The Vitamin D Metabolite Ratio (VMR) As a Predictor of Functional Biomarkers of Bone Health

Overview

Journal Clin Endocrinol (Oxf)

Specialty Endocrinology

Date 2017 Mar 3

PMID 28251655

Citations 8

Authors

John Aloia

Melissa Fazzari

Albert Shieh

Ruban Dhaliwal

Mageda Mikhail

Andrew N Hoofnagle

Lou Ragolia

Affiliations

Soon will be listed here.

Abstract

Context: The vitamin D metabolite ratio (VMR) (serum 24,25(OH) D /25(OH)D ) has been proposed as a biomarker of vitamin D sufficiency to replace serum 25(OH)D.

Objective: To examine the relationships of 24,25(OH) D and VMR to functional biomarkers of bone health following vitamin D supplementation.

Setting: An ambulatory research centre.

Design: Serum from a previous research study of dose response of PTH, calcium absorption and bone turnover to vitamin D supplementation was analysed for vitamin D metabolites (25(OH)D, 24,25(OH) D ).

Outcome: The relationship of serum 24,25(OH) D and VMR to calcium absorption, PTH and bone turnover markers was examined.

Results: Although there were strong correlations of serum 25(OH)D with 24,25(OH) D and free 25(OH)D, its correlation with VMR was lower. After vitamin D supplementation, the change in 25(OH)D, 24,25(OH) D and VMR was associated with the change in calcium absorption, PTH and CTX. The correlation of the change in PTH with the change in metabolites was the lowest for VMR. Moreover, estimated dose response for standardized values of vitamin D metabolites showed a beta-coefficient for VMR that was significantly less in magnitude compared to other metabolites.

Conclusion: Serum 24,25(OH) D is closely associated with the dose response of serum 25(OH)D to vitamin D supplementation. However, the VMR does not appear to be equivalent to either of these metabolites in its response to increasing vitamin D intake or its association with PTH. It is unlikely that VMR will replace 25(OH)D as a biomarker for vitamin D sufficiency.

Citing Articles

Short-Term Effects of Escalating Doses of Cholecalciferol on FGF23 and 24,25(OH) Vitamin D Levels: A Preliminary Investigation.

Pepe J, Colangelo L, Pilotto R, De Martino V, Ferrara C, Scillitani A Nutrients. 2024; 16(21).

PMID: 39519433 PMC: 11547203. DOI: 10.3390/nu16213600.

Investigation of the Vitamin D Metabolite Ratio (VMR) as a Marker of Functional Vitamin D Deficiency: Findings from the SarcoPhAge Cohort.

Ladang A, Gendebien A, Kovacs S, Demonceau C, Beaudart C, Peeters S Nutrients. 2024; 16(19).

PMID: 39408192 PMC: 11478400. DOI: 10.3390/nu16193224.

Vitamin D Metabolites in Nonmetastatic High-Risk Prostate Cancer Patients with and without Zoledronic Acid Treatment after Prostatectomy.

Stephan C, Ralla B, Bonn F, Diesner M, Lein M, Jung K Cancers (Basel). 2022; 14(6).

PMID: 35326710 PMC: 8946001. DOI: 10.3390/cancers14061560.

Vitamin D Metabolites: Analytical Challenges and Clinical Relevance.

Alonso N, Zelzer S, Eibinger G, Herrmann M Calcif Tissue Int. 2022; 112(2):158-177.

PMID: 35238975 PMC: 8892115. DOI: 10.1007/s00223-022-00961-5.

Factors Associated with Serum Vitamin D Metabolites and Vitamin D Metabolite Ratios in Premenopausal Women.

Toribio M, Priego-Capote F, Perez-Gomez B, Fernandez de Larrea-Baz N, Ruiz-Moreno E, Castello A Nutrients. 2021; 13(11).

PMID: 34836003 PMC: 8621214. DOI: 10.3390/nu13113747.

References

Hoofnagle A, Eckfeldt J, Lutsey P . Vitamin D-Binding Protein Concentrations Quantified by Mass Spectrometry. N Engl J Med. 2015; 373(15):1480-2. PMC: 4654614. DOI: 10.1056/NEJMc1502602. View

Cashman K, Hayes A, Galvin K, Merkel J, Jones G, Kaufmann M . Significance of serum 24,25-dihydroxyvitamin D in the assessment of vitamin D status: a double-edged sword?. Clin Chem. 2015; 61(4):636-45. DOI: 10.1373/clinchem.2014.234955. View

Cauley J, Danielson M, Boudreau R, Barbour K, Horwitz M, Bauer D . Serum 25-hydroxyvitamin D and clinical fracture risk in a multiethnic cohort of women: the Women's Health Initiative (WHI). J Bone Miner Res. 2011; 26(10):2378-88. PMC: 3304434. DOI: 10.1002/jbmr.449. View

Kaufmann M, Gallagher J, Peacock M, Schlingmann K, Konrad M, Deluca H . Clinical utility of simultaneous quantitation of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D by LC-MS/MS involving derivatization with DMEQ-TAD. J Clin Endocrinol Metab. 2014; 99(7):2567-74. PMC: 4079315. DOI: 10.1210/jc.2013-4388. View

Nielson C, Jones K, Chun R, Jacobs J, Wang Y, Hewison M . Free 25-Hydroxyvitamin D: Impact of Vitamin D Binding Protein Assays on Racial-Genotypic Associations. J Clin Endocrinol Metab. 2016; 101(5):2226-34. PMC: 4870848. DOI: 10.1210/jc.2016-1104. View

Aloia J, Mikhail M, Dhaliwal R, Shieh A, Usera G, Stolberg A . Free 25(OH)D and the Vitamin D Paradox in African Americans. J Clin Endocrinol Metab. 2015; 100(9):3356-63. PMC: 4570168. DOI: 10.1210/JC.2015-2066. View

Denburg M, Hoofnagle A, Sayed S, Gupta J, de Boer I, Appel L . Comparison of Two ELISA Methods and Mass Spectrometry for Measurement of Vitamin D-Binding Protein: Implications for the Assessment of Bioavailable Vitamin D Concentrations Across Genotypes. J Bone Miner Res. 2016; 31(6):1128-36. PMC: 4945118. DOI: 10.1002/jbmr.2829. View

Alzaman N, Dawson-Hughes B, Nelson J, DAlessio D, Pittas A . Vitamin D status of black and white Americans and changes in vitamin D metabolites after varied doses of vitamin D supplementation. Am J Clin Nutr. 2016; 104(1):205-14. PMC: 4919528. DOI: 10.3945/ajcn.115.129478. View

Cauley J, Lui L, Ensrud K, Zmuda J, Stone K, Hochberg M . Bone mineral density and the risk of incident nonspinal fractures in black and white women. JAMA. 2005; 293(17):2102-8. DOI: 10.1001/jama.293.17.2102. View

10.

Berg A, Powe C, Evans M, Wenger J, Ortiz G, Zonderman A . 24,25-Dihydroxyvitamin d3 and vitamin D status of community-dwelling black and white Americans. Clin Chem. 2015; 61(6):877-84. PMC: 4686255. DOI: 10.1373/clinchem.2015.240051. View

11.

Bosworth C, Levin G, Robinson-Cohen C, Hoofnagle A, Ruzinski J, Young B . The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D catabolism, is reduced in chronic kidney disease. Kidney Int. 2012; 82(6):693-700. PMC: 3434313. DOI: 10.1038/ki.2012.193. View

12.

Barrett-Connor E, Siris E, Wehren L, Miller P, Abbott T, Berger M . Osteoporosis and fracture risk in women of different ethnic groups. J Bone Miner Res. 2005; 20(2):185-94. DOI: 10.1359/JBMR.041007. View

13.

Aloia J, Dhaliwal R, Shieh A, Mikhail M, Fazzari M, Ragolia L . Vitamin D supplementation increases calcium absorption without a threshold effect. Am J Clin Nutr. 2013; 99(3):624-31. DOI: 10.3945/ajcn.113.067199. View

14.

Gilsanz V, Roe T, Mora S, Costin G, Goodman W . Changes in vertebral bone density in black girls and white girls during childhood and puberty. N Engl J Med. 1991; 325(23):1597-600. DOI: 10.1056/NEJM199112053252302. View

15.

St-Arnaud R . Targeted inactivation of vitamin D hydroxylases in mice. Bone. 1999; 25(1):127-9. DOI: 10.1016/s8756-3282(99)00118-0. View

16.

Aloia J, Talwar S, Pollack S, Yeh J . A randomized controlled trial of vitamin D3 supplementation in African American women. Arch Intern Med. 2005; 165(14):1618-23. PMC: 1464166. DOI: 10.1001/archinte.165.14.1618. View

17.

Li J, Specker B, Ho M, Tsang R . Bone mineral content in black and white children 1 to 6 years of age. Early appearance of race and sex differences. Am J Dis Child. 1989; 143(11):1346-9. DOI: 10.1001/archpedi.1989.02150230104034. View

18.

Aloia J, Dhaliwal R, Mikhail M, Shieh A, Stolberg A, Ragolia L . Free 25(OH)D and Calcium Absorption, PTH, and Markers of Bone Turnover. J Clin Endocrinol Metab. 2015; 100(11):4140-5. PMC: 4702446. DOI: 10.1210/jc.2015-2548. View

19.

St-Arnaud R, Arabian A, Travers R, Barletta F, Chapin K, Depovere J . Deficient mineralization of intramembranous bone in vitamin D-24-hydroxylase-ablated mice is due to elevated 1,25-dihydroxyvitamin D and not to the absence of 24,25-dihydroxyvitamin D. Endocrinology. 2000; 141(7):2658-66. DOI: 10.1210/endo.141.7.7579. View

20.

Nieves J, Cosman F, Grubert E, Ambrose B, Ralston S, Lindsay R . Skeletal effects of vitamin D supplementation in postmenopausal black women. Calcif Tissue Int. 2012; 91(5):316-24. DOI: 10.1007/s00223-012-9638-x. View