia; Hyperphosphatemia; Klotho Proteins; Mice; Models, Biological; Muscle, Smooth, Vascular; Phosphates; Renal Dialysis; Renal Insufficiency, Chronic; Vascular Diseases; Vitamin D

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a multifaceted definition used to help describe the systemic derangement of mineral bone metabolism in renal disease. This was previously referred to, rather simplistically, as 'renal osteodystrophy' or 'renal bone disease'. In this review, we will try to show the evidence relating these factors to cardiovascular morbidity and mortality and give some evidence as to the mechanisms for this. The treatments used for this condition are also integral to the increased cardiovascular mortality seen in renal patients and a summary of these effects will also be covered.

Topics: Bone Remodeling; Calcinosis; Calcium; Cardiovascular Diseases; Chronic Kidney Disease-Mineral and Bone Disorder; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Parathyroid Hormone; Phosphates; Renal Dialysis; Survival Rate; Vitamin D

Chronic kidney disease is associated with an increased risk of cardiovascular disease. Vitamin D deficiency is common in patients with chronic kidney disease. In epidemiological studies, vitamin D deficiency and absence of treatment with vitamin D is associated with increased cardiovascular mortality. Several possible mechanisms may explain how vitamin D can influence the development of cardiovascular disease. Clinical intervention studies are needed to clarify whether treatment with vitamin D decreases the risk of cardiovascular disease in chronic kidney disease.

Topics: Animals; Calcinosis; Cardiovascular Diseases; Heart Failure; Humans; Kidney Failure, Chronic; Renal Dialysis; Risk Factors; Vascular Diseases; Vitamin D; Vitamin D Deficiency

Patients with chronic kidney disease (CKD) reportedly have a high prevalence of aortic valve calcification (AVC). In population-based studies, AVC is considered a manifestation of systemic atherosclerosis. The association of AVC with atherosclerotic lesions has not been fully investigated in predialysis patients. The present study was performed to determine whether carotid artery lesions and peripheral artery disease (PAD) are associated with AVC in patients with CKD not on dialysis.. In total, 749 patients were included in this cross-sectional study. AVC was evaluated using echocardiography. Carotid artery lesions including carotid artery plaque (CAP) and PAD were simultaneously examined in each patient. A logistic regression analysis was applied to determine the factors associated with AVC.. AVC, CAP, and PAD were found in 201, 583, and 123 patients, respectively. In the multivariable analyses adjusted for covariates including the estimated glomerular filtration rate and makers of mineral metabolism (serum calcium, serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23), AVC was significantly associated with the presence of CAP [odds ratio (OR), 3.37; 95% confidence interval (CI), 1.43-7.95], the presence of PAD (OR, 1.76; 95% CI, 1.10-2.81), the CAP score (per 1.0-point increase) (OR, 1.06; 95% CI, 1.02-1.11), and the ankle-brachial blood pressure index (per 0.1-point increase) (OR, 0.83; 95% CI, 0.72-0.95).. AVC was associated with atherosclerotic lesions independent of kidney function and mineral metabolism. We consider that this association between AVC and atherosclerosis might reflect the burden of shared atherosclerotic risk factors.

Topics: Adult; Aged; Aged, 80 and over; Ankle Brachial Index; Aortic Valve; Aortic Valve Stenosis; Calcinosis; Calcium; Carotid Artery Diseases; Cross-Sectional Studies; Echocardiography; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Lansoprazole; Male; Middle Aged; Parathyroid Hormone; Peripheral Arterial Disease; Phosphorus; Renal Insufficiency, Chronic; Vitamin D; Young Adult

Ectopic calcification (EC), which is the pathological deposition of calcium and phosphate in extra-skeletal tissues, may be associated with hypercalcaemic and hyperphosphataemic disorders, or it may occur in the absence of metabolic abnormalities. In addition, EC may be inherited as part of several monogenic disorders and studies of these have provided valuable insights into the metabolic pathways regulating mineral metabolism. For example, studies of tumoural calcinosis, a disorder characterised by hyperphosphataemia and progressive EC, have revealed mutations of fibroblast growth factor 23 (FGF23), polypeptide N-acetyl galactosaminyltransferase 3 (GALNT3) and klotho (KL), which are all part of a phosphate-regulating pathway. However, such studies in humans are limited by the lack of available large families with EC, and to facilitate such studies we assessed the progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) for EC. This identified two mutants with autosomal recessive forms of EC, and reduced lifespan, designated Ecalc1 and Ecalc2. Genetic mapping localized the Ecalc1 and Ecalc2 loci to a 11.0 Mb region on chromosome 5 that contained the klotho gene (Kl), and DNA sequence analysis identified nonsense (Gln203Stop) and missense (Ile604Asn) Kl mutations in Ecalc1 and Ecalc2 mice, respectively. The Gln203Stop mutation, located in KL1 domain, was severely hypomorphic and led to a 17-fold reduction of renal Kl expression. The Ile604Asn mutation, located in KL2 domain, was predicted to impair klotho protein stability and in vitro expression studies in COS-7 cells revealed endoplasmic reticulum retention of the Ile604Asn mutant. Further phenotype studies undertaken in Ecalc1 (kl203X/203X) mice demonstrated elevations in plasma concentrations of phosphate, FGF23 and 1,25-dihydroxyvitamin D. Thus, two allelic variants of Kl that develop EC and represent mouse models for tumoural calcinosis have been established.

Topics: Alleles; Amino Acid Sequence; Animals; Calcinosis; Chlorocebus aethiops; Codon, Nonsense; COS Cells; Disease Models, Animal; Endoplasmic Reticulum; Ethylnitrosourea; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Genetic Loci; Genotype; Glucuronidase; Humans; Kidney; Klotho Proteins; Longevity; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Mutation, Missense; N-Acetylgalactosaminyltransferases; Phenotype; Phosphates; Polymorphism, Single Nucleotide; Polypeptide N-acetylgalactosaminyltransferase; Sequence Alignment; Vitamin D

Topics: Calcinosis; Calcium; Cryptogenic Organizing Pneumonia; Drug Therapy, Combination; Dyspnea; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Kidney Transplantation; Lung Diseases; Parathyroidectomy; Postoperative Complications; Tomography, X-Ray Computed; Vitamin D; Weight Gain

Hypertrophy and impaired mineralization are two processes closely associated with osteoarthritis (OA). 1,25-dihydroxyvitamin D(3) (1a,25(OH)(2)D(3)) and inorganic phosphate (Pi) are two important factors that are implicated in calcium and phosphate homeostasis of bone metabolism and both can be regulated by the circulating phosphaturic factor fibroblast growth factor 23 (FGF23). The objective of this study was to investigate the role of 1a,25(OH)(2)D(3) and Pi and the molecular mechanism through which they contribute to hypertrophy and mineralization in human osteoarthritic chondrocytes. For this purpose, primary human chondrocytes were obtained from articular cartilage which was collected after total knee replacement surgery in OA patients. FGF23, fibroblast growth factor receptor 1c (FGFR1c), vitamin D(3) receptor (VDR), and phosphate inorganic transporter-1 and -2 (PiT-1 and PiT-2) expression levels were evaluated and found to be significantly higher in OA chondrocytes compared with normal. In addition, we observed that the binding of FGF23 to FGFR1c was stronger in OA chondrocytes compared  with normal. Chromatin immunoprecipitation (ChIP) assay revealed, for the first time, the presence of two vitamin D response elements (VDREs) in the FGF23 promoter. Treatment of normal chondrocytes with 1a,25(OH)(2)D(3) or Pi resulted in significant up-regulation of VDR, FGF23, PiT-1, PiT-2 mRNA and protein levels, extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation and induction of hypertrophy markers collagen type X (COL10A1), osteopontin (OPN), osteocalcin (OC), catabolic markers metalloproteinase-13 (MMP-13) and the apoptotic marker caspase-9. Furthermore, VDR silencing in OA chondrocytes negatively regulated FGF23, COL10A1, OPN, OC, MMP-13 and caspase-9 expressions and ERK1/2 phosphorylation. Finally, combined VDR silencing and PiT-1, PiT-2 inhibition in OA chondrocytes resulted in additive down-regulation of FGF23 expression, ERK1/2 activation and COL10A1, OPN, OC, MMP-13 and caspase-9 expression levels. We propose that 1a,25(OH)(2)D(3) and Pi act synergistically through FGF23 signaling and ERK1/2 phosphorylation contributing to late hypertrophic events and impaired mineralization in osteoarthritic chondrocytes.

Topics: Aged; Blotting, Western; Calcinosis; Cartilage, Articular; Chondrocytes; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hypertrophy; Immunoprecipitation; Male; Middle Aged; Mitogen-Activated Protein Kinases; Oligonucleotide Array Sequence Analysis; Osteoarthritis; Phosphates; Promoter Regions, Genetic; Real-Time Polymerase Chain Reaction; Vitamin D; Vitamin D Response Element

Vitamin D has a number of pleiotropic effects in a variety of tissues, in addition to its well-known effects on mineral metabolism. To determine whether it has an effect on erythropoiesis, we studied the association of the components of the vitamin D axis with the prevalence and severity of anemia in chronic kidney disease. We measured the concentrations of 25-hydroxyvitamin D (25D), 1,25-dihydroxyvitamin D (1,25D), and hemoglobin in a cross-sectional study of 1661 subjects in SEEK, a multi-center cohort study of chronic kidney disease patients in the United States, of whom 41% met the criteria for anemia. The mean hemoglobin concentrations significantly decreased with decreasing tertiles of 25D and 1,25D. These linear trends remained significant after adjustment for age, gender, ethnicity, eGFR, diabetes, and parathyroid hormone. In similarly adjusted models, the lowest tertiles of 25D and 1,25D were independently associated with 2.8- and 2.0-fold increased prevalence of anemia compared with their respective highest tertiles. Patients with severe dual deficiency of 25D and 1,25D had a 5.4-fold prevalence of anemia compared with those replete in both. Our study shows that 25D and 1,25D deficiency are independently associated with decreased hemoglobin levels and anemia in chronic kidney disease. Whether this association is causal requires further study.

Topics: Anemia; Bone and Bones; Calcinosis; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus; Dihydroxycholecalciferols; Hemoglobins; Humans; Kidney Failure, Chronic; Parathyroid Hormone; Prevalence; Renal Insufficiency, Chronic; United States; Vitamin D; Vitamin D Deficiency

Familial tumoral calcinosis is characterized by ectopic calcifications and hyperphosphatemia. The disease is caused by inactivating mutations in fibroblast growth factor 23 (FGF23), Klotho (KL), and uridine diphosphate-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). In vitro studies indicate that GALNT3 O-glycosylates a phosphaturic hormone, FGF23, and prevents its proteolytic processing, thereby allowing secretion of intact FGF23. In this study we generated mice lacking the Galnt3 gene, which developed hyperphosphatemia without apparent calcifications. In response to hyperphosphatemia, Galnt3-deficient mice had markedly increased Fgf23 expression in bone. However, compared with wild-type and heterozygous littermates, homozygous mice had only about half of circulating intact Fgf23 levels and higher levels of C-terminal Fgf23 fragments in bone. Galnt3-deficient mice also exhibited an inappropriately normal 1,25-dihydroxyvitamin D level and decreased alkaline phosphatase activity. Furthermore, renal expression of sodium-phosphate cotransporters and Kl were elevated in Galnt3-deficient mice. Interestingly, there were sex-specific phenotypes; only Galnt3-deficient males showed growth retardation, infertility, and significantly increased bone mineral density. In summary, ablation of Galnt3 impaired secretion of intact Fgf23, leading to decreased circulating Fgf23 and hyperphosphatemia, despite increased Fgf23 expression. Our findings indicate that Galnt3-deficient mice have a biochemical phenotype of tumoral calcinosis and provide in vivo evidence that Galnt3 plays an essential role in proper secretion of Fgf23 in mice.

Topics: Alkaline Phosphatase; Animals; Calcinosis; Disease Models, Animal; Female; Fertility; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucuronidase; Glycosylation; Homeostasis; Hyperphosphatemia; Klotho Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; N-Acetylgalactosaminyltransferases; Phenotype; Polypeptide N-acetylgalactosaminyltransferase; Vitamin D

Familial tumoral calcinosis is a rare autosomal recessive disorder that was first described well in a report on four patients from one family in 1969. The disease leads to periarticular ectopic calcifications. The original report described patients from black, healthy, unrelated parents with sixteen children, seven of whom had the disease.. On the basis of retrospective chart reviews and interviews with surviving family members, we describe the long-term follow-up of this one family, encompassing as long as forty years. Of the sixteen siblings, seven had tumoral calcinosis.. All seven affected children had hyperphosphatemia. There were two subsequent generations comprising thirteen children and seven grandchildren with no instances of tumoral calcinosis. The seven affected patients were followed for as many as forty years and underwent an average of twenty-one operations (range, four to thirty-six operations) for the treatment of calcified lesions. The genetic defect has been identified as the GALNT3 gene, thus leading to the hyperphosphatemic form of the disease. Although two of the patients had died by the time of the present study, the remaining five provided accounts of the disease course, the response to surgery and to medical therapy, and the effect of therapy on their lives. Some members had relatively few lesions and surgical procedures (as few as four), whereas others had an unrelenting course of lesions, recurrences, and surgical procedures (as many as thirty-six, with numerous other procedures). Three patients had multiyear periods with few symptoms--one for seven years, one for twelve years, and one for fifteen years. No effective medical therapy was found to control the lesions, and operations were associated with a high recurrence rate.. Familial tumoral calcinosis has a varied natural history; some patients have an unrelenting course, while others may experience quiescent periods. The GALNT3 gene is responsible for the hyperphosphatemic form as seen in this family. Molecular testing may be of benefit to members of affected families, and future studies may help to explain the phenotypic variability among affected individuals. No medical or surgical treatment plan seemed to be effective for controlling the lesions in this family.

Topics: Calcinosis; Cause of Death; Comorbidity; Female; Follow-Up Studies; Humans; Hyperphosphatemia; Joint Diseases; Male; Mutation; N-Acetylgalactosaminyltransferases; Pedigree; Polypeptide N-acetylgalactosaminyltransferase; Vitamin D

Klotho-knockout mice (klotho(-/-)) have increased renal expression of sodium/phosphate cotransporters (NaPi2a), associated with severe hyperphosphatemia. Such serum biochemical changes in klotho(-/-) mice lead to extensive soft-tissue anomalies and vascular calcification. To determine the significance of increased renal expression of the NaPi2a protein and concomitant hyperphosphatemia and vascular calcification in klotho(-/-) mice, we generated klotho and NaPi2a double-knockout (klotho(-/-)/NaPi2a(-/-)) mice.. Genetic inactivation of NaPi2a activity from klotho(-/-) mice reversed the severe hyperphosphatemia to mild hypophosphatemia or normophosphatemia. Importantly, despite significantly higher serum calcium and 1,25-dihydroxyvitamin D levels in klotho(-/-)/NaPi2a(-/-) mice, the vascular and soft-tissue calcifications were reduced. Extensive soft-tissue anomalies and cardiovascular calcification were consistently noted in klotho(-/-) mice by 6 weeks of age; however, these vascular and soft-tissue abnormalities were absent even in 12-week-old double-knockout mice. Klotho(-/-)/NaPi2a(-/-) mice also regained body weight and did not develop the generalized tissue atrophy often noted in klotho(-/-) single-knockout mice.. Our in vivo genetic manipulation studies have provided compelling evidence for a pathological role of increased NaPi2a activities in regulating abnormal mineral ion metabolism and soft-tissue anomalies in klotho(-/-) mice. Notably, our results suggest that serum phosphate levels are the important in vivo determinant of calcification and that lowering serum phosphate levels can reduce or eliminate soft-tissue and vascular calcification, even in presence of extremely high serum calcium and 1,25-dihydroxyvitamin D levels. These in vivo observations have significant clinical importance and therapeutic implications for patients with chronic kidney disease with cardiovascular calcification.

Topics: Animals; Blood Vessels; Bone and Bones; Calcinosis; Calcium; Female; Glucuronidase; Humans; Hypophosphatemia; Klotho Proteins; Male; Mice; Mice, Knockout; Phosphates; Sodium-Phosphate Cotransporter Proteins, Type IIa; Vitamin D

Frequent injections of the hormonal form of vitamin D(3), 1,25 dihydroxyvitamin D(3) (1,25D3) reportedly inhibits autoimmune type 1 diabetes (T1D) in non-obese diabetic (NOD) mice by correcting some of the abnormalities in antigen-presenting cells which contribute the development of pathogenic T cell responses. This route of administration greatly elevates the levels of these compounds in the bloodstream for hours after treatment, which requires mice to be fed diets formulated to contain much reduced levels of Ca to avoid the toxic effects of hypercalcaemia. In the current work, we demonstrate that feeding 1,25D3 or its synthetic precursor, 1alpha(OH) vitamin D(3) (1alphaD3), as part of a T1D supportive chow diet containing normal levels of Ca, is an effective means of reducing the incidence of disease in NOD mice, but the doses required for protection elicited hypercalcaemia. However, T1D protection elicited by D3 analogue feeding appears, at least partially, to have an immunological basis, as splenic T cells from treated mice had a decreased capacity to adoptively transfer disease. Protection is associated with an increased proportion of T cells with CD4+ forkhead box P3+ regulatory phenotype within the islet infiltrate of treated animals. The 1alphaD3 precursor is converted rapidly to the active 1,25D3 isoform in vivo. However, feeding the 1alphaD3 analogue elicited stronger T1D protection than the 1,25D3 compound, but also induced more severe hypercalcaemia. In future, the dietary supplementation of novel low-calcaemic D3 analogues may enable their continuous delivery at levels that inhibit T1D development in susceptible humans consuming normal levels of Ca.

Topics: Administration, Oral; Animals; Autoimmune Diseases; Bone Density Conservation Agents; Calcinosis; Diabetes Mellitus, Type 1; Diet; Dietary Supplements; Female; Flow Cytometry; Hydroxycholecalciferols; Islets of Langerhans; Male; Mice; Mice, Inbred NOD; T-Lymphocytes; Vitamin D; Vitamins

Fibroblastic growth factor 23 (FGF23) regulates renal phosphate reabsorption and 1alpha-hydroxylase activity. Ablation of FGF23 results in elevated serum phosphate, calcium, and 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D] levels; vascular calcifications; and early death. For determination of the independent roles of hyperphosphatemia and excess vitamin D activity on the observed phenotypic abnormalities, FGF23 null mice were fed a phosphate- or vitamin D-deficient diet. The phosphate-deficient diet corrected the hyperphosphatemia, prevented vascular calcifications, and rescued the lethal phenotype in FGF23 null mice, despite persistent elevations of serum 1,25(OH)(2)D and calcium levels. This suggests that hyperphosphatemia, rather than excessive vitamin D activity, is the major stimulus for vascular calcifications and contributes to the increased mortality in the FGF23-null mouse model. In contrast, the vitamin D-deficient diet failed to correct either the hyperphosphatemia or the vascular calcifications in FGF23 null mice, indicating that FGF23 independently regulates renal phosphate excretion and that elevations in 1,25(OH)(2)D and calcium are not sufficient to induce vascular calcifications in the absence of hyperphosphatemia. The vitamin D-deficient diet also improved survival in FGF23 null mice in association with normalization of 1,25(OH)(2)D and calcium levels and despite persistent hyperphosphatemia and vascular calcifications, indicating that excessive vitamin D activity can also have adverse effects in the presence of hyperphosphatemia and absence of FGF23. Understanding the independent and context-dependent interactions between hyperphosphatemia and excessive vitamin D activity, as well as vascular calcifications and mortality in FGF23 null mice, may ultimately provide important insights into the management of clinical disorders of hyperphosphatemia and excess vitamin D activity.

Topics: Animals; Calcinosis; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Mice; Mice, Knockout; Phosphorus Metabolism Disorders; Vascular Diseases; Vitamin D

Arterial calcification is a common feature of atherosclerosis, occurring in >90% of angiographically significant lesions. Recent evidence from this and other studies suggests that development of atherosclerotic calcification is similar to osteogenesis; thus, we undertook the current investigation on the potential role of osteoregulatory factors in arterial calcification.. We studied two human populations (173 subjects) at high and moderate risk for coronary heart disease and assessed them for associations between vascular calcification and serum levels of the osteoregulatory molecules osteocalcin, parathyroid hormone, and 1alpha,25-dihydroxyvitamin D3 (1,25-vitamin D). Our results revealed that 1,25-vitamin D levels are inversely correlated with the extent of vascular calcification in both groups. No correlations were found between extent of calcification and levels of osteocalcin or parathyroid hormone.. These data suggest a possible role for vitamin D in the development of vascular calcification. Vitamin D is also known to be important in bone mineralization; thus, 1,25-vitamin D may be one factor to explain the long observed association between osteoporosis and vascular calcification.

Topics: Adult; Aged; Calcinosis; Calcium; Coronary Artery Disease; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Osteocalcin; Osteoporosis; Parathyroid Hormone; Predictive Value of Tests; Risk Factors; Vitamin D