Chin J Osteoporos September 2014 Vol 20 No. 9 develop this practical application guideline for vitamin and bone health in adult Chine

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1 Chin J Osteoporos September 2014 Vol 20 No. 9 Published online www. wanfangdate. com. cn doi /j. issn 中国老年学学会骨质疏松委员会维生素学科组专家委员会 1* 廖祥鹏 2 张增利 3 张红红 4 朱汉民 5 周建烈 6 黄琪仁汪之顼 8 王亮 9 刘忠厚 R68 A Vitamin deficiency ~ 5 25OH Application Guideline for Vitamin and Bone Health in Adult Chinese 2014 Standard Edition Vitamin Working Group of Oste oporosis Committe e of China Ge rontological Socie ty LIAO Xiangpeng 1 ZHANG Zengli 2 ZHANG Honghong 3 ZHU Hanmin 4 ZHOU Jianlie 5 HUANG Qiren 6 WANG Zhixue 7 WANG Liang 8 LIU Zhonghou 9 1. Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University Wuxi China 2. School of Public Health Suzhou University Suzhou China 3. General Hospital of PLA Beijing China 4. East China Hospital Affiliated to Fudan University Shanghai China 5. Vitamin Today Website Shanghai China 6. The Sixth People s Hospital Affiliated to Shanghai Jiaotong University Shanghai China 7. School of Public Health Nanjing Medical University Nanjing China 8. General Hospital of General Staff of PLA Beijing China 9. Osteoporosis Committee of China Gerontological Society Beijing China Corresponding author LIAO Xiangpeng lxp4848@ aliyun. com Abstract Vitamin may contribute to widespread effects in human health and vitamin deficiency may lead to the development of osteoporosis and to falls and fractures meanwhile there have been some conflicting guidelines and inconsistent practices about vitamin in the West. Given these conditions some specialists from Osteoporosis Committee of China Gerontological Society * lxp4848@ aliyun. com

100102 7 汪之顼 8 王亮 9 刘忠厚 R68 A 1006-7108 2014 09-1011-20 Vitamin deficiency 2013 2011 4 ~ 5 25OH Application Guideline for Vitamin and Bone Health in Adult Chinese 2014 Standard Edition Vitamin

2 Chin J Osteoporos September 2014 Vol 20 No. 9 develop this practical application guideline for vitamin and bone health in adult Chinese. This guideline includes Starter Edition and Standard Edition and the evidence of this guideline mainly comes from the guideline of National Osteoporosis Society in the UK 2013 the report of Institute of Medicine in the United States 2011 supported by some domestic literatures. This guideline addresses the management of vitamin deficiency in adult patients with or at risk of developing bone disease. It should be noted that the management of vitamin deficiency in childhood in pregnancy or in patients with severe or end-stage chronic kidney disease CK Stages 4 5 is beyond the topic of this guideline. Based on the published " Starter Edition" in this journal this " Standard Edition" goes further and the contents of this guideline includes the setting up of vitamin thresholds for adult Chinese assessment of vitamin status interpretation of 25OH measurement detailed plan of vitamin treatment and monitoring and prevention strategy for vitamin deficiency. Key words Vitamin Adult Chinese Bone Guideline OH

of Medicine in the United States 2011 supported by some domestic literatures.

3 Chin J Osteoporos September 2014 Vol 20 No Vitamin deficiency 25-25OH 25OH High-performance liquid 4 ~ 5 Vitamin Recommended nutrient Institute of Medicine Washington C USA Calciferol either 2 or 3 / 2 3 Vitamin 3 Cholecalciferol 3 Vitamin 2 Ergocalciferol 2 25-hydroxy vitamin 25OH 25- Calcidiol Calcifediol 1 25-dihydroxy vitamin 1 25 OH Calcitriol Chronic kidney disease CK Parathyroid hormone PTH Bone mineral density BM randomised controlled trial RCT Vitamin binding protein VBP chromatography HPLC Mass spectrometry MS Tandem MS 3-epi-25 OH C 3 epimer C 3 ietary reference intakes RI Estimated average requirement Endocrine Society Washington. C. USA National Osteoporosis Society Bath England 10 μg = 400 IU 2. 5 nmol /L 25OH = 1 ng /ml 25OH OH < 30 nmol /L 2. 5 nmol /L 2013 = 1 ng /ml Vitamin RIs deficiency 2 25OH 30 ~ nmol /L Vitamin inadequacy or EAR intake RNI Adequate intakes AI Tolerable upper intake level UL

Vitamin 2 Ergocalciferol 2 25-hydroxy vitamin 25OH 25- Calcidiol Calcifediol 1 25-dihydroxy vitamin 1 25 OH 2 1 25- Calcitriol Chronic kidney disease CK Parathyroid hormone PTH Bone mineral density

4 Chin J Osteoporos September 2014 Vol 20 No. 9 insufficiency 3 25OH 50 nmol /L OH 50 ~ 75 nmol /L 2. 25OH 4 25OH OH 25OH 9 25OH OH PTH OH PTH Zoledronate enosumab 25OH IU 6 ~ ~ 2000 IU / 4000 IU / 25OH 25 ~ 50 nmol /L ~ < 15% 15% 30% > 30% 25OH OH < 75 nmol /L Endocrine Society Washington. C. 600 IU / 3. 25OH PTH 25OH OH Osteoporosis Foundation Nyon Switzerland 18 National Osteoporosis Foundation Washington. C. USA Osteoporosis Canada Lips nmol /L < nmol /L PTH 80 ~ 100 nmol /L 17 USA 3 International

5 ~ 25 8. < 15% 15% 30% > 30% 25OH 9. 1 25OH < 75 nmol /L Endocrine Society Washington. C. 600 IU / 3. 25OH 1 1-3 PTH 25OH 10.

5 Chin J Osteoporos September 2014 Vol 20 No AHRQ 27 AHRQ OH PTH BM / 25OH PTH 2 25OH < 30 nmol /L 100 ~ 125 nmol /L 25OH 30 ~ nmol /L AHRQ 25OH BM 25OH 30 ~ 80 nmol /L AHRQ 25OH nmol /L 25OH < 50 nmol /L 20 ng /ml 25OH < 30 nmol /L 60% 25OH < 75 nmol /L 30 ng / AHRQ ml RCTs 90% modest BM BM AHRQ 25OH ~ 50 nmol /L 15 ~ 20 ng /ml 50 ~ 75 nmol /L PTH Bischoff-Ferrari 24 25OH PTH 16 ~ 20 ng /ml ~ ng /ml ng /ml OH < 25 nmol /L IU / 40% 18% PTH 25OH 28 25OH % 2% 25OH PTH

9 nmol /L AHRQ 25OH BM 25OH 30 ~ 80 nmol /L 1 1 2 AHRQ 25OH 27.

6 Chin J Osteoporos September 2014 Vol 20 No. 9 Table 1 1 Vitamin data of adult Chinese from different areas 25OH % % ng /ml < 20 ng /ml < 30 ng /ml * ~ ± ± ± CLIA ~ ~ 6 RIA 2009 Ling Lu ± ± CLIA ~ ~ 6 ELISA ~ ± RIA ~ ± ~ 2 RIA ± ± ~ 12 CLIA ~ ± ~ 8 CLIA RIA ELISA ± ± CLIA ± ± ~ 7 CLIA ~ ± ~ 10 ELISA ± ± ± ± ± ± ELISA ~ ± CLIA 2007 Wat WZ ± ± RIA ~ ± ELISA ~ ± ELISA 2012 Tao M ± ± ~ 7 CLIA 2010 Wang J ± < 15 ng /ml < 32 ng /ml Xiang F ± LC-MS ± % ~ RIA Woo Jean 36 ELISA * CLIA RIA LC-MS - ELISA Fig OH 1 istributions of serum 25OH means in adult Chinese by areas and peoples ata from Table 1

7 CLIA 40 2013 1995 41 2011 2012 43 2013 2010 45 2012 34 2009 46 2013 31 301 7 ~ 96 99. 3 3 ~ 6 ELISA 30 54 18 ~ 50 27. 6 ± 14. 1 RIA 42 27 1494 20 ~ 79 20. 4 ± 9. 0 52. 3 84.

7 Chin J Osteoporos September 2014 Vol 20 No Fig. 2 2 % 1 Incidences of vitamin deficiency in adult Chinese by areas Precentages ata from Table 1 25OH < 20 ng /ml 25OH < 30 ng /ml Osteoporosis Australia 57 25OH 50 nmol /L ~ 75 nmol /L OH < 50 nmol /L 25OH 25OH < 50 nmol / L 25OH 75 nmol /L 5% Threshold Cut-point 25OH < 75 nmol /L 30 ng /ml OH 50 nmol /L 97. 5% 25OH 25OH 50 nmol /L 25OH 25OH 20 ~ 70 ng /ml OH > 30 ng /ml 75molL / BM 59 3 BM 25OH 50 nmol /L 97. 5% nmol /L OH 50 nmol /L 6

Osteoporosis Australia 57 25OH 50 nmol /L 62 50 ~ 75 nmol /L 1 19 64 25OH < 50 nmol /L 25OH 25OH < 50 nmol / L 25OH 75 nmol /L 5% Threshold

8 Chin J Osteoporos September 2014 Vol 20 No nmol /L 25OH > 20 ng /ml ~ 75 nmol /L AHRQ AHRQ 2. 25OH 30 ~ nmol /L 25OH nmol /L 3 25OH 40 nmol /L 50% 4. 25OH 50 nmol / L 97. 5% 25OH < 30 nmol /L 25OH 50 ~ 75 nmol /L 25OH 30 ~ nmol /L 5 25OH 30 ~ nmol /L 50% 25OH OH 50 nmol /L 1. 25OH < 30 nmol /L 24 h 68 25OH 21 ~ 30 3 d OH 25OH < 50 nmol /L 25OH 3 25OH 56 Fig. 3 The relationship between serum 25OH and integrated bone health outcomes. Adapted from a schematic representation by National Osteoporosis Society in the UK.

9 nmol /L 5 25OH 30 ~ 49. 9 nmol /L 50% 25OH 40 67 25OH 50 nmol /L 1.

9 Chin J Osteoporos September 2014 Vol 20 No OH OH 2 25OH 4 ~ 15 h OH PTH nmol /L 1 25 OH 2 pmol 1 25 OH 2 /L 25OH 10 25OH 25- nmol /L 1 25 OH OH 25OH PTH 1α- 25OH PTH 25OH Fig Metabolism of vitamin Adapted from a schematic representation by National Osteoporosis Society in the UK. 25OH 25OH VBP 25OH 25OH 2 25OH 3 25OH VBP 80 ~ 90% 25OH 25- C3 10 ~ 20% 25OH 25OH 25OH nmol /L 25OH 80 Nichols Vitamin External Quality Assessment iasorin Scheme EQAS www. deqas. org Roche 25OH IS 25OH 3 25OH

25OH 25OH PTH 1α- 25OH PTH 25OH 77 79 4 Fig.

10 Chin J Osteoporos September 2014 Vol 20 No. 9 Tandem MS HPLC 25OH 4. PTH 25OH OH 25OH 2 25OH OH C OH 1. 25OH 2. 25OH 25OH 3 25OH 2 25OH 25OH 25OH 3. 25OH Fig Schematic representation that helps to define broad groups for clinical consideration and decision making. Adapted from a schematic representation by National Osteoporosis Society in the UK..

11 Chin J Osteoporos September 2014 Vol 20 No Paget 3. 25OH 50 nmol /L Zoledronate enosumab 8 25OH 25OH OH 25OH 84 25OH OH 50 nmol /L OH OH < 30 nmol /L OH 30 ~ nmol /L 25OH

2 65 3 1 4 25OH 50 nmol /L 2 3 3 2 3 2 3 3 3 2 3 2 7 2 3 85-87 88 25OH 89 2

12 Chin J Osteoporos September 2014 Vol 20 No titrated dosing strategy Zoledronate enosumab 25OH ~ 800 mg / http / /www. rheum. med. ed. ac. uk /calciumcalculator. php mg / IU IU / 25OH 30 ng /ml 1500 ~ 2000 IU / ~ 5000 IU / 75 ~ 125 μg ~ OH 1000 ~ 2000 IU / 300 Zoledronate enosumab 000IU IU

http / /www. rheum. med. ed. ac. uk /calciumcalculator.

13 Chin J Osteoporos September 2014 Vol 20 No OH 25OH IU IU IU IU 3800 IU IU ~ 2000 IU 25OH 4000 IU 1 25OH 2 1 / OH 3 25OH OH > nmol /L > 60 ng /ml 25OH > 500 nmol /L > 200 ng /ml g /dl ~ IU / IU / IU / 1 25OH < 500 nmol /L 2 3 EFSA 25OH IU / 100 μg / OH 20 ~ 25 μg 800 ~ 1000 IU mg /dl = mg /dl OH J 25OH 24 ~ 29 nmol /L 25OH 30 nmol /L

1 6 800 ~ 2000 IU 25OH 4000 IU 1 25OH 2 1 / 1 1 2 6 25OH 3 25OH 9 10 25OH > 150 104 nmol /L > 60 ng /ml 25OH > 500 nmol /L >

14 Chin J Osteoporos September 2014 Vol 20 No nmol /L 75 nmol /L ~ α- 25OH 1 25 OH IU / 3800 IU / IU / 10 mg /dl2. 63 mmol /L % nm B Ultraviolet B 290 ~ 315 nm 80 ~ 90% RNI 97% ~ 98% IU /

108 2400 IU / 3800 IU / 3 3800 IU / 10 mg /dl2.

15 Chin J Osteoporos September 2014 Vol 20 No IU / 400 IU / μg 400IU UL 50 μg 2000IU μg 600IU UL 50 μg 2000IU Holick MF. Vitamin deficiency J. N Engl J Med Francis RM Anderson FH Patel S et al. Calcium and vitamin in the prevention of osteoporotic fractures J. Qjm Holick MF Binkley NC Bischoff-Ferrari HA et al. Evaluation Treatment and Prevention of Vitamin eficiency an Endocrine Society Clinical Practice Guideline J. Journal of Clinical Endocrinology & Metabolism Bischoff-Ferrari HA Giovannucci E Willett WC et al. Estimation of optimal serum concentrations of 25-hydroxyvitamin for multiple health outcomes J. Am J Clin Nutr Bischoff-Ferrari HA. Optimal serum 25-hydroxyvitamin levels for multiple health outcomes. Sunlight Vitamin and Skin Cancer Springer Lips P. Vitamin deficiency and secondary hyperparathyroidism in the elderly consequences for bone loss and fractures and therapeutic implications J. Endocr Rev Sahota O Mundey MK San P et al. The relationship between vitamin and parathyroid hormone calcium homeostasis bone turnover and bone mineral density in postmenopausal women with established osteoporosis J. Bone Sahota O Gaynor K Harwood RH et al. Hypovitaminosis and functional hypoparathyroidism -the NoNoF Nottingham Neck of Femur study J. Age Ageing Prentice A Goldberg GR Schoenmakers I. Vitamin across the lifecycle physiology and biomarkers J. Am J Clin Nutr s-506s. 10 Francis RM. What do we currently know about nutrition and bone health in relation to United Kingdom public health policy with particular reference to calcium and vitamin J. Br J Nutr Patel S Hyer S Barron J. Glomerular filtration rate is a major determinant of the relationship between 25-hydroxyvitamin and parathyroid hormone J. Calcif Tissue Int Al-oanzi ZH Tuck SP Raj N et al. Assessment of vitamin status in male osteoporosis J. Clin Chem Sahota O Mundey MK San P et al. Vitamin insufficiency and the blunted PTH response in established osteoporosis the role of magnesium deficiency J. Osteoporos Int van der Wiel HE Lips P Nauta J et al. Biochemical parameters of bone turnover during ten days of bed rest and subsequent mobilization J. Bone Miner Vieth R Ladak Y Walfish PG. Age-related changes in the 25- hydroxyvitamin versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin J. J Clin Endocrinol Metab Lips P Chapuy MC awson-hughes B et al. An international comparison of serum 25-hydroxyvitamin measurements J. Osteoporos Int awson-hughes B Heaney RP Holick MF et al. Estimates of optimal vitamin status J. Osteoporos Int awson-hughes B Mithal A Bonjour JP et al. IOF position statement vitamin recommendations for older adults J. Osteoporos Int Foundation NO. NOF s Clinician s Guide to Prevention and Treatment of Osteoporosis Washington C 2014.

3 Holick MF Binkley NC Bischoff-Ferrari HA et al. Evaluation Treatment and Prevention of Vitamin eficiency an Endocrine Society Clinical Practice Guideline J.

16 Chin J Osteoporos September 2014 Vol 20 No Hanley A Cranney A Jones G et al. Vitamin in adult health and disease a review and guideline statement from Osteoporosis Canada J. Canadian Medical Association Journal E610-E Ross AC Taylor CL Yaktine AL et al. intakes for calcium and vitamin. National Academies Press ietary reference Washington C The 22 Chung M Balk EM Brendel M et al. Vitamin and calcium a systematic review of health outcomes J. Evid Rep Technol Assess Full Rep Cranney A Horsley T O onnell S et al. Effectiveness and safety of vitamin in relation to bone health J. Evid Rep Technol Assess Full Rep Bischoff-Ferrari HA awson-hughes B Willett WC et al. Effect of Vitamin on falls a meta-analysis J. Jama Bischoff-Ferrari HA awson-hughes B Staehelin HB et al. Fall prevention with supplemental and active forms of vitamin a meta-analysis of randomised controlled trials J. BMJ Boonen S Lips P Bouillon R et al. Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation evidence from a comparative metaanalysis of 45. randomized controlled trials J. J Clin Endocrinol Metab J Patient level pooled analysis of patients from seven major J vitamin fracture trials in US and Europe J. Bmj b Francis R. The vitamin paradox J. Rheumatology J J. 30. J J J J. 52 Tao M Shao H Gu J et al. Vitamin status of pregnant J Wat WZ Leung JY Tam S et al. Prevalence and impact of vitamin insufficiency in southern Chinese adults J. Ann J J Lu L Yu Z Pan A et al. Plasma 25-hydroxyvitamin concentration and metabolic syndrome among middle-aged and elderly Chinese individuals J. iabetes care J J J PTH J PTH J. women in Shanghai China J. J Matern Fetal Neonatal Med Wang J Yang F Mao M et al. High prevalence of vitamin and calcium deficiency among pregnant women and their newborns in Chengdu China J. World J Pediatr Nutr Metab Xiang F Jiang J Li H et al. High prevalence of vitamin 36 Woo J Lam CW Leung J et al. Very high rates of vitamin insufficiency in pregnant women working indoors and residing in insufficiency in women of child-bearing age living in Beijing and Guiyang China J. J Endocrinol Invest Hong Kong J. Br J Nutr ~

ietary reference Washington C The 22 Chung M Balk EM Brendel M et al. Vitamin and calcium a systematic review of health outcomes J. Evid Rep Technol Assess Full Rep 2009 183 1-420.

17 Chin J Osteoporos September 2014 Vol 20 No Francis R Aspray T Fraser W et al. Vitamin and bone health a practical clinical guideline for patient management. http / /www. nos. org. uk /document. doc id = Published Nowson CA McGrath JJ Ebeling PR et al. Vitamin and health in adults in Australia and New Zealand a position statement J. Med J Aust Looker A awson-hughes B Calvo M et al. Serum 25- hydroxyvitamin status of adolescents and adults in two seasonal subpopulations from NHANES III J. Bone Gutierrez OM Farwell WR Kermah et al. Racial differences in the relationship between vitamin bone mineral density and parathyroid hormone in the National Health and Nutrition Examination Survey J. Osteoporos Int Kung AW Yeung SS Lau KS. Vitamin receptor gene polymorphisms and peak bone mass in southern Chinese women J. Bone Powe CE Evans MK Wenger J et al. Vitamin -binding protein and vitamin status of black Americans and white Americans J. N Engl J Med Norris KC Williams SF. RAce /ethnicity serum 25- hydroxyvitamin d and heart disease J. JAMA Robinson-Cohen C Hoofnagle AN Ix JH et al. Racial differences in the association of serum 25-hydroxyvitamin concentration with coronary heart disease events J. Jama Holick MF Binkley NC Bischoff-Ferrari HA et al. Guidelines for Preventing and Treating Vitamin eficiency and Insufficiency Revisited J. Journal of Clinical Endocrinology & Metabolism Rosen CJ Abrams SA Aloia JF et al. IOM committee members respond to Endocrine Society vitamin guideline J. The Journal of Clinical Endocrinology & Metabolism avies J Smith J. NOS guidance on vitamin and bone health - clarity at last J. Prescriber Bouillon R Okamura WH Norman AW. Structure-function relationships in the vitamin endocrine system J. Endocr Rev Clemens TL Adams JS Nolan JM et al. Measurement of circulating vitamin in man J. Clin Chim Acta Barragry JM France MW Corless et al. Intestinal cholecalciferol absorption in the elderly and in younger adults J. Clin Sci Mol Med Clemens TL Zhou XY Myles M et al. Serum vitamin 2 and vitamin 3 metabolite concentrations and absorption of vitamin 2 in elderly subjects J. J Clin Endocrinol Metab Gallacher SJ Cowan RA Fraser W et al. Acute effects of intravenous 1 alpha-hydroxycholecalciferol on parathyroid hormone osteocalcin and calcitriol in man J. Eur J Endocrinol Gray RW Caldas AE Wilz R et al. Metabolism and excretion of 3H OH 2-vitamin 3 in healthy adults J. J Clin Endocrinol Metab Jones G. Pharmacokinetics of vitamin toxicity J. Am J Clin Nutr s-586s. 74 Papapoulos SE Clemens TL Sandler LM et al. The effect of renal function on changes in circulating concentrations of dihydroxycholecalciferol after an oral dose J. Clin Sci Lond Haddad JG Stamp T. Circulating 25-hydroxyvitamin in man J. The American journal of medicine Shepard RM eluca HF. Plasma concentrations of vitamin 3 and its metabolites in the rat as influenced by vitamin 3 or 25- hydroxyvitamin 3 intakes J. Archives of Biochemistry and Biophysics Zehnder Bland R Williams MC et al. Extrarenal expression of 25-hydroxyvitamin d 3-1 alpha-hydroxylase J. J Clin Endocrinol Metab Need AG O Loughlin P Morris HA et al. Vitamin metabolites and calcium absorption in severe vitamin deficiency J. J Bone Miner Res Fraser W. Hyperparathyroidism J. Lancet Herrmann M. The measurement of 25-hydroxy vitamin -an analytical challenge J. Clinical Chemistry and Laboratory Medicine Strathmann FG Sadilkova K Laha TJ et al. 3-epi-25 hydroxyvitamin concentrations are not correlated with age in a cohort of infants and adults J. Clin Chim Acta Atherton K Berry J Parsons T et al. Vitamin and chronic widespread pain in a white middle-aged British population evidence from a cross-sectional population survey J. Annals of the rheumatic diseases Straube S Andrew Moore R erry S et al. Vitamin and chronic pain J. Pain Zavon MR. Principles and Practice of Screening for isease J. Archives of Internal Medicine Trang HM Cole E Rubin LA et al. Evidence that vitamin 3 increases serum 25-hydroxyvitamin more efficiently than does vitamin 2 J. Am J Clin Nutr Armas LA Hollis BW Heaney RP. Vitamin 2 is much less effective than vitamin 3 in humans J. Journal of Clinical Endocrinology & Metabolism Romagnoli E Mascia ML Cipriani C et al. Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol vitamin 2 or cholecalciferol vitamin 3 in the elderly J. J Clin Endocrinol Metab

Vitamin and health in adults in Australia and New Zealand a position statement J. Med J Aust 2012 196 11 686-687. 58 Looker A awson-hughes B Calvo M et al.

18 Chin J Osteoporos September 2014 Vol 20 No Heaney RP Recker RR Grote J et al. Vitamin 3 is more potent than vitamin 2 in humans J. J Clin Endocrinol Metab E Tripkovic L Lambert H Hart K et al. Comparison of vitamin 2 and vitamin 3 supplementation in raising serum 25- hydroxyvitamin status a systematic review and meta-analysis J. Am J Clin Nutr Nugent C Roche K Wilson S et al. The effect of intramuscular vitamin cholecalciferol on serum 25OH vitamin levels in older female acute hospital admissions J. Ir J Med Sci Wang TJ Zhang F Richards JB et al. Common genetic determinants of vitamin insufficiency a genome-wide association study J. Lancet Grethen E McClintock R Gupta CE et al. Vitamin and hyperparathyroidism in obesity J. J Clin Endocrinol Metab Aarts E van Groningen L Horst R et al. Vitamin absorption consequences of gastric bypass surgery J. European Journal of Endocrinology Elnenaei MO Chandra R Mangion T et al. Genomic and metabolomic patterns segregate with responses to calcium and vitamin supplementation J. British journal of nutrition Chel V Wijnhoven HA Smit JH et al. Efficacy of different doses and time intervals of oral vitamin supplementation with or without calcium in elderly nursing home residents J. Osteoporos Int Ish-Shalom S Segal E Salganik T et al. Comparison of daily weekly and monthly vitamin 3 in ethanol dosing protocols for two months in elderly hip fracture patients J. Journal of Clinical Endocrinology & Metabolism Lips P uong T Oleksik A et al. A global study of vitamin status and parathyroid function in postmenopausal women with osteoporosis baseline data from the multiple outcomes of raloxifene evaluation clinical trial J. J Clin Endocrinol Metab Giusti A Barone A Razzano M et al. Persistence with calcium and vitamin in elderly patients after hip fracture J. J Bone Miner Metab Smith H Anderson F Raphael H et al. Effect of annual intramuscular vitamin on fracture risk in elderly men and women a population-based randomized double-blind placebo-controlled trial J. Rheumatology Oxford Sanders KM Stuart AL Williamson EJ et al. Annual highdose oral vitamin and falls and fractures in older women a randomized controlled trial J. Jama Segal E Zinnman H Raz B et al. Adherence to vitamin supplementation in elderly patients after hip fracture J. J Am Geriatr Soc Reid IR Bolland MJ Avenell A et al. Cardiovascular effects of calcium supplementation J. Osteoporos Int Rejnmark L Avenell A Masud T et al. Vitamin with calcium reduces mortality patient level pooled analysis of patients from eight major vitamin trials J. J Clin Endocrinol Metab Hannan FM Fairney A Johnston G. Vitamin deficiency masking primary hyperparathyroidism J. Ann Clin Biochem Pt National Institutes of Health. Vitamin fact sheet for health professionals. http / /ods. od. nih. gov /factsheets /Vitamin- HealthProfessional /. Published Hathcock JN Shao A Vieth R et al. Risk assessment for vitamin J. Am J Clin Nutr Tetens I. EFSA Panel on ietetic Products Nutrition and Allergies NA Scientific Opinion on the Tolerable Upper Intake Level of vitamin. European Food Safety Authority Sharma OP. Vitamin calcium and sarcoidosis J. Chest Jackson R LaCroix AZ Gass M et al. Calcium plus vitamin supplementation and the risk of fractures J. N Engl J Med Curhan GC Willett WC Rimm EB et al. A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones J. N Engl J Med Curhan GC Willett WC Speizer FE et al. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women J. Ann Intern Med RI J RIs J Chinese RIs

Comparison of vitamin 2 and vitamin 3 supplementation in raising serum 25- hydroxyvitamin status a systematic review and meta-analysis J. Am J Clin Nutr 2012 95 6 1357-1364.

19 Chin J Osteoporos September 2014 Vol 20 No IU IU IU IU IU / ~ 2000 IU IU OH IU IU 25OH Institute of Medicine 21 Washington C USA 2011 Endocrine Society Washington. C. USA UL EAR RNI UL AI EAR RA UL IU/ IU/ μg / μg / μg / 0 ~ IU 10 g 1000 IU 25μg AI 20 6 ~ IU 10μg 1500 IU 38 μg AI 20 1 ~ IU 10 μg 600 IU 15 μg 2500 IU 63 μg ~ IU 10 μg 600 IU 15 μg 3000 IU 75 μg ~ 8 9 ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg ~ ~ ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg > > IU 10 μg 800 IU 20 μg 4000 IU 100 μg ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg ~ ~ ~ IU 10 μg 600 IU 15μg 4000 IU 100 μg ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg > 65 > IU 10 μg 800 IU 20 μg 4000 IU 100 μg

USA 2011 Endocrine Society Washington. C.

20 Chin J Osteoporos September 2014 Vol 20 No Institute of Medicine Washington C USA Endocrine Society Washington. C. USA UL EAR RNI UL AI EAR RA UL IU/ IU/ μg / μg / μg / 14 ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg * 14 ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg ~ I U 10 μg 600 IU 15 μg 4000 IU 100 μg ~ IU 10 μg 600 IU 15 μg 4000 IU 100 μg * Endocrine Society Washington. C. USA 400 IU / 10 μg / IU / Institute of Medicine Washington C USA RI ietary Reference Intakes RA Recommended ietary Allowance AI Adequate Intakes AI RI 2. EAR Estimated Average Requirement EAR AI RNI = EAR + 2S EAR 5. UL Tolerable Upper Intake Level UL 3. RNI Recommended Nutrient Intake RNI RA 97% ~ 98% RNI AI RNI RNI UL UL RNI UL RNI

USA 21 2011 Endocrine Society Washington. C.

fibroblast growth factor, FGF D 25-OH Vit D D 25-OH Vit D [2] D 200 IU D D 25- OH Vit D D [3] 維生素 D 缺乏 D vitamin D deficiency 25-OH Vit D 10 ng/ml 25

fibroblast growth factor, FGF D 25-OH Vit D D 25-OH Vit D [2] D 200 IU D D 25- OH Vit D D [3] 維生素 D 缺乏 D vitamin D deficiency 25-OH Vit D 10 ng/ml 25 D 家庭醫業 1 2 3 4 前言維生素 D 的來源及合成 D vitamin D deficiency D D vitamin D insufficiency D D D 1 台北榮民總醫院家庭醫學部住院醫師 2 台北榮民總醫院家庭醫學部住院醫師 3 台北榮民總醫院家庭醫學部主治醫師 4 台北榮民總醫院家庭醫學部主任國立陽明大學醫學系教授兼家庭醫學科主任 vitamin D deficiency,