Top

Published in:

01-03-2012 | Original Article

Low serum vitamin D is associated with increased mortality in elderly men: MrOS Sweden

Authors: H. Johansson, A. Odén, J. Kanis, E. McCloskey, M. Lorentzon, Ö. Ljunggren, M. K. Karlsson, P. M. Thorsby, Å. Tivesten, E. Barrett-Connor, C. Ohlsson, D. Mellström

Published in: Osteoporosis International | Issue 3/2012

Abstract

Summary

In elderly man, low serum 25-hydroxyvitamin D (25(OH)D) was associated with a substantial excess risk of death compared to 25(OH)D values greater than 50–70 nmol/l, but the association attenuated with time.

Introduction

The aim of the present study was to determine whether poor vitamin D status was associated with an increase in the risk of death in elderly men.

Methods

We studied the relationship between serum 25(OH)D and the risk of death in 2,878 elderly men drawn from the population and recruited to the MrOS study in Sweden. Baseline data included general health and lifestyle measures and serum 25(OH)D measured by competitive RIA. Men were followed for up to 8.2 years (average 6.0 years).

Results

Mortality adjusted for comorbidities decreased by 5% for each SD increase in 25(OH)D overall (gradient of risk 1.05; 95% confidence interval 0.96–1.14). The predictive value of 25(OH)D for death was greatest below a threshold value of 50–70 nmol/l, was greatest at approximately 3 years after baseline and thereafter decreased with time.

Conclusions

Low serum 25(OH)D is associated with a substantial excess risk of death compared to 25(OH)D values greater than 50–70 nmol/l, but the association attenuates with time. These findings, if causally related, have important implications for intervention in elderly men.

Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, Wong JB, Egli A, Kiel DP, Henschkowski J (2009) Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 339:b3692PubMedCrossRef

Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, Thoma A, Kiel DP, Henschkowski J (2009) Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med 169(6):551–561. doi:10.1001/archinternmed.2008.600 PubMedCrossRef

Weber KT, Simpson RU, Carbone LD (2008) Vitamin D and calcium dyshomoeostasis-associated heart failure. Heart 94(5):540–541. doi:10.1136/hrt.2007.126359 PubMedCrossRef

Heaney RP (2005) The vitamin D requirement in health and disease. J Steroid Biochem Mol Biol 97(1–2):13–19. doi:10.1016/j.jsbmb.2005.06.020 PubMedCrossRef

Holick MF (2004) Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr 79(3):362–371PubMed

Bischoff-Ferrari HA, Shao A, Dawson-Hughes B, Hathcock J, Giovannucci E, Willett WC (2010) Benefit-risk assessment of vitamin D supplementation. Osteoporos Int 21(7):1121–1132. doi:10.1007/s00198-009-1119-3 PubMedCrossRef

Autier P, Gandini S (2007) Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 167(16):1730–1737. doi:10.1001/archinte.167.16.1730 PubMedCrossRef

Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, Cherubini A, Ferrucci L, Melzer D (2010) Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med 170(13):1135–1141. doi:10.1001/archinternmed.2010.173 PubMedCrossRef

Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zugel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311(5768):1770–1773. doi:10.1126/science.1123933 PubMedCrossRef

10.

Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E (2006) Epidemic influenza and vitamin D. Epidemiol Infect 134(6):1129–1140. doi:10.1017/s0950268806007175 PubMedCrossRef

11.

Laaksi I, Ruohola JP, Tuohimaa P, Auvinen A, Haataja R, Pihlajamaki H, Ylikomi T (2007) An association of serum vitamin D concentrations <40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr 86(3):714–717PubMed

12.

Liu N, Kaplan AT, Low J, Nguyen L, Liu GY, Equils O, Hewison M (2009) Vitamin D induces innate antibacterial responses in human trophoblasts via an intracrine pathway. Biol Reprod 80(3):398–406. doi:10.1095/biolreprod.108.073577 PubMedCrossRef

13.

Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA (2011) 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 96(1):53–58. doi:10.1210/jc.2010-2704 PubMedCrossRef

14.

Visser M, Deeg DJ, Puts MT, Seidell JC, Lips P (2006) Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission. Am J Clin Nutr 84(3):616–622, quiz 671–612PubMed

15.

Zittermann A, Schleithoff SS, Frisch S, Gotting C, Kuhn J, Koertke H, Kleesiek K, Tenderich G, Koerfer R (2009) Circulating calcitriol concentrations and total mortality. Clin Chem 55(6):1163–1170. doi:10.1373/clinchem.2008.120006 PubMedCrossRef

16.

Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W (2008) Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med 168(12):1340–1349. doi:10.1001/archinte.168.12.1340 PubMedCrossRef

17.

Melamed ML, Michos ED, Post W, Astor B (2008) 25-Hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 168(15):1629–1637. doi:10.1001/archinte.168.15.1629 PubMedCrossRef

18.

Ginde AA, Scragg R, Schwartz RS, Camargo CA Jr (2009) Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older U.S. adults. J Am Geriatr Soc 57(9):1595–1603. doi:10.1111/j.1532-5415.2009.02359.x PubMedCrossRef

19.

Kuroda T, Shiraki M, Tanaka S, Ohta H (2009) Contributions of 25-hydroxyvitamin D, co-morbidities and bone mass to mortality in Japanese postmenopausal women. Bone 44(1):168–172. doi:10.1016/j.bone.2008.03.023 PubMedCrossRef

20.

Michaelsson K, Baron JA, Snellman G, Gedeborg R, Byberg L, Sundstrom J, Berglund L, Arnlov J, Hellman P, Blomhoff R, Wolk A, Garmo H, Holmberg L, Melhus H (2010) Plasma vitamin D and mortality in older men: a community-based prospective cohort study. Am J Clin Nutr 92(4):841–848. doi:10.3945/ajcn.2010.29749 PubMedCrossRef

21.

Cawthon PM, Parimi N, Barrett-Connor E, Laughlin GA, Ensrud KE, Hoffman AR, Shikany JM, Cauley JA, Lane NE, Bauer DC, Orwoll ES, Cummings SR (2010) Serum 25-hydroxyvitamin D, parathyroid hormone, and mortality in older men. J Clin Endocrinol Metab 95(10):4625–4634. doi:10.1210/jc.2010-0638 PubMedCrossRef

22.

Kilkkinen A, Knekt P, Aro A, Rissanen H, Marniemi J, Heliovaara M, Impivaara O, Reunanen A (2009) Vitamin D status and the risk of cardiovascular disease death. Am J Epidemiol 170(8):1032–1039. doi:10.1093/aje/kwp227 PubMedCrossRef

23.

Pilz S, Dobnig H, Nijpels G, Heine RJ, Stehouwer CD, Snijder MB, van Dam RM, Dekker JM (2009) Vitamin D and mortality in older men and women. Clin Endocrinol (Oxf) 71(5):666–672. doi:10.1111/j.1365-2265.2009.03548.x CrossRef

24.

Semba RD, Houston DK, Bandinelli S, Sun K, Cherubini A, Cappola AR, Guralnik JM, Ferrucci L (2010) Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults. Eur J Clin Nutr 64(2):203–209. doi:10.1038/ejcn.2009.140 PubMedCrossRef

25.

Freedman DM, Looker AC, Chang SC, Graubard BI (2007) Prospective study of serum vitamin D and cancer mortality in the United States. J Natl Cancer Inst 99(21):1594–1602. doi:10.1093/jnci/djm204 PubMedCrossRef

26.

Szulc P, Claustrat B, Delmas PD (2009) Serum concentrations of 17beta-E2 and 25-hydroxycholecalciferol (25OHD) in relation to all-cause mortality in older men—the MINOS study. Clin Endocrinol (Oxf) 71(4):594–602. doi:10.1111/j.1365-2265.2009.03530.x CrossRef

27.

Bolland MJ, Bacon CJ, Horne AM, Mason BH, Ames RW, Wang TK, Grey AB, Gamble GD, Reid IR (2010) Vitamin D insufficiency and health outcomes over 5 y in older women. Am J Clin Nutr 91(1):82–89. doi:10.3945/ajcn.2009.28424 PubMedCrossRef

28.

Ensrud KE, Blackwell TL, Cauley JA, Cummings SR, Barrett-Connor E, Dam TT, Hoffman AR, Shikany JM, Lane NE, Stefanick ML, Orwoll ES, Cawthon PM (2011) Circulating 25-hydroxyvitamin D levels and frailty in older men: the osteoporotic fractures in men study. J Am Geriatr Soc 59(1):101–106. doi:10.1111/j.1532-5415.2010.03201.x PubMedCrossRef

29.

Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D’Agostino RB, Wolf M, Vasan RS (2008) Vitamin D deficiency and risk of cardiovascular disease. Circulation 117(4):503–511. doi:10.1161/circulationaha.107.706127 PubMedCrossRef

30.

Vitamin D nutritional policy in Europe (2009) Comité Permanente des Médecins Européen, http://cpme.dyndns.org:591/adopted/2009/CPME_AD_Brd_241009_179_final_EN.pdf. Accessed 24 Oct 2009

31.

Dawson-Hughes B, Mithal A, Bonjour JP, Boonen S, Burckhardt P, Fuleihan GE, Josse RG, Lips P, Morales-Torres J, Yoshimura N (2010) IOF position statement: vitamin D recommendations for older adults. Osteoporos Int 21(7):1151–1154. doi:10.1007/s00198-010-1285-3 PubMedCrossRef

32.

Johansson H, Oden A, Kanis J, McCloskey E, Lorentzon M, Ljunggren O, Karlsson MK, Tivesten A, Barrett-Connor E, Ohlsson C, Mellstrom D (2010) Low vitamin D is related to increased risk of death in elderly men. MrOS Sweden. J Bone Miner Res 25(Suppl 1):S6(1019)

33.

Orwoll E, Blank JB, Barrett-Connor E, Cauley J, Cummings S, Ensrud K, Lewis C, Cawthon PM, Marcus R, Marshall LM, McGowan J, Phipps K, Sherman S, Stefanick ML, Stone K (2005) Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study—a large observational study of the determinants of fracture in older men. Contemp Clin Trials 26(5):569–585. doi:10.1016/j.cct.2005.05.006 PubMedCrossRef

34.

Mellstrom D, Vandenput L, Mallmin H, Holmberg AH, Lorentzon M, Oden A, Johansson H, Orwoll ES, Labrie F, Karlsson MK, Ljunggren O, Ohlsson C (2008) Older men with low serum estradiol and high serum SHBG have an increased risk of fractures. J Bone Miner Res 23(10):1552–1560PubMedCrossRef

35.

Mellstrom D, Johnell O, Ljunggren O, Eriksson AL, Lorentzon M, Mallmin H, Holmberg A, Redlund-Johnell I, Orwoll E, Ohlsson C (2006) Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden. J Bone Miner Res 21(4):529–535PubMedCrossRef

36.

Johansson H, Oden A, Kanis J, McCloskey E, Lorentzon M, Ljunggren O, Karlsson MK, Orwoll E, Tivesten A, Ohlsson C, Mellstrom D (2010) Low bone mineral density is associated with increased mortality in elderly men: MrOS Sweden. Osteoporos Int. doi:10.1007/s00198-010-1331-1

37.

Lewis CE, Ewing SK, Taylor BC, Shikany JM, Fink HA, Ensrud KE, Barrett-Connor E, Cummings SR, Orwoll E (2007) Predictors of non-spine fracture in elderly men: the MrOS study. J Bone Miner Res 22(2):211–219PubMedCrossRef

38.

Washburn RA, Smith KW, Jette AM, Janney CA (1993) The Physical Activity Scale for the Elderly (PASE): development and evaluation. J Clin Epidemiol 46(2):153–162PubMedCrossRef

39.

Good P (ed) (2000) Permutation tests. Springer Verlag, New York

40.

Harrell FJ (2001) General aspects of fitting regression models: regression modeling strategies. Springer Science + Business Media, Inc, New York

41.

Hochberg MC, Lui L, Black DM, Cauley J, Cawthon PM, Ensrud K, Fredman L, Hillier TA, Cummings S (2010) Serum 25-hydroxyvitamin D levels. Mortality and risk of non-spine and hip fractures in older white women: data from the study of osteoporotic fractures. J Bone Miner Res 25(Suppl 1):s201(SA0361)

42.

Kanis JA, Johnell O, Oden A, Jonsson B, De Laet C, Dawson A (2000) Prediction of fracture from low bone mineral density measurements overestimates risk. Bone 26(4):387–391. doi:10.1016/s8756-3282(00)00238-6 PubMedCrossRef

43.

Luukinen H, Kakonen SM, Pettersson K, Koski K, Laippala P, Lovgren T, Kivela SL, Vaananen HK (2000) Strong prediction of fractures among older adults by the ratio of carboxylated to total serum osteocalcin. J Bone Miner Res 15(12):2473–2478. doi:10.1359/jbmr.2000.15.12.2473 PubMedCrossRef

44.

Ivaska KK, Gerdhem P, Vaananen HK, Akesson K, Obrant KJ (2010) Bone turnover markers and prediction of fracture: a prospective follow-up study of 1040 elderly women for a mean of 9 years. J Bone Miner Res 25(2):393–403. doi:10.1359/jbmr.091006 PubMedCrossRef

45.

Lind M, Oden A, Fahlen M, Eliasson B (2010) The shape of the metabolic memory of HbA1c: re-analysing the DCCT with respect to time-dependent effects. Diabetologia 53(6):1093–1098. doi:10.1007/s00125-010-1706-z PubMedCrossRef

46.

Platz EA, Leitzmann MF, Hollis BW, Willett WC, Giovannucci E (2004) Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancer. Cancer Causes Control 15(3):255–265. doi:10.1023/B:CACO.0000024245.24880.8a PubMedCrossRef

47.

Tsugawa N, Suhara Y, Kamao M, Okano T (2005) Determination of 25-hydroxyvitamin D in human plasma using high-performance liquid chromatography–tandem mass spectrometry. Anal Chem 77(9):3001–3007. doi:10.1021/ac048249c PubMedCrossRef

48.

Snellman G, Melhus H, Gedeborg R, Byberg L, Berglund L, Wernroth L, Michaelsson K (2010) Determining vitamin D status: a comparison between commercially available assays. PLoS One 5(7):e11555. doi:10.1371/journal.pone.0011555 PubMedCrossRef

49.

Lips P, Bouillon R, van Schoor NM, Vanderschueren D, Verschueren S, Kuchuk N, Milisen K, Boonen S (2010) Reducing fracture risk with calcium and vitamin D. Clin Endocrinol (Oxf) 73(3):277–285. doi:10.1111/j.1365-2265.2009.03701.x CrossRef

50.

Barnard K, Colon-Emeric C (2010) Extraskeletal effects of vitamin D in older adults: cardiovascular disease, mortality, mood, and cognition. Am J Geriatr Pharmacother 8(1):4–33. doi:10.1016/j.amjopharm.2010.02.004 PubMedCrossRef

Title: Low serum vitamin D is associated with increased mortality in elderly men: MrOS Sweden
Authors: H. Johansson
A. Odén
J. Kanis
E. McCloskey
M. Lorentzon
Ö. Ljunggren
M. K. Karlsson
P. M. Thorsby
Å. Tivesten
E. Barrett-Connor
C. Ohlsson
D. Mellström
Publication date: 01-03-2012
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 3/2012
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-011-1809-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Low serum vitamin D is associated with increased mortality in elderly men: MrOS Sweden

Abstract

Summary

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2012

The direct cost of acute hip fracture care in care home residents in the UK

Strontium uptake and effects in bone: reply to Fogelman and Blake

A limp in a pregnant woman as a first presentation of celiac disease

Prevalence of non-fracture short vertebral height is similar in premenopausal and postmenopausal women: the osteoporosis and ultrasound study

Comparable outcomes in fracture reduction and bone properties with RANKL inhibition and alendronate treatment in a mouse model of osteogenesis imperfecta

Adherence to osteoporosis medications amongst Singaporean patients