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Osteologie 2009; 18(02): 112-124
DOI: 10.1055/s-0037-1619888
Frakturen rund um das Hüftgelenk
Schattauer GmbH

Volkswirtschaftliche Bedeutung einer Vitamin-D-Anreicherung von Lebensmitteln

Eine gesundheitsökonomische Markov-Analyse unter besonderer Berücksichtigung hüftgelenksnaher FrakturenThe economic importance of vitamin D supplementation of food
Ch. von Domarus
1   Osteologisches Schwerpunktzentrum DVO, Zentrum für Biomechanik und Skelettbiologie, Klinik für Unfall-, Hand-, und Wiederherstellungschirurgie, Universitätsklinikum Hamburg Eppendorf
,
M. Amling
1   Osteologisches Schwerpunktzentrum DVO, Zentrum für Biomechanik und Skelettbiologie, Klinik für Unfall-, Hand-, und Wiederherstellungschirurgie, Universitätsklinikum Hamburg Eppendorf
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Further Information

Publication History

eingereicht: 25 March 2009

angenommen: 25 March 2009

Publication Date:
28 December 2017 (online)

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Zusammenfassung

Diese Arbeit zeigt auf, dass der Vitamin-D-Mangel in Deutschland wesentlich ausgeprägter ist als bisher wahrgenommen. Zum Erhalt der Skelettgesundheit stellt ein 25-(OH)-D-Serumspiegel von 30 ng/ml den unteren anzustrebenden Grenzwert dar. Die gegenwärtigen Herangehensweisen – von den zu niedrigen Richtwerten bezüglich der als sicher anzusehenden täglichen Vitamin- D-Aufnahme über die fehlende Erstattungsfähigkeit einer Vitamin-D-Supplementation bei Patienten mit Osteopenie ohne bereits stattgehabte Fraktur und den bestehenden Restriktionen einer Vitaminisierung von Lebensmitteln – sind nicht geeignet, hinsichtlich dieser Mangelsituation eine wirkungsvolle Abhilfe zu schaffen. Auf der Basis der Literatur wird gezeigt, dass eine Behebung des für die Volksgesundheit extrem relevanten Vitamin- D-Mangels durch sehr einfache Maßnahmen, wie eine orale Supplementation oder eine Nahrungsmittelanreicherung, möglich wäre und zwar behebbar mittels kostensenkender Lösungen. Unter Berücksichtigung der einzusparenden Kosten im Gesundheitssystem, die im onkologischen Bereich mit jährlich etwa 1,5 Milliarden Euro und im osteologischen Bereich mit etwa einer Milliarde Euro beziffert werden, besonders aber auch im Hinblick auf die jährlich vermeidbaren 23 400 koxalen Femurfrakturen und 39 250 tumor - assoziierten Todesfälle in Deutschland, besteht ein dringender politischer Handlungsbedarf zur Behebung dieses Mangels. In Kenntnis der Evidenzen in der Literatur erscheint es unverständlich, dass die Kostenträger im Gesundheitswesen nicht proaktiv eine Optimierung der Vitamin-D-Versorgung ihrer Versicherten anstreben, um so ihre Ausgabenbelastung zu verringern. In Bezug auf die dargestellte Bedeutung des Vitamin-D-Mangels für die Morbidität und die Mortalität der deutschen Bevölkerung sind aber nicht nur Kostenträger in der Verantwortung, sondern die politischen Entscheidungsträger müssen dringend Rahmenbedingungen schaffen, die es erlauben, diese existierende Gefährdung der Volksgesundheit zu beseitigen. Lösungen bestehen in der Kostenübernahme einer bevölkerungsweiten Vitamin- D-Supplementation durch die Kostenträger des Gesundheitssystems oder aber in der Zulassung der ausreichenden Anreicherung von Lebensmitteln mit Vitamin D und damit der Umsetzung der bestehenden EU-Norm (2002/46/EG) mit der entsprechenden Anpassung des deutschen Lebensmittelrechts.

Summary

Vitamin D deficiency is a major health concern in Germany. For optimal skeletal health the 25-(OH)-D serum levels should reach at least 30 ng/ml. The current situation that includes inadequate low levels of daily vitamin D doses that are regarded to be safe, the lack of reimbursability of vitamin D supplements in osteopenia without a prevalent fracture, and the restrictions in vitamin D supplementation of food, is not appropriate to solve this existing problem. Based on the data in current literature this paper shows that oral vitamin D supplementation or else fortification of food would be two easy, safe, and cost-effective ways to overcome this endemic health problem. In fact in light of 2.5 billion Euro possible annual savings for the German health care system, as well as 23 400 dispensable fractures of the proximal femur and a reduction of tumor associated deaths by 39 250 patients there is a strong need for political action in this regard. The latter especially as the German food law that precludes vitamin D fortification of food which is in power for some 80 years now is not only in sharp contrast to current scientific knowledge on vitamin D biology but also in contradiction to the guideline put forward by the European union (EU norm 2002/46/EG).

Schlüsselwörter

Skelettgesundheit - Vitamin-D-Mangel - Vitamin-D-Supplementation

Keywords

Skeletal health - vitamin D deficiency - vitamin D supplementation
 

  • Literatur

  • 1 Agar NS, Halliday GM, Barnetson RS. et al. The basal layer in human squamous tumors harbors more UVA than UVB fingerprint mutations: a role for UVA in human skin carcinogenesis. Proc Natl Acad Sci U S A 2004; 101 (14) 4954-4959.
    CrossrefPubMedGoogle Scholar
  • 2 Ahonen MH, Tenkanen L, Teppo L. et al. Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 2000; 11 (09) 847-852.
    CrossrefPubMedGoogle Scholar
  • 3 Albright F, Bauer W, Ropes M, Aub JC. Studies of calcium and phosphorus metabolism: IV. The Effect of the Parathyroid Hormone. J Clin Invest 1929; 07 (01) 139-181.
    CrossrefPubMedGoogle Scholar
  • 4 Amling M, Priemel M, Holzmann T. et al. Rescue of the skeletal phenotype of vitamin D receptor-ablated mice in the setting of normal mineral ion homeostasis: formal histomorphometric and biomechanical analyses. Endocrinology 1999; 140 (11) 4982-4987.
    CrossrefPubMedGoogle Scholar
  • 5 Andersen R, Brot C, Ovesen L. Towards a strategy for optimal vitamin D fortification (OPTIFORD). Nutr Metab Cardiovasc Dis 2001; 11 (Suppl. 04) 74-77.
    PubMedGoogle Scholar
  • 6 Barger-Lux MJ, Heaney RP, Dowell S. et al. Vitamin D and its major metabolites: serum levels after graded oral dosing in healthy men. Osteoporos Int 1998; 08 (03) 222-230.
    CrossrefPubMedGoogle Scholar
  • 7 Bischoff HA, Stähelin HB, Dick W. et al. Effects of Vitamin D and Calcium Supplementation on Falls: A Randomized Controlled Trial. J Bone Miner Res 2003; 18 (02) 343-351.
    CrossrefPubMedGoogle Scholar
  • 8 Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC. et al. Effect of Vitamin D on falls: a meta-analysis. JAMA 2004; 291 (16) 1999-2006.
    CrossrefPubMedGoogle Scholar
  • 9 Bischoff-Ferrari HA, Dietrich T, Orav EJ, Dawson-Hughes B. Positive association between 25-hydroxyvitamin D levels and bone mineral density: a population-based study of younger and older adults. Am J Med 2004; 116 (09) 634-639.
    CrossrefPubMedGoogle Scholar
  • 10 Bischoff-Ferrari HA, Willett WC, Wong JB. et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005; 293 (18) 2257-2264.
    CrossrefPubMedGoogle Scholar
  • 11 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 randomized controlled trials. J Clin Endocrinol Metab 2007; 92 (04) 1415-1423.
    CrossrefPubMedGoogle Scholar
  • 12 Bouillon R, Bischoff-Ferrari H, Willett W. Vitamin D and health: Perspectives from mice and man. J Bone Miner Res 2008; 23: 974-979.
    CrossrefPubMedGoogle Scholar
  • 13 Calvo MS, Whiting SJ, Barton CN. Vitamin D fortification in the United States and Canada: current status and data needs. Am J Clin Nutr 2004; 80 (Suppl. 06) 1710S-1716S.
    CrossrefPubMedGoogle Scholar
  • 14 Calvo MS, Whiting SJ, Barton CN. Vitamin D intake: a global perspective of current status. J Nutr 2005; 135 (02) 310-316.
    CrossrefPubMedGoogle Scholar
  • 15 Chapuy MC, Arlot ME, Duboeuf F. et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 1992; 327 (23) 1637-1642.
    CrossrefPubMedGoogle Scholar
  • 16 Chapuy MC, Pamphile R, Paris E. et al. Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study. Osteoporos Int 2002; 13 (03) 257-264.
    CrossrefPubMedGoogle Scholar
  • 17 Cooper C, Melton III LJ. Magnitude and impact of osteoporosis and fractures. In: Marcus R, Feldman D, Kelsey J. eds. Osteoporosis. New York: Academic Press; 1996: 419-434.
    Google Scholar
  • 18 Copp DH, Cameron EC, Cheney BA. et al. Evidence for calcitonin – a new hormone from the parathyroid that lowers blood calcium. Endocrinology 1962; 70: 638-649.
    CrossrefPubMedGoogle Scholar
  • 19 Copp DH, Cameron EC. Demonstration of a hypocalcemic factor (calcitonin) in commercial parathyroid extract. Science 1961; 134: 2038.
    PubMedGoogle Scholar
  • 20 Darnton-Hill I, Darnton-Hill I, Nalubola R. Fortification strategies to meet micronutrient needs: successes and failures. Proc Nutr Soc 2002; 61 (02) 231-241.
    CrossrefPubMedGoogle Scholar
  • 21 Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997; 337 (10) 670-676.
    CrossrefPubMedGoogle Scholar
  • 22 Dawson-Hughes B, Heaney RP, Holick MF. et al. Estimates of optimal vitamin D status. Osteoporos Int 2005; 16 (07) 713-716.
    CrossrefPubMedGoogle Scholar
  • 23 DVO (Dachverband der deutschsprachigen wissenschaftlichen Gesellschaften für Osteologie e.V. vertreten durch J. Pfeilschifter). Osteoporose Leitlinie. Prophylaxe, Diagnostik und Therapie bei Frauen ab der Menopause, bei Männern ab dem 60. Lebensjahr. Hrsg. Stuttgart, New York: Schattauer; 2006
    Google Scholar
  • 24 Eastell R, Barton I, Hannon RA. et al. Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 2003; 18 (06) 1051-1056.
    CrossrefPubMedGoogle Scholar
  • 25 Feskanich D, Ma J, Fuchs CS. et al. Plasma vitamin D metabolites and risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 2004; 13 (09) 1502-1508.
    PubMedGoogle Scholar
  • 26 Gannagé-Yared MH, Chemali R, Sfeir C. et al. Dietary calcium and vitamin D intake in an adult Middle Eastern population: food sources and relation to lifestyle and PTH. Int J Vitam Nutr Res 2005; 75 (04) 281-289.
    CrossrefPubMedGoogle Scholar
  • 27 Garland CF, Garland F. Do sunlight and vitamin D reduce the likelihood of colon cancer?. Int J Epidemiol 1980; 09: 227-231.
    CrossrefPubMedGoogle Scholar
  • 28 Garland CF, Garland FC. Gorham Epidemiologic evidence for different roles of ultraviolet A and B radiation in melanoma mortality rates. Ann Epidemiol 2003; 13 (06) 395-404.
    CrossrefPubMedGoogle Scholar
  • 29 Giovannucci E. The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). Cancer Causes Control 2005; 16 (02) 83-95.
    CrossrefPubMedGoogle Scholar
  • 30 Giovannucci E. The epidemiology of vitamin D and colorectal cancer: recent findings. Curr Opin Gastroenterol 2006; 22 (01) 24-29.
    CrossrefPubMedGoogle Scholar
  • 31 Gorham ED, Garland CF, Garland FC. et al. Vitamin D and prevention of colorectal cancer. J Steroid Biochem Mol Biol 2005; 97 (1–2): 179-194.
    CrossrefPubMedGoogle Scholar
  • 32 Goldzieher JW, Zerwekh JE, Castracane VD. Singlemonthly-dose vitamin D supplementation in elderly patients. Endocr Pract 1999; 05 (05) 229-232.
    CrossrefPubMedGoogle Scholar
  • 33 Graf JMvon der Schulenburg, Greiner W, Jost F. et al. the Hanover Consensus Group. German recommendations on health economic evaluation: Third and updated version of the Hanover consensus. Value in Health 2008; 02 (04) 539-544.
    Google Scholar
  • 34 Grant WB, Garland CF, Holick MF. Comparisons of estimated economic burdens due to insufficient solar ultraviolet irradiance and vitamin D and excess solar UV irradiance for the United States. Photochem Photobiol 2005; 81 (06) 1276-1286.
    CrossrefPubMedGoogle Scholar
  • 35 Grant WB, Holick MF. Benefits and requirements of vitamin D for optimal health: a review. Altern Med Rev 2005; 10: 94-111.
    PubMedGoogle Scholar
  • 36 Grant WB, Garland CF. Gorham An estimate of cancer mortality rate reductions in Europe and the US with 1.000 I.U of oral vitamin D per day. Recent Res Cancer Res 2007; 174: 228-236.
    Google Scholar
  • 37 Häussler B, Gothe H, Göl D. et al. Epidemiology, treatment and costs of osteoporosis in Germany – the BoneEVA Study. Osteoporos Int 2007; 18 (01) 77-84.
    CrossrefPubMedGoogle Scholar
  • 38 Halliday GM, Agar NS, Barnetson RS. et al. UV-A fingerprint mutations in human skin cancer. Photochem Photobiol 2005; 81 (01) 3-8.
    CrossrefPubMedGoogle Scholar
  • 39 Hanley DA, Davison KS. Vitamin D insufficiency in North America. J Nutr 2005; 135 (02) 332-337.
    CrossrefPubMedGoogle Scholar
  • 40 Hashemipour S, Larijani B, Adibi H. et al. Vitamin D deficiency and causative factors in the population of Tehran. BMC Public Health 2004; 25 (04) 38.
    Google Scholar
  • 41 Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr 2007; 85 (01) 6-18.
    CrossrefPubMedGoogle Scholar
  • 42 Heaney RP. Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr 2004; 80 (Suppl. 06) 1706S-1709S.
    CrossrefPubMedGoogle Scholar
  • 43 Heaney RP. Bone health. Am J Clin Nutr 2007; 85 (01) 300S-303S.
    CrossrefPubMedGoogle Scholar
  • 44 Heaney RP, Davies KM, Chen TC. et al. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 2003; 77 (01) 204-210.
    CrossrefPubMedGoogle Scholar
  • 45 Hintzpeter B, Mensink GB, Thierfelder W. et al. Vitamin D status and health correlates among German adults. Eur J Clin Nutr 2008; 62 (09) 1079-1089.
    CrossrefPubMedGoogle Scholar
  • 46 Hinzpeter B, Scheidt-Nave C, Müller MJ. et al. Higher prevalence of vitamin D deficiency is associated with immigrant background among children and adolescents in germany. J Nutr 2008; 138: 1482-1490.
    CrossrefPubMedGoogle Scholar
  • 47 Hirsch PF, Voelkel EF, Munson PL. Thyrocalcitonin: Hypocalcemic hypophosphatemic principle of the thyroid gland. Science 1964; 146: 412-413.
    CrossrefPubMedGoogle Scholar
  • 48 Hirsch PF, Lester GE, Talmage RV. Calcitonin, an enigmatic hormone: does it have a function?. J Musculoskelet Neuronal Interact 2001; 01 (04) 299-305.
    Google Scholar
  • 49 Holick MF. Environmental factors that influence the cutaneous production of vitamin D. Am J Clin Nutr 1995; 61: 638S-645S.
    CrossrefPubMedGoogle Scholar
  • 50 Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancer, and cardiovascular disease. Am J Clin Nutr 2004; 79: 362-371.
    CrossrefPubMedGoogle Scholar
  • 51 Holick MF. Vitamin D: its role in cancer prevention and treatment. Prog Biophys Mol Biol 2006; 92 (01) 49-59.
    CrossrefPubMedGoogle Scholar
  • 52 Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 2006; 81 (03) 353-373.
    CrossrefPubMedGoogle Scholar
  • 53 Icks A, Haastert B, Wildner M. et al. Trend of hip fracture incidence in Germany 1995–2004: a population-based study. Osteoporos Int 2008; 19 (08) 1139-1145.
    CrossrefPubMedGoogle Scholar
  • 54 Institute of Medicine, National Academy of Sciences. Dietary reference intakes of calcium, phosphorous, magnesium, vitamin D, and fluoride. Washington: National Academy Press; 1997
    Google Scholar
  • 55 Katan MB. Cost of foods fortified with plant sterols refunded by a health insurance company. Ned Tijdschr Geneeskd 2005; 149 (07) 330-332.
    PubMedGoogle Scholar
  • 56 Laaksi IT, Ruohola JP, Ylikomi TJ. et al. Vitamin D fortification as public health policy: significant improvement in vitamin D status in young Finnish men. Eur J Clin Nutr 2006; 60 (08) 1035-1038.
    CrossrefPubMedGoogle Scholar
  • 57 Lappe JM, Travers-Gustafson D, Davies KM. et al. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007; 85 (06) 1586-1591.
    CrossrefPubMedGoogle Scholar
  • 58 Li YC, Pirro AE, Amling M. et al. Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia. Proc Natl Acad Sci U S A 1997; 94 (18) 9831-9835.
    CrossrefPubMedGoogle Scholar
  • 59 Lips P, Duong T, Oleksik A. et al. A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial. J Clin Endocrinol Metab 2001; 86 (03) 1212-1221.
    CrossrefPubMedGoogle Scholar
  • 60 Lucas JA, Bolland MJ, Grey AB. et al. Determinants of vitamin D status in older women living in a subtropical climate. Osteoporos Int 2005; 16 (12) 1641-1648.
    CrossrefPubMedGoogle Scholar
  • 61 Matsuoka LY, Wortsman J, Hanifan N, Holick MF. Chronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin D. A preliminary study. Arch Dermatol 1988; 124 (12) 1802-1804.
    CrossrefPubMedGoogle Scholar
  • 62 McKenna MJ. Differences in vitamin D status between countries in young adults and the elderly. Am J Med 1992; 93: 69-77.
    CrossrefPubMedGoogle Scholar
  • 63 Meddeb N, Sahli H, Chahed M. et al. Vitamin D deficiency in Tunisia. Osteoporos Int 2005; 16 (02) 180-183.
    CrossrefPubMedGoogle Scholar
  • 64 Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin d levels and the risk of mortality in the general population. Arch Intern Med 2008; 168 (15) 1629-1637.
    CrossrefPubMedGoogle Scholar
  • 65 Melton 3rd LJ. Epidemiology worldwide. Endocrinol Metab Clin North Am 2003; 32 (01) 1-13.
    CrossrefPubMedGoogle Scholar
  • 66 Meyer C. Scientists probe role of vitamin D: deficiency a significant problem, experts say. JAMA 2004; 292 (12) 1416-1418.
    CrossrefPubMedGoogle Scholar
  • 67 Meyer HE, Falch JA, Søgaard AJ, Haug E. Vitamin D deficiency and secondary hyperparathyroidism and the association with bone mineral density in persons with Pakistani and Norwegian background living in Oslo, Norway, The Oslo Health Study. Bone 2004; 35 (02) 412-417.
    CrossrefPubMedGoogle Scholar
  • 68 Miller SC, Halloran BP, DeLuca HF, Jee WS. Role of vitamin D in maternal skeletal changes during pregnancy and lactation: a histomorphometric study. Calcif Tissue Int 1982; 34 (03) 245-252.
    CrossrefPubMedGoogle Scholar
  • 69 Moan J, Dahlback A, Setlow RB. Epidemiological support for an hypothesis for melanoma induction indicating a role for UVA radiation. Photochem Photobiol 1999; 70 (02) 243-247.
    CrossrefPubMedGoogle Scholar
  • 70 Narang NK, Gupta RC, Jain MK. Role of vitamin D in pulmonary tuberculosis. J Assoc Physicians India 1984; 32 (02) 185-188.
    PubMedGoogle Scholar
  • 71 National Institutes of Health. Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement 2000; 17 (01) 1-45.
    PubMedGoogle Scholar
  • 72 Norman AW, Bouillon R, Whiting SJ. et al. 13th Workshop consensus for vitamin D nutritional guidelines. J Steroid Biochem Mol Biol 2007; 103 (3–5): 204-205.
    CrossrefPubMedGoogle Scholar
  • 73 Omdahl JL, DeLuca HF. Regulation of vitamin D metabolism and function. Physiol Rev 1973; 53 (02) 327-372.
    CrossrefPubMedGoogle Scholar
  • 74 Ooms ME, Lips P, Roos JC. et al. Vitamin D status and sex hormone binding globulin: determinants of bone turnover and bone mineral density in elderly women. J Bone Miner Res 1995; 10 (08) 1177-1184.
    PubMedGoogle Scholar
  • 75 Ovesen L, Andersen R, Jakobsen J. Geographical differences in vitamin D status, with particular reference to European countries. Proc Nutr Soc 2003; 62 (04) 813-821.
    CrossrefPubMedGoogle Scholar
  • 76 Parfitt AM. The actions of parathyroid hormone on bone: relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone diseases. II. PTH and bone cells: bone turnover and plasma calcium regulation. Metabolism 1976; 25 (08) 909-955.
    CrossrefPubMedGoogle Scholar
  • 77 Park S, Johnson MA. Living in low-latitude regions in the United States does not prevent poor vitamin D status. Nutr Rev 2005; 63 (6 Pt 1): 203-209.
    CrossrefPubMedGoogle Scholar
  • 78 Pfeifer M, Begerow B, Minne HW. et al. Effectsof ashortterm vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 2000; 15 (06) 1113-1118.
    CrossrefPubMedGoogle Scholar
  • 79 Pientka L, Friedrich C. Die Kosten hüftgelenknaher Frakturen in Deutschland: Eine prospektive Untersuchung. Z Gerontol Geriat 1999; 32: 326-332.
    CrossrefPubMedGoogle Scholar
  • 80 Priemel M, von Domarus C, Klatte TO. et al. Bone mineralization defects and vitamin D deficiency. Histomorphometric analysis of iliac crest bone biopsies and circulating 25-[OH]-D in 675 patients. J Bone Min Res. (in press, 2009).
    Google Scholar
  • 81 Raiten DJ, Picciano MF. Vitamin D and health in the 21st century: bone and beyond. Executive summary. Am J Clin Nutr 2004; 80 (Suppl. 06) 1673S-1677S.
    CrossrefPubMedGoogle Scholar
  • 82 Riggs BL, Melton 3rd LJ. Involutional osteoporosis. N Engl J Med 1986; 314 (26) 1676-1686.
    CrossrefPubMedGoogle Scholar
  • 83 Rizzoli R, Boonen S, Brandi ML. et al. The role of calcium and vitamin D in the management of osteoporosis. Bone 2008; 42 (02) 246-249.
    CrossrefPubMedGoogle Scholar
  • 84 Rodan GA, Martin TJ. Therapeutic approaches to bone diseases. Science 2000; 289 5484 1508-1514.
    CrossrefPubMedGoogle Scholar
  • 85 Roux C, Bischoff-Ferrari HA, Papapoulos SE. et al. New insights into the role of vitamin D and calcium in osteoporosis management: an expert roundtable discussion. Curr Med Res Opin 2008; 24 (05) 1363-1370.
    CrossrefPubMedGoogle Scholar
  • 86 Ruohola JP, Laaksi I, Ylikomi T. et al. Association between serum 25(OH)D concentrations and bone stress fractures in Finnish young men. J Bone Miner Res 2006; 21 (09) 1483-1488.
    CrossrefPubMedGoogle Scholar
  • 87 Sahota O, Mundey MK, San P. et al. The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis. Bone 2004; 35 (01) 312-319.
    CrossrefPubMedGoogle Scholar
  • 88 Semba RD, Garrett E, Johnson BA. et al. Vitamin D deficiency among older women with and without disability. Am J Clin Nutr 2000; 72 (06) 1529-1534.
    CrossrefPubMedGoogle Scholar
  • 89 Stamp TC, Haddad JG, Twigg CA. Comparison of oral 25-hydroxycholecalciferol, vitamin D, and ultraviolet light as determinans of circulating 25-hydroxyvitamin D. Lancet 1977; 01: 1341-1343.
    Google Scholar
  • 90 Tangpricha V, Koutkia P, Rieke SM. et al. Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health. Am J Clin Nutr 2003; 77 (06) 1478-1483.
    CrossrefPubMedGoogle Scholar
  • 91 Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomized double blind controlled trial. BMJ 2003; 326 7387 469.
    CrossrefPubMedGoogle Scholar
  • 92 Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999; 69 (05) 842-856.
    CrossrefPubMedGoogle Scholar
  • 93 Vieth R, Pinto TR, Reen BS, Wong MM. Vitamin D poisoning by table sugar. Lancet 2002; 359 9307 672.
    CrossrefPubMedGoogle Scholar
  • 94 Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr 2001; 73 (02) 288-294.
    CrossrefPubMedGoogle Scholar
  • 95 Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab 1988; 67 (02) 373-378.
    CrossrefPubMedGoogle Scholar
  • 96 Whiting SJ, Calvo MS. Dietary recommendations for vitamin D: a critical need for functional end points to establish an estimated average requirement. J Nutr 2005; 135 (02) 304-309.
    CrossrefPubMedGoogle Scholar
  • 97 Whiting SJ, Calvo MS. Dietary recommendations to meet both endocrine and autocrine needs of Vitamin D. J Steroid Biochem Mol Biol 2005; 97 (1–2): 7-12.
    CrossrefPubMedGoogle Scholar
  • 98 Willis MS. The health economics of calcium and vitamin D3 for the prevention of osteoporotic hip fractures in Sweden. Int J Technol Assess Health Care 2002; 18 (04) 791-807.
    CrossrefPubMedGoogle Scholar
  • 99 Zethraeus N, Borgström F, Ström O. et al. Costeffectiveness of the treatment and prevention of osteoporosis – a review of the literature and a reference model. Osteoporosis Int 2007; 18: 9-23.
    CrossrefPubMedGoogle Scholar