Vitamin D supplementation to prevent depression and poor physical function in older adults: Study protocol of the D-Vitaal study, a randomized placebo-controlled clinical trial

BMC Geriatrics

Paul Lips⁴  Harm W.J. van Marwijk⁸  Martin den Heijer⁴  Maurits W. van Tulder²  Pierre M. Bet⁵  Jan. H. Smit⁷  Annemieke C. Heijboer⁶  Petra J.M. Elders³  Brenda W.J.H. Penninx⁷  Natasja M. van Schoor¹  Elisa J. de Koning¹ 

[1] Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, 1007 MB, The Netherlands;Department of Health Sciences, VU University, Amsterdam, 1007 MB, The Netherlands;Department of General Practice and Elderly Care Medicine, VU University Medical Center, Amsterdam, 1007 MB, The Netherlands;Department of Internal Medicine, Endocrine section, VU University Medical Center, Amsterdam, 1007 MB, The Netherlands;Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, 1007 MB, The Netherlands;Department of Clinical Chemistry, Endocrine Laboratory, VU University Medical Center, Amsterdam, 1007 MB, The Netherlands;Department of Psychiatry, VU University Medical Center/GGZ inGeest, A.J. Ernststraat 1187, Amsterdam, The Netherlands;Primary Care Research Centre, Institute of Population Health, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom

关键词: Supplementation;    Prevention;    Randomized clinical trial;    Older adults;    Physical performance;    Functional limitations;    Physical functioning;    Depressive symptoms;    Vitamin D;   

Others  :  1233964
DOI  :  10.1186/s12877-015-0148-3

 received in 2015-07-31, accepted in 2015-11-13,  发布年份 2015

【 摘 要 】

Background

Depressive symptoms and decreased physical functioning are interrelated conditions and common in older persons, causing significant individual and societal burden. Evidence suggests that vitamin D supplementation may be beneficial for both mental and physical functioning. However, previous randomized controlled trials have yielded inconsistent results and often had suboptimal designs. This study examines the effect of vitamin D supplementation on both depressive symptoms and physical functioning in a high-risk population of older persons with low vitamin D status.

Methods/design

The D-Vitaal study is a randomized, double-blind, placebo-controlled trial investigating the effects of a daily dose of 1200 IU vitamin D ₃versus placebo for one year on depressive symptoms and physical functioning (primary outcomes) in older adults. Participants (N = 155, age 60–80 years) were recruited from the general population. Eligibility criteria included the presence of depressive symptoms, ≥1 functional limitation and serum 25-hydroxyvitamin D levels between 15 and 50/70 nmol/L (depending on season). Secondary outcomes include incidence of major depressive disorder, anxiety symptoms, health-related quality of life, cognitive function and cost-effectiveness of the intervention.

Discussion

With this study, we aim to elucidate the effects of vitamin D supplementation on depressive symptoms and physical functioning in older persons who are at high risk of developing more substantial mental and physical problems. If effective, vitamin D supplementation can be a preventive intervention strategy that is easy to implement in the primary care setting.

Trial registration

Netherlands Trial Register NTR3845. Registered 6 February 2013.

【 授权许可】

   
2015 de Koning et al.

【 图 表 】

Fig. 1.

Fig. 2.

【 参考文献 】

• [1]Blazer DG: Depression in late life: review and commentary. J Gerontol A Biol Sci Med Sci 2003, 58:249-265.
• [2]Hall CA, Reynolds-Iii CF: Late-life depression in the primary care setting: challenges, collaborative care, and prevention. Maturitas 2014, 79:147-152.
• [3]Prina AM, Deeg D, Brayne C, Beekman A, Huisman M: The association between depressive symptoms and non-psychiatric hospitalisation in older adults. PLoS One 2012., 7Article ID e34821
• [4]Prins MA, Verhaak PFM, Hilbink-Smolders M, Spreeuwenberg P, Laurant MGH, van der Meer K, et al.: Outcomes for depression and anxiety in primary care and details of treatment: a naturalistic longitudinal study. BMC Psychiatry 2011, 11:180. BioMed Central Full Text
• [5]Braam AW, Prince MJ, Beekman ATF, Delespaul P, Dewey ME, Geerlings SW, et al.: Physical health and depressive symptoms in older Europeans. Results from EURODEP. Br J Psychiatry 2005, 187:35-42.
• [6]Bromberger JT, di Scalea TL: Longitudinal associations between depression and functioning in midlife women. Maturitas 2009, 64:145-159.
• [7]Penninx BW, Deeg DJ, van Eijk JT, Beekman AT, Guralnik JM: Changes in depression and physical decline in older adults: a longitudinal perspective. J Affect Disord 2000, 61:1-12.
• [8]Vink D, Aartsen MJ, Schoevers RA: Risk factors for anxiety and depression in the elderly: a review. J Affect Disord 2008, 106:29-44.
• [9]Nyunt MSZ, Lim ML, Yap KB, Ng TP: Changes in depressive symptoms and functional disability among community-dwelling depressive older adults. Int Psychogeriatr 2012, 24:1633-1641.
• [10]Beaudart C, Buckinx F, Rabenda V, Gillain S, Cavalier E, Slomian J, et al.: The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 2014, 99:4336-4345.
• [11]Gowda U, Mutowo MP, Smith BJ, Wluka AE, Renzaho AMN: Vitamin D supplementation to reduce depression in adults: meta-analysis of randomized controlled trials. Nutrition 2015, 31:421-429.
• [12]Shaffer JA, Edmondson D, Wasson LT, Falzon L, Homma K, Ezeokoli N, et al.: Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials. Psychosom Med 2014, 76:190-196.
• [13]IOM (Institute of Medicine): Dietary reference intakes for calcium and vitamin D. The National Academies Press, Washington DC; 2011.
• [14]Kuchuk NO, Pluijm SMF, van Schoor NM, Looman CWN, Smit JH, Lips P: Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum parathyroid hormone and markers of bone turnover in older persons. J Clin Endocrinol Metab 2009, 94:1244-1250.
• [15]Lips P, van Schoor NM, de Jongh RT: Diet, sun, and lifestyle as determinants of vitamin D status. Ann N Y Acad Sci 2014, 1317:92-98.
• [16]Lips P: Vitamin D, deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001, 22:477-501.
• [17]de Abreu DA F, Eyles D, Feron F: Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases. Psychoneuroendocrinology 2009, 34(1):S265-S277.
• [18]Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ: Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 2005, 29:21-30.
• [19]Annweiler C, Montero-Odasso M, Schott AM, Berrut G, Fantino B, Beauchet O: Fall prevention and vitamin D in the elderly: an overview of the key role of the non-bone effects. J Neuroeng Rehabil 2010, 7:50. BioMed Central Full Text
• [20]Kesby JP, Eyles DW, Burne THJ, McGrath JJ: The effects of vitamin D on brain development and adult brain function. Mol Cell Endocrinol 2011, 347:121-127.
• [21]Eyles DW, Burne THJ, McGrath JJ: Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol 2013, 34:47-64.
• [22]Holtzer R, Epstein N, Mahoney JR, Izzetoglu M, Blumen HM: Neuroimaging of mobility in aging: a targeted review. J Gerontol A Biol Sci Med Sci 2014, 69:1375-1388.
• [23]Hoogendijk WJG, Lips P, Dik MG, Deeg DJH, Beekman ATF, Penninx BWJH: Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Arch Gen Psychiatry 2008, 65:508-512.
• [24]Milaneschi Y, Hoogendijk W, Lips P, Heijboer AC, Schoevers R, van Hemert AM, et al.: The association between low vitamin D and depressive disorders. Mol Psychiatry 2014, 19:444-451.
• [25]Sohl E, de Jongh RT, Heijboer AC, Swart KMA, Brouwer-Brolsma EM, Enneman AW, et al.: Vitamin D status is associated with physical performance: the results of three independent cohorts. Osteoporos Int 2013, 24:187-196.
• [26]Wicherts IS, van Schoor NM, Boeke AJ, Visser M, Deeg DJH, Smit J, et al.: Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrinol Metab 2007, 92:2058-2065.
• [27]Milaneschi Y, Shardell M, Corsi AM, Vazzana R, Bandinelli S, Guralnik JM, et al.: Serum 25-hydroxyvitamin D and depressive symptoms in older women and men. J Clin Endocrinol Metab 2010, 95:3225-3233.
• [28]Khoraminya N, Tehrani-Doost M, Jazayeri S, Hosseini A, Djazayery A: Therapeutic effects of vitamin D as adjunctive therapy to fluoxetine in patients with major depressive disorder. Aust N Z J Psychiatry 2013, 47:271-275.
• [29]Kjaergaard M, Waterloo K, Wang CEA, Almas B, Figenschau Y, Hutchinson MS, et al.: Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case–control study and randomised clinical trial. Br J Psychiatry 2012, 201:360-368.
• [30]Mozaffari-Khosravi H, Nabizade L, Yassini-Ardakani SM, Hadinedoushan H, Barzegar K: The effect of 2 different single injections of high dose of vitamin D on improving the depression in depressed patients with vitamin D deficiency: a randomized clinical trial. J Clin Psychopharmacol 2013, 33:378-385.
• [31]Dhesi JK, Jackson SHD, Bearne LM, Moniz C, Hurley MV, Swift CG, et al.: Vitamin D supplementation improves neuromuscular function in older people who fall. Age Ageing 2004, 33:589-595.
• [32]Williams JA, Sink KM, Tooze JA, Atkinson HH, Cauley JA, Yaffe K, et al.: Low 25-hydroxyvitamin D concentrations predict incident depression in well-functioning older adults: the health, aging, and body composition study. J Gerontol A Biol Sci Med Sci 2015, 70:757-763.
• [33]Armstrong DJ, Meenagh GK, Bickle I, Lee ASH, Curran ES, Finch MB: Vitamin D deficiency is associated with anxiety and depression in fibromyalgia. Clin Rheumatol 2007, 26:551-554.
• [34]Motsinger S, Lazovich D, MacLehose RF, Torkelson CJ, Robien K: Vitamin D intake and mental health-related quality of life in older women: the Iowa Women's Health Study. Maturitas 2012, 71:267-273.
• [35]Sakalli H, Arslan D, Yucel AE: The effect of oral and parenteral vitamin D supplementation in the elderly: a prospective, double-blinded, randomized, placebo-controlled study. Rheumatol Int 2012, 32:2279-2283.
• [36]Schlogl M, Holick MF: Vitamin D and neurocognitive function. Clin Interv Aging 2014, 9:559-568.
• [37]Need AG, O'Loughlin PD, Morris HA, Coates PS, Horowitz M, Nordin BEC: Vitamin D metabolites and calcium absorption in severe vitamin D deficiency. J Bone Miner Res 2008, 23:1859-1863.
• [38]van Schoor NM, Knol DL, Deeg DJH, Peters FPAM, Heijboer AC, Lips P: Longitudinal changes and seasonal variations in serum 25-hydroxyvitamin D levels in different age groups: results of the Longitudinal Aging Study Amsterdam. Osteoporos Int 2014, 25:1483-1491.
• [39]Gezondheidsraad (Health Council of the Netherlands). Evaluatie van de voedingsnormen voor vitamine D (Evaluation of the dieatary reference values for vitamin D). http://www.gezondheidsraad.nl/nl/taak-werkwijze/werkterrein/gezonde-voeding/evaluatie-van-devoedingsnormen-voor-vitamine-d. (2008). Accessed 9 Nov, 2012.
• [40]van Wijngaarden JP, Swart KMA, Enneman AW, Dhonukshe-Rutten RAM, van Dijk SC, Ham AC, et al.: Effect of daily vitamin B-12 and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: B-PROOF, a randomized controlled trial. Am J Clin Nutr 2014, 100:1578-1586.
• [41]Radloff LS: The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1977, 1:385-401.
• [42]Bisschop MI, Kriegsman DMW, van Tilburg TG, Penninx BWJH, van Eijk JT, Deeg DJH: The influence of differing social ties on decline in physical functioning among older people with and without chronic diseases: the Longitudinal Aging Study Amsterdam. Aging Clin Exp Res 2003, 15:164-173.
• [43]Ware JEJ, Sherbourne CD: The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992, 30:473-483.
• [44]Chel V, Wijnhoven HAH, Smit JH, Ooms M, Lips P: Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents. Osteoporos Int 2008, 19:663-671.
• [45]Lips P, Wiersinga A, van Ginkel FC, Jongen MJ, Netelenbos JC, Hackeng WH, et al.: The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects. J Clin Endocrinol Metab 1988, 67:644-650.
• [46]Lips P: Interaction between vitamin D and calcium. Scand J Clin Lab Invest Suppl 2012, 243:60-64.
• [47]van de Rest O, van der Zwaluw N, Beekman ATF, de Groot LCPG, Geleijnse JM: The reliability of three depression rating scales in a general population of Dutch older persons. Int J Geriatr Psychiatry 2010, 25:998-1005.
• [48]Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, et al.: A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 1994, 49:M85-M94.
• [49]Freire AN, Guerra RO, Alvarado B, Guralnik JM, Zunzunegui MV: Validity and reliability of the short physical performance battery in two diverse older adult populations in Quebec and Brazil. J Aging Health 2012, 24:863-878.
• [50]Andrews G, Peters L: The psychometric properties of the Composite International Diagnostic Interview. Soc Psychiatry Psychiatr Epidemiol 1998, 33:80-88.
• [51]Beck AT, Epstein N, Brown G, Steer RA: An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol 1988, 56:893-897.
• [52]Julian LJ: Measures of anxiety: State-Trait Anxiety Inventory (STAI), Beck Anxiety Inventory (BAI), and Hospital Anxiety and Depression Scale-Anxiety (HADS-A). Arthritis Care Res (Hoboken ) 2011, 63(Suppl 11):S467-S472.
• [53]Klein M, Ponds RW, Houx PJ, Jolles J: Effect of test duration on age-related differences in Stroop interference. J Clin Exp Neuropsychol 1997, 19:77-82.
• [54]The measurement and valuation of health status using EQ-5D: a European perspective. Kluwer Academic publishers, Dordrecht; 2003.
• [55]Kind P, Dolan P, Gudex C, Williams A: Variations in population health status: results from a United Kingdom national questionnaire survey. BMJ 1998, 316:736-741.
• [56]Lin MR, Hwang HF, Hu MH, Wu HDI, Wang YW, Huang FC: Psychometric comparisons of the timed up and go, one-leg stand, functional reach, and Tinetti balance measures in community-dwelling older people. J Am Geriatr Soc 2004, 52:1343-1348.
• [57]Oostenbrink JB, Koopmanschap MA, Rutten FFH: Standardisation of costs: the Dutch Manual for Costing in economic evaluations. Pharmacoeconomics 2002, 20:443-454.
• [58]Bouwmans C, De Jong K, Timman R, Zijlstra-Vlasveld M, Van der Feltz-Cornelis C, Tan Swan S, et al.: Feasibility, reliability and validity of a questionnaire on healthcare consumption and productivity loss in patients with a psychiatric disorder (TiC-P). BMC Health Serv Res 2013, 13:217. BioMed Central Full Text
• [59]Stel VS, Smit JH, Pluijm SMF, Visser M, Deeg DJH, Lips P: Comparison of the LASA Physical Activity Questionnaire with a 7-day diary and pedometer. J Clin Epidemiol 2004, 57:252-258.
• [60]van Schoor NM, Lips P: Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab 2011, 25:671-680.
• [61]Heijboer AC, Blankenstein MA, Kema IP, Buijs MM: Accuracy of 6 routine 25-hydroxyvitamin D assays: influence of vitamin D binding protein concentration. Clin Chem 2012, 58:543-548.
• [62]Veer-Tazelaar PJ, van Marwijk HWJ, van Oppen P, van Hout HPJ, van der Horst HE, Cuijpers P, et al.: Stepped-care prevention of anxiety and depression in late life: a randomized controlled trial. Arch Gen Psychiatry 2009, 66:297-304.
• [63]Perera S, Mody SH, Woodman RC, Studenski SA: Meaningful change and responsiveness in common physical performance measures in older adults. J Am Geriatr Soc 2006, 54:743-749.
• [64]Hoogendijk E, van Groenou MB, van Tilburg T, Deeg D: Educational differences in functional limitations: comparisons of 55-65-year-olds in the Netherlands in 1992 and 2002. Int J Public Health 2008, 53:281-289.
• [65]van Buuren S, Oudshoorn C: Multivariate imputation by chained equations. TNO Prevention and Health, Public Health, Leiden; 2000.
• [66]World Health Organization: The global burden of disease 2004 update. http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/. (2008). Accessed 20 July 2015.
• [67]Spedding S: Vitamin D, and depression: a systematic review and meta-analysis comparing studies with and without biological flaws. Nutrients 2014, 6:1501-1518.
• [68]Lansdowne AT, Provost SC: Vitamin D3 enhances mood in healthy subjects during winter. Psychopharmacology (Berl) 1998, 135:319-323.
• [69]Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K: Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med 2008, 264:599-609.
• [70]Sanders KM, Stuart AL, Williamson EJ, Jacka FN, Dodd S, Nicholson G, et al.: Annual high-dose vitamin D3 and mental well-being: randomised controlled trial. Br J Psychiatry 2011, 198:357-364.
• [71]Dean AJ, Bellgrove MA, Hall T, Phan WMJ, Eyles DW, Kvaskoff D, et al.: Effects of vitamin D supplementation on cognitive and emotional functioning in young adults--a randomised controlled trial. PLoS One 2011., 6Article ID e25966
• [72]Bertone-Johnson ER, Powers SI, Spangler L, Larson J, Michael YL, Millen AE, et al.: Vitamin D supplementation and depression in the women's health initiative calcium and vitamin D trial. Am J Epidemiol 2012, 176:1-13.
• [73]Yalamanchili V, Gallagher JC: Treatment with hormone therapy and calcitriol did not affect depression in older postmenopausal women: no interaction with estrogen and vitamin D receptor genotype polymorphisms. Menopause 2012, 19:697-703.
• [74]Grady D, Halloran B, Cummings S, Leveille S, Wells L, Black D, et al.: 1,25-Dihydroxyvitamin D3 and muscle strength in the elderly: a randomized controlled trial. J Clin Endocrinol Metab 1991, 73:1111-1117.
• [75]Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C: Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 2000, 15:1113-1118.
• [76]Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, et al.: Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 2003, 18:343-351.
• [77]Kenny AM, Biskup B, Robbins B, Marcella G, Burleson JA: Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men. J Am Geriatr Soc 2003, 51:1762-1767.
• [78]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, 51:291-299.
• [79]Gallagher JC: The effects of calcitriol on falls and fractures and physical performance tests. J Steroid Biochem Mol Biol 2004, 89–90:497-501.
• [80]Sato Y, Iwamoto J, Kanoko T, Satoh K: Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial. Cerebrovasc Dis 2005, 20:187-192.
• [81]Bischoff-Ferrari HA, Conzelmann M, Stahelin HB, Dick W, Carpenter MG, Adkin AL, et al.: Is fall prevention by vitamin D mediated by a change in postural or dynamic balance? Osteoporos Int 2006, 17:656-663.
• [82]Bunout D, Barrera G, Leiva L, Gattas V, de la Maza MP, Avendano M, et al.: Effects of vitamin D supplementation and exercise training on physical performance in Chilean vitamin D deficient elderly subjects. Exp Gerontol 2006, 41:746-752.
• [83]Smedshaug GB, Pedersen JI, Meyer HE: Can vitamin D supplementation improve grip strength in elderly nursing home residents? A double-blind controlled trial. Scand J Food Nutrition 2007, 51:74-78.
• [84]Brunner RL, Cochrane B, Jackson RD, Larson J, Lewis C, Limacher M, et al.: Calcium, vitamin D supplementation, and physical function in the Women's Health Initiative. J Am Diet Assoc 2008, 108:1472-1479.
• [85]Moreira-Pfrimer LDF, Pedrosa MAC, Teixeira L, Lazaretti-Castro M: Treatment of vitamin D deficiency increases lower limb muscle strength in institutionalized older people independently of regular physical activity: a randomized double-blind controlled trial. Ann Nutr Metab 2009, 54:291-300.
• [86]Pfeifer M, Begerow B, Minne HW, Suppan K, Fahrleitner-Pammer A, Dobnig H: Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals. Osteoporos Int 2009, 20:315-322.
• [87]Songpatanasilp T, Chailurkit LO, Nichachotsalid A, Chantarasorn M: Combination of alfacalcidol with calcium can improve quadriceps muscle strength in elderly ambulatory Thai women who have hypovitaminosis D: a randomized controlled trial. J Med Assoc Thai 2009, 92(5):S30-S41.
• [88]Janssen HCJP, Samson MM, Verhaar HJJ: Muscle strength and mobility in vitamin D-insufficient female geriatric patients: a randomized controlled trial on vitamin D and calcium supplementation. Aging Clin Exp Res 2010, 22:78-84.
• [89]Lips P, Binkley N, Pfeifer M, Recker R, Samanta S, Cohn DA, et al.: Once-weekly dose of 8400 IU vitamin D(3) compared with placebo: effects on neuromuscular function and tolerability in older adults with vitamin D insufficiency. Am J Clin Nutr 2010, 91:985-991.
• [90]Witham MD, Crighton LJ, Gillespie ND, Struthers AD, McMurdo MET: The effects of vitamin D supplementation on physical function and quality of life in older patients with heart failure: a randomized controlled trial. Circ Heart Fail 2010, 3:195-201.
• [91]Zhu K, Austin N, Devine A, Bruce D, Prince RL: A randomized controlled trial of the effects of vitamin D on muscle strength and mobility in older women with vitamin D insufficiency. J Am Geriatr Soc 2010, 58:2063-2068.
• [92]Glendenning P, Zhu K, Inderjeeth C, Howat P, Lewis JR, Prince RL: Effects of three-monthly oral 150,000 IU cholecalciferol supplementation on falls, mobility, and muscle strength in older postmenopausal women: a randomized controlled trial. J Bone Miner Res 2012, 27:170-176.
• [93]Hornikx M, Van Remoortel H, Lehouck A, Mathieu C, Maes K, Gayan-Ramirez G, et al.: Vitamin D supplementation during rehabilitation in COPD: a secondary analysis of a randomized trial. Respir Res 2012, 13:84. BioMed Central Full Text
• [94]Kampman MT, Steffensen LH, Mellgren SI, Jorgensen L: Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial. Mult Scler 2012, 18:1144-1151.
• [95]Hara S, Kishimoto KN, Okuno H, Tanaka M, Saito H, Oizumi A, et al.: Effects of alfacalcidol on back extensor strength gained through back extensor exercise in postmenopausal women with osteoporosis. Am J Phys Med Rehabil 2013, 92:101-110.
• [96]McAlindon T, LaValley M, Schneider E, Nuite M, Lee JY, Price LL, et al.: Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial. JAMA 2013, 309:155-162.
• [97]Sanghi D, Mishra A, Sharma AC, Singh A, Natu SM, Agarwal S, et al.: Does vitamin D improve osteoarthritis of the knee: a randomized controlled pilot trial. Clin Orthop Relat Res 2013, 471:3556-3562.
• [98]Knutsen KV, Madar AA, Lagerlov P, Brekke M, Raastad T, Stene LC, et al.: Does vitamin D improve muscle strength in adults? A randomized, double-blind, placebo-controlled trial among ethnic minorities in Norway. J Clin Endocrinol Metab 2014, 99:194-202.
• [99]Wood AD, Secombes KR, Thies F, Aucott LS, Black AJ, Reid DM, et al.: A parallel group double-blind RCT of vitamin D3 assessing physical function: is the biochemical response to treatment affected by overweight and obesity? Osteoporos Int 2014, 25:305-315.
• [100]Rolighed L, Rejnmark L, Sikjaer T, Heickendorff L, Vestergaard P, Mosekilde L, et al.: No beneficial effects of vitamin D supplementation on muscle function or quality of life in primary hyperparathyroidism: results from a randomized controlled trial. Eur J Endocrinol 2015, 172:609-617.