Vitamin D Megadose: Definition, Efficacy in Bone Metabolism, Risk of Falls and Fractures

References

• Maldonado G, Guerrero R, Ríos C. Prevalencia de vitamina D en pacientes con enfermedades autoinmunes en Ecuador: estudio restrospectivo. Rev Colomb Reumatol. 2017;24(4):205–210. doi:10.1016/j.rcreu.2017.08.001
   Google Scholar
• Holick M. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–281. doi:10.1056/NEJMra07055317634462
   PubMed Web of Science ®Google Scholar
• Wacker M, Holick M. Sunlight and Vitamin D. Dermatol-Endocrinol. 2013;5(1):51–108. doi:10.4161/derm.24494
   PubMedGoogle Scholar
• Holick M, Chen T. Vitamin D deficiency: a world- wide problem with health consequences. Am J Clin Nutr. 2008;87(4):1080S–6S. doi:10.1093/ajcn/87.4.1080S18400738
   PubMed Web of Science ®Google Scholar
• Moon RJ, Curtis EM, Davies JH, Cooper C, Harvey NC. Seasonal variation in Internet searches for vitamin D. Arch Osteoporos. 2017;12(1):10–13. doi:10.1007/s11657-017-0322-728074448
   PubMed Web of Science ®Google Scholar
• Hernigou P, Sitbon J, Dubory A, Auregan JC. Vitamin D history part III: the “modern times”—new questions for orthopaedic practice: deficiency, cell therapy, osteomalacia, fractures, supplementation, infections. Int Orthop. 2019;43(7):1755–1771. doi:10.1007/s00264-019-04334-w31037319
   PubMed Web of Science ®Google Scholar
• Bischoff-Ferrari HA, Willett WC, Orav EJ, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012;367(1):40–49. doi:10.1056/NEJMoa110961722762317
   PubMed Web of Science ®Google Scholar
• Wahl DA, Cooper C, Ebeling PR, et al. A global representation of vitamin D status in healthy populations. Arch Osteoporos. 2012;7(1–2):155–172. doi:10.1007/s11657-012-0093-023225293
   PubMedGoogle Scholar
• Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–1930. doi:10.1210/jc.2011-038521646368
   PubMed Web of Science ®Google Scholar
• Christakos S, Li S, De La Cruz J, Bikle DD. New developments in our understanding of vitamin D metabolism, action and treatment. Metab Clin Exp. 2019;98:112–120. doi:10.1016/j.metabol.2019.06.01031226354
   PubMed Web of Science ®Google Scholar
• Heikinheimo RJ, Inkovaara JA, Harju EJ, et al. Annual injection of vitamin D and fractures of aged bones. Calcif Tissue Int. 1992;51(2):105–110. doi:10.1007/BF002984971422948
   PubMed Web of Science ®Google Scholar
• Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D 3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326(March):1–6.
   Google Scholar
• Smith H, Anderson F, Raphael H, Maslin P, Crozier S, Cooper C. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women–a population- based, randomized, double-blind, placebo-controlled trial. Rheumatology. 2007;46(12):1852–1857. doi:10.1093/rheumatology/kem24017998225
   PubMed Web of Science ®Google Scholar
• Tarcin O, Yavuz DG, Ozben B, et al. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab. 2009;94(10):4023–4030. doi:10.1210/jc.2008-121219584181
   PubMed Web of Science ®Google Scholar
• Sanders K, Stuart A, Williamson E, Simpson J, Kotowicz M, Young D. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18):1815–1822. doi:10.1001/jama.2010.59420460620
   PubMed Web of Science ®Google Scholar
• Cashman KD, Dowling KG, Škrabáková Z, et al. Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr. 2016;103(4):1033–1044. doi:10.3945/ajcn.115.12087326864360
   PubMed Web of Science ®Google Scholar
• van Schoor N, Lips P. Global overview of vitamin D status. Endocrinol Metab Clin North Am. 2017;46(4):845–870. doi:10.1016/j.ecl.2017.07.00229080639
   PubMed Web of Science ®Google Scholar
• Schleicher RL, Sternberg MR, Lacher DA, et al. The vitamin D status of the US population from 1988 to 2010 using standardized serum concentrations of 25-hydroxyVitamin D shows recent modest increases. Am J Clin Nutr. 2016;104(2):454–461. doi:10.3945/ajcn.115.12798527385610
   PubMed Web of Science ®Google Scholar
• Young NP, Weinshenker BG, Parisi JE, et al. Perivenous demyelination: association with encephalomyelitis and comparison with pathologically confirmed multiple sclerosis. Brain. 2010;133(2):33–348. doi:10.1093/brain/awp32119920064
   PubMed Web of Science ®Google Scholar
• Spiro A, Buttriss JL. Vitamin D: an overview of vitamin D status and intake in Europe. Nutr Bull. 2014;39(4):322–350. doi:10.1111/nbu.1210825635171
   PubMedGoogle Scholar
• Compston J, Cooper A, Cooper C, et al. UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos. 2017;12(1). doi:10.1007/s11657-017-0324-5.
   Web of Science ®Google Scholar
• Kanis J, McCloskey E, Johansson H, Cooper C, Rizzoli R, Reginster J. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2013;24(1):23–57.23079689
   PubMed Web of Science ®Google Scholar
• Lips P, Graafmans W, Ooms M, Bezemer P, Bouter L. Vitamin D supplementation and fracture incidence in elderly persons: a randomized, placebo- controlled clinical trial. Ann Intern Med. 1996;124(4):400–406. doi:10.7326/0003-4819-124-4-199602150-000038554248
   PubMed Web of Science ®Google Scholar
• Meyer H, Smedshaug G, Kvaavik E, Falch J, Tverdal A, Pedersen J. Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. J Bone Miner Res. 2002;17(4):709–715. doi:10.1359/jbmr.2002.17.4.70911918228
   PubMed Web of Science ®Google Scholar
• Gennari C. Calcium and vitamin D nutrition and bone disease of the elderly. Public Health Nutr. 2001;4(2b):547–559. doi:10.1079/PHN200114011683549
   PubMedGoogle Scholar
• Chapuy M, Arlot M, Duboeuf F. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med. 1992;327(23):1637–1642. doi:10.1056/NEJM1992120332723051331788
   PubMed Web of Science ®Google Scholar
• Dawson-Hughes B, Harris S, Krall E, Dallal G. 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. doi:10.1056/NEJM1997090433710039278463
   PubMed Web of Science ®Google Scholar
• Yong WC, Sanguankeo A, Upala S. Effect of vitamin D supplementation in chronic widespread pain: a systematic review and meta-analysis. Clin Rheumatol. 2017;36(12):2825–2833. doi:10.1007/s10067-017-3754-y28812209
   PubMed Web of Science ®Google Scholar
• Megadose vitamin supplementation and immunological function in the elderly. Nutr Rev. 1984;42(2):46–48. doi:10.1111/j.1753-4887.1984.tb02282.x6366636
   PubMed Web of Science ®Google Scholar
• Cavalcante IG, de M, Silva AS, et al. Effect of vitamin D3 supplementation and influence of BsmI polymorphism of the VDR gene of the inflammatory profile and oxidative stress in elderly women with vitamin D insufficiency vitamin D3 megadose reduces inflammatory markers. Exp Gerontol. 2015;66:10–16. doi:10.1016/j.exger.2015.03.01125827670
   PubMed Web of Science ®Google Scholar
• Pekkarinen T, Välimäki -V-V, Aarum S, et al. The same annual dose of 292000 IU of vitamin D3 (cholecalciferol) on either daily or four monthly basis for elderly women: 1-year comparative study of the effects on serum 25(OH)D3 concentrations and renal function. Clin Endocrinol (Oxf). 2010;72(4):455–461. doi:10.1111/j.1365-2265.2009.03637.x19486025
   PubMed Web of Science ®Google Scholar
• Khaw K, Stewart A, Waayer D, Lawes C, Toop L, Camargo Jr C. Effect of monthly high-dose vitamin D supplementation on falls and non-vertebral fractures: secondary and post-hoc outcomes from the randomised, double-blind, placebo-controlled ViDA trial. Lancet Diabetes Endocrinol. 2017;5(6):438–447. doi:10.1016/S2213-8587(17)30103-128461159
   PubMed Web of Science ®Google Scholar
• Witham MD, Price RJG, Struthers AD, et al. Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension the VitDISH randomized controlled trial. JAMA Intern Med. 2013;173(18):1672–1679. doi:10.1001/jamainternmed.2013.904323939263
   PubMed Web of Science ®Google Scholar
• Scragg R, Steward A, Waayer D. Effect of monthly high-dose vitamin D supplementation on cardiovascular disease in the vitamin D assessment study: a randomized clinical trial. JAMA Cardiol. 2017;6:608–616.
   Web of Science ®Google Scholar
• Trivedi D, Doll R, Khaw K. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. Br Med J. 2003;326(7387):469. doi:10.1136/bmj.326.7387.46912609940
   PubMed Web of Science ®Google Scholar
• The National Heart Lung and Blood Institute PETAL Clinical Trials Network. Early high-dose vitamin D3 for critically ill, vitamin D–deficient patients. N Engl J Med. 2019;381(26):2529–2540.31826336
   PubMed Web of Science ®Google Scholar
• Jia H, Lubetkin EI, DeMichele K, Stark DS, Zack MM, Thompson WW. Prevalence, risk factors, and burden of disease for falls and balance or walking problems among older adults in the U.S. Prev Med (Baltim). 2019;126(April):105737. doi:10.1016/j.ypmed.2019.05.025
   Web of Science ®Google Scholar
• Murray C, Lopez A. Global and regional descriptive epidemiology of disability: incidence, prevalence, health expectations and years lived with disability. Global Burden Dis. 1996;1:201–246.
   Google Scholar
• Tinetti M, Speechley M, Ginter S. Risk factors for falls among elderly persons living in the community. N Engl J Med. 1988;319:1701–1707.3205267
   PubMed Web of Science ®Google Scholar
• Blake A, Morgan K, Bendall M, et al. Falls by elderly people at home: prevalence and associated factors. Age Ageing. 1988;17(6):365–372. doi:10.1093/ageing/17.6.3653266440
   PubMed Web of Science ®Google Scholar
• Tromp A, Pluijm S, Smitt J. Fall-risk screening test: a prospective study on predictors for falls in community-dwelling elderly. J Clin Epidemiol. 2001;54(8):837–844. doi:10.1016/S0895-4356(01)00349-311470394
   PubMed Web of Science ®Google Scholar
• Ceglia L. Vitamin D and skeletal muscle tissue and function. Mol Aspects Med. 2008;29(6):407–414. doi:10.1016/j.mam.2008.07.00218727936
   PubMed Web of Science ®Google Scholar
• Bischoff-Ferrari HA, Dawson-Hughes B, John Orav E, et al. Monthly high-dose Vitamin D treatment for the prevention of functional decline a randomized clinical trial. JAMA Intern Med. 2016;176(2):175–183. doi:10.1001/jamainternmed.2015.714826747333
   PubMed Web of Science ®Google Scholar
• Snijder MB, Van Schoor NM, Pluijm SMF, Van Dam RM, Visser M, Lips P. Vitamin D status in relation to one-year risk of recurrent falling in older men and women. J Clin Endocrinol Metab. 2006;91(8):2980–2985. doi:10.1210/jc.2006-051016684818
   PubMed Web of Science ®Google Scholar
• Smith LM, Gallagher JC, Suiter C. Medium doses of daily vitamin D decrease falls and higher doses of daily vitamin D3 increase falls: a randomized clinical trial. J Steroid Biochem Mol Biol. 2017;173:317–322. doi:10.1016/j.jsbmb.2017.03.01528323044
   PubMed Web of Science ®Google Scholar
• Latham NK, Anderson CS, Lee A, Bennett DA, Moseley A, Cameron ID. A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the frailty interventions trial in elderly subjects (FITNESS). J Am Geriatr Soc. 2003;51(3):291–299. doi:10.1046/j.1532-5415.2003.51101.x12588571
   PubMed Web of Science ®Google Scholar
• Lyons RA, Johansen A, Brophy S, et al. Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation. Osteoporos Int. 2007;18(6):811–818. doi:10.1007/s00198-006-0309-517473911
   PubMed Web of Science ®Google Scholar
• Reid I, Horne A, Mihov B. Effect of monthly high-dose vitamin D on bone density in community-dwelling older adults substudy of randomized controlled trial. J Intern Med. 2017;282(5):452–460. doi:10.1111/joim.1265128692172
   PubMed Web of Science ®Google Scholar
• Burt LA, Billington EO, Rose MS, Raymond DA, Hanley DA, Boyd SK. Effect of high-dose vitamin D supplementation on volumetric bone density and bone strength. JAMA. 2019;322(8):736.31454046
   PubMed Web of Science ®Google Scholar
• Carbonare LD, Valenti MT, Del Forno F, Piacentini G, Pietrobelli A. Vitamin D daily versus monthly administration: bone turnover and adipose tissue influences. Nutrients. 2018;10(12):1–9.
   Web of Science ®Google Scholar
• Holmøy T, Lindstrøm JC, Eriksen EF, Steffensen LH, Kampman MT. High dose vitamin D supplementation does not affect biochemical bone markers in multiple sclerosis - a randomized controlled trial. BMC Neurol. 2017;17(1):1–6. doi:10.1186/s12883-017-0851-028056870
   PubMed Web of Science ®Google Scholar
• Ish-shalom S, Segal E, Salganik T, Raz B, Bromberg IL, Vieth R. Comparison of daily, weekly, and monthly vitamin elderly hip fracture patients. J Clin Endocrinol Metabol. 2008;93(September):3430–3435.
   Web of Science ®Google Scholar
• Singh V, Misra AK, Singh M, et al. An open ‑ label, randomized, 10 weeks prospective study on the efficacy of vitamin D (daily low dose and weekly high dose) in vitamin D deficient patients. J Family Med Prim Care. 2019;8(6):1958.31334162
   PubMedGoogle Scholar
• Pilz S, März W, Cashman KD, et al. Rationale and plan for vitamin D food fortification: a review and guidance paper. Front Endocrinol (Lausanne). 2018;9(JUL):1–16. doi:10.3389/fendo.2018.0037329403440
   PubMed Web of Science ®Google Scholar
• Ross AC, Manson JAE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–58. doi:10.1210/jc.2010-270421118827
   PubMed Web of Science ®Google Scholar
• Taylor PN, Davies JS. A review of the growing risk of vitamin D toxicity from inappropriate practice. Br J Clin Pharmacol. 2018;84(6):1121–1127. doi:10.1111/bcp.1357329498758
   PubMed Web of Science ®Google Scholar
• Blank S, Scanlon KS, Sinks TH, Lett S, Falk H. An outbreak of hypervitaminosis D associated with the overfortification of milk from a home-delivery dairy. Am J Public Health. 1995;85(5):656–659. doi:10.2105/AJPH.85.5.6567733425
   PubMed Web of Science ®Google Scholar
• Sempos C, Heijboer A, Biklee D, Billerslev J, Bouillon R, Brannon P. Vitamin D assays and the definition of hypovitaminosis D: results from the First International Conference on Controversies in Vitamin D. Br J Clin Pharmacol. 2018;84(10):2194–2207. doi:10.1111/bcp.1365229851137
   PubMed Web of Science ®Google Scholar
• Manson JAE, Cook NR, Lee IM, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380(1):33–44. doi:10.1056/NEJMoa180994430415629
   PubMed Web of Science ®Google Scholar
• Harms LR, Burne THJ, Eyles DW, McGrath JJ. Vitamin D and the brain. Best Pract Res Clin Endocrinol Metab. 2011;25(4):657–669. doi:10.1016/j.beem.2011.05.00921872806
   PubMed Web of Science ®Google Scholar
• Murad MH, Elamin KB, Abu Elnour NO, et al. The effect of vitamin D on falls: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(10):2997–3006. doi:10.1210/jc.2011-119321795448
   PubMed Web of Science ®Google Scholar
• Bolland MJ, Grey A, Gamble GD, Reid IR. Vitamin D supplementation and falls: a trial sequential meta-analysis. Lancet Diabetes Endocrinol. 2014;2(7):573–580. doi:10.1016/S2213-8587(14)70068-324768505
   PubMed Web of Science ®Google Scholar
• Bolland MJ, Grey A, Reid IR. Differences in overlapping meta-analyses of vitamin D supplements and falls. J Clin Endocrinol Metab. 2014;99(11):4265–4272. doi:10.1210/jc.2014-256225093621
   PubMed Web of Science ®Google Scholar
• German Nutrition Society (DGE). New reference values for vitamin D. Ann Nutr Metab. 2012;60(4):241–246. doi:10.1159/00033754722677925
   PubMed Web of Science ®Google Scholar
• Pludowski P, Karczmarewicz E, Bayer M, Carter G, Chelbna-Sokol D, Czech-Kowalska J. Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe – recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency. Endokrynol Pol. 2013;64(4):319–327. doi:10.5603/EP.2013.001224002961
   PubMed Web of Science ®Google Scholar
• Haq A, Wimalawansa S, Pludowski P, Al Anouti F. Clinical practice guidelines for vitamin D in the United Arab Emirates. J Steroid Biochem Mol. 2018;175:4–11. doi:10.1016/j.jsbmb.2016.09.021
   PubMed Web of Science ®Google Scholar