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Dermatoendocrinol. Apr 1, 2012; 4(2): 198–202.
PMCID: PMC3427200

Effect of follow-up time on the relation between prediagnostic serum 25-hydroxyvitamin D and all-cause mortality rate

Abstract

Evidence continues to mount that vitamin D reduces the risk and mortality rates of many types of disease. However, evidence from prospective cohort studies is sometimes weaker than that from case–control and ecological studies. A suggested reason for this discrepancy is that, because serum levels of 25-hydroxyvitamin D [25(OH)D] change over time, a single 25(OH)D concentration measurement taken at study enrollment does not reliably indicate 25(OH)D concentration related to the health outcome. To evaluate this suggestion further, this paper plots results from 12 prospective cohort studies of all-cause mortality rate vs. follow-up time. The regression fit to the hazard ratio per 20-nmol/l increase in serum 25(OH)D concentration vs. time increased from 0.82 (95% CI, 0.67–1.02) for 6 y to 0.96 (95% CI, 0.90–1.01) for 14 y. The value extrapolated for zero follow-up time was 0.72 (95% CI, 0.50–1.03), giving a hazard ratio reduction 3.5 times higher than the standard result from the meta-analysis [0.92 (95% CI, 0.89–0.95)]. Using the example of the Vitamin D Pooling Project of Rarer Cancers, this paper also discusses follow-up time’s effect in interpreting prospective cohort studies of cancer outcome. This paper recommends that meta-analyses of prospective cohort studies account for follow-up time and, if possible, that studies measure serum 25(OH)D concentration every 2–4 y.

Keywords: 25-hydroxyvitamin D, all-cause mortality rate, cancer, case–control studies, ecological studies, prospective cohort studies, ultraviolet-B

Introduction

Evidence for beneficial effects of solar ultraviolet-B (UVB) irradiance and vitamin D in reducing the risk of adverse health outcomes comes from a variety of study types: ecological, cross-sectional, case-control, cohort, and intervention. Vitamin D researchers consider the evidence of beneficial effects to be strong.1-3 However, others have conducted systematic reviews that find the evidence lacking4,5—partly because at the time of the reviews, few well-conducted randomized controlled trials (RCTs) with vitamin D existed to analyze its nonskeletal effects.6 Also, findings from cohort studies7,8sometimes disagree with results from ecological studies.9

A recent paper argued that prospective studies with long follow-up times lead to errors because the single serum 25-hydroxyvitamin D [25(OH)D] concentration measurement taken at study enrollment loses prognostic value over time.10 For breast cancer, the linear regression line fit to the relative risk increased from 0.61 for case–control studies with no follow-up period to 0.95 for a 7-y follow-up, whereas for colorectal cancer, the regression line fit increased from 0.48 for case-control studies with no follow-up to 0.72 for a 14-y follow-up. For prostate cancer, no statistically significant correlation emerged with respect to 25(OH)D concentration for any follow-up time between 4 and 28 y. Further support for this assertion is that a prospective study of breast cancer incidence found a strong inverse correlation with high vitamin D intake in the first 5 y after baseline dietary assessment (relative risk = 0.66; 95% CI, 0.46–0.94 compared with lowest-intake group), with the association diminishing over time.11 Also, for a nested case-control study of lymphoma in Finland, the odds ratio for chronic lymphocytic leukemia or small lymphocytic lymphoma was 0.41 (95% CI, 0.15–1.09) for follow-up time shorter than 7 y but was 1.15 (95% CI, 0.44–3.01) for follow-up longer than 7 y.12

A recent meta-analysis of all-cause mortality rate with respect to prediagnostic serum 25(OH)D concentration mentioned that the cohort studies with shorter follow-up times had a stronger association than those with longer follow-up.13 This paper uses the data in that study to extend that analysis of follow-up time’s role in cohort studies of health outcomes with respect to prediagnostic serum 25(OH)D concentration.

Results

Figure 1 is a scatterplot of the correlation coefficient for serum 25(OH)D concentration measurements vs. interval. The value changes from a zero intercept of 0.7 to 0.42 for 14 y. The square of the correlation coefficient gives the fraction of the variance explained by the model. The shortest interval is 1 y.

figure de-4-198-g1
Figure 1. Correlation coefficient of serum 25(OH)D concentration measured in two periods vs. follow-up period.

Figure 2 plots the hazard ratios vs. follow-up period. The regression fit to the hazard ratio per 20-nmol/l increase in serum 25(OH)D concentration vs. time increased from 0.82 (95% CI, 0.67–1.02) for 6 y to 0.96 (95% CI, 0.90–1.01) for 14 y. The zero follow-up time value is 0.72 (95% CI, 0.50–1.03). These values differ considerably from the values in the meta-analysis by Schöttker and colleagues13 of 0.92 (95% CI, 0.89–0.95), which corresponds to a value for 12 y for the regression fit in Figure 2. However, the mean follow-up time of all 12 studies weighted by the relative weights in Schöttker’s Figure 3 is 9.6 y. Thus, the results based on extrapolation to zero follow-up time find 3.5 times as great a risk reduction, whereas the ratio for 6 y is 2.3 times as great. Although the extrapolated 95% CI values for zero follow-up time are large, the values would be much smaller if the values were averaged, say, for each three values.

figure de-4-198-g2
Figure 2. Hazard ratios (HRs) for all-cause mortality rate per 20-nmol/l increase in serum 25(OH)D concentration, using data from Figure 3 in Schöttker et al.13 vs. follow-up period. The equations for the regression fits are: HR ...

Discussion

The results in Figure 2 suggest that a 20-nmol/l increase in vitamin D serum level reduces the risk of all-cause mortality rate by 18–28%. The 18% is similar to the 7–17% reduction achieved by increasing serum 25(OH)D concentration from 54 to 110 nmol/l, as estimated in a recent study based on the serum 25(OH)D concentration–disease outcome relation for diseases contributing the most to all-cause mortality rate: cancer, cardiovascular disease, diabetes mellitus, respiratory diseases, respiratory infections, and tuberculosis.14 This reduction in mortality rate would increase life expectancy by an estimated 2 y.

However, because the 25(OH)D concentration–mortality rate relation is nonlinear, changing rapidly for low serum 25(OH)D concentrations and very little above 80 nmol/l, determining a more precise estimate would require a more careful analysis. On the basis of Figure 4 in Zittermann and colleagues,15 the 8% reduction in Schöttker et al.13 is consistent with an increase of serum 25(OH)D from 50 to 70 nmol/l.

These results further support the assertion that the apparent risk of adverse health outcomes decreases with longer follow-up time. However, in nested case-control studies, shorter follow-up times have fewer cases and thus wider 95% CIs. The rationale for conducting nested case-control studies instead of case-control studies with no follow-up interval includes concerns about bias in selecting controls and that the disease may affect the health outcome. For mortality rates, death often comes after long-term illness, which can affect serum 25(OH)D concentrations. For cancer incidence rates, this concern is not as well founded: people who have cancer often do not find out until diagnosis through screening (for breast and colorectal cancer) or until they notice persistent pain for a short time. For breast cancer, case-control studies found much greater inverse correlations between serum 25(OH)D concentration and incidence than did nested case-control studies.10

This study recommends that meta-analyses of cohort study findings incorporate follow-up time, as demonstrated here. It also suggests comparing case-control study results with those of cohort studies by plotting the results vs. follow-up interval; if the data from both types of studies can be modeled with a linear or second-order regression fit without large deviations, the case-control results should be afforded more credibility. This study also recommends that prospective cohort studies regularly measure serum 25(OH)D concentration, perhaps every 2–4 y. Doing so would add additional costs to the studies but would yield more accurate results.

Thus, in studies such as the Vitamin D Pooling Project of Rarer Cancers,7 the disagreement with ecological studies may be due partly to the long mean follow-up time of 6.63 y. Some of the disagreement can also be due to the few cases for each type of cancer. Also, the role of solar UVB and vitamin D appears to be stronger for mortality rates than for incidence rates in ecological studies.17,18Ecological studies of the seven types of cancers in the Vitamin D Pooling Project of Rarer Cancers [endometrial, esophageal, gastric, kidney, ovarian, pancreatic cancer and non-Hodgkin lymphoma (NHL)] strongly support beneficial effects of solar UVB in reducing mortality rates.9 The evidence of beneficial effects for incidence rates for these types of cancer in ecological studies is weaker.17,18Results from prospective cohort studies also support a protective role of UVB irradiance for NHL19-21and 25(OH)D concentration for gastric22 and pancreatic23 cancer, with moderate support for a role of serum 25(OH)D concentration in ovarian cancer24,25but no support for endometrial cancer26 or NHL.17,27 However, long follow-up times could adversely affect some observational studies for endometrial and ovarian cancer and NHL.

There are some limitations of ecological studies. For one, there are risk-modifying factors that are not included in the analyses, such as physical activity, obesity rates, and immigration. For example, in the United States, there was considerable migration from the Northeast to the South and West in the second half of the twentieth century. The strength of the ecological approach is demonstrated in the fact that the results for many types of cancer are often repeated for different populations.9

This study offers additional support for the thesis that long follow-up times adversely affect nested case-control studies from prospective cohort studies regarding the role of prediagnostic serum 25(OH)D concentration in health outcomes such as all-cause mortality rate and many types of cancer. It is hoped that the research communities and health policy makers will take this thesis into account when analyzing epidemiological studies and making recommendations regarding vitamin D.

This study also indicates that observational studies can strongly support the UVB-vitamin D-disease reduction hypothesis if the existing studies in the journal literature are carefully assessed and systemic biases in the interpretation of the data are removed. Unfortunately, the Institute of Medicine Committee on Dietary Reference Intakes for Vitamin D and Calcium5 did not undertake that task. They opted instead to wait another 5–6 y for a “definitive” RCT of vitamin D supplementation.28 As Kristal29 and another paper in this issue30 pointed out, RCTs have several problems that, if not carefully addressed, can result in poor-quality studies. Ideally, results from all types of studies—clinical, cross-sectional, ecological, laboratory and observational—would be considered together and reasons for differences resolved.

Materials and Methods

Findings in the literature for the correlation coefficient for serum 25(OH)D concentrations for a single cohort for different measurement intervals (Table 1) are plotted vs. time. The correlation coefficients were of two types: Pearson coefficient and Spearman rank coefficient. Good agreement exists between the two types of coefficients. However, because the Pearson coefficient is more appropriate for continuous variables, it is used in the graph when both coefficients are given.

Table 1.
Correlations between serum 25(OH)D concentrations measured at different intervals

The data for this study are from a recent meta-analysis of prospective cohort studies of all-cause mortality rate.13 This study uses the statistics for the 12 studies included in that meta-analysis for hazard ratios per 20-nmol/l-increase in serum 25(OH)D concentration (Fig. 3 in Schöttker et al.13). The values are given in Table 2. These values are plotted vs. follow-up period. A complication exists in that the 25(OH)D-mortality rate relationship is nonlinear,15 but both Schöttker et al.13 and this study ignore that fact.

Table 2.
Statistics for the all-cause mortality rate data used in this study13

The data were plotted using KaleidaGraph 4.0 (Synergy Software).

Glossary

Abbreviations:

25(OH)D
25-hydroxyvitamin D
95% CI
95% confidence interval
NHL
non-Hodgkin lymphoma
RCT
randomized controlled trial
UVB
ultraviolet-B

Disclosure of Potential Conflicts of Interest

Disclosure of Potential Conflicts of Interest

W.B.G. receives funding from the UV Foundation (McLean, VA), Bio-Tech Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), and the Vitamin D Society (Canada).

References

1. Souberbielle JC, Body JJ, Lappe JM, Plebani M, Shoenfeld Y, Wang TJ, et al. Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice. Autoimmun Rev. 2010;9:709–15. doi: 10.1016/j.autrev.2010.06.009. [PubMed] [Cross Ref]
2. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Endocrine Society Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30. doi: 10.1210/jc.2011-0385. [PubMed] [Cross Ref]
3. Hollis BW. Short-term and long-term consequences and concerns regarding valid assessment of vitamin D deficiency: comparison of recent food supplementation and clinical guidance reports. Curr Opin Clin Nutr Metab Care. 2011;14:598–604. doi: 10.1097/MCO.0b013e32834be798. [PubMed] [Cross Ref]
4. IARC Working Group Report 5: Vitamin D and Cancer. IARC, Lyon, France. 2008. [PMC free article] [PubMed]
5. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, 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;96:53–8. doi: 10.1210/jc.2010-2704. [PMC free article] [PubMed] [Cross Ref]
6. Chung M, Balk EM, Brendel M, Ip S, Lau J, Lee J, et al. Vitamin D and calcium: a systematic review of health outcomes. Evid Rep Technol Assess (Full Rep)(183), 1-420. (Prepared by Tufts Evidence-based Practice Center under Contract No. 290-2007-10055-I). AHRQ Publication No. 09-E015, Rockville, MD: Agency for Healthcare Research and Quality. August 2009. http://www.ahrq.gov/downloads/pub/evidence/pdf/vitadcal/vitadcal.pdf)
7. Helzlsouer KJ, VDPP Steering Committee Overview of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol. 2010;172:4–9. doi: 10.1093/aje/kwq119. [PMC free article] [PubMed] [Cross Ref]
8. Grant WB. Relation between prediagnostic serum 25-hydroxyvitamin D level and incidence of breast, colorectal, and other cancers. J Photochem Photobiol B. 2010;101:130–6. doi: 10.1016/j.jphotobiol.2010.04.008. [PubMed] [Cross Ref]
9. Grant WB. Ecological studies of the UVB-vitamin D-cancer hypothesis. Anticancer Res. 2012;32:223–36. [review] [PubMed]
10. Grant WB. Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level: Implications for meta-analyses and setting vitamin D guidelines. Dermatoendocrinol. 2011;3:199–204. [PMC free article] [PubMed]
11. Robien K, Cutler GJ, Lazovich D. Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study. Cancer Causes Control. 2007;18:775–82. doi: 10.1007/s10552-007-9020-x. [PubMed] [Cross Ref]
12. Lim U, Freedman DM, Hollis BW, Horst RL, Purdue MP, Chatterjee N, et al. A prospective investigation of serum 25-hydroxyvitamin D and risk of lymphoid cancers. Int J Cancer. 2009;124:979–86. doi: 10.1002/ijc.23984. [PMC free article] [PubMed] [Cross Ref]
13. Schöttker B, Ball D, Gellert C, Brenner H. Serum 25-hydroxyvitamin D levels and overall mortality. A systematic review and meta-analysis of prospective cohort studies. Ageing Res Rev. 2012 doi: 10.1016/j.arr.2012.02.004. [PubMed] [Cross Ref]
14. Grant WB. An estimate of the global reduction in mortality rates through doubling vitamin D levels. Eur J Clin Nutr. 2011;65:1016–26. doi: 10.1038/ejcn.2011.68. [PubMed] [Cross Ref]
15. Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S. Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies. Am J Clin Nutr. 2012;95:91–100. doi: 10.3945/ajcn.111.014779. [PubMed] [Cross Ref]
16. Grant WB. An ecological study of cancer mortality rates in the United States with respect to solar ultraviolet-B doses, smoking, alcohol consumption and urban/rural residence. Dermatoendocrinol. 2010;2:68–76. doi: 10.4161/derm.2.2.13812. [PMC free article] [PubMed] [Cross Ref]
17. Boscoe FP, Schymura MJ. Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993-2002. BMC Cancer. 2006;6:264. doi: 10.1186/1471-2407-6-264. [PMC free article] [PubMed] [Cross Ref]
18. Chen W, Clements M, Rahman B, Zhang S, Qiao Y, Armstrong BK. Relationship between cancer mortality/incidence and ambient ultraviolet B irradiance in China. Cancer Causes Control. 2010;21:1701–9. doi: 10.1007/s10552-010-9599-1. [PubMed] [Cross Ref]
19. Hartge P, Lim U, Freedman DM, Colt JS, Cerhan JR, Cozen W, et al. Ultraviolet radiation, dietary vitamin D, and risk of non-Hodgkin lymphoma (United States) Cancer Causes Control. 2006;17:1045–52. doi: 10.1007/s10552-006-0040-8. [PubMed] [Cross Ref]
20. Kricker A, Armstrong BK, Hughes AM, Goumas C, Smedby KE, Zheng T, et al. Interlymph Consortium Personal sun exposure and risk of non Hodgkin lymphoma: a pooled analysis from the Interlymph Consortium. Int J Cancer. 2008;122:144–54. doi: 10.1002/ijc.23003. [PubMed] [Cross Ref]
21. Chang ET, Canchola AJ, Cockburn M, Lu Y, Wang SS, Bernstein L, et al. Adulthood residential ultraviolet radiation, sun sensitivity, dietary vitamin D, and risk of lymphoid malignancies in the California Teachers Study. Blood. 2011;118:1591–9. doi: 10.1182/blood-2011-02-336065. [PMC free article] [PubMed] [Cross Ref]
22. Ren C, Qiu MZ, Wang DS, Luo HY, Zhang DS, Wang ZQ, et al. Prognostic effects of 25-hydroxyvitamin D levels in gastric cancer. J Transl Med. 2012;10:16. doi: 10.1186/1479-5876-10-16. [PMC free article] [PubMed] [Cross Ref]
23. Wolpin BM, Ng K, Bao Y, Kraft P, Stampfer MJ, Michaud DS, et al. Plasma 25-hydroxyvitamin D and risk of pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2012;21:82–91. doi: 10.1158/1055-9965.EPI-11-0836. [PMC free article] [PubMed] [Cross Ref]
24. Toriola AT, Surcel HM, Calypse A, Grankvist K, Luostarinen T, Lukanova A, et al. Independent and joint effects of serum 25-hydroxyvitamin D and calcium on ovarian cancer risk: a prospective nested case-control study. Eur J Cancer. 2010;46:2799–805. doi: 10.1016/j.ejca.2010.05.019. [PubMed] [Cross Ref]
25. Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Meta-analysis: Circulating vitamin D and ovarian cancer risk. Gynecol Oncol. 2011;121:369–75. doi: 10.1016/j.ygyno.2011.01.023. [PubMed] [Cross Ref]
26. McCullough ML, Bandera EV, Moore DF, Kushi LH. Vitamin D and calcium intake in relation to risk of endometrial cancer: a systematic review of the literature. Prev Med. 2008;46:298–302. doi: 10.1016/j.ypmed.2007.11.010. [PMC free article] [PubMed] [Cross Ref]
27. Negri E. Sun exposure, vitamin D, and risk of Hodgkin and non-Hodgkin lymphoma. Nutr Cancer. 2010;62:878–82. doi: 10.1080/01635581.2010.509535. [PubMed] [Cross Ref]
28. Manson JE, Bassuk SS, Lee IM, Cook NR, Albert MA, Gordon D, et al. The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials. 2012;33:159–71. doi: 10.1016/j.cct.2011.09.009. [PMC free article] [PubMed] [Cross Ref]
29. Kristal AR. Are clinical trials the “gold standard” for cancer prevention research? Cancer Epidemiol Biomarkers Prev. 2008;17:3289–91. doi: 10.1158/1055-9965.EPI-08-1066. [PubMed] [Cross Ref]
30. Lappe J, Heaney RP. Why randomized controlled trials of calcium and vitamin D sometimes fail. Dermatoendocrinol. In press. [PMC free article] [PubMed]
31. Hofmann JN, Yu K, Horst RL, Hayes RB, Purdue MP. Long-term variation in serum 25-hydroxyvitamin D concentration among participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiol Biomarkers Prev. 2010;19:927–31. doi: 10.1158/1055-9965.EPI-09-1121. [PMC free article] [PubMed] [Cross Ref]
32. Rejnmark L, Lauridsen AL, Brot C, Vestergaard P, Heickendorff L, Nexo E, et al. Vitamin D and its binding protein Gc: long-term variability in peri- and postmenopausal women with and without hormone replacement therapy. Scand J Clin Lab Invest. 2006;66:227–38. doi: 10.1080/00365510600570623. [PubMed] [Cross Ref]
33. Platz EA, Hankinson SE, Hollis BW, Colditz GA, Hunter DJ, Speizer FE, et al. Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and adenomatous polyps of the distal colorectum. Cancer Epidemiol Biomarkers Prev. 2000;9:1059–65. [PubMed]
34. Jorde R, Sneve M, Hutchinson M, Emaus N, Figenschau Y, Grimnes G. Tracking of serum 25-hydroxyvitamin D levels during 14 years in a population-based study and during 12 months in an intervention study. Am J Epidemiol. 2010;171:903–8. doi: 10.1093/aje/kwq005. [PubMed] [Cross Ref]
35. Visser M, Deeg DJH, Puts MTE, Seidell JC, Lips P. Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission. Am J Clin Nutr. 2006;84:616–22, quiz 671-2. [PubMed]
36. Pilz S, Dobnig H, Nijpels G, Heine RJ, Stehouwer CD, Snijder MB, et al. Vitamin D and mortality in older men and women. Clin Endocrinol (Oxf) 2009;71:666–72. doi: 10.1111/j.1365-2265.2009.03548.x. [PubMed] [Cross Ref]
37. Semba RD, Houston DK, Bandinelli S, Sun K, Cherubini A, Cappola AR, et al. Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults. Eur J Clin Nutr. 2010;64:203–9. doi: 10.1038/ejcn.2009.140. [PMC free article] [PubMed] [Cross Ref]
38. Cawthon PM, Parimi N, Barrett-Connor E, Laughlin GA, Ensrud KE, Hoffman AR, et al. Osteoporotic Fractures in Men (MrOS) Research Group Serum 25-hydroxyvitamin D, parathyroid hormone, and mortality in older men. J Clin Endocrinol Metab. 2010;95:4625–34. doi: 10.1210/jc.2010-0638. [PMC free article] [PubMed] [Cross Ref]
39. Jia X, Aucott LS, McNeill G. Nutritional status and subsequent all-cause mortality in men and women aged 75 years or over living in the community. Br J Nutr. 2007;98:593–9. doi: 10.1017/S0007114507725163. [PubMed] [Cross Ref]
40. 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;168:1629–37. doi: 10.1001/archinte.168.15.1629. [PMC free article] [PubMed] [Cross Ref]
41. Virtanen JK, Nurmi T, Voutilainen S, Mursu J, Tuomainen TP. Association of serum 25-hydroxyvitamin D with the risk of death in a general older population in Finland. Eur J Nutr. 2011;50:305–12. doi: 10.1007/s00394-010-0138-3. [PubMed] [Cross Ref]
42. Szulc P, Claustrat B, Delmas PD. Serum concentrations of 17β-E2 and 25-hydroxycholecalciferol (25OHD) in relation to all-cause mortality in older men--the MINOS study. Clin Endocrinol (Oxf) 2009;71:594–602. doi: 10.1111/j.1365-2265.2009.03530.x. [PubMed] [Cross Ref]
43. Hutchinson MS, Grimnes G, Joakimsen RM, Figenschau Y, Jorde R. Low serum 25-hydroxyvitamin D levels are associated with increased all-cause mortality risk in a general population: the Tromsø study. Eur J Endocrinol. 2010;162:935–42. doi: 10.1530/EJE-09-1041. [PubMed] [Cross Ref]
44. Michaëlsson K, Baron JA, Snellman G, Gedeborg R, Byberg L, Sundström J, et al. Plasma vitamin D and mortality in older men: a community-based prospective cohort study. Am J Clin Nutr. 2010;92:841–8. doi: 10.3945/ajcn.2010.29749. [PubMed] [Cross Ref]
45. Bates CJ, Hamer M, Mishra GD. A study of relationships between bone-related vitamins and minerals, related risk markers, and subsequent mortality in older British people: the National Diet and Nutrition Survey of People Aged 65 Years and Over. Osteoporos Int. 2012;23:457–66. doi: 10.1007/s00198-011-1543-z. [PMC free article] [PubMed] [Cross Ref]
46. Kestenbaum B, Katz R, de Boer I, Hoofnagle A, Sarnak MJ, Shlipak MG, et al. Vitamin D, parathyroid hormone, and cardiovascular events among older adults. J Am Coll Cardiol. 2011;58:1433–41. doi: 10.1016/j.jacc.2011.03.069. [PMC free article] [PubMed] [Cross Ref]

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