Abstract
Summary
In this meta-analysis, we evaluated the association between serum 25-hydroxyvitamin D (25(OH) vitamin D) level and the risk of total fractures and hip fractures. Low serum 25(OH) vitamin D level is associated with an increased risk of total and hip fractures.
Introduction
Data on the association between serum 25(OH) vitamin D level and the risk of fractures are conflicting. This study aimed to provide a summary of prospective cohort or nested case–control studies on the association between serum 25(OH) vitamin D level and the risk of total fractures and hip fractures.
Methods
We identified relevant studies by searching the PubMed, EMBASE, and OVID databases from their inception to June 1, 2016. We included published prospective cohort or nested case–control studies evaluating the associations of serum 25(OH) vitamin D level with the fracture risk. Two reviewers abstracted the data independently. Relative risks (RRs) with 95% confidence intervals (CIs) were derived throughout the whole analysis.
Results
Sixteen prospective cohort studies and three nested case–control studies were included. We found that low serum 25(OH) vitamin D level was significantly associated with the risk of total fractures (RR 1.25, 95% CI 1.06–1.43; I 2 = 31.3%, p for heterogeneity = 0.15) and hip fractures (RR 1.48, 95% CI 1.29–1.68; I 2 = 0%, p for heterogeneity = 0.51). The hip fracture risk was increased by 40% for each SD decrease in serum 25(OH) vitamin D level (RR 1.40, 95% CI 1.20–1.61; I 2 = 0%, p for heterogeneity = 0.51). The per SD decrease in serum 25(OH) vitamin D level was not associated with the increased risk of total fractures (RR 1.14, 95% CI 0.93–1.35; I 2 = 63.2%, p for heterogeneity = 0.04).
Conclusions
Our study suggests that low serum 25(OH) vitamin D level is associated with increased risks of total and hip fractures. In the analyzed studies, the per SD decrease in serum 25(OH) vitamin D level was associated with the hip fracture risk but not with the total fracture risk.
Similar content being viewed by others
References
Wu ZJ, He JL, Wei RQ, Liu B, Lin X, Guan J, Lan YB (2015) C-reactive protein and risk of fracture: a systematic review and dose-response meta-analysis of prospective cohort studies. Osteoporos Int 26:49–57
Xiao F, Qu X, Zhai Z, Jiang C, Li H, Liu X, Ouyang Z, Gu D (2015) Association between loop diuretic use and fracture risk. Osteoporos Int 26:775–784
Zhang X, Yu Z, Yu M, Qu X (2015) Alcohol consumption and hip fracture risk. Osteoporos Int 26:531–542
Thorin MH, Wihlborg A, Akesson K, Gerdhem P (2015) Smoking, smoking cessation, and fracture risk in elderly women followed for 10 years. Osteoporos Int
Mazziotti G, Biagioli E, Maffezzoni F, Spinello M, Serra V, Maroldi R, Floriani I, Giustina A (2015) Bone turnover, bone mineral density, and fracture risk in acromegaly: a meta-analysis. J Clin Endocrinol Metab 100:384–394
Johansson H, Kanis JA, Oden A et al (2014) A meta-analysis of the association of fracture risk and body mass index in women. J Bone Miner Res 29:223–233
Qu X, Zhang X, Zhai Z, Li H, Liu X, Li H, Liu G, Zhu Z, Hao Y, Dai K (2014) Association between physical activity and risk of fracture. J Bone Miner Res 29:202–211
Iolascon G, Di Pietro G, Gimigliano F (2009) Vitamin D supplementation in fractured patient: how, when and why. Clin Cases Miner Bone Metab 6:120–124
Tanner SB, Harwell SA (2015) More than healthy bones: a review of vitamin D in muscle health. Ther Adv Musculoskelet Dis 7:152–159
Cummings SR, Browner WS, Bauer D, Stone K, Ensrud K, Jamal S, Ettinger B (1998) Endogenous hormones and the risk of hip and vertebral fractures among older women. Study of Osteoporotic Fractures Research Group. N Engl J Med 339:733–738
Garnero P, Munoz F, Sornay-Rendu E, Delmas PD (2007) Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study. Bone 40:716–722
Cauley JA, Lacroix AZ, Wu L et al (2008) Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Ann Intern Med 149:242–250
van Schoor NM, Visser M, Pluijm SM, Kuchuk N, Smit JH, Lips P (2008) Vitamin D deficiency as a risk factor for osteoporotic fractures. Bone 42:260–266
Cauley JA, Danielson ME, Boudreau R et al (2011) Serum 25-hydroxyvitamin D and clinical fracture risk in a multiethnic cohort of women: the Women’s Health Initiative (WHI). J Bone Miner Res 26:2378–2388
Chan R, Chan CC, Woo J, Ohlsson C, Mellstrom D, Kwok T, Leung PC (2011) Serum 25-hydroxyvitamin D, bone mineral density, and non-vertebral fracture risk in community-dwelling older men: results from Mr. Os, Hong Kong. Arch Osteoporos 6:21–30
Nakamura K, Saito T, Oyama M, Oshiki R, Kobayashi R, Nishiwaki T, Nashimoto M, Tsuchiya Y (2011) Vitamin D sufficiency is associated with low incidence of limb and vertebral fractures in community-dwelling elderly Japanese women: the Muramatsu Study. Osteoporos Int 22:97–103
Robinson-Cohen C, Katz R, Hoofnagle AN, Cauley JA, Furberg CD, Robbins JA, Chen Z, Siscovick DS, de Boer IH, Kestenbaum B (2011) Mineral metabolism markers and the long-term risk of hip fracture: the cardiovascular health study. J Clin Endocrinol Metab 96:2186–2193
Barbour KE, Houston DK, Cummings SR et al (2012) Calciotropic hormones and the risk of hip and nonspine fractures in older adults: the Health ABC Study. J Bone Miner Res 27:1177–1185
Holvik K, Ahmed LA, Forsmo S, Gjesdal CG, Grimnes G, Samuelsen SO, Schei B, Blomhoff R, Tell GS, Meyer HE (2013) Low serum levels of 25-hydroxyvitamin D predict hip fracture in the elderly: a NOREPOS study. J Clin Endocrinol Metab 98:3341–3350
Kauppi M, Impivaara O, Maki J, Heliovaara M, Jula A (2013) Quantitative ultrasound measurements and vitamin D status in the assessment of hip fracture risk in a nationally representative population sample. Osteoporos Int 24:2611–2618
Looker AC (2013) Serum 25-hydroxyvitamin D and risk of major osteoporotic fractures in older U.S. adults. J Bone Miner Res 28:997–1006
Bleicher K, Cumming RG, Naganathan V, Blyth FM, Le Couteur DG, Handelsman DJ, Waite LM, Seibel MJ (2014) U-shaped association between serum 25-hydroxyvitamin D and fracture risk in older men: results from the prospective population-based CHAMP study. J Bone Miner Res 29:2024–2031
Buchebner D, McGuigan F, Gerdhem P, Malm J, Ridderstrale M, Akesson K (2014) Vitamin D insufficiency over 5 years is associated with increased fracture risk—an observational cohort study of elderly women. Osteoporos Int 25:2767–2775
Steingrimsdottir L, Halldorsson TI, Siggeirsdottir K et al (2014) Hip fractures and bone mineral density in the elderly—importance of serum 25-hydroxyvitamin D. PLoS One 9:e91122
Tanaka S, Kuroda T, Yamazaki Y, Shiraki Y, Yoshimura N, Shiraki M (2014) Serum 25-hydroxyvitamin D below 25 ng/mL is a risk factor for long bone fracture comparable to bone mineral density in Japanese postmenopausal women. J Bone Miner Metab 32:514–523
Cauley JA, Greendale GA, Ruppert K, Lian Y, Randolph JF Jr, Lo JC, Burnett-Bowie SA, Finkelstein JS (2015) Serum 25 hydroxyvitamin D, bone mineral density and fracture risk across the menopause. J Clin Endocrinol Metab 100:2046–2054
Swanson CM, Srikanth P, Lee CG et al (2015) Associations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D with bone mineral density, bone mineral density change, and incident nonvertebral fracture. J Bone Miner Res 30:1403–1413
Takiar R, Lutsey PL, Zhao D, Guallar E, Schneider AL, Grams ME, Appel LJ, Selvin E, Michos ED (2015) The associations of 25-hydroxyvitamin D levels, vitamin D binding protein gene polymorphisms, and race with risk of incident fracture-related hospitalization: twenty-year follow-up in a bi-ethnic cohort (the ARIC Study). Bone 78:94–101
Lai JK, Lucas RM, Clements MS, Roddam AW, Banks E (2010) Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies. BMC Public Health 10:331
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535
Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605
Zhang J, Yu KF (1998) What's the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA 280:1690–1691
McNutt LA, Wu C, Xue X, Hafner JP (2003) Estimating the relative risk in cohort studies and clinical trials of common outcomes. Am J Epidemiol 157:940–943
Dong JY, Zhang YH, Tong J, Qin LQ (2012) Depression and risk of stroke: a meta-analysis of prospective studies. Stroke 43:32–37
Bonequi P, Meneses-Gonzalez F, Correa P, Rabkin CS, Camargo MC (2013) Risk factors for gastric cancer in Latin America: a meta-analysis. Cancer Causes Control 24:217–231
Dong JY, Zhang YH, Qin LQ (2011) Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies. J Am Coll Cardiol 58:1378–1385
Holick MF (2009) Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol 19:73–78
Holick MF (2006) High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 81:353–373
Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H (2009) Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk. Aliment Pharmacol Ther 30:113–125
Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H (2010) Meta-analysis: serum vitamin D and breast cancer risk. Eur J Cancer 46:2196–2205
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558
Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634
Begg CB (2002) A comparison of methods to detect publication bias in meta-analysis by P. Macaskill, S. D. Walter and L. Irwig, Statistics in Medicine, 2001; 20:641–654. Stat Med 21:1803; author reply 1804
Sutton AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR (2000) Empirical assessment of effect of publication bias on meta-analyses. BMJ 320:1574–1577
Sakuma M, Endo N, Oinuma T (2007) Serum 25-OHD insufficiency as a risk factor for hip fracture. J Bone Miner Metab 25:147–150
Ghose RR (2005) Vitamin D deficiency and muscle weakness in the elderly. N Z Med J 118:U1582
Azali P, Barbasso Helmers S, Kockum I, Olsson T, Alfredsson L, Charles PJ, Piehl Aulin K, Lundberg IE (2013) Low serum levels of vitamin D in idiopathic inflammatory myopathies. Ann Rheum Dis 72:512–516
Wijnia JW, Wielders JP, Lips P, van de Wiel A, Mulder CL, Nieuwenhuis KG (2013) Is vitamin D deficiency a confounder in alcoholic skeletal muscle myopathy? Alcohol Clin Exp Res 37(Suppl 1):E209–E215
Koeckhoven E, van der Leeden M, Roorda LD, van Schoor NM, Lips P, de Zwart A, Dekker J, van der Esch M, Lems WF (2016) The association between serum 25-hydroxy vitamin D level and upper leg strength in patients with knee osteoarthritis: results of the Amsterdam osteoarthritis cohort. J Rheumatol 43:1400–1405
Orces CH (2016) Prevalence of clinically relevant muscle weakness and its association with vitamin D status among older adults in Ecuador. Aging Clin Exp Res
Snijder MB, van Schoor NM, Pluijm SM, van Dam RM, Visser M, Lips P (2006) Vitamin D status in relation to one-year risk of recurrent falling in older men and women. J Clin Endocrinol Metab 91:2980–2985
Rothenbacher D, Klenk J, Denkinger MD et al (2014) Prospective evaluation of renal function, serum vitamin D level, and risk of fall and fracture in community-dwelling elderly subjects. Osteoporos Int 25:923–932
Olmos JM, Hernandez JL, Garcia-Velasco P, Martinez J, Llorca J, Gonzalez-Macias J (2016) Serum 25-hydroxyvitamin D, parathyroid hormone, calcium intake, and bone mineral density in Spanish adults. Osteoporos Int 27:105–113
Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B (2005) Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 293:2257–2264
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 169:551–561
Weaver CM, Alexander DD, Boushey CJ, Dawson-Hughes B, Lappe JM, LeBoff MS, Liu S, Looker AC, Wallace TC, Wang DD (2016) Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos Int 27:367–376
Eom CS, Lee HK, Ye S, Park SM, Cho KH (2012) Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis. J Bone Miner Res 27:1186–1195
Acknowledgements
None.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
None
Electronic supplementary material
Table S1
Exclusion articles during full-text articles assessment process. (DOC 62 kb)
Rights and permissions
About this article
Cite this article
Feng, Y., Cheng, G., Wang, H. et al. The associations between serum 25-hydroxyvitamin D level and the risk of total fracture and hip fracture. Osteoporos Int 28, 1641–1652 (2017). https://doi.org/10.1007/s00198-017-3955-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-017-3955-x