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A Acronyms, Abbreviations, and Glossary ACRONYMS AND ABBREVIATIONS 25-hydroxyvitamin D In this report, 25OHD (also referred to as calcidiol or calcifediol); indicates no distinction between D2 and D3 forms. When relevant, forms distinguished as 25OHD2 and 25OHD3. 1,25-dihydroxyvitamin D In this report, calcitriol. Ercalcitriol refers to 1,25-dihydroxyvitamin D2, but in this report, the term “calcitriol” will be used for both. 24,25-dihydroxyvitamin D In this report, 24,25(OH)2D. Agency for Healthcare Research and Quality AHRQ Adequate Intake AI All-laboratory trimmed mean ALTM Acceptable Macronutrient Distribution Range AMDR Alpha-Tocopherol Beta-Carotene Cancer Prevention Study ATBC Beck Depression Inventory BDI Bone mineral apparent density BMAD Bone mineral content BMC Bone mineral density BMD Body mass index BMI Bone volume BV 523

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524 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D Canadian Community Health Survey CCHS Centers for Disease Control and Prevention CDC Control group CG Canadian Health Measures Survey CHMS Confidence interval CI Canadian Nutrient File CNF Competitive protein binding assay CPBA Cardiovascular disease CVD Cytochrome P450 CYP Vitamin D binding protein DBP Vitamin D External Quality Assurance Scheme DEQAS Deoxyribonucleic acid DNA Dietary Reference Intake DRI Dual-energy X-ray absorptiometry DXA Estimated Average Requirement EAR European Prospective Investigation into Cancer and EPIC Nutrition Epidémiologie de l’Ostéoporose study EPIDOS Fibroblast-like growth factor-23 FGF23 Femoral neck FN Gas chromatography GC Glomerular filtration rate GFR Health Professionals Follow-up Study HPFS Hazard ratio HR Inflammatory bowel disease IBD Interferon IFN Immunoglobulin Ig Intervention group IG Ischemic heart disease IHD Interleukin IL Institute of Medicine IOM Intact parathyroid hormone iPTH International Unit IU Mini-Mental State Examination for Koreans K-MMSE

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525 APPENDIX A Liquid chromatography LC Lowest-observed-adverse-effect level LOAEL Lumbar spine LS Least squares mean LSM Milk-alkali syndrome MAS Mini-Mental State Examination MMSE Month(s) mo Messenger ribonucleic acid mRNA Osteoporotic Fractures in Men Study MrOS Mass spectrometry; Multiple sclerosis MS Tandem mass spectrometry MS/MS Not applicable NA Normocalcemic NCa National Center for Health Statistics NCHS National Cancer Institute NCI Not determined ND National Health and Nutrition Examination Survey NHANES Nurses’ Health Study NHS National Institutes of Health NIH National Institute of Standards and Technology NIST No-observed-adverse-effect level NOAEL Nonobese diabetic NOD Not reported NR Not significant NS Osteoarthritis OA Oral contraceptive OC Osteoporosis OP Odds ratio OR Osteoid volume OV Prostate, Lung, Colorectal, and Ovarian Cancer Screening PLCO Trial Postmenopausal PM Profile of Mood States POMS Parathyroid hormone PTH Parathyroid hormone–related protein PTHrP Rheumatoid arthritis RA Receptor activator for nuclear factor κ B RANK

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526 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D Randomized controlled trial RCT Recommended Dietary Allowance RDA Randomised Evaluation of Calcium and/Or vitamin D trial RECORD Radioimmunoassay RIA Recommended Nutrient Intake RNI Relative risk RR Standard deviation SD Standard error SE Standard error of the mean SEM Systemic lupus erythematosus SLE Single-photon absorptiometry SPA Sun protection factor SPF Standard Reference Material SRM Tuberculosis; Total body TB T helper Th Total hip TH Trochanter Tr Transient receptor potential cation channel, vanilloid TRPV6 family member 6 Treatment Tx United Kingdom UK Tolerable Upper Intake Level UL United States U.S. U.S. Department of Agriculture USDA Ultraviolet UV Ultraviolet B UVB Vitamin D–dependent rickets VDDR Vitamin D receptor VDR Vitamin D–responsive element VDRE Vascular endothelial growth factor VEGF Women’s Health Initiative WHI What We Eat in America WWEIA Week(s) wk Year(s) y

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527 APPENDIX A GLOSSARY Achlorhydria A lack of hydrochloric acid in the digestive juices in the stomach. Adenoma A benign epithelial tumor of glandular origin. Adequate Intake The recommended average daily intake level of a nutrient based on observed or experimentally determined approximations or es- timates of intakes that are assumed to be adequate for a group (or groups) of apparently healthy people; used when the Recom- mended Dietary Allowance cannot be determined. Adipokines Cytokines, growth factors, and other proteins produced and se- creted by adipose tissue. Adipose tissue A connective tissue consisting chiefly of fat cells surrounded by reticular fibers and arranged in lobular groups or along the course of one of the smaller blood vessels. Amenorrhea Abnormal suppression or absence of menstruation. Anorexia The symptom of poor appetite whatever the cause. Anorexia nervosa A psychophysiological disorder usually occurring in teenage women that is characterized by fear of becoming obese, a distorted self-image, a persistent aversion to food, and severe weight loss, and that is often marked by hyperactivity, self-induced vomiting, amenorrhea, and other physiological changes. Antigen Any substance that stimulates an immune response in the body. Antirachitic Cures or prevents rickets. Asthma A chronic inflammatory disease of the airways. Autism A complex developmental disability that typically appears during the first few years of life; is the result of a neurological disorder that affects the normal functioning of the brain, impacting de- velopment in the areas of social interaction and communication skills.

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528 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D Biomarker A biochemical, physiological, behavioral, or other alteration that can be measured in the body or its products that influences, pre- dicts, or is associated with an established or possible outcome, health impairment, or disease. Body mass index An indirect measure of body fat calculated as the ratio of a person’s body weight to the square of a person’s height: BMI (kg/m2) = weight (kilograms)/height (meters)2 BMI (lb/in2) = weight (pounds)/height (inches)2 × 703 Bone mineral content The hardness of bone results from its mineral content in the or- ganic matrix. Bone mineral density A measure of bone density that reflects the strength of bones as represented by calcium content. Calcification Impregnation with calcium or calcium salts; hardening, as of tis- sue, by such impregnation. Calcinosis The abnormal deposition of calcium salts in a part or tissue of the body. Calcitonin A peptide hormone, produced by the thyroid gland in humans, that acts to lower plasma calcium and phosphate levels without augmenting calcium accretion. Calcitriol Another name for 1,25-dihydroxyvitamin D. Calcium A mineral found mainly in the hard part of bones, where it is stored; it is essential for healthy bones and is important for muscle contraction, heart action, nervous system maintenance, and nor- mal blood clotting. Calciuria The presence of calcium in the urine. Cancer A malignant and invasive growth or tumor. Cardiovascular disease Any abnormal condition characterized by dysfunction of the heart and blood vessels; includes atherosclerosis (especially coronary heart disease), cerebrovascular disease, and hypertension.

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529 APPENDIX A Chondrocyte A connective tissue cell that occupies a lacuna within the cartilage matrix. Chylomicron One of the microscopic particles of fat occurring in chyle (a diges- tive fluid) and in the blood, especially after a meal high in fat. Computed tomography Tomography used in diagnostic studies of internal bodily struc- tures, in which computer analysis of a series of cross–sectional scans made along a single axis of a bodily structure or tissue is used to construct a three-dimensional image of that structure. Creatinine One of the nonprotein constituents of blood, a breakdown prod- uct of creatinine (protein used to make adenosine triphosphate). Increased quantities of serum creatinine are found in advanced stages of renal disease. Crohn’s disease A chronic inflammatory disease of the intestines that primarily causes ulcerations (breaks in the lining) of the small and large intestines, but can affect the digestive system anywhere from the mouth to the anus. Cut-point A specified quantitative measure used to demarcate the pres- ence or absence of a health-related condition; often used in interpreting measures obtained from analysis of blood (example: blood measures below “x” ng/mL indicate a deficiency state for Nutrient Y). Cytochrome Any of a class of iron-containing proteins important to cell respira- tion as catalysts of oxidation–reduction reactions. Depression A condition of general emotional dejection and withdrawal; sad- ness greater and more prolonged than that warranted by any ob- jective reason. Dermis The sensitive connective tissue layer of the skin located below the epidermis, containing nerve endings, sweat and sebaceous glands, and blood and lymph vessels. Diabetes mellitus A group of metabolic diseases characterized by high blood sugar (glucose) levels that result from defects in insulin secretion or ac- tion, or both.

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530 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D Diabetes, type 1 An autoimmune disease that occurs when T cells attack and deci- mate the β-cells in the pancreas that are needed to produce insu- lin, so that the pancreas makes too little insulin (or no insulin); there is a genetic predisposition to type 1 diabetes, and the disease tends to occur in childhood, adolescence, or early adulthood (be- fore age 30), but it may have its clinical onset at any age. Diabetes, type 2 Disease in which the β-cells of the pancreas produce insulin but the body is unable to use it effectively because the cells of the body are resistant to the action of insulin; also known as insulin- resistant diabetes, non-insulin-dependent diabetes, and adult-onset diabetes. Dietary Reference Intake A set of four distinct nutrient-based reference values that replaced the former Recommended Dietary Allowance in the United States. These include Estimated Average Requirement (EAR), Recom- mended Dietary Allowance (RDA), Adequate Intake (AI), and Tolerable Upper Intake Level (UL). Dose–response assessment Determination of the relationship between nutrient intake (dose) and some criterion of either adequacy or adverse effect. Dual-energy X-ray absorptiometry Means of measuring bone density with two X-ray beams with dif- fering energy levels aimed at an individual’s bones. Emesis The act or process of vomiting. Endocrine Pertaining to hormones and the glands that make and secrete them into the bloodstream through which they travel to affect distant organs. Epidermis The nonvascular outer protective layer of the skin, covering the dermis. Ergosterol A plant sterol that is converted into vitamin D by ultraviolet radiation. Estimated Average Requirement The average daily nutrient intake level that is estimated to meet the requirements of half of the healthy individuals in a particular life stage and gender group.

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531 APPENDIX A Estradiol The most potent naturally occurring estrogen. Etiology Causes and origins of disease. Fibroblast A cell ubiquitous in connective tissue that makes and secretes collagen. Glucocorticoid Any of a group of steroid-like compounds, such as hydrocorti- sone, that are produced by the adrenal cortex, are involved in carbohydrate, protein, and fat metabolism, and are used as anti- inflammatory agents. Hematocrit The percentage by volume of packed red blood cells in a given sample of blood after centrifugation. Homeostasis A property of cells, tissues, and organisms that allows the main- tenance and regulation of the stability and constancy needed to function properly. Hormone A substance, usually a peptide or a steroid, produced by one tissue and conveyed in the bloodstream to another to effect physiological activity, such as growth or metabolism. Hydroxyapatite The principal bone salt that provides the compressional strength of vertebrate bone. Hypercalcemia A higher than normal level of calcium in the blood. Hypercalciuria Excess calcium in the urine. Hyperglycemia A high blood sugar; an elevated level specifically of the sugar glu- cose in the blood. Hypertension/hypertensive Systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg. Hypophosphatemia Abnormally low concentrations of phosphates in the blood.

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532 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D Inflammatory bowel disease Any of several incurable and debilitating diseases of the gastro- intestinal tract characterized by inflammation and obstruction of parts of the intestine. Influenza An acute, commonly epidemic disease occurring in several forms, caused by numerous rapidly mutating viral strains and character- ized by respiratory symptoms and general prostration. Ligand An ion, a molecule, or a molecular group that binds to another chemical entity to form a larger complex. LOAEL The lowest intake (or experimental dose) of a nutrient at which an adverse effect has been identified. Lumisterol A naturally occurring compound that is part of the vitamin D fam- ily of steroid compounds. Macrophage A type of white blood cell that ingests foreign material. Menopause The state of an absence of menstrual periods for 12 months. Metabolic syndrome Also called insulin resistance syndrome and Metabolic Syndrome X. A group of conditions that increase risk of heart disease, dia- betes, and stroke. The five conditions are high blood pressure, high blood sugar levels, high levels of circulating triglycerides, low levels of circulating high-density lipoprotein, and excess fat in the abdominal area. Microsome A small particle in the cytoplasm of a cell, typically consisting of fragmented endoplasmic reticulum to which ribosomes are attached. Milk-alkali syndrome Caused by the ingestion of large amounts of calcium and absorb- able alkali with resulting hypercalcemia; if untreated, can lead to metastatic calcification and renal failure. Morbidity Illness or disease. Mortality A fatal outcome; death.

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533 APPENDIX A Multiple sclerosis A disease in which the nerves of the central nervous system (brain and spinal cord) degenerate. Natriuresis Excretion of excessive amounts of sodium in the urine. Neoplasm A new, often uncontrolled growth of abnormal tissue; tumor. Nephrocalcinosis Renal lithiasis characterized by diffusely scattered foci of calcifica- tion in the kidneys. Nephrolithiasis Calculi in the kidneys. NOAEL The highest intake (or experimental dose) of a nutrient at which no adverse effect has been observed. Nutrient A substance (such as a chemical element or inorganic compound) that an organism needs to live and grow; a substance used in an or- ganism’s metabolism that must be taken in from its environment. Nutriture A state of nutrition in the body. Osteoblast A cell from which bone develops. Osteoclast A large multinucleate cell found in growing bone that resorbs bony tissue, as in the formation of canals and cavities. Osteocyte A branched cell imbedded in the matrix of bone tissue. Osteogenesis Formation and development of bony tissue. Osteoid Resembling bone; the bone matrix, especially before calcification. Osteomalacia The softening of bone, the depletion of calcium from bone; may be caused by poor dietary intake or poor absorption of calcium and other minerals needed to harden bones and can be a charac- teristic feature of vitamin D deficiency in adults. Osteopenia A condition of bone in which decreased calcification, decreased density, or reduced mass occurs.

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534 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D Osteoporosis A condition characterized by a decrease in bone density (a de- crease in bone strength that results in fragile bones); leads to abnormally porous bone that is compressible, like a sponge. Parathyroid gland A gland that regulates calcium, located behind the thyroid gland in the neck, which secretes parathyroid hormone. Parathyroid hormone A hormone that is made by the parathyroid gland and that is criti- cal to calcium and phosphorus balance. Perimenopause The interval in which a women’s body begins its transition into menopause. Periosteal Pertaining to the periosteum, the membrane covering the bones. Phosphate A form of phosphoric acid; calcium phosphate makes bones and teeth hard. Polyuria The excessive passage of urine, resulting in profuse urination and urinary frequency. Preeclampsia A toxic condition developing in late pregnancy characterized by a sudden rise in blood pressure, generalized edema, proteinuria, se- vere headache, and visual disturbances that may result in eclampsia (convulsive or coma state) if untreated. Previtamin D3 A short-lived intermediate form arising from exposure of provi- tamin D3 (7-dehydrocholesterol) in the skin to UVB irradiation. Body heat quickly changes previtamin D3 into vitamin D3. Prohormone An intraglandular precursor of a hormone. Provitamin D3 (7-dehydrocholesterol) A provitamin present in the skin of humans as well as the milk of mammals that becomes vitamin D3 when exposed to ultraviolet light. Recommended Dietary Allowance The average daily dietary intake level that is sufficient to meet the nutrient requirements of nearly all (97.5 percent) healthy indi- viduals in a particular life stage and gender group.

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535 APPENDIX A Rheumatoid arthritis An autoimmune disease that causes chronic inflammation of the joints. Rickets A disorder caused by a deficiency of vitamin D, calcium, or phos- phate, which leads to softening and weakening of the bones and is seen most commonly in children 6 to 24 months of age. Sarcoidosis A disease that results from a specific type of inflammation of tis- sues of the body that can appear in almost any body organ, often starting in the lungs or lymph nodes. Scleroderma A pathological thickening and hardening of the skin caused by swelling and thickening of fibrous tissue. Systemic lupus erythematosus A chronic, autoimmune, inflammatory disease of connective tissue that causes fever, weakness, fatigue, joint pains, and skin lesions on the face, neck, or arms. Tachysterol An isomer of ergosterol that forms vitamin D2 when irradiated with ultraviolet light. Tolerable Upper Intake Level The highest average daily nutrient intake level that is likely to pose no risk of adverse effects to almost all individuals in the general population. As intake increases above the Tolerable Upper Intake Level, the potential risk of adverse effects may increase. Transgenic Having genetic material (deoxyribonucleic acid) from another species. Tuberculosis A highly contagious infection caused by the bacterium called My- cobacterium tuberculosis. Ultraviolet Pertaining to electromagnetic radiation having wavelengths in the range of approximately 5 to 400 nm; shorter than visible light, but longer than X-rays. Ultraviolet B Medium wavelength (280 to 320 nm) ultraviolet rays from the sun; help synthesis of vitamin D3; the “burning” rays in the ultraviolet spectrum.

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536 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D Vasodilatation Relaxation or widening of the blood vessels; leads to a lowered blood pressure. Vitamin D Also referred to as calciferol; comprises a group of fat-soluble seco- sterols. The two major forms are vitamin D2 and vitamin D3 (both vitamin D2 and vitamin D3 can be synthesized commercially and may be found in dietary supplements or fortified foods; they differ only in their side chain structure). Vitamin D2 Also referred to as ergocalciferol; originates from plants and is found in the human diet. Vitamin D3 Also referred to as cholecalciferol; is synthesized in the skin of humans from 7-dehydrocholesterol and is also consumed in the diet via the intake of animal-based foods. Vitamin D–resistant rickets An inherited form of rickets characterized by high concentrations of phosphate in the blood due to defective renal tubular reabsorp- tion of phosphate and subnormal absorption of dietary calcium.