Index

Acidemia, radiographic findings, 880 Akt Anticonvulsants, metabolism Arne, vitamin D therapy, 1898 cell differentiation induction via vitamin D, effects, 1257-1258 Actin, vitamin D binding protein complex, 1628-1629 Antimicrobial peptides, vitamin D effects on 65-66 leukemia signaling and vitamin D effects, expression, 1781-1783, 1813-1814 Actinic keratosis, vitamin D therapy, 1739 AP-l, see Activator protein-l 1898 photoprotection mechanisms of vitamin D Apoptosis Activator protein-l (AP-l), cell compounds, 1948 breast cancer cells, 1658-1659 differentiation induction via Alcohol calbindin D function, 369-370 vitamin D, 1631 alcoholism cancer and vitamin D, 1602-1603 AD, see Alzheimer's disease cirrhosis and bone loss leukemia, 1737 ADAM17, vitamin D renoprotective actions, clinical features, 1312 osteoclast, 339 1342-1345 epidemiology, 1311-1312 prostate cancer, 1685 Adipocyte pathogenesis, 1312-1313 Arsenic trioxide, leukemia treatment with vitamin D effects, 770-773 treatment, 1313 vitamin D combination therapy, vitamin D sequestration, 1019 hypophosphatemia, 1175 1740 Adolescent vitamin D metabolism effects, 1259-1260 Arteriosclerosis asthma and vitamin D status, 671 Aldosterone, see Renin-angiotensin system calcium-sensing receptor defects, calcium 1417-1418 absorption enhancers, 653-654 chemical synthesis, 1490-1491 vitamin D retention markers, 667 history of development, 1489-1490 calcium, phosphate, and vitamin D diabetes and vitamin D status, 671 multiple sclerosis treatment, 1865 excess effects, 1141 influenza and vitamin D status, osteoporosis management, 1491-1495 fibroblast growth factor-23/klothol 671 Alien, repression, vitamin D axis, 1413-1414 pubertal bone acquisition, 657-659 202-203 intervention studies vitamin D Alkaline phosphatase, vitamin D effects in animal models, 549-550 deficiency prevalence, 659-660 bone, 416 humans, 1408-1409 intake recommendations, 671-672 Alkalosis, hypophosphatemia, 1174 overview of actions, 1406-1408 intervention trials Allergic rhinitis, vitamin D studies, 2013 parathyroid hormone receptor signaling, bone response, 667-669 All-trans retinoic acid (ATRA), leukemia 1414-1415 muscle response, 669 treatment with vitamin D toxicity and ectopic calcification, 590 status influences combination therapy, 1739-1740 toxicity studies, 1409-1411, 1415-1416 age and pubertal maturation, 662 Alopecia vitamin D analog risks, 1418-1419 latitude and season, 661-662 hereditary vitamin-D resistant rickets Arthritis, see Osteoarthritis; Psoriatic obesity, 662 association, 1200, 1223-1224 arthritis; Rheumatoid arthritis race and socioeconomic status, 662 rickets association, 814 Arthroplasty, see Orthopedics sex differences, 662, 669-671 Aluminum toxicity, radiographic findings, 5-ASA, see 5-Aminosalicylic acid status markers 874-875 Association studies bone turnover markers, 666 Alzheimer's disease (AD), vitamin D candidate gene association studies, la:,25-dihydroxyvitamin D, 663-664 studies, 575 1027-1028 fractional calcium absorption, 5-Aminosalicylic acid (5-ASA), genome-wide association studies, 664-665 inflammatory bowel disease 1028-1029 25-hydroxyvitamin D, 659 management, 1885 overview, 1027 intact parathyroid hormone, 664 Analogs, see Vitamin D analogs Asthma AF-2 Anaphylaxis, vitamin D studies, 2012-2013 adolescent vitamin D status, 671 mutation, 239 Angiogenesis clinical features, 2001-2002 vitamin D receptor activation, 105, 108, 110, inhibition by vitamin D in cancer, control, 2008-2010 148,151 1595-1597 intervention trials of vitamin D in acute AFM, see Atomic force microscopy prostate cancer and vitamin D inhibition, respiratory infection, 2005-2006 Aging, see also Elderly; Falls; Fracture 1688-1689 observational studies of vitamin D, klotho studies, 754 vitamin D receptor functions, 543-544 2004 metabolic bone disease, 807 Angiotensin, see Renin-angiotensin system pathogenesis, 2006-2008 vitamin D receptor as longevity nuclear Animal feed prospects for study, 2014 receptor, 160-161 biofortification, 999 vitamin D deficiency during pregnancy and vitamin D synthesis effects, 16 vitamin D intake recommendations, 87-88 late effects on child, 687

2057 2058 INDEX

Atherosclerosis glucocorticoid-induced osteoporosis metabolism, 411-413 Bon endothelial dysfunction, 1975-1976 therapy, 1240-1241 sources, 412-413 optimal vitamin D status, 1079-1080 vitamin D metabolism effects, 1262 vitamin D receptor BPH vitamin D BL269, 1475 bacterial artificial chromosome clones Brai intervention studies, 555-556, BL314,1475 studies, 123 ca 1408-1409 BL562,1475 function, 437-438 d~ observational studies, 555 Bladder cancer, vitamin D studies, Wnt in homeostasis, 242-243 overview of actions, 1406-1408 1765-1766 Bone histomorphometry Vitamin D and Omega-3 Trial background, BMD, see Bone mineral density biopsy 2045 BMPs, see Bone morphogenetic proteins adverse effects, 846 Atomic force microscopy (AFM), Body size, vitamin D synthesis effects, indications, 846 inl mineralization analysis, 387 986-987 technique, 845-846 kr Atopic dermatitis, vitamin D studies, Bolus dosing, vitamin D, 1001-1002 bone turnover analysis 2012-2014 Bone, see also Collagen; Fracture; activation frequency, 852 ne ATRA, see All-trans retinoic acid Mineralization; Oral skeleton; formation rates, 852 AUF-I, 430, 500 Osteoblast; Osteoclast; Osteocyte; mineralizing perimeter, 852 vit Autoimmune disease, see specific diseases Rickets; Runx2 remodeling periods, 853 vit Autoimmune polyglandular syndrome bariatric surgery effects, 1016-1018 limitations, 848 type 1, hypocalcemia, 1095 biopsy, see Bone histomorphometry methodology, 846-847 Autophagy calbindin D function, 366-367 mineralization assessment breast cancer, 1658-1659 calcium-sensing receptor function, 437-438 , adjusted apposition rate, 850 BRC innate immunity, 1815 ~-catenin-vitaminD receptor interactions, mineral apposition rate, 849-850 Brea~ 156,243-244 mineralization lag time, 850 BAC, see Bacterial artificial chromosome chromatin remodeling, 311-313 osteoid maturation time, 850 Brem Bacterial artificial chromosome (BAC), CYP27Bl function, 412-413, 587 osteoid measurement, 849 cel vitamin D receptor clones epigenetic mechanism for lineage tetracycline labeling, 848-849 bone cell activity, 123 commitment, 309-310 osteomalacia transgenes in mice, 123-124 fetal development, 626 focal osteomalacia, 852 Bariatric surgery, see Obesity fibroblast growth factor-23 coordination of generalized osteomalacia, 851-852 Basal cell carcinoma, see Skin cancer renal phosphate handling with bone prospects, 857 B cell mineralization and turnover, referents, 847 CYP27Bl/vitamin D receptor knockout 757-758 remodeling studies, 594-596 formation balance assessment vitamin D receptor agonist effects, endochondral bone formation in formation, 853-854 1798-1799 development, 301-303 resorption, 854-855 Benign prostatic hyperplasia (BPH) nuclear organization of regulatory indices, 846 epidemiology, 1931 machinery, 306-308 structural assessment medical treatment, 1933 signaling in formation determinants of bone strength, 855 CY pathogenesis, 1931-1933 bone morphogenetic proteins, 304 three-dimensional approaches, 856 vitamin D receptor agonist studies fibroblast growth factors, 304 two-dimensional approaches, 856 inflammation inhibition, 1935-1936 Wnt, 304-305 terminology, 847-848 lower urinary tract symptoms, gene expression within context of nuclear theory, 846 est! 1931-1933 architecture, 309-311 Bone mineral density (BMD) int~ overview, 1803 gene transactivation by vitamin D receptor, genome-wide association studies, prospects for study, 1937-1938 113, 117-118 1034-1035 pre prostate cell growth control, maternal vitamin D deficiency effects on glucocortiCOid-induced osteoporosis and pro 1933-1934 child later in life, 687 vitamin D response, 1238-1241 vita urethra dysfunction, 1936-1937 mechanical load response, 325-326 idiopathic hypercalciuria and reduction, Beta cell, see Diabetes metastasis and chemokines in osteoclast 1363-1365 vita Bile acids, see also regulation, 340-341 measurement, see Dual-energy X-ray Ii derivatives osteoarthritis changes, 1956-1957 absorptiometry; Quantitative metabolism and regulation by nuclear parathyroid hormone function, 730-732 computed tomography v receptors, 1511-1514 parathyroid hormone-related protein optimal vitamin D status, 1073 pathophysiology, 777 function, 734-735 osteoporosis effects of calcium and vitamin structures, 1510 pregnancy and lactation effects, D supplementation, 1133-1134 synthesis and metabolism, 760, 1511-1512 682-684 pubertal bone acquisition, 657-658, types, 775 pubertal bone acquisition, 657-658 660-661 BroWl vitamin A effects on synthesis, 764-765 remodeling, 323-325, 813 Bone morphogenetic proteins (BMPs), bone vitamin D receptor scaffolding of regulatory components for formation signaling, 304 BSP,sl bile acid synthesis regulation, 765-766 combinatorial control of gene Bone scinitigraphy Bumi binding, 766 expression, 313-315 metabolic bone disease diagnosis, 817 BXL-6 detoxification role, 765-766 turnover, 335 overview, 883 BXLOl interaction overview, 1509-1511 turnover markers as vitamin D status Bone sialoprotein (BSP), mineralization role Biliopancreatic diversion, see Obesity markers in adolescence, 666 and vitamin D effects, 392-393, CaffeiJ Bisphosphonates vitamin D 416-417 Calbir INDEX 2059

Bone volume, CYP27B1 knockout studies, apoptosis role, 369-370 hypocalcemia and dietary deficiency, 1099 587 calcium absorption role, 353 influx and adipocyte metabolism, 769 BPH, see Benign prostatic hyperplasia discovery, 363 intake Brain forms, 363 developing countries, 652 nes calbindin D function, 369-370 functions food fortification, 653 developmental vitamin D deficiency bone, 366-367 recommendations in infants and behavioral effects in later life, 568-569 intestine, 364-366 children, 649-650 dietary restriction, 567-568 kidney, 366, 478-480 recommendations gene expression effects in later life, 568 nervous tissue, 368-369 infants, 649-650 structural alterations, 576 pancreas, 367-368 infants and children, 649-650 inflammation, 571 reproductive tissues, 368 toddlers, 650-651 knockout mouse studies of vitamin D genes neuroprotective actions of vitamin D, 572 system, 569-570 calbindin-D9k osteoporosis studies of supplementation neurological and psychiatric disorder genomic organization, 371 bone mineral density effects, 1133-1134 studies of vitamin D, 570-575 regulation by miscellaneous steroids, fracture prevention vitamin D metabolites, 566 371-372 calcium and vitamin D, 1137 vitamin D receptor vitamin D regulation, 371 meta-analysis, 1138-1139 developmental expression, 567 calbindin-D28k safety of supplements, 1139 distribution, 566 genomic organization, 370 single annual dosing, 1136 non-neuronal cells, 566-567 regulation by miscellaneous steroids, secondary prevention, 1139-1140 BRCA1, vitamin D induction, 1661 370-371 parathyroid hormone expression Breast, see Breast cancer; Lactation; vitamin D regulation, 370 regulation, 498-499 Mammary gland knockout mice, 353, 365-366 pregnancy and lactation effects on Breast cancer prospects for study, 373-374 metabolism, 679-682 cell culture effects of vitamin D renal function, 366, 478-480 prostate cancer intake studies, 972-973 apoptosis and autophagy, 1658-1659 structure, 364-365 retention markers in adolescence, 66 overview, 1658 tissue distribution, 373 rickets and deficiency, 1118-1120 target genes and pathways Calcium absorption angiogenesis, invasion and metastasis, cancer studies, 1438-1439 bariatric surgery effects, 1019-1021 52 1662 leukemia studies, 1741 CYP27B1 in intestine, 585 estrogen metabolism and signaling, modification for receptor antagonism, dietary calcium intake as regulator of 1659-1660 184-186 efficiency, 350, 614-617 growth factor signaling, 1660 psoriasis management, 1438 enhancers for children and adolescents, inflammation pathways, 1660 Calcitonin 653-654 miscellaneous genes and pathways, calcium-sensing receptor effects, 433 fetal, 629-630 1661-1662 clinical applications, 739-740 fractional calcium absorption as vitamin D stress pathways, 1660-1661 CYP24A1 expression regulation, 1531 status marker in adolescence, CYP27B1/vitamin D receptor knockout functional overview, 739 664-665 855 studies, 590-591 gene, 738 glucocorticoid-induced osteoporosis, 1238 856 epidemiological studies of vitamin D history of study, 737-738 25-hydroxyvitamin D role, 620 6 status, 1667-1668 pathophysiology, 739 idiopathic hypercalciuria estrogen in pathogenesis, 1657 receptor, 738 intestinal increase, 1360-1362 intervention trials with vitamin D and secretion regulation, 738-739 renal reabsorption decrease, 1362-1363 analogs, 1665 vitamin D metabolism effects, 1249-1250 infants, 650 prevention with vitamin D, 1667 Calcium, see also Hypercalcemia; kinetics, 349 prospects for study, 1668 Hypercalciuria; Hypocalcemia location and timing in gut, 614 is and vitamin D intake and risk analysis, absorption, see Calcium absorption models 1241 1572-1578 body compartments, 607-609 active versus passive mechanisms, uction, vitamin D sensitivity determinants channel blockers and vitamin D 617-618 ligand availability and metabolism, metabolism effects, 1263 facilitated diffusion, 352-353 -ray 1662-1663 channels, see L-type calcium channels; paracellular movement through tight t~ve I vitamin D receptor Voltage-sensitive calcium channels junctions, 355 i expression and regulation, 1663 colorectal cancer effects of intake, transcaltachia, 354-355 polymorphisms and risk, 1668 1719-1721 vesicular transport, 353-354 bdvitamin prognostic significance, 1664 experimental autoimmune encephalitis optimal vitamin D status, 1071-1073 f-U34 resistance, 1664 prevention, 1856-1857 overview, 349-350, 1299-1300 f658, Brown tumor, radiographic findings, extracellular fluid concentration regulation premature infants,648 870-871 bone mineralization, 609 prospects for study, 355 lPs), bone BSP, see Bone sialoprotein deficiency, 611 race effects, 651-652 Bum injury, hypophosphatemia, 1175 diet, 611-612 renal tubular reabsorption BXL-628,1439 obligatory loss, 609-610 calcium-sensing receptor regulation, ~is,817 BXL0124,1439 parathyroid hormone 434-435 independent mechanisms, 612 CYP27B1 role, 585-586 lzation role Caffeine, 1267 mediated response, 610-611 overview, 471-472 92-393, I Calbindin D fetal metabolism, 625-627 vitamin D effects, 473-475 2060 INDEX

Calcium absorption (Continued) CYP24Al dysregulation, 1535-1536 rapid actions sex and race differences, 669-670 epidemiology of vitamin 0 and risk definition, 511 vitamin 0 receptor control, 351 breast cancer, 1575-1576 membrane signaling, 512-513 vitamin 0 status effects, 350-352 colon cancer, 1572-1574 models, 511-512 Calcium-sensing receptor (CaSR) esophageal cancer, 1577 physiological relevance ofnongenomic vit calcimimetic activators for intake studies, 1571 regulation of matrix vesicles, t hyperparathyroidism treatment, miscellaneous cancers, 1576-1577 513-515 440-443 mortalityI survival impact, 1581-1584 CaSR, see Calcium-sensing receptor calcium binding, 426-427 ovarian cancer, 1576-1577 Catechol-o-methyltransferase (COMT), calcium homeostasis maintenance overview, 1569, 1592-1593 developmental vitamin 0 hypercalcemia defense, 429 predicted 25-hydroxyvitamin 0 levels, deficiency effects in adult brain .. mechanisms, 429-430 1571-1572 expression, 568 overview, 425, 427-428 prospects for study, 1584-1586 I3-Catenin cardiovascular disease defects, 1417-1418 prostate cancer, 1574-1575 keratinocyte stem cell function, 536-537 colon cancer, 444-446 study design oncogenic activity, 156 ( expression regulation, 427 prospective studies, 1570-1571 osteoblast signaling, 243-244

hypocalcemia gene mutations, 1095 randomized trials, 1570, 1580-1581 signaling via Wnt, 235-237 0 keratinocyte function, 444 sun exposure skin signaling, 244-245 F knockout mouse, 429,433,526 case-control studies, 1578-1580 vitamin 0 inhibition, 238-241 vita parathyroid hormone secretion regulation, ecological studies of regional vitamin 0 receptor interactions Cell d 727-728 exposure, 1578 bone, 156,243-244 ker, polymorphisms, 446-447 surrogate of vitamin 0 status, 1572 colon, 114, 156, 239 leu] prospects for study, 447-449 total cancer risk, 1577 keratinocytes, 156-158 osh prostate cancer, 446 extrarenal vitamin 0 synthesis, 779 Cathelicidin antimicrobial peptide (CAMP) ostl renin secretion regulation, 443-444 growth inhibition by vitamin 0, 1594, 1608 respiratory disease, 2011-2012 osh structure, 426 knockout mice of vitamin 0 system studies, vitamin 0 effects on expression, 1781-1783, vita tissue distribution and function 590-593 2012 ir bone, 437-439 metastasis inhibition by vitamin 0, Caw see Voltage-sensitive calcium channels c· breast, 440 1595-1597 Caveolin 0: cartilage, 435-437 oncogenes, 1599 vitamin 0 effects, 2032 intestine, 439 optimal vitamin 0 status, 1077-1078 vitamin 0 plasma membrane receptor kidney, 433-435, 475-478 parathyroid hormone-related protein interactions, 283-284 parathyroid gland, 430-433 levels, 1597-1598 CBP, see CREB-binding protein placenta, 439-440 tumor suppressor genes, 1599, 1601-1602 CC, see Chief complaint

Calreticulin, parathyroid hormone vitamin 0 analog studies, 1437 CCNC, vitamin 0 regulation of expression, 0' expression regulation, 496 Vitamin 0 and Omega-3 Trial background, 219 pi CAMP, see Cathelicidin antimicrobial 2044-2045 CD14 pi peptide vitamin 0 receptor breast cancer expression, 1660 si Cancer, see also Metastasis; speCifiC cancers functional overview, 1591-1592 vitamin 0 effects on expression, 1780-1781 angiogenesis inhibition by vitamin 0, polymorphisms, 1593-1594 CD483,1480 1595-1597 resistance and vitamin 0 metabolism, C0503,1480 cell cycle effects of vitamin 0 1606-1608 C0504,1480 breast cancer, 1658 Wnt signaling, 235-237, 238-241 C0509,1480 cell-type specificity of inhibition, Candidate gene C04409,1506 tr, 1642-1643 association studies, 1027-1028 C04420, 1499 GI/S block vitamin 0 binding protein, 1032-1034 C04420, 1506 c-Myc downregulation, 1641-1642 vitamin 0 receptor, 1031-1032 C04528, 1506 p21 upregulation, 1637-1640 CAR, see Constitutive androstane receptor Cdks, see Cyclin-dependent kinases CF, see p27 upregulation, 1637-1640 Cardiac fibrosis, see Heart CONKIA, see p21 CH50c retinoblastoma protein regulation, Cardiac hypertrophy, see Heart CONKIB, see p27 Cherni 1640-1641 Cardiomyocyte, vitamin 0 function, 1976 COP, vitamin 0 receptor interactions, 201 G2/M retardation and polyploidization, Cartilage, see also Chondrocyte C/EBP Chernl 1642 calcium-sensing receptor function, 435-437 cell differentiation induction via vitamin 0, overview, 1598-1602 CYP27Bl function, 587-588 1631 Chief! prostate cancer, 1683 mineralization, 384-385 CYP24Al expression regulation, 1531 cellular effects of vitamin 0 osteoarthritis homeostasis and vitamin 0, Celiac disease, bone loss Childr apoptosis, 1602-1603 1955-1956 clinical features, 1305 calci cell cycle, 1598-1602 properties, 507 epidemiology, 1304-1305 cald differentiation, 1603-1604 vitamin 0 regulation pathogenesis, 1305 food growth factors and receptors, 1604-1605 1,25-dihydroxyvitamin 03 function, treatment, 1305 proliferation inhibition and stimulation 509-511 Cell cycle pseu 0, 1594, 1608-1609 24,25-dihydroxyvitamin 03 function, checkpoints, 1631-1632 clinical trials of vitamin 0, 1594-1595 509-511 driving mechanisms, 1632-1633 soda combination therapy with vitamin 0, overview, 507-509 leukemia, 1736-1737 vitar 1605-1606 prospects for study, 515-516 regulation de INDEX 2061

DNA replication licensing control, intake recommendations, 649-650 vitamin 0 deficiency 1635-1636 status influences overview, 717, 1342 Gl/S phase, 1633-1635 age and pubertal maturation, 662 kidney transplantation G2/M phase, 1636-1637 latitude and season, 661-662 post-transplantation, 1294 vitamin 0 effects in cancer obesity, 662 pre-transplantation, 1292-1293 breast cancer, 1658 race and socioeconomic status, 661-662 vitamin 0 receptor alterations cell-type specificity of inhibition, sex differences, 662 homologous upregulation defects, 1642-1643 ChIP, see Chromatin immunoprecipitation 1333-1335 Gl/S block , see lct,25-Dihydroxy­ miscellaneous resistance mechanisms, c-Myc downregulation, 1641-1642 vitamin 0 3 1335-1337 p21 upregulation, 1637-1640 Chondrocyte polymorphisms, 1335 p27 upregulation, 1637-1640 CYP24Al in maturation, 48 Chronic obstructive pulmonary disease retinoblastoma protein regulation, CYP27Bl function, 589-590 (COPO) 1640-1641 origins, 321 acute exacerbations, 2010-2011 G2/M retardation and polyploidization, vitamin 0 receptor function, 436-437 clinical features, 2002 1642 Chromatin pathogenesis, 2010 overview, 1598-1602 osteocalcin gene organization, 312-313 Chugaev reaction, 87 prostate cancer, 1684 remodeling in bone, 311-313 Chvostek's sign, 813 vitamin 0 receptor targets, 219 Chromatin immunoprecipitation (ChIP) Cimetidine, vitamin 0 metabolism effects, Cell differentiation vitamin 0 receptor studies, 111-115, 199, 1264 keratinocyte, 533-534, 537-538, 594 214,220 Cipt see p21 leukemia, 1736 vitamin 0 response element studies, 218 Cirrhosis, see Alcohol; Primary biliary osteoblast, 305-306 Chromatin-looping model, vitamin 0 cirrhosis osteoclast, 338-339 receptor transactivation, 152-153 CKO, see Chronic kidney disease osteocyte, 327-328 Chromatin unit, structure, 214 CLONI4, idiopathic hypercalciuria defects, vitamin 0 effects Chronic kidney disease (CKO) 1364, 1366 initial signals, 1626, 1628 bone effects, 1340 Clinical and Translational Science Center c-Myc downregulation, 1641-1642 calcium-sensing receptor (CTSC), Vitamin 0 and Omega-3 osteoblasts calcimimetic activators for treabnent of Trial,2052-2053 cell culture studies, 326-327 uremic hyperparathyroidism, Clothing, vitamin 0 synthesis effects, direct actions, 327-328, 414-417 441-442 16-17,989 transcriptional control, 305-306 secondary hyperparathyroidism, Cognition, vitamin 0 studies, 575 voltage-sensitive calcium channels, 442-443 Collagen 462-463 cardiovascular disease and vitamin 0 bone type I collagen expression and overview in cancer, 1603-1604 status, 1989-1990 vitamin 0 regulation, 402-405, 415 principal models in cancer, 1625-1626 CYP24Al activity, 49-50 mineralization role and vitamin 0 effects, prostate cancer, 1685-1686 CYP24Al dysregulation, 1537-1539 392 signaling CYP27Bl Colorectal cancer (CRC) Akt, 1628-1629 direct inhibition, 1330 calcium-sensing receptor, 444-446 mitogen-activated protein kinase, extrarenal enzyme alterations, CYP24Al expression regulation 1629-1630 1331-1333 calcium intake, 1719-1721 p35, 1630-1631 induction suppression, 1328-1330 folate intake and epigenetic regulation, protein kinase C, 1628 overview of studies, 32-33 1723-1724 transcription factors substrate availability, 1328 hyperproliferation and tumor activator protein-I, 1631 epidemiology, 716 progression, 1716-1717 C/EBP(3, 1631 intestine effects, 1338 polymorphisms and RNA splicing, Spl, 1631 parathyroid gland effects, 502, 1338-1340 1718-1719 CF, see Cystic fibrosis peritonitis, 781 sex hormones, 1721-1722 CH5036249,1483 renal mass reduction, 1327-1328 CYP27Bl expression regulation Chemiluminescence assay, renin-angiotensin system in calcium intake, 1719-1721 25-hydroxyvitamin 0, 829 pathophysiology, 717-718 folate intake and epigenetic regulation, Chemotherapy, hyperphosphatemia vitamin 0 analog therapy 1723-1724 induction, 1176 analog types, 1556 hyperproliferation and tumor Chief complaint (CC), metabolic bone animal model studies, 1556-1559 progression, 1716 disease, 809 cardiovascular disease outcomes, 1563 polymorphisms and RNA splicing, Children end-stage renal disease, 1560-1563 1718-1719 calcium absorption enhancers, 653-654 prospects for study, 1563-1564 sex hormones, 1721-1722 calcium intake recommendations, 649-651 stage 3-4 disease, 1559-1560 dietary factors, 1711-1712 food fortification with calcium and vitamin survival impact, 1561-1563 epidemiology, 1711-1712 0,653 vitamin 0 protective factors, 1712-1714 pseudo-vitamin 0 deficiency management, catabolism alterations, 1330-1331 vitamin 0 1192-1193 intervention studies, 557 chemoprevention mechanisms, soda intake effects on bone health, 652 observational studies, 556-557 1714-1715 vitamin 0 synthesis defects, 1325-1333 deficiency and pathogenesis, 1713-1714 deficiency prevalence, 659-660 therapy, 718, 1346-1348 intake and risk analysis, 1572-1574 2062 INDEX

Colorectal cancer (CRC) (Continued) Crystal structure C23 hydroxylation, 45 vitamin 0 receptor CYP27AI, 34-36 C24 oxidation, 43-46 expression, 444-446, 1718 CYP27B1 and homology models, 34-36 multifunctional activity, 45-46, 1528 target gene transactivation, 114-115 peroxisome proliferator-activating overview, 43-44 c( Wnt signaling, 237-238, 241-242 receptor-y, 104 chondrocyte maturation role, 48 -. Colorimetric assay, vitamin 0, 85 vitamin 0 receptor chronic kidney disease activity, 49-50 ., Commercial aspects, vitamin 0 antagonism structural basis colorectal cancer expression regulation assays adamantyl analog complexes, 186 calcium intake, 1719-1721 25-hydroxyvitamin 03, 87 calcipotriol modification for receptor folate intake and epigenetic regulation, provitamins, 86 antagonism, 184-186 1723-1724 vitamin 0, 84-86 22-butyl-1,24-dihydroxyvitamin 0 3 hyperproliferation and tumor historical perspective, 73-74 derivative complexes, 182-185 progression, 1716-1717 market, 88-90 C-2a;-substituted vitamin 0 analog polymorphisms and RNA splicing, dl metabolite manufacture complexes, 179-181 1718-1719 dl 1-hydroxyvitamin 03, 83 hVDRa bound to vitamin 0, 172-175, sex hormones, 1721-1722 dl di 25-hydroxyvitamin 0 3, 83-84 177 crystal structure, 34-36 provitamins ligand-binding domain bound to dental expression, 524 OJ photoconversion to vitamin 0, 79-83 superagonists discovery, 28-29 ex synthesis 14-epi analogs, 178-179 dysregulation and disease 7-dehydrocholesterol, 74-78 20-epi analogs, 176, 178 cancer, 1536-1537 ex ergosterol, 78-79 2-substituted, 19-nor analogs, 178 chronic kidney disease, 1537-1539 storage and shipping, 90 lithocholic acid derivative binding diabetes, 1537 Computed tomography (CT), see also 3-ketolithocholic acid, 1519 overview, 1534-1535 Quantitative computed lithocholic acid acetate/propionate, X-linked hypophosphatemia, 1535-1536 tomography 1519 expression regulation, 155, 219,586, microcomputed tomography unmodified lithocholic acid, 747-748,1529-1534 applications, 899-900 1517-1519 fracture repair role, 50-51 biomechanical analysis, 898-899 nonsteroidal ligand complexes gene methylation, 1533-1534 image acquisition YR301-rVOR ligand-binding domain glucocorticoid effects, 1236 conventional, 894, 896 complex, 181 inhibitors synchrotron radiation, 896 zVDR ligand-binding domain bound azoles, 1539-1540 morphometric analysis, 898 to C0578 analog, 181-182 CTA018, 1542 quantitative analysis, 897-898 overview, 139, 148 CTA091, 1540-1542 in vivo imaging, 896-897 zVDR ligand-binding domain genistein, 1541 mineralization analysis, 385 vitamin 0 complex, 175 overview, 36, 51-52 multidetector computed tomography gemini complex, 182 tetralone-based inhibitors, 1543 applications, 892 CsA, see Cyclosporine A Vl0400, 1541 biomechanical analysis, 894 CT, see Computed tomography knockout mouse, 155,748 densitometric analysis, 893-894 CTA018, CYP24A1 inhibition, 1542 oncogenic activity, 48-49 image acquisition, 892-893 CTA091, CYP24A1 inhibition, 1540-1542 overview of features, 23-26 morphometric analysis, 894 CTSC, see Clinical and Translational Science overview of features, 23-26, 1525 t principles, 891-892 Center physiological function, 30 fur COMT, see Catechol-o-methyltransferase Cubilin post-transcriptional regulation, 1533 glu Congestive heart failure, see Heart failure knockoutmouse,64 promoter and transcription factor binding he, Constitutive androstane receptor (CAR), osteoblast production, 342 sites, 1529-1532 hY] vitamin 0 receptor comparison, CY613,1469 prospects for study, 1543 inu 144-146 CY616,1469 prostate cancer inh COPO, see Chronic obstructive pulmonary CY625,1468 expression, 1680-1681 inti disease CY628,1468 inhibitor therapy, 1691 kn( Coronary artery disease, see Atherosclerosis CY941,1466 renal activity, 473, 482 Cortical bone, magnetic resonance imaging CY943,1466 structure, 36, 46-48, 1527-1528 rna applications, 915-916 CYlO06, 1466 structure-function relationships, 46-48, c contrast, 913 CYlO010, 1466 1526-1527 I; image analysis, 915 CYlOO12,1466 substrate specificity, 29-30 r porosity,913 Cyclin-dependent kinases (Cdks) tissue distribution, 1528-1529 F pulse sequences, 914-915 cell cycle regulation, 1632-1636 vitamin 0 analog metabolism, 1447-1449 r, water quantification, 913-914 vitamin 0 upregulation, 1637-1640 vitamin 0 toxicity and inhibition, 1391 Corticosteroids, see Glucocorticoids Cyclooxygenase (COX) CYP27B1 COX, see Cyclooxygenase prostate cancer and inflammation, 1687 bone,412-413,587,784 CRC, see Colorectal cancer vitamin 0 analog inhibition of COX-2, 1451 brain,568 S' CREB-binding protein (CBP) Cyclosporine A (CsA), vitamin 0 calcium transport role, 584-586 Runx2 interactions, 314 metabolism effects, 1268 chronic kidney disease rnu vitamin 0 receptor activation, 108, 112, 115 CYP24A1 direct inhibition, 1330 osb Crohn's disease, see Inflammatory bowel breast cancer expression, 1661 extrarenal enzyme alterations, ove disease catalyzed reactions 1331-1333 par INDEX 2063

induction suppression, 1328-1330 prostate cancer, 1681 cell culture, 1826, 1828 overview of studies, 32-33 pseudo-vitamin D deficiency mutations, overview, 1825-1826 substrate availability, 1328 1189-1190 cardiovascular risks and vitamin D colorectal cancer expression regulation structure, 31 interactions, 1981-1983 calcium intake, 1719-1721 tissue distribution, 31-32 classification, 1825 folate intake and epigenetic regulation, vasculature, 542-543 CYP24A1 dysregulation, 1537 " 1723-1724 vitamin D toxicity control, 1390-1391 epidemiology, 1825 hyperproliferation and tumor CYP2R1 gestational diabetes mellitus and vitamin D progression, 1716 discovery, 26, 28 status, 702 polymorphisms and RNA splicing, mutation and disease, 28 25-hydroxyvitamin D measurement, 1718-1719 overview of features, 23-26 1923-1924 sex hormones, 1721-1722 physiological relevance, 26, 28 ketoacidosis and hypophosphatemia, deficiency and disease, 584, 750 structure, 28 1175 dendritic cell, 783, 792-793 CYP3A4 optimal vitamin D intake and status, dental expression, 524 overview of features, 23-26 1080-1081, 1924 discovery, 31 physiological function, 30-31 type 1 disease DNA methylation, 230-232 substrate specificity, 30 clinical perspectives of vitamin D, expression regulation, 33,229-232,583, vitamin D receptor induction, 216 1836-1837 586,619, 747-748 Cystic fibrosis (CF), cathelicidin genetic predisposition studies, extrarenal vitamin D synthesis, see also antimicrobial peptide expression, 1835-1836 Vitamin D toxicity 1783 immune function overview, 1829 diseases Cytochromes P450, see CYPs islet transplantation and recurrence cancer, 782 prevention with vitamin D, 1835 noninfectious granuloma-forming Dahl salt-sensitive rat, 547-548 primary prevention in animal models by diseases, 780-781 DBP, see Vitamin D binding protein vitamin D overview, 779 DC, see Dendritic cell analogs, 1833 sarcoidosis, 778 Deficiency, see Vitamin D deficiency combination studies, 1833-1834 systemic lupus erythematosus, 781 7-Dehydrocholesterol early intervention, 1830-1832 tuberculosis, 780 assays, 86-87 late intervention, 1832-1833 peritonitis, 781 chemical synthesis, 74-78 supplementation studies in prevention, immune system, 782-783 photochemical conversion to vitamin D, 1834 intestine, 896 79-83 vitamin D deficiency, 1834-1835 mammary gland, 786 structure, 272 vitamin D receptor agonist studies, 180 ovary, 785 Dementia, vitamin D studies, 575 type 2 disease pancreas, 784-785 Dendritic cell (DC) epidemiological studies of vitamin D parathyroid gland, 784 CYP27B1 expression, 783,792-793 case-control studies, 1911 placenta,783-784 experimental autoimmune encephalitis confounding, 1923 prostate, 785 function, 1860-1861 cross-sectional studies, 1911 regulation, 787-794 vitamin D receptor agonist effects longitudinal observational cohort skin,784 chemokine production, 1795-1796 studies, 1911-1916 testes, 785 inhibitory receptor upregulation, race differences, 1924 functional overview, 583 1794-1795 seasonal and geographic studies, glucocorticoid effects, 1236 overview, 1790-1791 1910-1911 heart,550 regulatory T cell enhancement, epidemiology, 1907 hypocalcemia and deficiency, 1098 1793-1794 supplementation studies of vitamin D, immune system, 1780 tolerance induction, 1791-1793, 1796 1916-1921 inhibitors, 36 Dental health, see Oral skeleton vitamin D interactions intestinal expression, 351-352 Dentin, mineralization, 381, 384-385 beta cell function, 1908-1909 knockout mouse, 31, 327, 395-396, 549, 569, Dentin matrix protein 1 (DMP1), vitamin D inflammation, 1910 584-597 regulation of expression in insulin sensitivity, 1909-1910 macrophage enzyme osteocytes, 418 vitamin D cytokine regulation, 791 Dentin sialophosphoprotein (DSPP), deficiency during pregnancy and late lack of CYP24A1 competition, 790-791 mutation, 524 effects on child, 687-688 nitric oxide, 792 Dent's disease, 64 intervention studies, 557 pathogen-associated molecular patterns, Deoxycorticosterone acetate-salt rat, 547 Diarylrnethane vitamin D receptor ligands 792 Depression, vitamin D studies, 574-575 characterization in vivo, 1501-1502 regulation insensitivity to parathyroid Developing countries, calcium intake, 652 identification, structure, and biological hormone, calcium, and phosphate, DEXA, see Dual-energy X-ray characterization, 1498-1500 787-790 absorptiometry DICKKOPF-1 (DKK-1), Wnt inhibition and subcellular localization and kinetics, Diabetes vitamin D regulation, 241, 305 787 adolescent vitamin D status, 671 DICKKOPF-4 (DKK-4), Wnt inhibition and multiple sclerosis polymorphisms, 1852 beta cell, vitamin D effects vitamin D regulation, 241-242 osteoclasts,418 deficiency effects, 1827-1828 Differentiation, see Cell differentiation overview of features, 23-26 metabolite studies DiGeorge sequence, hypocalcemia, parathyroid hormone induction, 155 animal models, 1826-1827 1094-1095 2064 INDEX

7,20-Dihydro-2-methylene-19-nor-1a, Dual-energy X-ray absorptiometry (DEXA) cancer studies, 1438-1439 tt 25-dihydroxyvitamin D, isomers, bone mineral density determination, 884 Falls vi 1433 metabolic bone disease diagnosis, 817 rheumatoid arthritis patient risks, 1961 1,25-Dihydroxy-26,27-F6-vitamin D3, see Dyslipidemia, cardiovascular risks and vitamin D studies Falecalcitrol vitamin D interactions, 1983 impact on risks, 936-937, 1145-1148 1,25-Dihydroxy-19-nor-vitamin Dz, see observational studies, 2028 EB1089, breast cancer trials, 1665 randomized controlled studies, 1,25-Dihydroxyvitamin D, see also Vitamin EBV, see Epstein-Barr virus 2028-2029 Fish D; Vitamin D3 sterol ED-71, 1439, 1446 Fanconi syndrome Fluc activation pathway, 8, 23-24 ElF domain, homology between nuclear type, 1, 1171-1172 cartilage receptors, 102-103 type, 2, 1172 c-Fn function, 509-511 EGF, see Epidermal growth factor treatment, 1172 di membrane signaling, 512-513 Eldecalcitol Farnesoid X receptor (FXR) ov circulating concentrations in diseases, 839 development, 1492 bile acids pr detection osteoporosis management, 1492-1495 derivatives for modulation, 1514-1515 Foca overview, 833-834 vitamin D binding protein affinity, 1493 metabolism regulation, 1513 radioimmunoassay, 836 Elderly, see also Aging; Falls; Osteoporosis vitamin D receptor comparison, 144,146 radioreceptor assay, 834-836 optimal vitamin D status, 1069-1076 FDB187E, 1478 Folat dietary calcium response, 7 Endometriosis, vitamin D studies, 697, 700 FDB198E, 1478 discovery as active form of vitamin D Endothelial cell, see Vasculature Fetus hydroxylation Enhancer calcium metabolism, 625-627 Food enzymes, see CYP2R1; CYP3A4; linking to regulated genes, 118 heart development, 550-551 Food CYP24A1; CYP27B1; Hydroxylases vitamin D receptor, 121-123 parathyroid gland development, 494-495 stimulators, 7 Epidermal growth factor (EGF), breast vitamin D studies FOX< inactivation, 23-24 cancer signaling, 1660 animal studies, 627-628 optimal vitamin D status, 1070 Epilepsy, vitamin D studies, 571 human studies FOX( pharmacokinetics, 1042 Epstein-Barr virus (EBV), multiple association studies, 630-632 renal synthesis, 472-473 sclerosis role, 1845-1846 intervention studies, 630 Fracto stability in serum or plasma, 841 ERE-Bp, see Estrogen response element overview, 628-630 toxicity, see Vitamin D toxicity binding protein FGF, see Fibroblast growth factor Frac~ vitamin D status marker in adolescence, , see Vitamin Dz FGF-23, see Fibroblast growth factor-23 opl 663-664 Ergosterol Fibroblast growth factor (FGF), see also 21,25-Dihydroxyvitamin D3, discovery, 8 chemical synthesis, 78-79 Fibroblast growth factor-23 oslo 24,25-Dihydroxyvitamin D3 photochemical conversion to vitamin D, bile acids and FGF15 F cartilage 79-83 bone formation signaling, 304 function, 509-511 ERK, see Mitogen-activated protein kinases Fibroblast growth factor-23 (FGF23) membrane signaling, 513 Esophageal cancer chronic kidney disease response, circulating concentrations in diseases, 839 vitamin D intake and risk analysis, 1577 1325-1326, 1330 vitamin D studies, 1764 clinical significance, 754-755 detection P extraction, 832-833 Estrogen CYP24A1 expression regulation, 1534 Sl high-performance liquid breast cancer CYP27B1/vitamin D receptor interactions, v chromatography, 833 pathogenesis, 1657 588 rep. overview, 832 vitamin D effects on metabolism and expression regulation, 155-156, 248 C radioimmunoassay, 833 signaling, 1659-1660 FGF23-klotho-bone-kidneyaxis, 2, discovery, 7-8 estradiol and vitamin D metabolism effects, 749-752 Diuretics, see Thiazide diuretics 1252-1253 hypophosphatemia defects, 1160-1165 vi DKK-1, see DICKKOPF-1 multiple sclerosis sex differences, knockout mouse, 155-156, 626, 633 trau DKK-4, see DICKKOPF-4 1863-1865 neonatal levels, 632-633 fi: DMP1, see Dentin matrix protein 1 rescue of blunted breast development and nephrocalcinosis and cardiovascular fr DNA methyltransferase function with estradiol and calcification role, 1413-1414 ht CYP24A1 expression regulation, 1534 tamoxifen, 265 osteocyte production coordination of renal n< CYP27B1 expression regulation, 230-231 Estrogen response element binding protein phosphate handling with bone st DNA microarray, vitamin D receptor target (ERE-BP), gene cloning and mineralization and turnover, vital gene expression analysis, 219-220 expression, 264 751-752 d< DNA replication, licensing control, Ethanol, see Alcohol parathyroid hormone expression fa 1635-1636 Ethnicity, see Race regulation, 501-502, 752 m Dot map, vitamin D3 sterol side-chain Ets-1, vitamin D receptor interactions, 200 phosphate extracellular fluid concentration OF conformational dynamics, Experimental autoimmune encephalitis, see regulation, 613 Functil 274-276 Multiple sclerosis phosphate homeostasis regulation, 325, FV521, Ezetimibe, vitamin D metabolism effects, 358, 752-753 FV604, activity, 1438 1261 prospects for study, 754-755 FV639, cancer studies, 1438-1439 receptor, see Klotho FV689, DPP-1023,1500 FAK, see Focal adhesion kinase rickets mutations, 750 FV708, DRIP, see MED-1 complex Falecalcitrol signaling, 156 FV721, DSPp, see Dentin sialophosphoprotein activity, 1438 synthesis, 749 FXR, Sf INDEX 2065

tumor calcinosis mutations, 1173 GADD45A, vitamin D regulation of GM15,1467 vitamin D expression, 219 GM38A,1467 counter-regulatory hormone activity, GALNT3, tumor calcinosis mutations, GM38B,1467 752-753 1173 Gl phase, see Cell cycle metabolism effects, 1248-1249 GA0182,1466 G2 phase, see Cell cycle regulation of expression in osteocytes, Gastrectomy; see Postgastrectomy bone Graft rejection, see Organ transplantation 417-418 disease Granulocyte-macrophage colony- Fish farming, biofortification, 999 Gastric bypass, see Obesity stimulating factor (GM-CSF), Fluoride, vitamin D metabolism effects, Gastric cancer, vitamin D studies, 1764 functional overview, 1734 1268 Cc, multiple sclerosis polymorphisms, Growth, vitamin D deficiency during c-Fms, osteoclast signaling 1852-1853 pregnancy and late effects on differentiation, 338-339 Gcm-2, parathyroid development, 494 child,687 overview, 337-338 GDM, see Gestational diabetes mellitus Growth hormone (GH), vitamin D precursor proliferation, 338 GDNF, see Glial-derived neurotrophic factor metabolism effects, 1250 Focal adhesion kinase (FAK), bone Gemini GWAS, see Genome-wide association study mechanical load response, leukemia studies, 1745 325-326 transcriptional cycling studies, 222 Hair cycle, vitamin D receptor role, Folate, intake and epigenetic regulation of zVDR ligand-binding domain gemini 157-158, 534-536, 593-594 vitamin D system in colon cancer, crystal structure, 182 Hairless (Hr) 1723-1724 Genetic hypercalciuric rat, see Idiopathic keratinocyte stem cell function, 536-537 Food allergy, vitamin D studies, 2013 hypercalciuria vitamin D receptor repression, 202 Food fortification, calcium and vitamin D, Genistein HAT, see Histone acetytransferase 653,992,994,997-998,1000 CYP24Al inhibition, 51, 541 HCC, see Hepatocellular carcinoma FOXOl, osteoblast transcriptional control of prostate cancer management with vitamin HDAC, see Histone deacetylase differentiation, 306 D, 1692-1693 Head and neck cancer, vitamin D studies, FOX03, vitamin D regulation of expression, Genome-wide association study (GWAS) 1766-1767 161 bone mineral density, 1034-1035 Heart, see also Atherosclerosis Fractal analysis, bone histomorphometry, data analysis, 1035-1036 cardiomyocyte and vitamin D function, 856 overview, 1028-1029 1976 Fracture sequencing, 1029-1030 cardioprotective actions of vitamin D, optimal vitamin D status and risk, vitamin D levels in serum, 1036-1037 1345-1346 1073-1074, 1148 Gestational diabetes mellitus (GDM), cardiovascular mortality as endpoint in osteoporotic fracture prevention vitamin D status, 702 vitamin D observational and primary prevention GH, see Growth hormone interventional studies, 1983-1987 calcium and vitamin D, 1137 Ghrelin, bariatric surgery effects, 1017-1018 clinical cardiovascular outcomes in vitamin meta-analysis, 1137-1139 Glial-derived neurotrophic factor (GDNF), D observational and interventional safety of supplements, 1139 vitamin D effects, 570, 573 studies, 1987-1989 vitamin D, 1134-1137 Glioma, vitamin D studies, 1766 CYP27Bl expression, 550 prospects for study, 1140 Glucocorticoids transplantation and vitamin D deficiency, secondary prevention, 1139-1140 CYP24Al expression regulation, 1531-1532 1292 vitamin D analog studies, 1140 inflammation mediation, 1235-1236 vitamin D receptor repair, see also Orthopedics inflammatory bowel disease management, developmental role, 550-551 CYP24Al role, 50-51 1885 expression, 550 24-hydroxylated metabolite multiple sclerosis treatment, 1865-1866 fibrosis supplementation, 51 neuroprotective actions of vitamin D, 573 animal studies, 552-553 vitamin D supplementation, 936-937 osteoporosis vitamin D intervention studies, trauma and impact of vitamin D bisphosphonate therapy, 1240-1241 553-554 fixation, 929 calcium absorption, 1238 hypertrophy fragility fracture, 927-928 induction mechanisms, 1234 animal studies, 551-552 healing, 928-929 serum vitamin D metabolites, 1236 vitamin D intervention studies, 553 nonunion, 929-930 vitamin D therapy vitamin D signaling in cardiovascular stress and insufficiency fractures, 931 bone mineral density response, remodeling and myocardial vitamin D in prevention 1238-1240 function, 1404-1406 dosing, 1148, 1150 preparations, 1240 Heart failure fall prevention, 1146-1148 prostate cancer management with vitamin vitamin D intervention studies, 556 mechanisms, 1145-1146 D,1692 vitamin D status observational studies, optimal vitamin D status, 1148 receptors, 1234 556 Functional genetic studies, 1030 vitamin D metabolism effects, 1236-1238, Hedgehog, keratinocyte stem cell function, FV521, 1476 1258-1259 537 FV604, 1476 vitamin D receptor regulation, 1235 Helicobacter pylori, vitamin D and infection, FV639, 1476 GM-CSF, see Granulocyte-macrophage 1778 FV689, 1476 colony-stimulating factor Hematopoiesis FV708, 1476 GM7,1467 growth factors, 1733-1734 FV721,1476 GM8,1467 overview, 1733-1734 FXR, see Famesoid X receptor GM14,1467 vitamin D effects 2066 INDEX

Hematopoiesis (Continued) multi-level, multi-site cis-binding Humoral hypercalcemia of malignancy 25-}­ leukemia, see Leukemia regulation of gene expression, (HHM), parathyroid hormone­ normal hematopoiesis, 1734-1735 262-264 related protein function role, 737 25-}­ vitamin D receptor overview, 258-262 HVDRR, see Hereditary vitamin-D resistant blood cells, 1733 HHM, see Humoral hypercalcemia of rickets Hyg knockout mouse studies, 1734 malignancy Hydroxyapatite, see Bone; Mineralization Hyp lymphoid cells, 1734 HHRH, see Hereditary hypophosphatemic let-Hydroxylase, see CYP27Bl cli myeloid cells, 1733 rickets with hypercalciuria 24-Hydroxylase, see CYP24A1 di Heparin, vitamin D metabolism effects, High-performance liquid chromatography Hydroxylases, see also CYP2R1; CYP3A4; di 1263-1264 (HPLC) CYP24A1; CYP27AI; CYP27B1 en Hepatitis, bone loss 24,25-dihydroxyvitamin D, 831 calcium-sensing receptor effects in chronic active disease 25-hydroxyvitamin D, 828-829 proximal tubule, 433 clinical features, 1311 vitamin D assay, 85-86, 824-825 crystal structures and homology models, epidemiology, 1310-1311 High-resolution peripheral quantitative 34-36 pathogenesis, 1311 computed tomography (HR­ drug effects, 1257-1269 treatment, 1311 pQCT), see Quantitative computed hormone effects, 1245-1256 viral disease, 1311 tomography inhibitors, 36 Hepatocellular carcinoma (HCC), vitamin D Hip replacement, see Orthopedics overview of features, 23-26 studies, 1765 Histomorphometry, see Bone prospects for study, 36, 38 Hereditary hypophosphatemic rickets with histomorphometry sequence alignment, 24, 27 hypercalciuria (HHRH) Histone acetytransferase (HAT), see also stimulators, 7 clinical presentation, 1169-1170 speCifiC enzymes 11-J3-Hydroxysteroid dehydrogenase gene defects, 1170 transcriptional regulation in chromatin (l1I3-HSD), vitamin D stimulation en< pathophysiology, 1170 context, 211 and glucocorticoid-induced treatment, 1170-1171 vitamin D receptor regulation, 106, 194, 229 osteoporosis role, 1233-1234 tre Hereditary vitamin-D resistant rickets Histone deacetylase (HDAC), see also 1et-Hydroxyvitamin D2- see Doxercalciferol (HVDRR) speCifiC enzymes 1et-Hydroxyvitamin D3 HYPI alopecia association, 1200, 1223-1224 transcriptional regulation in chromatin chemical synthesis, 83 biochemical findings, 1199-1200 context, 211 leukemia studies, 1741 Hypl case examples, 1205-1208 vitamin D receptor regulation, 194, 201, 230 25-Hydroxyvitamin D HYPI cats, 1218 Historical perspective, vitamin D studies adverse effects of large fluctuations, 1044, cal cell studies, 1203-1204, 1209 commercial production, 73-74 1047 clinical presentation, 1198-1201 discovery, 4 calcium-sensing receptor effects in kidney, dogs, 1218-1219 hormonal form, 6-7, 97-99 433-434 history of study, 1197-1198 isolation of nutritional forms,S chemical synthesis, 83-84 pathophysiology, 1200 metabolites, 7-8 circulating concentrations in diseases, 839 hYl prenatal diagnosis, 1222 photobiology, 4-5, 13-14 detection pri prospects for study, 1224-1225 physiological functions chemiluminescence assay, 831 spontaneous healing, 1222-1223 calcium mobilization from bone, 5-6 commercial synthesis assays, 87 rad synonyms, 1197 intestinal absorption of calcium and high-performance liquid treatment phosphorous,S chromatography, 828-829 calcium, 1220-1222 renal reabsorption of calcium and liquid chromatography-mass vitamin D, 1219-1220 phosphorous, 6 spectrometry, 831-832 Hype vitamin D analogs, 1223 receptor discovery, 99 overview, 827-828 vitamin D receptor defects tuberculosis, 1818 radioimmunoassay, 829-830 clir coactivator binding mutations, 1217 HIV, see Human immunodeficiency virus reporting, 840 hYi compound heterozygous mutations, hnRNPs, see Heterogeneous nuclear discovery, 7 phI 1217-1218 ribonucleoproteins endogenous production, 1385-1386 tre, deletions, 1214 HOXAlO, vitamin D regulation of intestinal calcium absorption role, 620 disease without mutations, 1219 expression, 700-702 kidney, 482 Hype DNA-binding domain mutations, HPLC see High-performance liquid measurement in hypertension and diabetes 1210-1211 chromatography type, 2, 1923-1924 care heterodimerization-affecting mutations, Hr, see Hairless normal levels, 839-840 1216-1217 HR-pQCT, see High-resolution peripheral optimal level, 1048-1050,1069,1131-1133, epic ligand-binding domain mutations, quantitative computed 1148 c; 1214-1216 tomography pharmacokinetics, 1042 CI miscellaneous mutations, 1218 11 J3-HSD, see 11-J3-Hydroxysteroid predicted levels in cancer epidemiology, CI nonsense mutations, 1211-1213 dehydrogenase 1571-1572 1< overview, 1209-1210 Human immunodeficiency virus (HIV) serum levels, 619-620 RNA splicing-disrupting mutations, protease inhibitors for leukemia treatment stability in serum or plasma, 841 1213-1214 with vitamin D combination toxicity, 1381-1384 51 Heterogeneous nuclear ribonucleoproteins therapy, 1740-1741 vitamin D status marker in adolescence, epi< (hnRNPs) psoriasis management in patients, 663 25-t C family, 258-262 1896-1897 vitamin D supplementation effects on domains, 260-261 vitamin D and infection, 1779 conversion, 1055-1056 opli INDEX 2067

25-Hydroxyvitamin D-la.-hydroxylase, see intake, 1924 IBD, see Inflammatory bowel disease CYP27Bl status, 1079-1080 Ichthyosis, vitamin D therapy, 1897-1898 25-Hydroxyvitamin D-24-hydroxylase, see sunlight and blood pressure, 715 IDBPs, see Intracellular vitamin D binding CYP24Al supplementation studies of vitamin D, proteins Hygiene hypothesis, 1881 1922-1923 Idiopathic hypercalciuria (IH) Hypercalcemia, see also Vitamin D toxicity vitamin D genetic hypercalciuric rat clinical manifestations, 1392-1393 deficiency, 715 bone density, 1373 diagnosis of vitamin D toxicity, 1393-1394 interactions establishment, 1369-1370 differential diagnosis, 1382 inflammation, 1910 intestinal calcium transport, 1370 endogenous vitamin D toxicity renin-angiotensin-aldosterone low calcium diet response, 1373 25-hydroxyvitamin D production, system, 1910 mineral balance, 1370 1385-1386 intervention studies renal calcium handling, 1370 lymphoma, 1388-1389 animal models, 548-549 serum and urine chemistries, 1370 prevention, 795 clinical studies, 554-555,715-716 vitamin D levels, 1370-1371 sarcoidosis, 1386-1387 status observational studies, 554 vitamin D receptor expression, treatment, 795-796 Hypocalcemia 1371-1373 tuberculosis, 1387 biochemical changes, 1093-1094 overview, 1359-1360 exogenous vitamin D toxicity, 1381-1385 calcium deficiency, 1099 pathogenesis treatment, 1394-1395 calcium-sensing receptor gene mutations, bone mineral density reduction, Hypercalciuria, see also Hereditary 1095 1363-1365 hypophosphatemic rickets with classification, 1094-1100 calcium absorption hypercalciuria clinical manifestations, 1091-1092 intestinal increase, 1360-1362 endogenous vitamin D toxicity treatment, hyperphosphatemia in induction, 1099 renal reabsorption decrease, 795-796 illness induction, 1100 1362-1363 treatment in endogenous vitamin D management calcium balance, 1367-1368 intoxication, 795-796 acute, 1100-1101 genetics, 1364, 1366 Hypercalciuria, see Idiopathic long-term, 1101-1103 models, 1366-1367 hypercalciuria medication induction, 1100 parathyroid hormone levels, 1367 Hyperlipidemia, see Dyslipidemia mineralization acceleration as cause, renal histopathology in calcium oxalate Hyperparathyroidism 1099-1100 nephrolithiasis, 1360 calcium-sensing receptor calcimimetic neonatal, 1097, 1100-1101 vitamin D elevation, 1362, 1368-1369 activators for treatment parathyroid hormone pathophysiology, 1374 secondary hyperparathyroidism in defects in disease treatment chronic kidney disease, 442-443 autoimmune polyglandular syndrome dietary calcium restriction, 1374 uremic hyperparathyroidism, 441-442 type, 1, 1095 thiazide diuretics, 1375 hypercalcemia, 1381-1382 DiGeorge sequence, 1094-1095 vitamin D analogs and risks of stone primary disease and surgical guidelines, gene mutations, 1095 formation, 1375 732 infiltrative disease, 1095 IEBp, see Intracellular estrogen-binding radiographic findings pseudohypoparathyroidism, 1096 protein renal osteodystrophy, 869 radiation, 1095 IFN-y, see Interferon-y secondary hyperparathyroidism, surgical patients, 1095 IGF-I, see Insulin-like growth factor-I 867-869 prevention, 1092 IGFBP genes Hyperphosphatemia, see also Tumor signs and symptoms, 813 cancer, 1605 calcinosis vitamin D deficiency in etiology vitamin D regulation, 216, 219 clinical signs and symptoms, 1176-1177 CYP27Bl deficiency, 1098 IH, see Idiopathic hypercalciuria hypocalcemia induction, 1099 malabsorption, 1098 Infant phosphate load disorders, 1175-1176 malnutrition, 1097-1098 calcium treatment from abnormal phosphate load, vitamin D receptor defects and intake recommendations, 649-650 1178 resistance, 1098-1099 metabolism, 632-633 Hypertension, see also Renin-angiotensin vitamin D in long-term maintenance of developmental vitamin D deficiency system eucalcemia, 1092-1093 behavioral effects in later life, cardiovascular risks and vitamin D Hypomagnesemia, parathyroid hormone 568-569 interactions, 1980-1981 dysfunction, 1096-1097 dietary restriction, 567-568 epidemiological studies of vitamin D Hypoparathyroidism, overview, 732 gene expression effects in later life, 568 case-control studies, 1921-1922 Hypophosphatemia, see also Fanconi structural alterations, 576 confounding, 1923 syndrome; Hereditary premature infants, 648-649, 702 cross-sectional studies, 1921-1922 hypophosphatemic rickets with vitamin D studies in development longitudinal observational cohort hypercalciuria; X-linked animal studies, 633-635 studies, 1922 hypophosphatemia human studies race differences, 1924 clinical presentation, 1176-1177 overview, 635-637 seasonal and geographic studies, 1921 common pathogenesis pathway, intervention studies, 637-638 epidemiology, 1907 1160-1165 association studies, 638-640 25-hydroxyvitamin D measurement, glucose induction, 1174 vitamin D 1923-1924 treatment from abnormal phosphate load, intake recommendations, 649-650 optimal vitamin D 1178 supplementation, 650-651 2068 INDEX

Inflammation vitamin D synthesis in colon, 1715 parathyroid hormone role, 729-730 \' benign prostatic hyperplasia and vitamin D vitamin D absorption, 1300 vitamin D effects, 473-475 vit, analog inhibition, 1935-1936 Intracellular estrogen-binding protein plasma membrane calcium pump, 480 o brain, 571 (lEBP),266-267 stones, see Idiopathic hypercalciuria \' breast cancer pathways, 1660 Intracellular vitamin D binding proteins transplantation and vitamin D deficiency, vit2 central nervous system inflammation and (IDBPs) 1292-1293 vitamin D synthesis, 1857 effect on vitamin D synthesis, 266 TRPV5 and TRPV6 function, 480-482 Latitu glucocorticoid mediation, 1235-1236 functions, 265-266 vitamin D vita pregnancy and immune tolerance, 1863 types, 265 functions, 1340-1341 prostate cancer and vitamin D effects, vitamin D analog binding, 1451 metabolism vita 1686-1688 Ion channels, vitamin D potentiation 24-hydroxylase activity, 473 LC/~ renoprotective actions of vitamin D, through nongenomic action, 279, vitamin D3 synthesis, 473 1342-1345 290 renoprotection, 1342-1345 LCAI vascular vitamin D receptor functions, 544 Islet transplantation, diabetes recurrence vitamin D receptor function, 433-435, vasculature and vitamin D, 1977-1978 prevention with vitamin D, 1835 475-478 LDLR vitamin D binding protein role, 66-67 Kip1, see p27 Left sl Inflammatory bowel disease (IBD) Jaw osteonecrosis Klotho Left v' animal models, 1884-1885 risk factors, 527-528 FGF23-klotho-bone-kidneyaxis, Leptir classification, 1879 vitamin D status and supplementation, 749-753 bari colorectal cancer risks, 1715 527-528 hormonal actions, 754-755 bon environmental factors, 1881 Jejunoileal bypass, see Obesity knockout mouse, 325 vita epidemiology, 1879 IN,1499 nephrocalcinosis and cardiovascular Leuke genetics, 1880 JNK, see Jun N-terminal kinase calcification role, 1413-1414 com hygiene hypothesis, 1881 Jun N-terminal kinase GNK), rickets mutations, 753 al immune response photoprotection mechanisms of tumor calcinosis mutations, 1173 ar overview, 1882-1883 vitamin D compounds, 1948 vitamin D regulation of expression, 160 d Tcell regulation by vitamin D, 1883-1884 Knockout mouse hI treatment Keratinocyte calbindin D, 353, 365-366 immunosuppression, 1885-1886 calcium-sensing receptor function, 444 calcium-sensing receptor, 429, 436, 526 irl vitamin D, 1886 [}-catenin-vitamin D receptor interactions, cancer and vitamin D system studies, ki vitamin D hypothesis, 1881-1882 156-158 590-593 M vitamin D receptor agonist studies, CYP27B1 in differentiation, 594 cubilin,64 1802-1803 differentiation, 533-534, 537-538, 594 CYP24Al, 155,748 Influenza, adolescent vitamin D status, 671 stem cells CYP27B1, 31, 327, 395-396, 569, 584-597 V2 Infrared spectroscopy quantification, 536 fibroblast growth factor-23, 155-156, intel mineralization analysis, 396 signaling pathways, 536-537 626,633 vitamin D, 86 sunburn cells, see Sun exposure klotho, 325 vital Innate immunity, see speCifiC components vitamin D in homeostasis, 1755 low-density lipoprotein receptor, 550 an Insulin, vitamin D metabolism effects, Ketoconazole MARRS,460 1251-1252 CYP24A1 inhibition, 1540 MBD4,233 Insulin-like growth factor-I (lGF-I) vitamin D metabolism effects, 1260 MED-1 complex, 198-199 breast cancer signaling, 1660 K-homology splicing regulator protein megalin, 63-65 vitamin D inhibition in cancer (KSRP), 430, 501 parathyroid hormone, 429, 436, 586 overview, 1605 Kidney, see also Chronic kidney disease parathyroid hormone-related protein,302 prostate cancer, 1686 calbindin D function, 366, 478-480 TRPV5,585-586 ap vitamin D metabolism effects, 1250-1251 calcium tubular reabsorption TRPV6,585 ce Insulin resistance, see also Metabolic calcium-sensing receptor regulation, vitamin D binding protein, 57, 62-63,395 ce syndrome 434-435 vitamin D receptor, 141, 143-144,160,481, im cardiovascular risks and vitamin D CYP27Bl role, 585-586 497-409,523,525-526,536,549,570, kiJ interactions, 1981-1983 overview, 471-472 584-597, 627, 749, 772-774, tr, vitamin D intervention studies, 557 parathyroid hormone role, 729-730 1076-1077, 1130, 1201, 1734, 1978, LG1901 vitamin D status observational studies, 557 vitamin D effects, 473-475 2034-2035 LG190: Intact parathyroid hormone, see Parathyroid calcium-sensing receptor function, 433-435 Wnt, 242 LG190 hormone cancer, see Renal cell carcinoma KS018,1482 LG190: Intake recommendations, see Vitamin D fibroblast growth factor-23 coordination of KS176, 1479, 1504 Lieben status renal phosphate handling with bone KS291, 1479 Linkag Interferon-y (lFN-y), vitamin D metabolism mineralization and turnover, KS512,1479 .anim effects, 1256 753-754 KS532, 1462-1463 over Intestine, see also Colorectal cancer functional overview in mineral KS699,1473 Liquid absorption, see Calcium absorption; homeostasis, 471 KSRP, see K-homology splicing regulator Phosphate absorption parathyroid hormone function, 729-730 protein calbindin D function, 364-366 phosphate tubular reabsorption Lithiun calcium-sensing receptor function, 439 defects, see Hyperphosphatemia; Lactation CYP27B1, 894 Hypophosphatemia bone mineral content and density Lithod vitamin D receptor function, 439 overview, 472 overview, 683 INDEX 2069

weaning effects, 683-684 crystal structures Magnetic resonance imaging (MRl) vitamin D and calcium metabolism 3-ketolithocholic acid, 1519 cortical bone imaging overview, 680 lithocholic acid acetate/propionate, 1519 applications, 915-916 weaning effects, 682 unmodified lithocholic acid, 1517-1519 contrast, 913 vitamin D deficiency effects on infant, docking models, 1519-1520 image analysis, 915 688-689 overview, 1515-1517 porosity,913 Latitude Liver, see also Hepatitis; Primary biliary pulse sequences, 914-915 vitamin D status influences, 661-662, cirrhosis water quantification, 913-914 987-988 cancer, see Hepatocellular carcinoma principles, 905-907 vitamin D synthesis effects, 15, 17 transplantation trabecular bone imaging LC/MS, see Liquid chromatography-mass bone loss, 1313 image processing spectrometry vitamin D deficiency, 1292 coil sensitivity correction, 909 LCA derivatives, see Lithocholic acid vitamin D metabolism, 1300-1302 segmentation, 909-910 derivatives Liver X receptor (LXR) image registration, 912-913 LDLR, see Low-density lipoprotein receptor bile acid metabolism regulation, 1512-1513 morphometric analysis, 910-912 Left shift, resting membrane potential, 461 vitamin D receptor comparison, 144, 146 pulse sequences, 908-909 Left ventricular hypertrophy, see Heart Loading dose signal-to-noise considerations, 906-907 Leptin concept, 1058-1059 spatial resolution, 907-908 bariatric surgery effects, 1017 toxicity, 1059-1060 Malignant hyperthermia, bone effects, 1017 vitamin D2, 1059 hyperphosphatemia, 1176 vitamin D metabolism effects, 1249 Low-density lipoprotein, see Dyslipidemia Mammary gland, see also Breast cancer; Leukemia Low-density lipoprotein receptor (LDLR), Lactation combination therapy with vitamin D knockout mouse, 550 calcium-sensing receptor function, 440 all-trans retinoic acid, 1739-1740 Low-density lipoprotein receptor-related CYP27Bl expression, 784-785 arsenic trioxide, 1740 proteins (LRPs) parathyroid hormone-related protein chemotherapy, 1740 bone formation signaling, 305 function, 733-737 human immunodeficiency virus protease LRP5 vitamin D receptor expression and inhibitor, 1741 bone health role, 243 function, 440, 1665-1667 iron chelating agents, 1740 vitamin D regulation of expression, 154 MAPK, see Mitogen-activated protein kinase kinase inhibitors, 1740 Wnt coreceptors, 235-237, 243, 251 Market, vitamin D, 88-90 MDM2 antagonists, 1740 Lower urinary tract symptoms, see Benign MARRS, see Membrane-associated rapid nonsteroidal anti-inflammatory drugs, prostatic hyperplasia response, steroid-binding protein 1740 LTCC, see L-type calcium channels Matrix extracellular phosphoglycoprotein valproic acid, 1741 L-type calcium channels (LTCC), vitamin D (MEPE, hypophosphatemia role, intervention trials in myelodysplastic effects, 2032 1162-1163 syndrome, 1735, 1743 Lung Matrix Gla protein (MGP), vitamin D effects vitamin D effects developmental role of vitamin D, 2011 in bone, 416 analog studies transplantation and vitamin D deficiency, Maxacalcitol C-16-enes, 1742-1743 1292 activity, 1438, 1445-1446 calcipotriol, 1741 Lung cancer, vitamin D studies, 1764-1765 cancer studies, 1438-1439, 1446 20-epi vitamin D3' 1743 LXR, see Liver X receptor protein binding, 1446-1447 gemini analogs, 1743 LY2108491, 1483, 1500 MBD4 la-hydroxyvitamin D3, 1741 LY2109866, 1483, 1500 CYP27Bl expression regulation, 232 paracalcitol, 1743 Lymphoma knockout mouse, 233 apoptosis, 1737 endogenous vitamin D toxicity, 1388-1389 parathyroid hormone signaling-induced cell cycle, 1736-1737 extrarenal vitamin D production, 779 transcriptional derepression, cell differentiation, 1736 232-233 immune response, 1738-1739 M phase, see Cell cycle 2MbisP, see 2-Methylene-19-nor-la­ kinases, 1739 M-CSF, see Macrophage colony-stimulating hydroxybishomopregnacalciferol transcription factors, 1738 factor 2MD, 1140, 1439 LG190090, 1483, 1500 Macrophage, CYP27Bl MDCT, see Multidetector computed LGI90119, 1500 cytokine regulation, 791 tomography LG190155, 1483 lack of CYP24Al competition, 790-791 MDM2, antagonists for leukemia treatment LG190178, 1483, 1500 nitric oxide regulation, 792 with vitamin D combination Lieberman-Burchard reaction, 87 pathogen-associated molecular patterns, therapy, 1740 Linkage analysis 792 MOS, see Myelodysplastic syndrome .animal studies, 1027 regulation insensitivity to parathyroid MED-l complex overview, 1026-1027 hormone, calcium, and phosphate, knockout mice, 198-199 Liquid chromatography-mass 787-790 vitamin D receptor activation, 106, 108, 112, spectrometry (LC/MS), subcellular localization and kinetics, 787 115, 198-199,534 25-hydroxyvitamin D, 829-830 Macrophage colony-stimulating factor (M­ Medical history, metabolic bone disease Lithium, vitamin D metabolism effects, CSF), functional overview, diagnosis 1268-1269 1731-1733 chief complaint, 809 Lithocholic acid (LCA) derivatives, vitamin Magnesium, see also Hypomagnesemia family history, 812 D receptor interactions hypocalcemia management, 1101 past history, 811 2070 INDEX

Medical history, metabolic bone disease tetracycline labeling, 846-847 overview of model, 1853-1854 diagnosis (Continued) calcium extracellular fluid concentration prevention studies present illness, 810-811 regulation, 609 calcium, 1856-1857 review of systems, 812 CYP27B1 function, 587 cholecalciferol, 1854-1855 social history, 811-812 definition, 381 ultraviolet light, 1855-1856 Megalin dentin,381 vitamin D3, 1855 knockout mouse, 63-65 enamel, 381 transforming growth factor-p expression. osteoblast production, 342 hydroxyapatite properties, 384 1860 structure, 63 hypocalcemia from acceleration, 1099-1100 vitamin D amelioration and Tcell tissue distribution, 63-64 mechanisms in bone, cartilage, and dentin, mechanisms vitamin D transport, 64 384-385 activation-induced cell death Melanin, vitamin D synthesis effects, 14-15, osteoporosis/ostemalacia defects, 396 sensitivity, 1862 19,984-986 pathology, 382 chemokine synthesis inhibition, 1862 Melanoma, see Skin cancer phosphate extracellular fluid concentration nitric oxide synthase inhibition of Membrane-associated rapid response, regulation, 612 induction, 1862-1863 Must steroid-binding protein (MARRS) physical chemistry, 382-384 overview, 1861-1862 knockout mouse, 460 vitamin D deficiency, animal model vitamin D receptor expression on Tcells c-My transcaltachia role, 354 studies, 390-396 overview, 1858 vitamin D analog binding, 1450 vitamin D regulation regulatory T cells, 1859-1860 vitamin D plasma membrane receptor, 283 physicochemical effects, 389-390 Th1 cells, 1858 Myel Meningioma-1 (MN1), vitamin D receptor protein mediators ThZ cells, 1858-1859 interactions, 201 bone sialoprotein, 392-393 Th17 cells, 1859 MEPE, see Matrix extracellular collagen,392 genetics NaPi phosphoglycoprotein extracellular matrix proteins, 383 CYP27B1 polyrnorphisrns, 1852 NCoJ MESA, see Multiethnic Study of knockout and transgenic mice, 386 GC polyrnorphisms, 1852-1853 Atherosclerosis osteocalcin, 393 HLA-DR, 1850-1851 NCol Meta-analysis, genetic studies, 1030 osteopontin, 393 vitamin D receptor polyrnorphisms, Metabolic syndrome Mitogen-activated protein kinase (MAPK) 1851-1852 Neon optimal vitamin D status, 1080-1081 bone mechanical load response, 326 pregnancy and immune tolerance, 1863 vitamin D intervention studies, 557 cell differentiation induction via vitamin D, prospects for study, 1866-1868 Neon vitamin D status observational studies, 557 1629-1630 sex differences and estrogen, 1863-1865 cal, Metallothionein, photoprotection cross-talk of vitamin D signaling, 283 treatment with vitamin D hY] mechanisms of vitamin D CYP24A1 expression regulation, 1530 costs, 1866 pn compounds, 1948 leukemia signaling and vitamin D effects, glucocorticoid comparison, 1865-1866 viti Metastasis 1739 irnmunomodulatory therapy breast cancer, 1662 muscle signaling and vitamin D effects, comparison, 1866 inhibition by vitamin D, 1595-1597 2034 relapsing-remitting multiple sclerosis, parathyroid hormone-related protein in osteoblast signaling and vitamin D effects, 1865 bone metastasis, 737 328-329 vitamin D binding protein levels, 1853 prostate cancer and vitamin D inhibition, photoprotection mechanisms of vitamin D vitamin D-multiple sclerosis hypothesis, Neph 1689 compounds, 1948 1843-1844 radiographic findings in calcification, vitamin D regulation through nongenomic vitamin D receptor agonist studies, Nerv' 869-872 action,281 1801-1802 2-Methylene-19-nor-1~­ Mitogen-activated protein kinase vitamin D status hydroxybishomopregnacalciferol phosphatase-5 (MKP5), vitamin D analysis, 1846-1847 Nem (2MbisP), activity, 1429-1430 effects in prostate cancer, 1688 deficiency in patients, 1847 MGP, see Matrix Gla protein MKP5, see Mitogen-activated protein kinase longitudinal disease, 1848 New Microcomputed tomography, see Computed phosphatase-5 relapse and remission, 1848-1850 bOi tomography MN1, see Meningioma-1 risk analYSis, 1847-1848 eve Mineralization Monocyte, CYP27B1, 781 sun exposure inverse correlation, 1846 inb analysis MRl, see Magnetic resonance imaging vitamin D supplementation and atomic force microscopy, 387 MS, see Multiple sclerosis relapse-remitting disease, inb localization, 385 Multidetector computed tomography 1849-1850 nuclear magnetic resonance, 389 (MDCT), see Computed Muscle riel quantification, 385, 387 tomography optimal vitamin D status, 1081 NF-K: small-angle X-ray scattering, 387 Multiethnic Study of Atherosclerosis parathyroid hormone actions, 2035 NGF, transmission electron microscopy, 387 (MESA), 1409 strength, orthopedic rehabilitation and Nitri, in vitro studies, 389 Multiple sclerosis (MS) vitamin D, 933-934 X-ray diffraction, 387-388 central nervous system inflammation and vitamin D Nitri, bone histomorphometry assessment vitamin D synthesis, 1857 falls studies ph, adjusted apposition rate, 848 course, 1844-1845 observational studies, 2028 mineral apposition rate, 847-848 Epstein-Barr virus role, 1845-1846 randomized controlled studies, viti mineralization lag time, 848 etiology, 1845 2028-2029 osteoid maturation time, 849 experimental autoimmune encephalitis fracture prevention, 1145 NMR osteoid measurement, 847 dendritic cell function, 1860-1861 intervention trials in adolescence, 669 NO,~ INDEX 2071

mechanisms of action N002 vitamin 0 status, 662, 773-774 genomic actions, 2030-2031 innate immunity, 1812-1813 OCN, see Osteocalcin non-genomic actions, 2031-2034 vitamin 0 effects on expression, 1781 Olestra, vitamin 0 metabolism effects, 1268 morphology studies, 2029-2030 Nonsteroidal anti-inflammatory drugs OPG, see Osteoprotegerin myopathy and deficiency, 2024-2025 (NSAIDs) OPN, see Osteopontin overview of function, 2023-2024 leukemia treatment with vitamin 0 Optimal vitamin 0 status, see Vitamin 0 physical performance studies combination therapy, 1740 status observational studies, 2025-2026 prostate cancer management with vitamin Oral skeleton randomized controlled studies, 0,1693-1694 dental rickets, 522-524 2026-2028 NOS, see Nitric oxide synthase dento-maxillofacial skeleton properties, prospects for study, 2035-2036 NSAIDs, see Nonsteroidal anti­ 521-522 vitamin 0 receptor inflammatory drugs parathyroid hormone-related protein knockout mouse studies, 2034-2035 NSHPT, see Neonatal severe function in teeth, 737 polymorphisms, 2035 hyperparathyroidism rare diseases, 522 Mushroom, irradiation for biofortification, Nuclear factor-KB (NF-KB), vitamin 0 effects vitamin 0 999 in prostate cancer, 1688 bioactivation, 524-526 c-Myc, vitamin 0 downregulation and Nuclear magnetic resonance (NMR), development role, 526 effects on cell cycle and mineralization analysis, 389 pathology, 526-529 differentiation, 1641-1642 Nutrition, see also Vitamin 0 status prospects for study, 529-530 Myelodysplastic syndrome (MDS), vitamin biofortification, 998-999 therapeutic applications, 527-528 o effects, 1735, 1743-1744 early views, 3 Organ transplantation food composition data, 995-996 bone loss and treatment with vitamin 0 NaPi lIb, see SLC34A2 food fortification with calcium and vitamin analogs, 1294-1296 NCoA62/SKIP, vitamin 0 receptor 0,653,992,994,997-998,1000 graft rejection and vitamin 0 role, 1291 activation, 199-200 geographic differences, 957 immune function of vitamin 0, 1291-1292 NCoR, vitamin 0 receptor repression, lifestyle strategies for vitamin 0 status vitamin 0 deficiency 201-202 improvement, 100 post-transplantation Neonatal severe hyperparathyroidism natural food sources, 996-997 heart, 1294 (NSHPT), mouse model, 430 NWPs, see New World primates long-term, 1293-1294 Neonate perioperative, 1293 calcium metabolism, 632-633 OA, see Osteoarthritis pre-transplantation hypocalcemia, 1097, 1100-1101 Obesity heart, 1292 premature infants, 648-649, 702 bariatric surgery kidney, 1292-1293 vitamin 0 studies bone loss liver, 1292, 1313 animal studies, 633-635 clinical features, 1308 lung, 1292 human studies epidemiology, 1306-1307 Orlistat, vitamin 0 metabolism effects, 1268 association studies, 638-640 overview, 1016-1018 Orthopedics, see also Fracture intervention studies, 637-638 pathogenesis, 1308 falls and vitamin 0 impact, 936-937, overview, 635-637 treatment, 1308 1145-1148 Nephrolithiasis, see Idiopathic calcium absorption effects, 1019-1021 muscle strength and rehabilitation, hypercalciuria complications 935-937 Nerve growth factor (NGF), medical, 1015-1016 pediatric orthopedics neuroprotective actions of vitamin surgical, 1013-1015 rickets, 931-933 0,572-573 epidemiology, 1009-1010 slipped capital femoral epiphysis, 933 Neuroprotection, vitamin 0 mechanisms, health benefits, 1015 total joint arthroplasty and vitamin 0 572-573 indications, 1010-1011 impact New World primates (NWPs) types osteoarthritis, 934-935 bone disease, 253-254 adjustable silicone gastric banding, periprosthetic fracture, 935 evolution, 253 1013 thigh pain, 935 intracellular estrogen-binding protein, biliopancreatic diversion, 1011-1011 trauma and vitamin 0 impact 266-267 biliopancreatic diversion with fixation,929 intracellular vitamin 0 binding proteins, duodenal switch, 1012-1013 fragility fracture, 927-930 265-266 jejunoileal bypass, 1011 healing, 928-929 rickets, 251, 254-255 roux-en-Y gastric bypass, 1013 nonunion, 929-930 NF-KB, see Nuclear factor-KB sleeve gastrectomy, 1013 stress and insufficiency fractures, 931 NGF, see Nerve growth factor vertical banded gastroplasty, 1013 vitamin 0 supplementation, 937-938 Nitric oxide (NO), CYP27B1 regulation in vitamin 0 status, 1018-1019 Osteoarthritis (OA) macrophages, 792 vitamin 0 supplementation, 1020-1021 bone changes, 1956-1957 Nitric oxide synthase (NOS) cardiovascular risks and vitamin 0 cartilage homeostasis and vitamin 0, photoprotection mechanisms of vitamin 0 interactions, 1979-1980 1955-1956 compounds, 1948 epidemiology, 1009 clinical fea tures, 1955 vitamin 0 inhibition of induction, etiology, 1009 progression and vitamin 0 status, 1862-1863 pathophysiology, 1009 1957-1960 NMR, see Nuclear magnetic resonance vitamin 0 deficiency and adiposity, radiographic findings in X-linked NO, see Nitric oxide 770-773 hypophosphatemia, 875 2072 INDEX

Osteoarthritis (OA) (Continued) handling with bone mineralization Ovarian cancer, vitamin D intake and risk cail synovial changes, 1957-1958 and turnover, 750 analysis, 1576-1577 total joint arthroplasty and vitamin D functions, 325-326 Ovary, CYP27B1 expression, 783 call impact, 934-935 gene expression regulation by vitamin D 22-Oxa-1,25-dihydroxyvitamin D3, see vitamin D receptor polymorphisms, 1958 dentin matrix protein,!, 418 Maxacalcitol chr Osteoblast fibroblast growth factor-23, 417-418 Oxidative stress coli bone remodeling, 323-325 parathyroid hormone function, 731 reactive nitrogen species, 1814-1815 CY calcium-sensing receptor function, 437 properties, 322-323 reactive oxygen species, 1814 CY collagen type I expression and vitamin D Osteoid vitamin D effects, 1814-1815 de\ regulation, 402-405 maturation time, 850-851 disl differentiation and vitamin D effects measurement, 847 P16, vitamin D regulation of expression, 219 eXF cell culture studies, 326-327 Osteomalacia, see also Vitamin D deficiency p21 c direct actions, 327-328, 414-417 bone histomorphometry assessment parathyroid tumor downregulation, 432 c voltage-sensitive calcium channels, focal osteomalacia, 852 Runx2 interactions, 314 f, 462-463 generalized osteomalacia, 851-853 vitamin D regulation of expression, 160, 21' fi mechanical load response, 325-326 etiology, 817 vitamin D upregulation in G1/S block, F origins, 321, 330 mineralization defects, 396 1637-1640 F parathyroid hormone function, 731 radiographic findings p27 V phosphate homeostasis regulation, 325 overview, 815-816, 863-865 parathyroid tumor downregulation, 432 fibr properties, 321-322 X-linked hypophosphatemia, 873 vitamin D regulation of expression, 219 ger signaling pathway regulation by vitamin D treatment, 816-820 vitamin D upregulation in G1/S block, F mitogen-activated protein kinase, Osteopenia, premature infants, 648 1637-1640 s 328-329 Osteopontin (OPN) p35, cell differentiation induction via tJ Wnt, 329-330 arteriosclerosis studies, 1408 vitamin D, 1630-1631 glu survival and vitamin D influences, bariatric surgery effects, 1017 p38, see Mitogen-activated protein kinases hYI 463-464 functions, 393 p53 d transcriptional control of differentiation, vitamin D effects, 416 photoprotection mechanisms of vitamin 0 305-306 Osteoporosis compounds, 1949 vitamin D receptor function, 437-438 bone effects of vitamin D, 1129-1130 vitamin D regulation of expression, 160 Wnt signaling, 243-244 bone mineral density effects of calcium and p160, vitamin D receptor activation, 106 Osteocalcin (OCN) vitamin D supplementation, p300 chromatin organization of gene, 312-313 1133-1134 Runx2 interactions, 314 mineralization role and vitamin D effects, fracture prevention vitamin D receptor activation, 108,112 393 primary prevention PAD, see Peripheral arterial disease vitamin D regulation of expression, calcium and vitamin D, 1137 Palmitoylation, vitamin D plasma P 106-107, 113, 154, 417, 1234-1235 meta-analysis, 1137-1139 membrane receptor, 284 idic Osteoclast safety of supplements, 1139 Pancreas, see also Diabetes int< adhesion and migration, 340 vitamin D, 1134-1137 bone loss in disease apoptosis, 339 secondary prevention, 1139-1140 clinical features, 1308 kne bone metastasis and chemokines in vitamin D analog studies, 1140 epidemiology, 1308 lac! osteoclast regulation, 340-341 prospects for study, 1140 pathogenesis, 1308 MB calcitonin role, 739-740 genetic factors, 1130-1134 treatment, 1309 calcium-sensing receptor function, 438 glucocortiCOid-induced osteoporosis calbindin D function, 367-368 mel cannabinoid receptors, 341 bisphosphonate therapy, 1240-1241 CYP27B1,782-783 b functional overview, 336-337 calcium absorption, 1238 Pancreatic cancer, vitamin D studies, P fusion, 340 mechanisms, 1234 1767-1768 mu inhibition strategies, 341-342 serum vitamin D metabolites, 1236 Paracalcitol, leukemia studies, 1743 opt origins, 335 vitamin D therapy Parathyroid gland phe osteoblast activator secretion, 340 bone mineral density response, calcium-sensing receptor pre, parathyroid hormone function, 1238-1240 calcimimetic activators for hyperfunction pro 730-731 preparations, 1240 treatment, 440-443 recl properties, 335-336 25-hydroxyvitamin D optimal levels, function, 430-433 ren; RANK signaling 1131-1133 CYP27B1,782 sea differentiation, 338-339 mineralization defects, 396 development, 494-495 trar overview, 337-338, 731 parathyroid hormone analogs for vitamin D receptor vita precursor proliferation, 338 management, 733 function, 430-433 vita vitamin D effects radiographic findings, 869 knockout effects, 586 Paratl endogenous vitamin D, 418-419 vitamin D analog management Parathyroid hormone (PTH), see also exogenous vitamin D, 418 alfacalcidol, 1491-1495 Hyperparathyroidism; lact vitamin D receptor function, 438-439 eldecalcitol, 1492-1495 Hypoparathyroidism end Osteocyte Osteoprotegerin (OPG) analogs for osteoporosis management, 733 differentiation and vitamin D effects, pregnancy, 680 arteriosclerosis and receptor signaling, kno 327-328 RANKL binding, 730-731 1414-1415 dev fibroblast growth factor-23 production Osteosclerosis, radiographic findings, biosynthesis, 493 pre; coordination of renal phosphate 868 bone function, 730-732, 748-749 his! INDEX 2073

calcium extracellular fluid concentration gene, 733 vitamin D binding protein role, 1047 regulation, 610-611 processing, 733-734 vitamin Dz supplementation, 1052-1053 calcium-sensing receptor effects, 430-433, receptors, 734 PHEX 727-728 nuclear hormone, 734 dental rickets defects, 523-524 chronic kidney disease, 1325-1326 functions FGF23 regulation, 155 collagen synthesis inhibition in bone, 304 bone, 734-735 mineralization role, 394 CYP24Al expression regulation, 1534 mammary gland, 735-736 X-linked hypophosphatemia defects, CYP27Bl induction, 155 placenta, 736 1167-1168 development role, 625 teeth,737 Phosphate, see also Hyperphosphatemia; discovery, 725 vasculature, 736-737 Hypophosphatemia expression regulation pathophysiology, 737 body compartments, 612 calcium, 498-499 cancer levels, 1597-1598 disorder classification, 1159-1160 calreticulin, 496 vitamin D metabolism effects, 1247-1248 extracellular fluid concentration regulation, feedback regulation, 137, 155 Paricalcitol 612 fibroblast growth factor-23, 501-502, 727 activity, 1438 fibroblast growth factor-23 role in phosphate, 499, 727 cancer studies, 1438-1439 homeostasis, 751-753 prospects for study, 502-503 chronic kidney disease management homeostasis regulation, 1155-1157 vitamin D, 495-498, 727 animal model studies, 1556-1559 load disorders fibroblast growth factor-23 relationship, 752 cardiovascular disease outcomes, 1563 alcoholism, 1175 gene end-stage renal disease, 1560-1563 alkalosis, 1174 promoter sequences, 494-495 stage 3-4 disease, 1559-1560 burns, 1175 structure, 493-494, 725-726 survival impact, 1561-1563 clinical presentation, 1176-1178 transcription factors, 725 Parkinson's disease (PD), vitamin D studies, diabetic ketoacidosis, 1175 glucocorticoid effects, 1237-1238 570 glucose administration, 1174 hypocalcemia PBC, see Primary biliary cirrhosis malabsorption, 1174 defects in disease pcas, see Polycystic ovary syndrome nutritional recovery syndrome, 1175 autoimmune polyglandular syndrome PD, see Parkinson's disease phosphate deprivation, 1173-1174 type, 1, 1095 PDDR, see Pseudo-vitamin D deficiency treatment, 1178 DiGeorge sequence, 1094-1095 Periodontal disease, vitamin D studies, 527 parathyroid hormone expression gene mutations, 1095 Periosteal reaction, radiographic findings, regulation, 499 infiltrative disease, 1095 871 vitamin D metabolism modulation, pseudohypoparathyroidism, 1096 Peripheral arterial disease (PAD), vitamin D 1157-1159 radiation, 1095 status observational studies, 555 Phosphate absorption surgery, 1095 Peritonitis, extrarenal vitamin D dietary phosphate intake as regulator, prevention, 1092 production, 779 356-357 idiopathic hypercalciuria levels, 1367 Peroxisome proliferator-activating receptor­ malabsorption, 1174 intact parathyroid hormone as vitamin D 1> (PPAR-1», vitamin D regulation overview, 618-619 status marker in adolescence, 664 of expression, 219 phosphatonin regulation, 358 knockout mouse, 429,436,586 Peroxisome proliferator-activating receptor­ prospects for study, 358 lactation, 681 y (PPAR-y) renal reabsorption, see Kidney MBD4 in signaling-induced transcriptional crystal structure, 104 SLC34A2 role, 356 derepression, 232-233 prostate cancer management with ligands, vitamin D receptor control, 357-358 messenger RNA 1692 vitamin D status effects, 357 binding proteins, 499-501 PGC-lrx, vitamin D receptor interactions, Phosphoinositol 3-kinase signaling, see Akt processing, 494 201 Phosphoinositols, vitamin D receptor muscle actions, 2035 PGEz, see Prostaglandin Ez interactions, 284 optimal vitamin D status, 1070-1071 Pharmacology, vitamin D Phospholipase A z (PLAz), vitamin D phosphate homeostasis regulation, 325 body storage, 1055 regulation through nongenomic pregnancy, 679 clinical trials, 1045-1046 action, 281 processing, 727 dosing Phospholipase C (PLC), vitamin D receptors, 728-729 adults, 1050-1052 regulation through nongenomic renal function, 729-730 infants, 1050 action, 281-282 secretion regulation, 727-728 25-hydroxyvitamin D optimal level, Photobiology, see also Sun exposure transcaltachia induction, 354-355 1048-1050, 1069, 1131-1133, 1148 cancer risk assessment, 19 vitamin D metabolism effects, 1245-1247 ideal drug features, 1041 history of study, 4-5,13-14 vitamin D responsive element, 405, 495 loading dose influences on vitamin D synthesis Parathyroid hormone-related protein concept, 1058-1059 clothing, 16-17, 989 (PTHrP) toxicity, 1059-1060 glass and Plexiglas, 16 lactation, 681 vitamin Dz, 1059 latitude, 15, 17,987-988 endochondral bone formation role, metabolism overview, 821-823, 981-982, race, 19 302-303 1042-1044 season, 15, 17 knockout mouse, 302 pharmacokinetics, 1042, 1054-1056 sunscreen, 15-17 development role, 626, 633 prospects for study, 1060-1061 time of day, 15, 17 pregnancy, 679 sun exposure as vitamin D dose, 1053-1054 photolysis of provitamin D3 into history of study, 733 toxicity and safety issues, 1056-1058 previtamin D3, 14-15 2074 INDEX

Photobiology (Continued) vitamin D toxicity, 689 , 1695-1696 Pull skin synthesis of vitamin D, 981 Pregnane X receptor (PXR) chemotherapy, 1693 sunlight and dietary vitamin D in health, bile acid metabolism regulation, 1512-1514 CYP24A1 inhibitors, 1691 PXR 16,18-19 vitamin D receptor comparison, 144-150 genistein, 1692-1693 tanning salons and vitamin D synthesis, Preinitiation complex (PIC), vitamin D glucocorticoids, 1692 qBE 1752-1753 receptor interactions, 194, 198, 203 nonsteroidal anti-inflammatory drugs, vitamin D synthesis assessment from sun Premenstrual syndrome (PMS), vitamin D 1693-1694 qCT exposure studies, 697 peroxisome proliferator-activated objective measures, 990-991 Primary biliary cirrhosis (PBC), bone loss receptor-y ligands, 1692 Qua questionnaires, 991 clinical features, 1310 retinoids, 1692 Physical examination, metabolic bone epidemiology, 1309-1310 growth factor modulation, 1686 disease diagnosis, 810-813 pathogenesis, 1310 intake and risk analYSiS, 1574-1575, 1677 Qua treatment, 1310-1311 metastasis inhibition, 1689 m D D Physical performance, see Muscle Progesterone, vitamin metabolism effects, vitamin deficiency hypothesis m PIC, see Preinitiation complex 1254 overview, 964-965 Qua Pim-1,430 Prolactin, vitamin D metabolism effects, serological studies, 971-972 lx: Pin1, parathyroid hormone messenger RNA 1251 vitamin D receptor, 446 hi binding, 501 Prostaglandin E2 (PGE2), vitamin D Protein kinase C (PKC) PKC, see Protein kinase C metabolism effects, 1255-1256 cell differentiation induction via vitamin 0, PLA2, see Phospholipase A2 Prostaglandin synthesis, see 1630 Placenta Cyclooxygenase CYP24A1 expression regulation, 1530 calcium-sensing receptor function, 439-440 Prostate, see also Benign prostatic leukemia signaling and vitamin 0 effects, CYP27B1,783-784 hyperplasia 1739 mineral transport, 626 CYP27B1, 783 Protein phosphatases parathyroid hormone-related protein vitamin D receptor, 1678 PPlc and vitamin D plasma membrane function, 736 vitamin D synthesis, 965-966 receptor interactions, 284 vitamin D receptor function, 439-440 Prostate cancer vitamin D regulation through nongenomic Plasma membrane calcium pump androgen interactions with calcitriol, action,279 renal function, 480 1681-1682 Proton pump inhibitors (PPIs), vitamin 0 tissue distribution, 480, 482 animal models, 1682-1683 metabolism effects, 1265 Platelet function, vitamin D receptor calcium-sensing receptor, 446 PsA, see Psoriatic arthritis knockout mouse studies, 1978 CYP24A1, 1680-1681 Pseudohypoparathyroidism, hypocalcemia, RA,l PLc, see Phospholipase C CYP27B1, 1681 1096 Race PMS, see Premenstrual syndrome epidemiology Pseudo-vitamin D deficiency (PDDR) cal Polycystic ovary syndrome (pCaS), vitamin calcium intake studies, 974-975 biochemical findings, 1189 cal D studies, 696-699 prospects for study, 975 calcitriol therapy di, adults, 1193 Postgastrectomy bone disease study types, 965-966 hy clinical features, 1303-1304 subclinical disease, 966 children, 1192-1193 MI epidemiology, 1302-1303 sunlight, 969, 972-973,1676-1677 overview, 1191-1192 pathogenesis, 1304 vitamin D receptor polymorphisms, short-term effects, 1192 skI 969-970 clinical manifestations, 1187-1189 treatment, 1304 ski PPAR-o, see Peroxisome proliferator­ etiology, 1675 CYP27B1 mutations, 1189-1190 activating receptor-o hormonal factors, 1676 history of study, 1187 vito PPAR-y, see Peroxisome proliferator­ treatment, 1675-1676 pregnancy, 1193-1194 activating receptor-y vitamin D Psoriasis viti PPIs, see Proton pump inhibitors analog studies, 1683-1684 calcipotriol therapy, 1438 Radi( Preeclampsia, vitamin D status, 701-702 angiogenesis inhibition, 1688-1689 history of study, 1891 lex, Pregnancy anti-inflammatory effects, 1686-1688 pathogenesis, 1891-1892 24,: bone effects anti-proliferative and pro-differentiation vitamin D system in skin, 1892-1894 25­ bone mineral content and density, activity, 1677-1678 vitamin D therapy Radi( 682-683 apoptosis, 1685 biological effects, 1894-1895 cell culture studies of growth effects children, 1896 long-term effects, 684 RAN. immune tolerance, 1863 cancer cell lines, 1678-1679 clinical studies, 1895-1897 difl primary prostate cells, 1679 combination therapies, 1896 optimal vitamin D status, 1082 OVE resistance, 1679-1680 human immunodeficiency virus, pseudo-vitamin D deficiency, 1193-1194 pre vitamin D and calcium metabolism, virally transformed cells, 1679 1896-1897 RANI 679-680 cell cycle arrest, 1684-1685 nails, 1896 bor vitamin D deficiency during pregnancy cell differentiation, 1685-1686 scalp, 1896 der late effects on child chemoprevention studies, 1689-1690 Psoriatic arthritis (PsA) viu asthma, 687 clinical trials clinical features, 1966 bone mass, 687 analogs, 1695 vitamin D therapy, 1966 Rb,se diabetes, 687-688 calcitriol, 1695 PTH, see Parathyroid hormone RCc, cholecalciferol, 1694-1695 PTHrp, see Parathyroid hormone-related growth,687 Read maternal effects, 685, 701-702 summary, 1696-1697 protein neonate effects, 685-687, 702-703 combination therapy Puberty, see Adolescent INDEX 2075

Pulse sequence, see Magnetic resonance Regulatory T cells, see T cell polyrnorphisms, 1961-1962 imaging Renal cell carcinoma (RCq, vitamin 0 vitamin 0 status PXR, see Pregnane X receptor studies, 1767 animal studies, 1962 Renal osteodystrophy, see Chronic kidney human studies, 1962-1964 qBEI, see Quantitative backscattering disease RhoA electron imaging Renin-angiotensin system, see also vitamin 0 analog effects in benign prostatic qCT, see Quantitative computed Hypertension hyperplasia, 1934 tomography cascade, 707-708 vitamin 0 transcriptional activity role, 239 Quantitative backscattering electron chronic kidney disease, 716-718 RIA, see Radioimmunoassay imaging (qBEI), mineralization CYP27Bl/vitamin 0 receptor knockout Rickets, see also Hereditary vitamin-O analysis, 387 studies, 589-590 resistant rickets; Quantitative computed tomography (qCT) functional overview, 707-708 Hypophosphatemia; Vitamin 0 metabolic bone disease diagnosis, 815 inhibitors, 710-711 deficiency mineralization analysis, 385 renin and regulation of production and biochemical findings, 1111-1113 Quantitative computed tomography secretion calcium deficiency, 1118-1120 bone mineral density detennination, 884 calcium-sensing receptor, 443-444 clinical presentation, 1110-1111 high-resolution peripheral quantitative overview, 708-710 dental rickets, 522-524 computed tomography transcriptional regulation, 710 developmental studies, 629, 635, 652 applications vitamin 0 receptor, 443-444, 589-590, epidemiology, 1108-1110 cross-sectional studies, 901-902 712 etiology, 817 longitudinal studies, 902-903 vitamin 0 regulation fibroblast growth factor-23 mutations, 750 hardware, 900 analogs as inhibitors, 713-714 growth plate, 1114-1115 image analysis inhibition mechanisms, 711-713 history of study, 4, 13-14, 1107-1108 biomechanical analysis, 903 pathophysiological implications, klotho mutations, 753 densimetric analysis, 902 714-715 New World primate, 251, 254-255 longitudinal analysis, 903 vitamin 0 status effects, 716, 1976-1977 optimal vitamin 0 status in morphometric analysis, 902-903 Reproductive function, see also Lactation; supplementation, 1068-1069 overview, 901-902 Pregnancy pathogenetic spectrum, 1120-1121 positioning, 900-901 animal models, 695-696 pediatric orthopedics, 929-931 tomography, 901 male reproduction, 700 prevention, 1116-1118 vitamin 0 studies radiographic findings RA, see Rheumatoid arthritis endometriosis, 697, 700 overview, 813-814, 860-863 Race fertility, 700-701 X-linked hypophosphatemia, 875 calcium absorption effects, 651-652 polycystic ovary syndrome, 696-699 radiological findings, 861-863, 1113-1114 calcium metabolism effects, 669-670 premenstrual syndrome, 697 treatment, 818-822, 1115-1116 diabetes type 2 differences, 1924 Respiratory syncytial virus (RSV) vitamin 0 response element binding hypertension differences, 1924 clinical features of infection, 2000 proteins Multiethnic Study of Atherosclerosis, intervention trials of vitamin 0 in acute humans, 255-258 1409 respiratory infection, 2005-2006 New World primates, 255 skeletal accretion effects, 670-671 observational studies of vitamin 0, 2005 Rifampicin, vitamin 0 metabolism effects, skin pigmentation and vitamin 0 synthesis Response element, see Estrogen response 1266-1267 effects, 14-15, 19,984-986 element binding protein; Vitamin RNA polymerase II vitamin 0 status influences in children and o response element heterogeneous nuclear ribonucleoprotein adolescents, 662, 955, 957 Retinoblastoma protein (Rb), vitamin 0 regulation, 262 vitamin 0 synthesis effects, 14-15, 19 regulation in Gl/S block, Mediator-O complex recruitment, 198 Radioimmunoassay (RIA) 1640-1641 RNA processing coupling, 200 lo:,25-dihydroxyvitamin 0, 836-837 Retinoid X receptor (RXR) ROCK, vitamin 0 analog effects in benign 24,25-dihydroxyvitamin 0, 836 chronic kidney disease effects, 1336 prostatic hyperplasia, 1934 25-hydroxyvitamin 0, 834-835 CYF24Al expression regulation, ROS, see Reactive oxygen species Radioreceptor assay (RRA)O:,25­ 1532-1533 Rosenheim reaction, 87 dihydroxyvitamin 0, 1, 835-837 keratinocyte stem cell function, 536 Roux-en-Y gastric bypass, see Obesity RANK, osteoclast signaling vitamin 0 analogs and heterodimerization RRA, see Radioreceptor assay differentiation, 338-339 response, 1442 RSV, see Respiratory syncytial virus overview, 337-338 vitamin 0 receptor transactivation role, Runx2 precursor proliferation, 338 107-108,110,113-116,140,151-152, bone gene expression within context of RANKL 1234 nuclear architecture, 311 bone remodeling, 323-325 Rhabdomyolysis, hyperphosphatemia, coregulatory factor interactions, 314 dental expression, 525 1175-1176 endochondral bone formation role, 303, 313 vitamin 0 regulation of expression, 98, 113, Rheumatoid arthritis (RA) epigenetic regulation, 312 152-154, 415 bone loss, 1961 osteoblast transcriptional control of Rb, see Retinoblastoma protein clinical features, 1960 differentiation, 305-306, 309 RCc, see Renal cell carcinoma fall risks, 1961 RXR, see Retinoid X receptor Reactive oxygen species (ROS), immune function, 1961 neuroprotective actions of vitamin vitamin 0 receptor Salkowski reaction, 86 0,572 agonist studies, 1799-1800 Sarcoidosis, vitamin 0 toxicity 2076 INDEX

Sarcoidosis, vitamin D toxicity (Continued) phosphate absorption role, 356 Stroke, cerebrovascular mortality as Tam CYP27Bl role, 777-778 vitamin D regulation of expression, 218 endpoint in vitamin D evidence for endogenous intoxication, SLC34A3, hereditary hypophosphatemic observational and interventional TC, 778-779, 1386-1387 rickets with hypercalciuria studies, 1983-1987 Tce extrarenal production, 778-779 mutations, 1170 Strut analysis, bone histomorphometry, 856 d SAXS, see Small-angle X-ray scattering SLE, see Systemic lUpus erythematosus Sun exposure, see also Photobiology; Skin C SCF, see Stem cell factor Sleeve gastrectomy, see Obesity cancer SCFE, see Slipped capital femoral epiphysis Slipped capital femoral epiphysis (SCFE), blood pressure studies, 715 ex Schizophrenia, vitamin D studies, 573-574 vitamin D and pediatric cancer risk studies relative to vitamin D Scleroderma, vitamin D therapy, 1898 orthopedics, 933 case-control studies, 1578-1580 Sclerostin (SOST), bone health role, 243 Smad3, vitamin D receptor interactions, 200 ecological studies of regional exposure, Season Small-angle X-ray scattering (SAXS), 1578 vitamin D status influences in children and mineralization analysis, 387 surrogate of vitamin D status, 1572 adolescents, 661-662 SMC, see Smooth muscle cell cultural practices and preferences, vitamin D synthesis effects, 15, 17 Smooth muscle cell (SMC), see also 989-990 Sex differences Vasculature DNA damage and repair, 1943-1944 calcium metabolism, 669-670 calcium, phosphate, and vitamin D excess immune suppression, 1944 skeletal accretion, 670-671 effects, 1141-1143 influences on vitamin D synthesis vitamin D status in children and vitamin D function, 1974-1975 clothing, 16-17, 989 adolescents, 662 SMRT, vitamin D receptor repression, glass and Plexiglas, 16 SFRPI 201-202 latitude, 15, 17,987-988 bone formation signaling, 305 Socioeconomic status, vitamin D status race, 19 OF bone health role, 243 influences in children and season, 15, 17 re; SG340, 1475 adolescents, 662 sunscreen, 15-17 SG396,1475 Sodium-dependent phosphate transporters time of day, 15, 17 SG402,1475 hereditary hypophosphatemic rickets with multiple sclerosis inverse correlation, 1846 vii Shipping, vitamin D, 90 hypercalciuria defects, 1170 photocarcinogenesis, 1944-1945 SHR, see Spontaneously hypertensive rat phosphate homeostasis, 1156-1157 photoprotection studies of vitamin D T-cel Silica cartridge chromatography, vitamin D, Soft drinks, intake effects on bone health, compounds bo 824, 826, 834 652 DNA damage, 1946 TC Skin SOST, see Sclerostin immune suppression, 1946 TC diseasessee speCifiC diseases Sp1, cell differentiation induction via mechanisms vitamin D analogs for hyperproliferative vitamin D, 1631 Akt, 1948 vii skin disorder management, S phase, see Cell cycle genomic and non-genomic pathways, 1899-1900 Sphingosine, photoprotection mechanisms 1947-1948 W Skin, see also Hair cycle; Keratinocyte of vitamin D compounds, 1948 Jun N-terminal kinase, 1948 TCF~ barrier function and vitamin D role, 534 Spontaneously hypertensive rat (SHR), metallothionein, 1948 TEM barrier function of vitamin D, 1815-1816 547-549 mitogen-activated protein kinase, 1948 Test! CYP27Bl, 782 Squamous cell carcinoma, see Skin cancer nitric oxide synthase, 1948 Teste optimal vitamin D status in disease Src p53, 1949 prevention, 1076-1077 vitamin D plasma membrane receptor sphingosine, 1948 Tetra pigmentation and vitamin D synthesis interactions, 28 photocarcinogenesis, 1946 effects, 14-15, 19,984-986 vitamin D regulation through nongenomic prospects, 1949-1950 TGF· vitamin D synthesis, see Photobiology action, 281 sunburn cells, 1945-1946 TGR Skin cancer SRC-l, vitamin D receptor activation, 106, prostate cancer, 967, 970-971 de CYP27Bl/vitamin D receptor knockout 108, 111, 195-198 skin cancer risk assessment, 19 ml studies, 590 SRC-2, vitamin D receptor activation, 106, surrogate vitamin D dose, 1053-1054, Theo photocarcinogenesis, 1944-1946 108, 111, 195-198 1572 sun exposure risk assessment versus SRC-3, vitamin D receptor activation, 106, tuberculosis historical perspective, 1818 Thia: vitamin D deficiency, 19, 1756-1757 108, 111, 195-198 vitamin D synthesis assessment from sun idi ultraviolet exposure risks, 1751-1752 Star volume, bone histomorphometry, exposure vitamin D effects 856 objective measures, 990-991 vi! basal cell carcinoma, 1754-1755 Statins, vitamin D metabolism effects, questionnaires, 991 Thin chemoprevention, 1752 1260-1261 Suprasterols, photobiology, 14 keratinocyte function, 1753 Status, see Vitamin D status SW123,1478 Thyr melanoma, 1755-1756, 1764 Stem cell factor (SCF), 1732 SW931,1478 Thyr prospects for study, 1757 Steroid and xenobiotic receptor (SXR), SXR, see Steroid and xenobiotic receptor risk potentiation studies, 1753 CYP24Al expression regulation, Systemic lupus erythematosus (SLE) Time squamous cell carcinoma, 1755-1756 1533 clinical features, 1962, 1965 vitamin D therapy, 1898 Steroid hormone receptor extrarenal vitamin D production, 779 TIO, SKIP, see NCoA62/SKIP coregulators, 252 immune function, 1965 TLC, SL117,1470 mechanism of action, 254-255 vitamin D receptor agonist studies, 1801 TL& SL137, 1470 Stomach, see Gastric cancer; vitamin D status TNF· SL142,1470 Postgastrectomy bone disease animal studies, 1965 TNF! SLC34A2 Storage, vitamin D, 90 human studies, 1965-1966 INDEX 2077

Tanning salons, vitamin D synthesis, Toll-like receptors (TLRs) renal function, 480-482 1750-1751 activation, 1812 tissue distribution, 372 TC, see Tumor calcinosis classification, 1812 vitamin D regulation of expression, Tcell pathogen detection, 1811-1812 113-114, 153-154, 160, 218 classification, 1789 tuberculosis and vitamin D effects, Tuberculosis CYP27B1/vitamin D receptor knockout 1816-1817 clinical relevance of vitamin D status, studies, 594-596 vitamin D effects on expression, 1780 1817-1818 experimental autoimmune encephalitis Tortelli-Jaffe reaction, 87 drug effects on vitamin D metabolism, vitamin D amelioration mechanisms Total parenteral nutrition (TPN), bone loss 1266-1267 activation-induced cell death clinical features, 1314 endogenous vitamin D toxicity, 1387 sensitivity, 1862 epidemiology, 1313-1314 extrarenal vitamin D production, 778-779 chemokine synthesis inhibition, 1862 pathogenesis, 1314 genetics, 1816 nitric oxide synthase inhibition of treatment, 1314 history of vitamin D and sunshine studies, induction, 1862-1863 Toxicity; see Vitamin D toxicity 1818 overview, 1861-1862 TPN, see Total parenteral nutrition innate immunity and vitamin D role, 1811, vitamin D receptor Trabecular bone, magnetic resonance 1816-1817 overview, 1858 imaging vitamin D deficiency and therapy, 1778, regulatory T cells, 1859-1860 image processing 2002-2003 Thl cells, 1858 coil sensitivity correction, 907 Tumor calcinosis (TC) Th2 cells, 1858-1859 segmentation, 909-910 clinical presentation, 1172-1173 Th17 cells, 1859 image registration, 912-913 gene mutations optimal vitamin D status, 1078-1079 morphometric analysis, 910-912 FGF23,1173 regulatory T cell enhancement by pulse sequences, 906-907 GALNT3, 1173 tolerogenic dendritic cells, signal-to-noise considerations, 906-908 klotho, 1173 1793-1794 spatial resolution, 905-906 Tumor-induced osteomalcia (TIO), ,1846 vitamin D receptor agonist effects, Trabecular bone pattern factor, bone 1159-1165 1797-1798 histomorphometry, 854 Tumor necrosis factor-a (TNF-a) T-cell factors (TCFs) Transcaltachia, 354-355 inflammatory bowel disease therapeutic bone formation signaling, 305 Transcriptional cycling targeting, 1885-1886 TCF-4 and cancer, 1605 impact, 221 vitamin D metabolism effects, 1256 TCF-4 and vitamin D regulation, 114,117, models, 220-221 TX522,1462-1463 241-242 TRANSFAC, vitamin D response element TX527, 1462-1463 vitamin D inhibition of f3-catenin discovery. 218 complexes, 238-241 Transforming growth factor-f3 (TGF-f3) Ulcerative colitis bone loss, see also Wnt signaling, 236 breast cancer signaling, 1660 Inflammatory bowel disease TCFs, see T-cell factors cancer growth inhibition via vitamin D, clinical features, 1306 TEM, see Transmission electron microscopy 1604 epidemiology. 1305 Testes, CYP27Bl expression, 783 chronic kidney disease, 1334 pathogenesis, 1306 Testosterone, vitamin D metabolism effects, experimental autoimmune encephalitis treatment, 1306 1253-1254 expression, 1860 Ultraviolet radiation, see Photobiology; Sun Tetracycline, labeling in bone prostate cancer, 1686 exposure histomorphometry, 846-847 Transmission electron microscopy (TEM), UNR, parathyroid hormone messenger TGF-f3, see Transforming growth factor-f3 mineralization analysis, 387 RNA binding, 500-501 TGR5, bile acid studies Transplantation, see Organ transplantation derivatives for modulation, 1514-1515 Trousseau's sign, 811 Valproic acid, leukemia treatment with metabolism regulation, 1514 TRPV4, osteoclast effects, 339 vitamin D combination therapy, Theophylline, vitamin D metabolism TRPV5 1741 effects, 1267-1268 calcium renal tubular reabsorption, 435 Vascular endothelial growth factor (VEGF), Thiazide diuretics functions, 372 see also Angiogenesis idiopathic hypercalciuria management, gene endochondral bone fonnation role, 303 1375 genomic organization, 372 Vasculature, see also Angiogenesis; vitamin D metabolism effects, 1262-1263 vitamin D regulation, 372 Arteriosclerosis; Atherosclerosis; Thin-layer chromatography (TLC), vitamin kidney expression, 366 Heart D,86 knockout mouse, 585-586 bimodal response of vitamin D dose, Thyroid cancer, vitamin D studies, 1763 osteoclast effects, 339 1403-1404 Thyroid hormone, vitamin 0 metabolism renal function, 480-482, 585-586 clinical cardiovascular outcomes in vitamin effects, 1254-1255 vitamin D regulation of expression, 114 D observational and interventional Time of day, vitamin D synthesis effects, 15, TRPV6 studies, 1987-1989 17 calcium absorption role, 352, 585 coagulation system and vitamin 0 effects, no, see Tumor-induced osteomalcia developmental regulation, 627-628, 634 1978-1979 TLC, see Thin-layer chromatography functions, 373 CYP27Bl expression, 542-543 TLRs, see Toll-like receptors gene inflammation, 1977-1978 TNF-a, see Tumor necrosis factor-a genomic organization, 372-373 mortality as endpoint in vitamin D TNFSF11, vitamin D regulation of vitamin D regulation, 373 observational and interventional expression, 218-219 knockout mouse, 585 studies, 1983-1987 2078 INDEX

Vasculature (Continued) food fortification, 653, 992, 994, 997-998, prostaglandin E2 effects, 1255-1256 E-I parathyroid hormone-related protein 1000 rifampicin, 1266-1267 hy function, 736-737 glucocorticoid effects on metabolism, testosterone effects, 1253-1254 platelet function, 1978 1236-1238 thyroid hormone effects, 1254-1255 hy smooth muscle cells history of study tumor necrosis factor-a effects, 1256 int calcium, phosphate, and vitamin 0 commercial production, 73-74 osteoporosis supplementation studies excess effects, 1141-1413 discovery, 4 bone mineral density effects, 1133-1134 kie vitamin 0 function, 1974-1975 hormonal form, 6-7, 97-99 fracture prevention let sympathetic nervous system and vitamin 0 isolation of nutritional forms, 5 primary prevention, 1134-1139 I effects, 1979 metabolites, 7-8 secondary prevention, 1139-1140 vitamin 0 intervention studies in animal photobiology, 4-5, 13-14 pharmacology, see Pharmacology, models physiological functions vitamin 0 arteriosclerosis, 549-550 intestinal absorption of calcium and phosphate modulation of metabolism, hypertension, 548-549 phosphorous, 5 1157-1159 I vitamin 0 receptor functions calcium mobilization from bone, 5-6 ring numbering, 1461 rni animal studies renal reabsorption of calcium and storage and shipping, 90 no Dahl salt-sensitive rat, 547-548 phosphorous, 6 Vitamin 02 no deoxycorticosterone acetate-salt rat, intake recommendations, see also Vitamin 0 commercial applications, 88-89 547 status dietary considerations, 1001 salt-induced hypertension, 547-548 animals, 88 loading dose, 1059 spontaneously hypertensive rat, humans, 18,20, 87 pharmacokinetics, 1042 547 infants and children, 650-651 structure, 821 blood coagulation and fibrinolysis, intake, see Vitamin 0 status supplementation, 1052-1053 546-547 intestinal absorption, 1300 Vitamin 0 analogs, see also speCifiC analogs osl cell studies intracellular vitamin 0 binding proteins, acyclic analogs, 1479-1482 angiogenesis, 543-544 265-266 A-ring endothelium, 543 metabolism derivatives, 1431 pI1 inflammation, 544 aluminum toxicity effects, 1265-1266 hydroxyls, 1430 pSI vasoactivity, 543 calcitonin effects, 1249-1250 benign prostatic hyperplasia studies rir overview, 541-542,1974 drug effects inflammation inhibition, 1935-1936 sid prospects for study, 557 anticonvulsants, 1257-1258 lower urinary tract symptoms, to> smooth muscle studies bisphosphonates, 1262 1931-1932 vit calcium deposition, 546 caffeine, 1267 overview, 1803 cell proliferation, 545-546 calcium channel blockers, 1263 prospects for study, 1937-1938 vit vasoactivity,544-545 cimetidine, 1264 prostate cell growth control, 1933-1934 VOR, see Vitamin 0 receptor cyclosporine A, 1268 urethra dysfunction, 1936-1937 VORE, see Vitamin 0 response element ethanol, 1259-1260 bile acid derivatives, see also Lithocholic VORL-I, 1499, 1506 fluoride, 1268 acid derivatives VORM2, 1499-1501 glucocorticoids, 1258-1259 bone loss management in organ VOS, see Vitamin 03 sterol heparin, 1263-1264 transplantation, 1294-1296 VOUPl, see Vitamin O-upregulated protein­ ketoconazole, 1260 calcemic action minimization, 1429-1430, 1 lithium, 1268-1269 1438 VEGF, see Vascular endothelial growth olestra, 1268 cardiovascular risks, 1418-1419 factor orlistat, 1268 CD-ring analogs Vertical banded gastroplasty, see Obesity proton pump inhibitors, 1265 C-ring, 1467-1469, 1474, 1477 VID400, 36, 1540-1541 rifampicin, 1266-1267 O-ring, 1470-1477 VITAL, see Vitamin 0 and Omega-3 Trial statins, 1260-1261 identification, structure, and biological Vitamin A theophylline, 1267-1268 characterization, 1502-1504 bile acid synthesis suppression, 764-765 thiazide diuretics, 1262-1263 overview, 1431-1432, 1461, 1465, 1467 discovery, 3-4 estradiol effects, 1252-1253 CF-ring analogs, 1477-1478 excess considerations in vitamin 0 status, fibroblast growth factor-23 effects, chronic kidney disease management 1002 1248-1249 analog types, 1556 Vitamin B complex, discovery, 3-4 growth hormone effects, 1250 animal model studies, 1556-1559 Vitamin 0, see also specific forms insulin effects, 1251-1252 cardiovascular disease outcomes, 1563 circulating concentrations in diseases, insulin-like growth factor-I effects, end-stage renal disease, 1560-1563 837 1250-1251 prospects for study, 1563-1564 Vitar definition, 979 interferon-y effects, 1256 stage 3-4 disease, 1559-1560 act detection, see also specific fonns leptin effects, 1249 survival impact, 1561-1563 art chemical synthesis and assays, 84-87 overview, 823-825, 981-982, 1042-1044, cis-triene structure, 1430 Cal extraction, 825-826 1300-1302 clinical availability, 1438, 1492 fw high-performance liquid parathyroid hormone effects, 1245-1247 cyclooxygenase inhibition, 1451 chromatography, 85-86, parathyroid hormone-related protein CYP24Al metabolism, 1447-1449 826-827 effects, 1247-1248 decalin analogs, 1465-1466 gel serum, 825 progesterone effects, 1254 diabetes type 1 prevention, 1833 inf silica cartridge chromatography, 826 prolactin effects, 1251 14-epi analogs, 1462-1465 kn INDEX 2079

E-ring analogs, 1478-1480 multiple sclerosis levels, 1853 organ transplantation studies hyperproliferative skin disorder polymorphisms, 65 pre-transplantation management, 1899-1900 prospects for study; 67-68 heart, 1292 hypocalcemia management, 1100-1103 structure, 58-60 kidney, 1292-1293 intracellular vitamin 0 binding protein synthesis and turnover, 60 liver, 1292 binding, 1451 vitamin 0 analog interactions, 1445-1447 lung, 1292 kidney stone formation risks, 1375 vitamin 0 pharmacology role, 1047 post-transplantation leukemia studies vitamin 0 toxicity and levels, 1391-1392 heart, 1294 9 C-16-enes, 1742-1743 Vitamin 0 deficiency, see also Pseudo­ long-term, 1293-1294 140 calcipotriol, 1741 vitamin 0 deficiency; Rickets; perioperative, 1293 20-epi vitamin 03,1743 Vitamin 0 status; specific diseases peripheral arterial disease observational gemini analogs, 1743 adiposity effects, 770-773 studies, 555 m, 1a-hydroxyvitamin 0 3, 1741 age-dependent signs and symptoms, pregnancy paracalcitol, 1743 807-808 late effects on child miscellaneous compounds, 1505-1507 atherosclerosis observational studies, 555 asthma, 687 non-genomic rapid actions, 1449-1451 autoimmune disease, 1799 bone mass, 687 non-secosteroidal compounds beta cell function, 1827-1828 diabetes, 687-688 bis- and tris-aromatic triols, 1503, 1505 brain effects of developmental vitamin 0 growth,687 diarylmethane ligands deficiency maternal effects, 685, 701-702 characterization in vivo, 1501-1502 behavioral effects in later life, 568-569 neonate effects, 685-687, 702-703 identification, structure, and biological dietary restriction, 567-568 prevalence in children and adolescents, characterization, 1498-1500 gene expression effects in later life, 568 659-660 overview, 1481, 1483-1484, 1497-1498 structural alterations, 576 prostate cancer osteoporosis management calcium extracellular fluid concentration overview, 965-966 alfacalcidol, 1491-1495 regulation, 611 serological studies, 970-972 eldecalcitol, 1492-1495 cancer studies with knockout mice, risk groups, 959 prostate cancer studies, 1683-1684, 1695 590-593 skin cancer risk assessment versus vitamin psoriasis management, 1894-1897 chronic kidney disease observational o deficiency, 18 ring numbering, 1461 studies, 556-557, 717 sun exposure in prevention, 16-19 side chain modifications, 1432-1433 colorectal cancer pathogenesis, 1713-1714 Vitamin 0 External Quality Assessment toxicity, 1384-1385 heart failure observational studies, 556 Scheme, 839-840 vitamin 0 binding protein interactions, history of study, 861-862 Vitamin 0-25-hydroxylase, see CYP2R1; 1445-1447 hypertension observational studies, 554, CYP3A4; CYP27Al vitamin 0 receptor binding, see also Vitamin 715 Vitamin 0 and Ornega-3 Trial (VITAL) 1934 o receptor hypocalcemia etiology ancillary studies, 2052-2053 22-butyl-1,24-dihydroxyvitamin 03 CYP27B1 deficiency, 1098 blood collection, 2050 lic derivative complexes, 182-185 malabsorption, 1098 compliance monitoring, 2051 C-2a-substituted vitamin 0 analog malnutrition, 1097-1098 design, 2047-2048 complexes, 179-181 vitamin 0 receptor defects and follow-up and endpoints, 2050-2051 coactivator/ corepressor recruitment resistance, 1098-1099 goals, 2043 1430, response, 1443-1444 infants, 636-637 monitoring and safety, 2051 DNA binding response, 1443 insulin resistance and diabetes participants ligand binding, 1441 observational studies, 557 characteristics, 2049 ligand-binding domain bound to lactating mothers and effects on infant, eligibility criteria, 2048 superagonists 688-689 recruitment and enrollment, 2048-2049 14-epi analogs, 178-179 metabolic bone disease diagnosis randomization, 2049 'cal 20-epi analogs, 176, 178 bone scintigraphy, 817 rationale, 2046 2-substituted, 19-nor analogs, 178 dual-energy X-ray absorptiometry, 815 statistical power, 2052 467 ligand-dependent regulation, 1444-1445 laboratory testing, 813, 815 vitamin 0 nuclear translocation effects, 1442 medical history dose, 2046-2047 phosphorylation response, 1442 chief complaint, 809 intake assessment, 2049-2050 retinoid X receptor heterodimerization family history, 812 Vitamin 0 receptor (VOR) response, 1442 past history, 811 activation 563 zVOR ligand-binding domain bound to present illness, 810-811 coactivators, 106, 139, 195-201 vitamin 0, 175 review of systems, 812 differential activation, 106 Vitamin 0 binding protein (OBP) social history; 811-812 integrated model of coregulator activity, actin complex, 65-66 physical examination, 812-815 203-204 arteriosclerosis studies, 1410-1411 quantitative computed tomography, 817 analog effects, see Vitamin 0 analogs candidate gene studies, 1032-1033 X-ray, 815-816 bacterial artificial chromosome clones functions mineralization animal model studies, bone cell activity, 123 overview, 57 390-396 transgenes in mice, 123-124 vitamin 0 transport, 60-65 multiple sclerosis, 1847 bile acids gene, 57-58 myopathy; 2024-2025 binding, 765 inflammation role, 66-67 optimal vitamin 0 status, see Vitamin 0 detoxification role, 764-765 knockout mouse, 57,62-63,395 status synthesis regulation, 764 2080 INDEX

Vitamin D receptor (VDR) (Continued) experimental autoimmune encephalitis and coactivator binding mutations, 1217 b bile acids expression on T cells compound heterozygous mutations, interactions, 1515-1517 overview, 1858 1217-1218 metabolism regulation, 1514 regulatory T cells, 1859-1860 deletions, 1214 biochemical properties, 100-101 Thl cells, 1858 DNA-binding domain mutations, brain function, 566-567 Th17 cells, 1859 1210-1211 breast cancer Th2 cells, 1858-1859 heterodimerization-affecting mutations, expression and regulation, 1663 functions 1216-1217 polymorphisms and risk, 1668 bone and mineral regulatory gene ligand-binding domain mutations, prognostic significance, 1664 expression, 154 1214-1216 resistance, 1664 feedback control of vitamin D actions, miscellaneous mutations, 1218 breast function, 440 154-156 nonsense mutations, 1211-1213 calcium absorption control in intestine, 351 longevity, 160-161 overview, 1209-1210 candidate gene studies, 1031-1032 neoclassical functions of liganded and RNA splicing-disrupting mutations, chondrocyte function, 436-437 unliganded receptor, 158-160 1213-1214 chronic kidney disease alterations overview, 97-99, 144-145 immunoregulation by agonists, homologous upregulation defects, Wnt/~cateninsignaling crosstalk, 1789-1799 1333-1335 156-157 intestinal function, 439 miscellaneous resistance mechanisms, gene keratinocyte function, 444 1335-1337 cloning, 101-102 kidney function, 434-435 polymorphisms, 1335 enhancers, 121-123 knockout mouse, 141, 143-144, 160,481, v colon cancer, 444-446 intracellular receptor gene family, 102 497-409,523,525-526,536,549,570, conformational ensemble model organization, 120-121 584-597,627, 747,772-77~ alternative ligand-binding pocket genetic hypercalciuric rat activity, 1076-1077, 1130, 1201, 1734, 1978, evidence, 286-289 1371-1373 2034-2035 overlapping two-pocket model, 285-287 genomic versus nongenomic signaling ligand structures and specificity, 278, 291 overview, 284-285 cross-talk,282-283 membrane binding, 284 crystal structure discrimination, 271 nuclear receptor superfamily, 144-147 antagonism structural basis nongenomic actions osteoblast function, 437-438 adamantyl analog complexes, 186 examples, 280, 289-291 osteoclast function, 438-439 calcipotriol modification for receptor ion channels, 279 parathyroid function, 430-433 antagonism, 184-186 kinases, 281 parathyroid hormone expression 22-butyl-1,24-dihydroxyvitamin D3 phosphatases, 279 regulation, 495-498 derivative complexes, 182-185 phospholipases, 281-282 phosphate absorption control in intestine, C-2a;-substituted vitamin D analog structural determinants, see Vitamin D3 357 complexes, 179-181 sterol placenta function, 439-440 hVDRa bound to vitamin D, 172-175, W286R mutation and calcium signaling, plasma membrane receptors 177 290-291 palmitoylation, 284 ligand-binding domain bound to genomics structural/scaffolding proteins, superagonists bone cell gene transactivation, 113, 283-284 v 14-epi analogs, 178-179 117-118 types, 283 Viti 20-epi analogs, 176, 178 chromatin immunoprecipitation, polymorphisms, 148,446,527,669, b 2-substituted, 19-nor analogs, 178 111-115 966-970, 1593-1594, 1779, lithocholic acid derivative binding colon cancer gene transactivation, 1851-1852, 1958, 1961-1962,200~ unmodified lithocholic acid, 1517-1519 114-115 2035 3-ketolithocholic acid, 1519 DNA binding and dynamics at target post-translational modification, 124 lithocholic acid acetate/propionate, 1519 genes, 111-112 renin secretion regulation, 443-444, nonsteroidal ligand complexes enhancer linking to genes, 118 589-590 YR301-rVDR ligand-binding domain intestinal gene transactivation, 113-114, repressors complex, 181 116-117 corepressors, 201-203 zVDR ligand-binding domain bound to overarching principles of gene integrated model of coregulator activity, CD578 analog, 181-182 regulation, 116-118 203-204 overview, 139, 148 glucocorticoid regulation, 1235 response element, see Vitamin D response zVDR ligand-binding domain heart element gemini binding, 182 developmental role, 550-551 stability, 124 E vitamin D binding, 175 expression, 550 superagonist structure-based design, g discovery, 8-9, 99 fibrosis 187-188 g domains animal studies, 552-553 tissue distribution, 99-100,137,430-440 g DNA-binding domain, 103-104, vitamin D intervention studies, transcriptional regulation of expression II 147-148,213,1201 554-555 heterologous transcriptional regulation, n E/F domain homology between nuclear hypertrophy 119-120 P receptors, 102-103 animal studies, 551-552 homologous transcriptional regulation, Sl ligand-binding domain, 104-105, vitamin D intervention studies, 553 120 V 148-150,213, 1201 hereditary vitamin-D resistant rickets overview, 118-119 overview, 102-103, 139-140, 171-172 defects tissue-specific expression, 120 INDEX 2081

transcriptional transactivation, see also Vitamin D status, see also Vitamin D skin disease, 1076-1077 specific genes; Vitamin D response deficiency orthopedic impact, see Orthopedics element adolescents, see Adolescent osteoarthritis, 1955-1958 chromatin-looping model, 152-153 bariatric surgery effects, 1018-1019 phosphate absorption effects, 357 conformational change, 105, 151 breast cancer trials, 1667-1668 physiological factors, 983-988 coregulators, 108-110, 115, 193-204, calcium absorption effects, 350-352 rheumatoid arthritis, 1962-1964 212-213 chronic kidney disease observational sex differences in children and adolescents, osteocalcin as model, 106-107 studies, 556-557 662 overview, 150-154, 1202-1203 determinants, 980-982 social and cultural factors, 988-990 polarity of response element binding, diabetes, 55, 671, 687-688, 702 sun exposure as surrogate of vitamin D 108 food fortification, 653, 992, 994, 997-998, status, 1572 response elements in genes, 140-143 1000 systemic lupus erythematosus, retinoid X receptor role, 107-108, 110, genome-wide association studies of serum 1962-1965 113-116,140 levels, 1036-1037 vitamin D supplementation, 999-1002, target genes geographic studies 1020-1021 analysis, 220 Africa, 955, 957 vitamin D synthesis assessment from sun cell cycle regulation, 219 Asia, 955-956 exposure classical targets, 218-219 ethnic differences, 662, 957, 959 objective measures, 990-991 relative expression, 219 Europe, 950, 952-954 questionnaires, 991 transcriptional cycling, 220-222 global studies using central laboratory Vitamin D toxicity, see also Hypercalcemia vascular functions facility, 957 arteriosclerosis studies, 590, 1409-1411, animal studies Middle East, 954-955 1415-1416 Dahl salt-sensitive rat, 547-548 North America, 947-950 clinical manifestations, 1392-1393 deoxycorticosterone acetate-salt rat, nutrition, 959 diagnosis, 1393-1394 547 Oceania, 957-958 endogenous intoxication salt-induced hypertension, 547-548 overview, 947 diagnosis, 794 spontaneously hypertensive rat, 547 South America, 950-951 diseases blood coagulation and fibrinolysis, intake cancer, 781 546-547 assessment, 991-992 lymphoma, 1388-1389 cell studies recommendations noninfectious granuloma-forming angiogenesis, 543-544 animals, 87-88 diseases, 780-781 endothelium, 543 estimation, 982-984 overview, 779 inflammation, 544 humans, 18,20,87 peritonitis, 779 vasoactivity,543 overview, 992-993 sarcoidosis, 778-780, 1386-1387 overview, 541-542 United States, 993, 995 systemic lupus erythematosus, 779 smooth muscle studies latitude influences, 661-662, 987-988 tuberculosis, 780-781, 1387 calcium deposition, 546 lifestyle strategies for improvement, 25-hydroxyvitamin D production, cell proliferation, 545-546 1002-1004 1385-1386 vasoactivity, 544-545 multiple sclerosis hypercalcemia vitamin D toxicity role, 1389-1390 analysis, 1846-1847 prevention, 795 Vitamin D response element (VDRE) deficiency in patients, 1847 treatment, 795-796 binding proteins in vitamin D resistance longitudinal disease, 1848 hypercalciuria treatment, 793-794 humans, 255-258 relapse and remission, 1848-1850 prevention, 795 New World primates, 255 risk analysis, 1847-1848 risk assessment, 794-795 bone type I collagen gene, 405 sun exposure inverse correlation, 1846 screening, 795 clusters, 215-216 obesity, 662, 773-774 treatment, 795-796 CYP24A1, 1529-1530 optimal vitamin D status exogenous toxicity DR3-type, 214-215 adults and elderly, 1069-1076 1,25-dihydroxyvitamin D, 1384 DR4-type, 215 cancer, 1077-1078 25-hydroxyvitamin D, 1381-1384 DR6-type, 215 cardiovascular and metabolic disease, vitamin D analogs, 1384-1385 E-box negative elements 1079-1080 hyperphosphatemia, 1172 coregulator switching in transrepression, diabetes, 1080-1081, 1924 loading dose, 1059-1060 229 25-hydroxyvitamin D optimal level, mechanisms mediation of transrepression, 228-229 1048-1050,1069,1131-1133,1148 CYP24A1 inhibition, 1391 ER9-type, 215 hypertension, 1924 CYP27B1 control, 1390-1391 gene type distribution, 140-143 immune function, 1078-1079 general mechanisms, 1389 genome-wide analysis, 116 metabolic syndrome, 1080-1081 vitamin D binding protein levels, genome-wide screening, 218 muscle function, 1081 1391-1392 multiple elements per gene, 216-217 musculoskeletal health, 1148 vitamin D receptor role, 1389-1390 negative elements, 217, 228-229 overview, 620-622, 1067-1068, pregnancy, 689 parathyroid hormone, 405, 495 2045-2046 radiographic findings in intoxication, 880, screening in silico, 217-218 pregnancy, 1081 883 vitamin D receptor binding prospects for study, 1082-1083 supplement pharmacology and safety overview, 214 rickets prevention with vitamin D issues, 1056-1058 polarity, 108, 152 supplementation, 1068-1069 treatment, 1394-1395 2082 INDEX

Vitamin 03 sterol (VDS) hair cycle, 157-158,593 extraskeletal ossification, 876-877 chemistry, 271-272 inhibitors, 237 osteoarthritis, 877 conformational dynamics of seco-B-rings keratinocyte stem cell function, 536 osteomalacia, 875-876 and A-rings, 272-274 knockout mice, 242 rickets, 875 conformational ensemble, 275-276 osteoblast signaling, 243-244 recessive disease, 1172 metabolism, 275 osteoblast signaling and vitamin 0 effects, treatment, 1169 nongenomic activity structural features and 329-330 XM612,1468 molecular dynamics signaling XM615,1469 agonists, 276-278 noncanonical pathways, 237 XM720, 1469 antagonists, 277-278 overview, 235-237 XM804, 1469 pharmacokinetics, 1042 skin signaling, 244-245 XM806, 1468 side-chain conformational dynamics, vitamin 0 inhibition, 238-241 X-ray 274-276 WU442,1470 acidemia, 880 structure, 823 WU507, 1470 aluminum toxicity, 874-875 Vitamin O-upregulated protein-1 (VOUP1), WU515,1470 brown tumor, 870-871 cancer role, 1602 WY10061,1471 differential diagnoses, 880, 882-883 Voltage-sensitive calcium channels (VSCCs) WY10071,1472 hyperparathyroidism calcium homeostasis overview, 457 WY1036, 1471 renal osteodystrophy, 869-870 families, 458 WY1037, 1472 secondary hyperparathyroidism, osteoblast mediation via vitamin 0 WY1038, 1471 867-869 differentiation, 462-463 WY1039, 1473 metabolic bone disease diagnosis, 815-816 survival, 463-464 WY1046, 1472 metastatic calcification, 871-874 subunits, 458-459 WY1048, 1473 oncogenic rickets/ osteomalacia, 879-881 vitamin 0 actions, 460-461 WYll06,1472 osteomalacia, 865-867 VSCCs, see Voltage-sensitive calcium WY1112,1471 osteoporosis, 871 channels WYl113, 1473 osteosclerosis, 870 WY1116, 1472 periosteal reaction, 871 Weaning, see Lactation WY578,1474 rickets, 862-865, 1113-1114 Wheezing WY619, 1474 vitamin 0 intoxication, 880, 883 clinical features in children, 2001 WY718,1474 X-linked hypophosphatemia intervention trials of vitamin 0 in acute WY722, 1473 bone modeling abnormalities, 876 respiratory infection, 2005-2006 WY821, 1471 extraskeletal ossification, 876-877 observational studies of vitamin 0, WY838,1474 osteoarthritis, 877 2003-2004 WY906,1474 osteomalacia, 875-876 WINAC, vitamin 0 receptor interactions, WY9361, 1471 rickets, 875 200-201,227-230 X-ray diffraction (XRO) Windaus synthesis, 7-dehydrocholesterol, XLH, see X-linked hypophosphatemia crystallography, see Crystal structure 76 X-linked hypophosphatemia (XLH) mineralization analysis, 387-388 Wnt clinical presentation, 1165 XRO, see X-ray diffraction bone formation signaling, 304-305 CYP24A1 dysregulation, 1535-1536 bone homeostasis, 242-243 pathogenesis, 1169 Yeast, irradiation for biofortification, 999 cancer role, 237-238, 241-242 pathophysiology, 1165-1167 YR301,1500 coreceptors, 156, 235 PHEX defects, 1167-1168 DICKKOPF inhibition and vitamin 0 radiographic findings ZG1368, 1468, 1504 regulation, 241-242 bone modeling abnormalities, 876 ZG1423, 1469

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