Note: Page numbers of article titles are in boldface type. A A Diabetes Outcome Progression Trial (ADOPT), 194 Adaptive immunity, 129 131 ADOPT (A Diabetes Outcome Progression Trial), 194 Aging, vitamin D metabolism changes with, 6 7 AIPC Study of Calcitriol Enhancing Taxotere study, 169 170 Alkaline phosphatase, in osteomalacia, 83 84, 89 Alopecia, in hereditary vitamin D-resistant rickets, 97, 101 102 Alzheimer disease, in diabetes mellitus, 193 194 Androgens, in vitamin D metabolism, 4, 22 23 Angiogenesis inhibition, calcitriol in, 165 166 Antigen-presenting cells, 128 129, 181 182 Antiinflammatory effects, of calcitriol, 163 165 Apoptosis, calcitriol effects in, 163 ASCENT (AIPC Study of Calcitriol Enhancing Taxotere) study, 169 170 Autoimmune diseases, vitamin D for, 149 150 B B lymphocytes, vitamin D and, 131, 152 153, 183 Belsey assay, 31 Beta cells, pancreatic, vitamin D and, 183 184, 189 190 Biopsy, bone, for osteomalacia, 89 90 Bligh-Dyer procedure, 37 Blindness, in diabetes mellitus, 193 Bone biopsy of, for osteomalacia, 89 90 demineralization of, 62 63. See also Osteomalacia; Osteoporosis. Bone mineral density, measurement of, for osteomalacia, 88 Bone pain in hereditary vitamin D-resistant rickets, 97 in osteomalacia, 84, 86 Bone scan, for osteomalacia, 87 88 Breastfeeding. See Mother-infant pairs. BXL-628 vitamin D analog, 210, 214, 219 C Calcipotriol, 210, 213, 216 Calcitonin in fetus, 65 66 in vitamin D metabolism, 4 6 Rheum Dis Clin N Am 38 (2012) 233 242 doi:10.1016/s0889-857x(12)00025-7 rheumatic.theclinics.com 0889-857X/12/$ see front matter ª 2012 Elsevier Inc. All rights reserved.
234 Calcitriol, 210. See also 1,25-Dihydroxyvitamin D 3. analogs of, 213 214, 220 anticancer effects of, 161 178 animal models of, 166 167 clinical studies of, 167 170 epidemiology and, 161 162 mechanisms of, 162 166 Calcitroic acid, synthesis of, 3 Calcium homeostasis of, in mother-infant pair, 65 69 in vitamin D metabolism, 3 metabolism of, in kidney disease, 115 116 supplementation with for rickets, 100 101 with vitamin D, 110 Cancer prevention and treatment, vitamin D for, 49 50, 143 147, 161 178 analogs, 216 217 animal models of, 166 167 clinical studies of, 167 170 epidemiology and, 161 162 mechanisms of, 162 166 Cardiovascular disease in diabetes mellitus, 193 vitamin D and, 50, 119, 153 154 Cathelicidin, 50, 119 120, 126 129 Choices for Health Outcomes in Caring for ESRD (CHOICE) study, 119 Cholecalciferol. See Vitamin D 3. Chromatin immunoprecipitation analysis, of vitamin D action, 18 22 Chromatography, for vitamin D, 32 Circulating forms, of vitamin D, of 29 44 Competitive protein-bound assay, 30 31 Crohn disease, 133 CTA016, 211 CYP27B1 gene mutations, in 1a Hydroxylase deficiency, 94 97 Cytochrome P450 enzymes, in vitamin D metabolism, 1 2 Cytokines, vitamin D and, 183 D DBP protein, in diabetes mellitus, 188 189 7-Dehydrocholesterol, 1,25-dihydroxyvitamin D 3 synthesis from, 1 2 Dementia, in diabetes mellitus, 193 194 Dendritic cells, 128 129, 181 182 DEQAS (Vitamin D External Quality Assessment Scheme), 34, 36, 39 40 Diabetes mellitus, vitamin D and, 150, 179 206 complications of, 192 194 gestational, 192 in deficiency, 50 maturity onset, 188 type 1, 132 133, 180 186 animal models of, 184 185
235 beta cells and, 183 184 clinical trials of, 185 186 environmental factors in, 181 genetic factors in, 180 181 immune system modulation in, 181 183 type 2, 154, 186 192 animal studies of, 190 beta cells and, 189 190 clinical trials of, 190 192 epidemiology and, 186 187 genetic factors in, 188 189 lifestyle in, 187 188 DiaSorin vitamin D analysis systems, 31 37 Differentiation, of cancer cells, calcitriol effects in, 162 163 Dihydrotachysterol, 209, 213 1,25-Dihydroxyvitamin D 3, 212. See also Calcitriol. action of, 3 7 analogs of, 210, 213 214 circulating, 29 44 normal levels of, 38 39 quantitation of, 37 38 stability in plasma, 39 standardized analytical methods for, 39 40 for cancer, 168 in gene expression regulation, 13 27 structure of, 208 synthesis of, 1 2 Direct physical detection methods, 32, 38 Dual-energy x-ray absorptiometry, for osteomalacia, 88 E EB1089 (seocalcitol), 168, 210, 213, 216 ED71 vitamin D analog, 210, 213 Environmental factors in diabetes mellitus, 181 in vitamin D synthesis, 63 65. See also Ultraviolet radiation and sunlight. Ergocalciferol. See Vitamin D 2. Estrogens, in vitamin D metabolism, 4, 22 23 European Community-sponsored Concerted Action on the Epidemiology and Prevention of Diabetes, 185 F Falls, in vitamin D deficiency, 49, 107 113 Fibroblast growth factors, in vitamin D metabolism, 4, 117 Fractures in diabetes mellitus, 194 in osteomalacia, 88 prevention of, 107 113
236 G Gait, abnormal, in osteomalacia, 86, 108 109 Genetic disorders, in vitamin D action, 93 106 1a hydroxylase deficiency, 94 97 VDR protein defects, 97 102 Genetic factors, in diabetes mellitus, 180 181, 188 189 Gestational diabetes, 192 Growth arrest, of cancer cells, calcitriol effects in, 162 163 H Heart attack prevention, 193 Hereditary vitamin D-resistant rickets, 97 102 alopecia in, 97, 101 102 clinical features of, 97 genetic factors in, 97 100 mouse models of, 100 treatment of, 100 101 Histone methyltransferases, in vitamin D metabolism, 3 1a Hydroxylase body distribution of, 95 deficiency of, 94 97 extra-renal, 222 in vitamin D metabolism, 6 7 replacement of, 215 25-Hydroxyvitamin D, 212 circulating, 29 44 analytic recovery of, 32 34 clinical reporting of, 35 37 normal levels of, 35 quantitation of, 30 32 stability in plasma, 35 standardized analytical methods for, 39 40 structure of, 208 25-Hydroxyvitamin D 3 24-hydroxylase, 3 Hyperparathyroidism in hereditary vitamin D-resistant rickets, 97 in kidney disease, 116 in obesity, 187 in osteomalacia, 87, 89 vitamin D analogs for, 214 216 Hyperphosphatemia, in kidney disease, 116 Hypertension, vitamin D for, 153 154, 193 Hypocalcemia in 1a hydroxylase deficiency, 95 in osteomalacia, 89 in rickets, 62 63, 97 Hypophosphatemia in 1a hydroxylase deficiency, 95 in osteomalacia, 89 Hypovitaminosis D. See Vitamin D deficiency.
237 I IDS Diagnostics analytical system, 35 36 Immune system, vitamin D and, 125 139 adaptive, 129 131 disorders related to, 131 133 historical perspective of, 125 126 in diabetes mellitus, 181 183 innate, 126 129, 150 153 Inecalcitol, for cancer, 168 Infantile nutritional rickets, 61 79 causes of, 62 65 clinical features of, 62 63 epidemiology of, 62 65 geographical factors in, 62 65, 68 69 mother-infant pair in calcium homeostasis and, 65 69 prevention of, 70 74 vitamin D deficiency consequences in, 69 70 pathogenesis of, 64 65 Inflammatory bowel disease, 133 Innate immunity, 126 129, 150 153 Insulin resistance, in obesity, 187 188 Interferons, vitamin D and, 183 Interleukins, vitamin D and, 183 Invasion, by cancer cells, calcitriol effects on, 163 K KH 1060, 213 Kidney disease of, 115 123 calcium metabolism in, 115 116 in diabetes mellitus, 192 193 mineral bone disorder in, 116, 118 119 phosphorus an, 118 vitamin D analogs for, 215 vitamin D physiology and, 117 vitamin D supplementation for, 118 120 vitamin D hydroxylases in, 3 7 Kloltho protein, in vitamin D metabolism, 4 KS 176, 211 L Lactation, vitamin D deficiency in. See Mother-infant pairs. LG 190090, 211 Liaison assay, 31 32 Liquid chromatography, for vitamin D, 32, 36 37 Liver, vitamin D clearance in, 220 221 Looser s zone, in osteomalacia, 87
238 Low vitamin D status, 45 59 assessment of, 45 46, 50 51 consequences of, 49 50 definition of, 46 prevalence of, 46 49 supplementation for, 51 53 LY2109866, 214 M Macrophages, vitamin D and, 6, 126 128 Mass spectrometry, for vitamin D, 32, 36 37 Maturity onset diabetes, 188 Maxacalcitol, 213 MC903, 213 Membrane-activated rapid response to steroids receptor, 221 Metabolic syndrome, 187 Metalloproteinases, calcitriol effects on, 163 Metastasis, calcitriol effects in, 163 Mitogen-activated protein kinase phosphatase-5, calcitriol effects on, 164 Monocytes, vitamin D hydroxylases in, 6 Mother-infant pairs, vitamin D deficiency in calcium homeostasis and, 65 69 consequences of, 69 70 prevention of, 70 74 Multiple sclerosis, vitamin D and, 132, 149 150 Muscle dysfunction, in vitamin D deficiency, 49 N Nerve damage, in diabetes mellitus, 193 194 NF-kB, calcitriol effects on, 164 165 Nichols analysis systems, 31 O Obesity, 187 188 Osteitis fibrosa cystica, in osteomalacia, 87 Osteocalcin, 17 18 Osteomalacia differential diagnosis of, 84, 86 in vitamin D deficiency, 81 91 biochemical changes in, 89 clinical manifestations of, 83 86 diagnosis of, 89 90 evolution of, 82 83 fractures in, 88 historical perspective of, 81 82 radiology for, 87 88 treatment of, 90 versus osteoporosis, 82
239 Osteopathy, in vitamin D deficiency, 82 83 Osteoporosis evolution of, 82 83 versus osteomalacia, 82 Oxacalcitriol, 210 P Pancreatic beta cells, vitamin D and, 183 184, 189 190 Parathyroid hormone in fetus, 65 66 in vitamin D metabolism, 3, 21 22, 117 Paricalcitol, for cancer, 168 Paricalcitol benefits in Renal Failure Induced Cardiac Morbidity (PRIMO) trials, 119 Phosphate, in vitamin D metabolism, 3 Phosphorus, metabolism of, in kidney disease, 118 Pigmentation, skin, vitamin D synthesis and, 62 64, 68 69 Placenta, vitamin D metabolism in, 6 Plasma cells, vitamin D and, 131 Pommer, Gustav, on osteomalacia, 81 82 Pregnancy. See also Mother-infant pairs. circulating vitamin D levels in, 38 39 diabetes mellitus in, 185 gestational diabetes in, 192 vitamin D metabolism in, 6 PRIMO (Paricalcitol benefits in Renal Failure Induced Cardiac Morbidity) trials, 119 Prodrugs, of vitamin D, 209, 212 213 Progesterone, in vitamin D metabolism, 4 Prolactin, in vitamin D metabolism, 5 6 Prostaglandins, calcitriol effects on, 164 Prostate cancer, vitamin D for, 147 Protrusio acetabuli, in osteomalacia, 87 Psoriasis, vitamin D and vitamin D analogs for, 147 149, 216 217 R Radiography, for osteomalacia, 87 88 Radioimmunoassays, 31, 38 Radionuclide bone scan, for osteomalacia, 87 88 Radioreceptor assays, 37 Random-access automated instrumentation, for vitamin D measurement, 31 32 Receptor activator of NF-kB ligand (RANKL), 15, 21 22 Respiratory infections, in vitamin D deficiency, 50 Rickets hereditary vitamin D-resistant, 97 102 historical perspective of, 142 infantile, 61 79 Roche Diagnostics assay system, 32 RUNX2 protein, action of, 18 S Sarcoidosis, 143 Scapula, pseudofracture of, 87
240 SDZ 89 443, 211 Secosterol ring structure, 208 209 Sensory neuropathy, in diabetes mellitus, 193 194 Seocalcitol (EB1089), 168, 210, 213, 216 Skin pigmentation, vitamin D synthesis and, 62 64, 68 69 SL 117, 211 Snail transcription factor, in cancer, 147 148 Stress-activated kinase signaling, calcitriol effects on, 164 Stroke prevention, vitamin D for, 193 Sunlight. See Ultraviolet radiation and sunlight. T T lymphocytes, vitamin D and, 129 131, 152 153, 182 183 TEI-9647, 211 Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, 165 166 Tuberculosis, vitamin D and, 132, 150 151 U Ultraviolet radiation and sunlight, 1, 72 cancer incidence related to, 143 144, 161 162 diabetes mellitus risk and, 181 inadequate exposure to, 63 65 recommendations for, 52 V VID-400, 211 Vision loss, in diabetes mellitus, 193 Vitamin D action of genetic defects in, 93 106 in muscle health, 108 109 assessment of, 29 44, 45 46, 50 51 cardiovascular effects of, 119 circulating forms of, 29 44 controversies over, 46 48 diabetes and. See Diabetes mellitus. for cancer prevention. See Cancer prevention and treatment. for extraskeletal health, 141 160 for fracture prevention, 107 113 immune system and, 125 139, 150 153 in kidney disease. See Kidney. infantile rickets and, 61 79 low status of, 45 59 metabolism of, 1 11, 45 46, 146 in kidney disease, 117 in mother-infant pair, 65 69 natural metabolites of, 208, 210, 212 physiology of, 116 117
sources of, 141 142 structure of, 28 supplementation with, 51 53 approaches to, 51 52 for fracture prevention, 107 113 for kidney disease, 118 120 for osteomalacia, 90 in diabetes mellitus, 185, 192 in mother-infant pair, 70 74 in pregnancy, 185 vitamin D 2 versus vitamin D 3,53 synthesis of, 63 65 toxicity of, 52 53 Vitamin D 2, 212 213 analogs of, 209, 212 213 structure of, 209 versus vitamin D 3, for supplementation, 53 Vitamin D 3 analogs of, 208 1,25-dihydroxyvitamin D 3 synthesis from, 1 2 structure of, 208 versus vitamin D 2, for supplementation, 53 Vitamin D analogs, 207 232 activating enzymes for, 217 218 clinical applications of, 214 217 criteria affecting action of, 217 221 1,25-dihydroxyvitamin D 3 analogs, 210, 213 214 for cancer, 147, 167 170 future of, 221, 223 224 hepatic clearance of, 220 221 mechanisms of action of, 221 222 natural metabolites, 208, 210, 212 nongenomic effects of, 221 prodrugs, 209, 212 213 receptors for, 221 target cell catabolic enzymes and, 219 220 vitamin D binding protein and, 218 vitamin D receptor interactions with, 218 219 Vitamin D binding protein action of, 1 3 vitamin D analogs and, 218 Vitamin D deficiency clinical features of, 142 geographical factors in, 62 65, 68 69, 142 historical perspective of, 142 143 in Crohn disease, 133 in diabetes mellitus, 132 133 in multiple sclerosis, 132 in tuberculosis, 132, 150 151 infantile nutritional rickets in, 61 79 intrauterine effects of, 70 241
242 Vitamin D (continued) low vitamin D status and, 45 59 obesity in, 187 osteomalacia in, 81 91 screening for, 50 51 Vitamin D External Quality Assessment Scheme (DEQAS), 34, 36, 39 40 Vitamin D hydroxylases, 1, 3, 6 7 Vitamin D receptor, 13 27 binding activity of, 208 cancer and, 147 diabetes mellitus and, 180 181, 188 189 function of, 14 15, 108 109 genes of, 180 181, 188 189 in autoimmune diseases, 150 in cancer cells, 166 in gene regulation, 18 23 in mother-infant pair, 69 70 innate immune system and, 126 129 structure of, 14 15 target genes of, 15 18 vitamin D analog interactions with, 218 219 W Walking, difficulty with, in osteomalacia, 86, 108 109 Weakness in osteomalacia, 84, 86 in vitamin D deficiency, 49 Women s Health Initiative, 192 Z ZG 1368, 211 ZK159222, 211