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Published in: Osteoporosis International 7/2013

01-07-2013 | Original Article

Non-linear relationship between serum 25-hydroxyvitamin D concentration and subsequent hip fracture

Authors: L. de Koning, D. Henne, B. R. Hemmelgarn, P. Woods, C. Naugler

Published in: Osteoporosis International | Issue 7/2013

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Abstract

Summary

Serum 25-OH vitamin D levels were compared in 254 hip fracture subjects and 2,402 matched control subjects. There was a significant inverse association between 25-OH vitamin D and hip fracture only between 0 and 70 nmol/L.

Introduction

Vitamin D is integral to bone metabolism, however the utility of serum 25-OH vitamin D as a risk marker for hip fractures is controversial.

Methods

We conducted a case–control study of patients admitted to the hospitals with hip fractures in Calgary, Alberta, (catchment population 1.4 million) between January 1, 2007 and August 31, 2011. We searched the laboratory information system of Calgary Laboratory Services for serum 25-OH vitamin D levels within 6 months prior to admission on patients admitted to hospital with hip fractures. Cases were identified through the Calgary Laboratory Services laboratory information system and were matched to controls for age, sex, and month of testing. The hip fracture–25-OH vitamin D association was examined using multiple linear and spline regression.

Results

Of 305 subjects initially identified with hip fractures, serum 25-OH vitamin D levels were available for 254 (83 %). These were matched to 2,402 control subjects. We observed a significant (p < 0.01) non-linear relationship such that 25-OH vitamin D was inversely associated with hip fracture only below 70 nmol/L (odds ratio = 0.81 per 10 nmol/L increase; 95 % CI 0.86–0.93).

Conclusions

The utility of 25-OH vitamin D level as a risk marker for hip fracture depends on the cut-off level used and was of potential use only for lower levels of 25-OH vitamin D.
Literature
2.
go back to reference Singh RJ (2008) Are clinical laboratories prepared for accurate testing of 25-hydroxy vitamin D? Clin Chem 54:221–223PubMedCrossRef Singh RJ (2008) Are clinical laboratories prepared for accurate testing of 25-hydroxy vitamin D? Clin Chem 54:221–223PubMedCrossRef
3.
go back to reference Bischoff-Ferrari HA, Can U, Staehelin HB, Platz A, Henschkowski J, Michel BA, Dawson-Hughes B, Theiler R (2008) Severe vitamin D deficiency in Swiss hip fracture patients. Bone 42:597–602PubMedCrossRef Bischoff-Ferrari HA, Can U, Staehelin HB, Platz A, Henschkowski J, Michel BA, Dawson-Hughes B, Theiler R (2008) Severe vitamin D deficiency in Swiss hip fracture patients. Bone 42:597–602PubMedCrossRef
4.
go back to reference Simonelli C, Weiss TW, Morancey J, Swanson L, Chen YT (2005) Prevalence of vitamin D inadequacy in a minimal trauma fracture population. Curr Med Res Opin 21:1069–1074PubMedCrossRef Simonelli C, Weiss TW, Morancey J, Swanson L, Chen YT (2005) Prevalence of vitamin D inadequacy in a minimal trauma fracture population. Curr Med Res Opin 21:1069–1074PubMedCrossRef
5.
go back to reference Khadgawat R, Brar KS, Gahlo M, Yadav CS, Malhotra R, Guptat N, Tandon N (2010) High prevalence of vitamin D deficiency in Asian-Indian patients with fragility hip fracture: a pilot study. J Assoc Physicians India 58:539–543PubMed Khadgawat R, Brar KS, Gahlo M, Yadav CS, Malhotra R, Guptat N, Tandon N (2010) High prevalence of vitamin D deficiency in Asian-Indian patients with fragility hip fracture: a pilot study. J Assoc Physicians India 58:539–543PubMed
6.
go back to reference Nurmi I, Kaukonen JP, Lüthje P, Naboulsi H, Tanninen S, Kataja M, Kallio ML, Leppilampi M (2005) Half of the patients with acute hip fracture suffer from hypovitaminosis D: a prospective study in southeastern Finland. Osteoporois Int 16:2018–2024CrossRef Nurmi I, Kaukonen JP, Lüthje P, Naboulsi H, Tanninen S, Kataja M, Kallio ML, Leppilampi M (2005) Half of the patients with acute hip fracture suffer from hypovitaminosis D: a prospective study in southeastern Finland. Osteoporois Int 16:2018–2024CrossRef
7.
go back to reference Cauley JA, Parimi N, Ensrud KE, Bauer DC, Cawthon PM, Cummings SR, Hoffman AR, Shikany JM, Barrett-Connor E, Orwoll E, Osteoporotic Fractures in Men (MrOS) Research Group (2010) Serum 25 hydroxyvitamin D concentrations and the risk of hip and nonspine fractures in older men. J Bone Miner Res 25:545–553PubMedCrossRef Cauley JA, Parimi N, Ensrud KE, Bauer DC, Cawthon PM, Cummings SR, Hoffman AR, Shikany JM, Barrett-Connor E, Orwoll E, Osteoporotic Fractures in Men (MrOS) Research Group (2010) Serum 25 hydroxyvitamin D concentrations and the risk of hip and nonspine fractures in older men. J Bone Miner Res 25:545–553PubMedCrossRef
8.
go back to reference Looker AC, Mussolino ME (2008) Serum 25 hydroxyvitamin D and hip fracture risk in older US white adults. J Bone Miner Res 23:143–150PubMedCrossRef Looker AC, Mussolino ME (2008) Serum 25 hydroxyvitamin D and hip fracture risk in older US white adults. J Bone Miner Res 23:143–150PubMedCrossRef
9.
go back to reference Bakhtiyarova S, Lesnyak O, Kyznesova N, Blankenstein MA, Lips P (2006) Vitamin D status among patients with hip fracture and elderly control subjects in Yekaterinburg, Russia. Osteoporosis Int 17:441–446CrossRef Bakhtiyarova S, Lesnyak O, Kyznesova N, Blankenstein MA, Lips P (2006) Vitamin D status among patients with hip fracture and elderly control subjects in Yekaterinburg, Russia. Osteoporosis Int 17:441–446CrossRef
10.
go back to reference Moniz C, Dew T, Dixon T (2005) Prevalence of vitamin D inadequacy in osteoporotic hip fracture patients in London. Curr Med Res Opin 21:1891–1894PubMedCrossRef Moniz C, Dew T, Dixon T (2005) Prevalence of vitamin D inadequacy in osteoporotic hip fracture patients in London. Curr Med Res Opin 21:1891–1894PubMedCrossRef
11.
go back to reference Sakuma M, Endo N, Oinuma T, Hayami T, Endo E, Yazawa T, Watanabe K, Watanabe S (2006) Vitamin D and intact PTH status in patients with hip fracture. Osteoporosis Int 17:1608–1614CrossRef Sakuma M, Endo N, Oinuma T, Hayami T, Endo E, Yazawa T, Watanabe K, Watanabe S (2006) Vitamin D and intact PTH status in patients with hip fracture. Osteoporosis Int 17:1608–1614CrossRef
12.
go back to reference Jang WY, Chung MS, Baek GH, Song CH, Cho HE, Gong HS (2012) Vitamin D levels in post-menopausal Korean women with a distal radius fracture. Injury 43:237–241PubMedCrossRef Jang WY, Chung MS, Baek GH, Song CH, Cho HE, Gong HS (2012) Vitamin D levels in post-menopausal Korean women with a distal radius fracture. Injury 43:237–241PubMedCrossRef
13.
go back to reference Weatherall M (2000) A meta-analysis of 25 hydroxyvitamin D in older people with fracture of the proximal femur. N Z Med J 113:137–140PubMed Weatherall M (2000) A meta-analysis of 25 hydroxyvitamin D in older people with fracture of the proximal femur. N Z Med J 113:137–140PubMed
14.
go back to reference Nuti R, Martini G, Valenti R, Gambera D, Gennari L, Salvadori S, Avanzati A (2004) Vitamin D status and bone turnover in women with acute hip fracture. Clin Orthop Relat Res 422:208–213PubMedCrossRef Nuti R, Martini G, Valenti R, Gambera D, Gennari L, Salvadori S, Avanzati A (2004) Vitamin D status and bone turnover in women with acute hip fracture. Clin Orthop Relat Res 422:208–213PubMedCrossRef
15.
go back to reference Cauley JA, Lacroix AZ, Wu L, Horwitz M, Danielson ME, Bauer DC, Lee JS, Jackson RD, Robbins JA, Wu C, Stanczyk FZ, LeBoff MS, Wactawski-Wende J, Sarto G, Ockene J, Cummings SR (2008) Serum 25 hydroxyvitamin D concentrations and the risk of hip fractures. Ann Intern Med 149:242–250PubMedCrossRef Cauley JA, Lacroix AZ, Wu L, Horwitz M, Danielson ME, Bauer DC, Lee JS, Jackson RD, Robbins JA, Wu C, Stanczyk FZ, LeBoff MS, Wactawski-Wende J, Sarto G, Ockene J, Cummings SR (2008) Serum 25 hydroxyvitamin D concentrations and the risk of hip fractures. Ann Intern Med 149:242–250PubMedCrossRef
16.
go back to reference Cauley JA, Danielson ME, Boudreau R, Barbour KE, Horwitz MJ, Bauer DC, Ensrud KE, Manson JE, Wactawski-Wende J, Shikany JM, Jackson RD (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 26:2378–2388PubMedCrossRef Cauley JA, Danielson ME, Boudreau R, Barbour KE, Horwitz MJ, Bauer DC, Ensrud KE, Manson JE, Wactawski-Wende J, Shikany JM, Jackson RD (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 26:2378–2388PubMedCrossRef
17.
go back to reference Porthouse J, Cockayne S, King C, Saxon L, Steele E, Aspray T, Baverstock M, Birks Y, Dumville J, Francis R, Iglesias C, Puffer S, Sutcliffe A, Watt I, Torgerson DJ (2005) Randomized controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 330:1003PubMedCrossRef Porthouse J, Cockayne S, King C, Saxon L, Steele E, Aspray T, Baverstock M, Birks Y, Dumville J, Francis R, Iglesias C, Puffer S, Sutcliffe A, Watt I, Torgerson DJ (2005) Randomized controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 330:1003PubMedCrossRef
18.
go back to reference Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SA, Black HR, Blanchette P, Bonds DE, Brunner RL, Brzyski RG, Caan B, Cauley JA, Chlebowski RT, Cummings SR, Granek I, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Johnson KC, Judd H, Kotchen JM, Kuller LH, Langer RD, Lasser NL, Limacher MC, Ludlam S, Manson JE, Margolis KL, McGowan J, Ockene JK, O’Sullivan MJ, Phillips L, Prentice RL, Sarto GE, Stefanick ML, Van Horn L, Wactawski-Wende J, Whitlock E, Anderson GL, Assaf AR, Barad D, Investigators W’s H I (2006) Calcium plus vitamin D supplementation and the risks of fractures. N Engl J Med 354:669–683PubMedCrossRef Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SA, Black HR, Blanchette P, Bonds DE, Brunner RL, Brzyski RG, Caan B, Cauley JA, Chlebowski RT, Cummings SR, Granek I, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Johnson KC, Judd H, Kotchen JM, Kuller LH, Langer RD, Lasser NL, Limacher MC, Ludlam S, Manson JE, Margolis KL, McGowan J, Ockene JK, O’Sullivan MJ, Phillips L, Prentice RL, Sarto GE, Stefanick ML, Van Horn L, Wactawski-Wende J, Whitlock E, Anderson GL, Assaf AR, Barad D, Investigators W’s H I (2006) Calcium plus vitamin D supplementation and the risks of fractures. N Engl J Med 354:669–683PubMedCrossRef
19.
go back to reference Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, Anderson FH, Cooper C, Francis RM, Donaldson C, Gillespie WJ, Robinson CM, Torgerson DJ, Wallace WA, RECORD Trial Group (2005) Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomized placebo-controlled trial. Lancet 365:1621–2628PubMedCrossRef Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, Anderson FH, Cooper C, Francis RM, Donaldson C, Gillespie WJ, Robinson CM, Torgerson DJ, Wallace WA, RECORD Trial Group (2005) Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomized placebo-controlled trial. Lancet 365:1621–2628PubMedCrossRef
20.
go back to reference DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group (2010) Patient level pooled analysis of 68,500 patients from seven major vitamin D fracture trials in US and Europe. BMJ 340:b5463CrossRef DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group (2010) Patient level pooled analysis of 68,500 patients from seven major vitamin D fracture trials in US and Europe. BMJ 340:b5463CrossRef
21.
go back to reference Sanders KM, Pasco JA, Ugoni AM, Nicholson GC, Seeman E, Martin TJ, Skoric B, Panahi S, Kotowicz MA (1998) The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community: the Geelong Osteoporosis Study. J Bone Miner Res 13:1337–1342PubMedCrossRef Sanders KM, Pasco JA, Ugoni AM, Nicholson GC, Seeman E, Martin TJ, Skoric B, Panahi S, Kotowicz MA (1998) The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community: the Geelong Osteoporosis Study. J Bone Miner Res 13:1337–1342PubMedCrossRef
22.
go back to reference Lips P, Bouillon R, Jongen MJ, van Ginkel FC, van der Vijgh WJ, Netelenbos JC (1985) The effect of trauma on serum concentrations of vitamin D metabolites in patients with hip fracture. Bone 6:63–67PubMedCrossRef Lips P, Bouillon R, Jongen MJ, van Ginkel FC, van der Vijgh WJ, Netelenbos JC (1985) The effect of trauma on serum concentrations of vitamin D metabolites in patients with hip fracture. Bone 6:63–67PubMedCrossRef
23.
go back to reference Mak JCS, Stuart-Harris J, Cameron ID, Mason RS (2010) Oral vitamin D replacement after hip fracture: a comparative review. J Am Geriatr Soc 58:382–417PubMedCrossRef Mak JCS, Stuart-Harris J, Cameron ID, Mason RS (2010) Oral vitamin D replacement after hip fracture: a comparative review. J Am Geriatr Soc 58:382–417PubMedCrossRef
24.
go back to reference Lüthje P, Nurmi-Lüthje I, Kaukonen JP, Kuurne S, Naboulsi H, Kataja M (2009) Undertreatment of osteoporosis following hip fracture in the elderly. Arch Gerontol Geriatr 49:153–157PubMedCrossRef Lüthje P, Nurmi-Lüthje I, Kaukonen JP, Kuurne S, Naboulsi H, Kataja M (2009) Undertreatment of osteoporosis following hip fracture in the elderly. Arch Gerontol Geriatr 49:153–157PubMedCrossRef
25.
go back to reference Byszewski AM, Cranney A, Man-Son-Hing M, Azad N, Amos S (2006) Evaluation of in-hospital management of fracture risk in older patients: a chart review study of tertiary prevention. Arch Gerontol Geriatr 42:319–328PubMedCrossRef Byszewski AM, Cranney A, Man-Son-Hing M, Azad N, Amos S (2006) Evaluation of in-hospital management of fracture risk in older patients: a chart review study of tertiary prevention. Arch Gerontol Geriatr 42:319–328PubMedCrossRef
26.
go back to reference Carnevale V, Nieddu L, Romagnoli E, Bona E, Piemonte S, Scillitani A, Minisola S (2006) Osteoporosis intervention in ambulatory patients with previous hip fracture: a multicentric, nationwide Italian study. Osteoporosis Int 17:478–483CrossRef Carnevale V, Nieddu L, Romagnoli E, Bona E, Piemonte S, Scillitani A, Minisola S (2006) Osteoporosis intervention in ambulatory patients with previous hip fracture: a multicentric, nationwide Italian study. Osteoporosis Int 17:478–483CrossRef
27.
go back to reference Jennings LA, Auerbach AD, Maselli J, Pekow PS, Lindenauer PK, Lee SJ (2010) Missed opportunities for osteoporosis treatment in patients hospitalized for hip fracture. J Am Geriatr Soc 58:650–657PubMedCrossRef Jennings LA, Auerbach AD, Maselli J, Pekow PS, Lindenauer PK, Lee SJ (2010) Missed opportunities for osteoporosis treatment in patients hospitalized for hip fracture. J Am Geriatr Soc 58:650–657PubMedCrossRef
28.
go back to reference Harrington JT, Broy SB, Derosa AM, Licata AA, Shewmon DA (2002) Hip fracture patients are not treated for osteoporosis: a call to action. Arthritis Rheum 47:651–654PubMedCrossRef Harrington JT, Broy SB, Derosa AM, Licata AA, Shewmon DA (2002) Hip fracture patients are not treated for osteoporosis: a call to action. Arthritis Rheum 47:651–654PubMedCrossRef
29.
go back to reference Giusti A, Barone A, Razzano M, Oliveri M, Pizzonia M, Palummeri E, Pioli G (2009) Persistence with calcium and vitamin D in elderly patients after hip fracture. J Bone Miner Metab 27:95–100PubMedCrossRef Giusti A, Barone A, Razzano M, Oliveri M, Pizzonia M, Palummeri E, Pioli G (2009) Persistence with calcium and vitamin D in elderly patients after hip fracture. J Bone Miner Metab 27:95–100PubMedCrossRef
30.
go back to reference Segal E, Zinman C, Raz B, Ish-Shalom S (2009) Low patient compliance—a major negative factor in elderly hip fracture patients supplemented with 800 IU of vitamin D3 daily. Arch Gerontol Geriatr 49:364–367PubMedCrossRef Segal E, Zinman C, Raz B, Ish-Shalom S (2009) Low patient compliance—a major negative factor in elderly hip fracture patients supplemented with 800 IU of vitamin D3 daily. Arch Gerontol Geriatr 49:364–367PubMedCrossRef
31.
go back to reference Hanley DA, Cranney A, Jones G, Whiting SJ, Leslie WD, Cole DE, Atkinson SA, Josse RG, Feldman S, Kline GA, Rosen C, Guidelines Committee of the Scientific Advisory Council of Osteoporosis Canada (2010) Vitamin D in adult health and disease: a review and guideline statement from Osteoporosis Canada. CMAJ 182:E610–E618PubMedCrossRef Hanley DA, Cranney A, Jones G, Whiting SJ, Leslie WD, Cole DE, Atkinson SA, Josse RG, Feldman S, Kline GA, Rosen C, Guidelines Committee of the Scientific Advisory Council of Osteoporosis Canada (2010) Vitamin D in adult health and disease: a review and guideline statement from Osteoporosis Canada. CMAJ 182:E610–E618PubMedCrossRef
32.
go back to reference Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson JE, Murad MH, Kovacs CS (2012) The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev 33:456–492PubMedCrossRef Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson JE, Murad MH, Kovacs CS (2012) The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev 33:456–492PubMedCrossRef
Metadata
Title
Non-linear relationship between serum 25-hydroxyvitamin D concentration and subsequent hip fracture
Authors
L. de Koning
D. Henne
B. R. Hemmelgarn
P. Woods
C. Naugler
Publication date
01-07-2013
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 7/2013
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-012-2249-6

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