Skip to main content
Top
Published in: Osteoporosis International 2/2016

01-02-2016 | Original Article

Association of 25-hydroxyvitamin D with areal and volumetric measures of bone mineral density and parathyroid hormone: impact of vitamin D-binding protein and its assays

Authors: T. O. Jemielita, M. B. Leonard, J. Baker, S. Sayed, B. S. Zemel, J. Shults, R. Herskovitz, M. R. Denburg

Published in: Osteoporosis International | Issue 2/2016

Login to get access

Abstract

Summary

A comparison of the association of different forms of 25-hydroxyvitamin D [25(OH)D] with parathyroid hormone (PTH) and with areal and volumetric bone mineral density (BMD) demonstrated that bioavailable and free 25(OH)D do not provide a better index of vitamin D status in terms of bone health compared to total 25(OH)D.

Introduction

This study aims to compare measures of vitamin D-binding protein (DBP) using a monoclonal versus polyclonal ELISA and assess correlations of total versus estimated free and bioavailable 25(OH)D with BMD and PTH concentrations.

Methods

DXA and peripheral quantitative CT (pQCT) scans were obtained in 304 adults (158 black, 146 white), ages 21–80 years. Free and bioavailable 25(OH)D were calculated from total 25(OH)D, DBP, and albumin concentrations. Multivariable linear regression with standardized beta coefficients was used to evaluate associations of bone measures and PTH with total, free, and bioavailable 25(OH)D.

Results

Measures of DBP obtained using a monoclonal versus polyclonal ELISA were not correlated (r s = 0.02, p = 0.76). Free and bioavailable 25(OH)D based on the polyclonal assay were lower in black versus white participants (p < 0.0001); this race difference was not evident using the monoclonal assay. Adjusted for age, sex, calcium intake, and race, all forms of 25(OH)D were negatively associated with PTH, but the absolute coefficient was greatest for total 25(OH)D (−0.34, p < 0.001) versus free/bioavailable 25(OH)D (−0.18/−0.24 depending on DBP assay, p ≤ 0.003). In analyses stratified on race, none of the measures of 25(OH)D were associated with BMD across DXA and pQCT sites.

Conclusions

The monoclonal versus polyclonal ELISA yielded highly discrepant measures of DBP, particularly among black individuals, likely related to established race differences in DBP polymorphisms. Contrary to prior studies, our findings indicate that using DBP to estimate bioavailable and free 25(OH)D does not provide a better index of vitamin D status in terms of bone health.
Literature
2.
3.
go back to reference Valimaki VV, Alfthan H, Lehmuskallio E, Loyttyniemi E, Sahi T, Stenman UH, Suominen H, Valimaki MJ (2004) Vitamin D status as a determinant of peak bone mass in young Finnish men. J Clin Endocrinol Metab 89(1):76–80CrossRefPubMed Valimaki VV, Alfthan H, Lehmuskallio E, Loyttyniemi E, Sahi T, Stenman UH, Suominen H, Valimaki MJ (2004) Vitamin D status as a determinant of peak bone mass in young Finnish men. J Clin Endocrinol Metab 89(1):76–80CrossRefPubMed
4.
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 risk for hip fractures. Ann Intern Med 149(4):242–250PubMedCentralCrossRefPubMed 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 risk for hip fractures. Ann Intern Med 149(4):242–250PubMedCentralCrossRefPubMed
5.
go back to reference Gerdhem P, Ringsberg KA, Obrant KJ, Akesson K (2005) Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Osteoporos Int 16(11):1425–1431. doi:10.1007/s00198-005-1860-1 CrossRefPubMed Gerdhem P, Ringsberg KA, Obrant KJ, Akesson K (2005) Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Osteoporos Int 16(11):1425–1431. doi:10.​1007/​s00198-005-1860-1 CrossRefPubMed
6.
go back to reference Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, Lyons RA, Flicker L, Wark J, Jackson RD, Cauley JA, Meyer HE, Pfeifer M, Sanders KM, Stahelin HB, Theiler R, Dawson-Hughes B (2012) A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med 367(1):40–49. doi:10.1056/NEJMoa1109617 CrossRefPubMed Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, Lyons RA, Flicker L, Wark J, Jackson RD, Cauley JA, Meyer HE, Pfeifer M, Sanders KM, Stahelin HB, Theiler R, Dawson-Hughes B (2012) A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med 367(1):40–49. doi:10.​1056/​NEJMoa1109617 CrossRefPubMed
7.
8.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
10.
go back to reference Prentice RL, Pettinger MB, Jackson RD, Wactawski-Wende J, Lacroix AZ, Anderson GL, Chlebowski RT, Manson JE, Van Horn L, Vitolins MZ, Datta M, LeBlanc ES, Cauley JA, Rossouw JE (2013) Health risks and benefits from calcium and vitamin D supplementation: Women’s Health Initiative clinical trial and cohort study. Osteoporos Int 24(2):567–580. doi:10.1007/s00198-012-2224-2 PubMedCentralCrossRefPubMed Prentice RL, Pettinger MB, Jackson RD, Wactawski-Wende J, Lacroix AZ, Anderson GL, Chlebowski RT, Manson JE, Van Horn L, Vitolins MZ, Datta M, LeBlanc ES, Cauley JA, Rossouw JE (2013) Health risks and benefits from calcium and vitamin D supplementation: Women’s Health Initiative clinical trial and cohort study. Osteoporos Int 24(2):567–580. doi:10.​1007/​s00198-012-2224-2 PubMedCentralCrossRefPubMed
12.
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, Women’s Health Initiative I (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354(7):669–683. doi:10.1056/NEJMoa055218 CrossRefPubMed 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, Women’s Health Initiative I (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354(7):669–683. doi:10.​1056/​NEJMoa055218 CrossRefPubMed
16.
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, Group RT (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 randomised placebo-controlled trial. Lancet 365(9471):1621–1628. doi:10.1016/S0140-6736(05)63013-9 CrossRefPubMed 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, Group RT (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 randomised placebo-controlled trial. Lancet 365(9471):1621–1628. doi:10.​1016/​S0140-6736(05)63013-9 CrossRefPubMed
17.
go back to reference Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC (2010) Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 303(18):1815–1822. doi:10.1001/jama.2010.594 CrossRefPubMed Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC (2010) Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 303(18):1815–1822. doi:10.​1001/​jama.​2010.​594 CrossRefPubMed
18.
19.
20.
go back to reference Barrett-Connor E, Siris ES, Wehren LE, Miller PD, Abbott TA, Berger ML, Santora AC, Sherwood LM (2005) Osteoporosis and fracture risk in women of different ethnic groups. J Bone Miner Res 20(2):185–194. doi:10.1359/JBMR.041007 CrossRefPubMed Barrett-Connor E, Siris ES, Wehren LE, Miller PD, Abbott TA, Berger ML, Santora AC, Sherwood LM (2005) Osteoporosis and fracture risk in women of different ethnic groups. J Bone Miner Res 20(2):185–194. doi:10.​1359/​JBMR.​041007 CrossRefPubMed
22.
go back to reference Fang J, Freeman R, Jeganathan R, Alderman MH (2004) Variations in hip fracture hospitalization rates among different race/ethnicity groups in New York City. Ethn Dis 14(2):280–284PubMed Fang J, Freeman R, Jeganathan R, Alderman MH (2004) Variations in hip fracture hospitalization rates among different race/ethnicity groups in New York City. Ethn Dis 14(2):280–284PubMed
23.
go back to reference Finkelstein JS, Lee ML, Sowers M, Ettinger B, Neer RM, Kelsey JL, Cauley JA, Huang MH, Greendale GA (2002) Ethnic variation in bone density in premenopausal and early perimenopausal women: effects of anthropometric and lifestyle factors. J Clin Endocrinol Metab 87(7):3057–3067CrossRefPubMed Finkelstein JS, Lee ML, Sowers M, Ettinger B, Neer RM, Kelsey JL, Cauley JA, Huang MH, Greendale GA (2002) Ethnic variation in bone density in premenopausal and early perimenopausal women: effects of anthropometric and lifestyle factors. J Clin Endocrinol Metab 87(7):3057–3067CrossRefPubMed
24.
go back to reference Greendale GA, Sowers M, Han W, Huang MH, Finkelstein JS, Crandall CJ, Lee JS, Karlamangla AS (2012) Bone mineral density loss in relation to the final menstrual period in a multiethnic cohort: results from the Study of Women’s Health Across the Nation (SWAN). J Bone Miner Res 27(1):111–118. doi:10.1002/jbmr.534 PubMedCentralCrossRefPubMed Greendale GA, Sowers M, Han W, Huang MH, Finkelstein JS, Crandall CJ, Lee JS, Karlamangla AS (2012) Bone mineral density loss in relation to the final menstrual period in a multiethnic cohort: results from the Study of Women’s Health Across the Nation (SWAN). J Bone Miner Res 27(1):111–118. doi:10.​1002/​jbmr.​534 PubMedCentralCrossRefPubMed
25.
go back to reference Harris SS, Soteriades E, Coolidge JA, Mudgal S, Dawson-Hughes B (2000) Vitamin D insufficiency and hyperparathyroidism in a low income, multiracial, elderly population. J Clin Endocrinol Metab 85(11):4125–4130PubMed Harris SS, Soteriades E, Coolidge JA, Mudgal S, Dawson-Hughes B (2000) Vitamin D insufficiency and hyperparathyroidism in a low income, multiracial, elderly population. J Clin Endocrinol Metab 85(11):4125–4130PubMed
26.
go back to reference Nesby-O’Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, Allen C, Doughertly C, Gunter EW, Bowman BA (2002) Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr 76(1):187–192PubMed Nesby-O’Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, Allen C, Doughertly C, Gunter EW, Bowman BA (2002) Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr 76(1):187–192PubMed
27.
28.
go back to reference Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG (1986) Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab 63(4):954–959CrossRefPubMed Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG (1986) Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab 63(4):954–959CrossRefPubMed
29.
go back to reference Bikle DD, Siiteri PK, Ryzen E, Haddad JG (1985) Serum protein binding of 1,25-dihydroxyvitamin D: a reevaluation by direct measurement of free metabolite levels. J Clin Endocrinol Metab 61(5):969–975CrossRefPubMed Bikle DD, Siiteri PK, Ryzen E, Haddad JG (1985) Serum protein binding of 1,25-dihydroxyvitamin D: a reevaluation by direct measurement of free metabolite levels. J Clin Endocrinol Metab 61(5):969–975CrossRefPubMed
30.
go back to reference Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I (2011) Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 26(7):1609–1616. doi:10.1002/jbmr.387 PubMedCentralCrossRefPubMed Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I (2011) Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 26(7):1609–1616. doi:10.​1002/​jbmr.​387 PubMedCentralCrossRefPubMed
31.
go back to reference White P, Cooke N (2000) The multifunctional properties and characteristics of vitamin D-binding protein. Trends Endocrinol Metab 11(8):320–327CrossRefPubMed White P, Cooke N (2000) The multifunctional properties and characteristics of vitamin D-binding protein. Trends Endocrinol Metab 11(8):320–327CrossRefPubMed
32.
go back to reference Arnaud J, Constans J (1993) Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP). Hum Genet 92(2):183–188CrossRefPubMed Arnaud J, Constans J (1993) Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP). Hum Genet 92(2):183–188CrossRefPubMed
33.
34.
go back to reference Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, Tamez H, Zhang D, Bhan I, Karumanchi SA, Powe NR, Thadhani R (2013) Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med 369(21):1991–2000. doi:10.1056/NEJMoa1306357 PubMedCentralCrossRefPubMed Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, Tamez H, Zhang D, Bhan I, Karumanchi SA, Powe NR, Thadhani R (2013) Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med 369(21):1991–2000. doi:10.​1056/​NEJMoa1306357 PubMedCentralCrossRefPubMed
35.
go back to reference Bikle DD, Gee E (1989) Free, and not total, 1,25-dihydroxyvitamin D regulates 25-hydroxyvitamin D metabolism by keratinocytes. Endocrinology 124(2):649–654CrossRefPubMed Bikle DD, Gee E (1989) Free, and not total, 1,25-dihydroxyvitamin D regulates 25-hydroxyvitamin D metabolism by keratinocytes. Endocrinology 124(2):649–654CrossRefPubMed
36.
go back to reference Chun RF, Lauridsen AL, Suon L, Zella LA, Pike JW, Modlin RL, Martineau AR, Wilkinson RJ, Adams J, Hewison M (2010) Vitamin D-binding protein directs monocyte responses to 25-hydroxy- and 1,25-dihydroxyvitamin D. J Clin Endocrinol Metab 95(7):3368–3376. doi:10.1210/jc.2010-0195 PubMedCentralCrossRefPubMed Chun RF, Lauridsen AL, Suon L, Zella LA, Pike JW, Modlin RL, Martineau AR, Wilkinson RJ, Adams J, Hewison M (2010) Vitamin D-binding protein directs monocyte responses to 25-hydroxy- and 1,25-dihydroxyvitamin D. J Clin Endocrinol Metab 95(7):3368–3376. doi:10.​1210/​jc.​2010-0195 PubMedCentralCrossRefPubMed
41.
go back to reference Leonard MB, Elmi A, Mostoufi-Moab S, Shults J, Burnham JM, Thayu M, Kibe L, Wetzsteon RJ, Zemel BS (2010) Effects of sex, race, and puberty on cortical bone and the functional muscle bone unit in children, adolescents, and young adults. J Clin Endocrinol Metabol 95(4):1681–1689. doi:10.1210/jc.2009-1913 CrossRef Leonard MB, Elmi A, Mostoufi-Moab S, Shults J, Burnham JM, Thayu M, Kibe L, Wetzsteon RJ, Zemel BS (2010) Effects of sex, race, and puberty on cortical bone and the functional muscle bone unit in children, adolescents, and young adults. J Clin Endocrinol Metabol 95(4):1681–1689. doi:10.​1210/​jc.​2009-1913 CrossRef
42.
go back to reference Subar AF, Thompson FE, Kipnis V, Midthune D, Hurwitz P, McNutt S, McIntosh A, Rosenfeld S (2001) Comparative validation of the Block, Willett, and National Cancer Institute food frequency questionnaires: the Eating at America’s Table Study. Am J Epidemiol 154(12):1089–1099CrossRefPubMed Subar AF, Thompson FE, Kipnis V, Midthune D, Hurwitz P, McNutt S, McIntosh A, Rosenfeld S (2001) Comparative validation of the Block, Willett, and National Cancer Institute food frequency questionnaires: the Eating at America’s Table Study. Am J Epidemiol 154(12):1089–1099CrossRefPubMed
43.
go back to reference Hollis BW (1997) Quantitation of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D by radioimmunoassay using radioiodinated tracers. Methods Enzymol 282:174–186CrossRefPubMed Hollis BW (1997) Quantitation of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D by radioimmunoassay using radioiodinated tracers. Methods Enzymol 282:174–186CrossRefPubMed
44.
go back to reference Clive DR, Sudhaker D, Giacherio D, Gupta M, Schreiber MJ, Sackrison JL, MacFarlane GD (2002) Analytical and clinical validation of a radioimmunoassay for the measurement of 1,25 dihydroxy vitamin D. Clin Biochem 35(7):517–521CrossRefPubMed Clive DR, Sudhaker D, Giacherio D, Gupta M, Schreiber MJ, Sackrison JL, MacFarlane GD (2002) Analytical and clinical validation of a radioimmunoassay for the measurement of 1,25 dihydroxy vitamin D. Clin Biochem 35(7):517–521CrossRefPubMed
45.
go back to reference Gao P, Scheibel S, D’Amour P, John MR, Rao SD, Schmidt-Gayk H, Cantor TL (2001) Development of a novel immunoradiometric assay exclusively for biologically active whole parathyroid hormone 1–84: implications for improvement of accurate assessment of parathyroid function. J Bone Miner Res 16(4):605–614. doi:10.1359/jbmr.2001.16.4.605 CrossRefPubMed Gao P, Scheibel S, D’Amour P, John MR, Rao SD, Schmidt-Gayk H, Cantor TL (2001) Development of a novel immunoradiometric assay exclusively for biologically active whole parathyroid hormone 1–84: implications for improvement of accurate assessment of parathyroid function. J Bone Miner Res 16(4):605–614. doi:10.​1359/​jbmr.​2001.​16.​4.​605 CrossRefPubMed
46.
go back to reference Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium (2011) Dietary reference intakes for calcium and vitamin D. In: Ross AC, Taylor CL, Yaktine AL, Del Valle HB (eds) National Academies Press, Washington DC Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium (2011) Dietary reference intakes for calcium and vitamin D. In: Ross AC, Taylor CL, Yaktine AL, Del Valle HB (eds) National Academies Press, Washington DC
50.
go back to reference M’Buyamba-Kabangu JR, Fagard R, Lijnen P, Bouillon R, Lissens W, Amery A (1987) Calcium, vitamin D-endocrine system, and parathyroid hormone in black and white males. Calcif Tissue Int 41(2):70–74CrossRefPubMed M’Buyamba-Kabangu JR, Fagard R, Lijnen P, Bouillon R, Lissens W, Amery A (1987) Calcium, vitamin D-endocrine system, and parathyroid hormone in black and white males. Calcif Tissue Int 41(2):70–74CrossRefPubMed
52.
Metadata
Title
Association of 25-hydroxyvitamin D with areal and volumetric measures of bone mineral density and parathyroid hormone: impact of vitamin D-binding protein and its assays
Authors
T. O. Jemielita
M. B. Leonard
J. Baker
S. Sayed
B. S. Zemel
J. Shults
R. Herskovitz
M. R. Denburg
Publication date
01-02-2016
Publisher
Springer London
Published in
Osteoporosis International / Issue 2/2016
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-015-3296-6

Other articles of this Issue 2/2016

Osteoporosis International 2/2016 Go to the issue