Abstract
Vitamin D is derived from skin production through exposure to ultraviolet light and from oral intake of natural foods, fortified foods and supplements. While the principal source of vitamin D is skin production, oral intake has primacy over sunlight exposure in both the correction and prevention of privational vitamin D deficiency. Vitamin D deficiency is associated causally with rickets in childhood and osteomalacia in adulthood, but the evidence is inconsistent and inconclusive for a causal association with cancer, infections, autoimmune diseases and cardiovascular disease.
Measurement of serum 25-hydroxyvitamin D (25OHD) is the best marker of vitamin D supply. It is not a clinical outcome, but is a measure of risk of skeletal disease. Adequate supply corresponds to a 25OHD level ranging from 30–50 nmol/L (12–20 ng/ml). A value below 30 nmol/L (12 ng/ml) constitutes an increase in risk of skeletal disease. In those at risk, the clinician must decide whether it is necessary to advise empirically about ensuring adequate intake according to the dietary reference intakes of the 2011 Institute of Medicine (IOM) Report, or to proceed with initial biochemical tests such as serum calcium, phosphorus, total alkaline phosphatase and parathyroid hormone (PTH). Additional tests include bone turnover markers, bone densitometry, bone imaging and rarely dynamic bone histomorphometry. Patients who are diagnosed with vitamin D deficiency should be divided into those who are sun-deprived (privational vitamin deficiency) and those who are disease-related such as those with intestinal, liver or kidney disorders. The principal differential diagnosis for vitamin D-related bone disease is hypophosphataemic bone disease, especially that mediated by excessive fibroblast growth factor 23 (FGF23).
Regarding treatment, those with privational vitamin D deficiency should be managed according to IOM recommendations with respect to vitamin D and calcium requirements. Patients with disease-specific causes may require higher intakes of calcium and vitamin D. High dose vitamin D therapy should be avoided; instead, 1α,25-dihydroxyvitamin D is preferable in refractory cases with close metabolic supervision. Patients with severe hyperparathyroidism secondary to chronic malabsorption may need parathyroid surgery.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
DeLuca HF. Historical overview of vitamin D. In: Feldman D, Pike JW, Adams JS, editors. Vitamin D. 3rd ed. London: Academic; 2011. p. 3–22.
McKenna MJ. Differences in vitamin D status between countries in young adults and the elderly. Am J Med. 1992;93(1):69–77.
Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC: National Academies Press; 2011.
Jones G, Prosser DE. The activating enzymes of vitamin D metabolism. In: Feldman D, Pike JW, Adams JS, editors. Vitamin D. London: Academic; 2011. p. 23–42.
Hewison M, Adams JS. Extrarenal 1α-hydroxylase. In: Feldman D, Pike JW, Adams JS, editors. Vitamin D. 3rd ed. London: Academic; 2011. p. 777–804.
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 Metabol. 2011;96(1):53–8.
Aloia JF. The 2011 report on dietary reference intake for vitamin D: where do we go from here? J Clin Endocrinol Metabol. 2011;96(10):2987–96.
Rosen CJ, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, et al. IOM Committee Members Respond to Endocrine Society Vitamin D Guideline. J Clin Endocrinol Metabol. 2012;97: 1146–52.
Parfitt AM, Gallagher JC, Heaney RP, Johnston CC, Neer R, Whedon GD. Vitamin D and bone health in the elderly. Am J Clin Nutr. 1982;36(5 Suppl):1014–31.
Parfitt AM, Rao DS, Stanciu J, Villanueva AR, Kleerekoper M, Frame B. Irreversible bone loss in osteomalacia. Comparison of radial photon absorptiometry with iliac bone histomorphometry during treatment. J Clin Invest. 1985;76(6):2403–12.
Parfitt AM. Osteomalacia and related disorders. In: Avioli LV, Krane SM, editors. Metabolic bone disease and clinically related disorders. 3rd ed. Boston: Academic; 1998. p. 327–86.
Vieth R. The pharmacology of vitamin D. In: Feldman D, Pike JW, Adams JS, editors. Vitamin D. 3rd ed. London: Academic; 2011. p. 1041–66.
Roth HJ, Schmidt-Gayk H, Weber H, Niederau C. Accuracy and clinical implications of seven 25-hydroxyvitamin D methods compared with liquid chromatography-tandem mass spectrometry as a reference. Ann Clin Biochem. 2008;45(Pt 2):153–9.
Carter GD, Jones JC. Use of a common standard improves the performance of liquid chromatography-tandem mass spectrometry methods for serum 25-hydroxyvitamin-D. Ann Clin Biochem. 2009;46 (Pt 1):79–81.
Farrell CJ, Martin S, McWhinney B, Straub I, Williams P, Herrmann M. State-of-the-art vitamin D assays: a comparison of automated immunoassays with liquid chromatography-tandem mass spectrometry methods. Clin Chem. 2012;58(3):531–42.
Heijboer AC, Blankenstein MA, Kema IP, Buijs MM. Accuracy of 6 routine 25-hydroxyvitamin D assays: influence of vitamin D binding protein concentration. Clin Chem. 2012;58(3):543–8.
Joint Committee for Traceability in Laboratory Medicine. Database of higher-order reference materials, measurement methods/procedures and services. [cited 2012 28/08/2012]; Available from: http://www.bipm.org/jctlm/search.do?type=isRM_IUPAC&analyteCategory=Metabolites+and+substrates&matrixCategory=&searchStringMixed=CAS63283-36-3%23%23%2325-hydroxyvitamin+D3.
Wallace AM, Gibson S, de la Hunty A, Lamberg-Allardt C, Ashwell M. Measurement of 25-hydroxyvitamin D in the clinical laboratory: current procedures, performance characteristics and limitations. Steroids. 2010;75(7):477–88.
Hollis BW. Comparison of equilibrium and disequilibrium assay conditions for ergocalciferol, cholecalciferol and their major metabolites. J Steroid Biochem. 1984;21(1):81–6.
Coldwell RD, Trafford DJ, Makin HL, Varley MJ, Kirk DN. Specific estimation of 24,25-dihydroxyvitamin D in plasma by gas chromatography–mass spectrometry. Clin Chem. 1984;30(7): 1193–8.
Lensmeyer G, Poquette M, Wiebe D, Binkley N. The C-3 epimer of 25-hydroxyvitamin D(3) is present in adult serum. J Clin Endocrinol Metab. 2012;97(1): 163–8.
Shah I, James R, Barker J, Petroczi A, Naughton DP. Misleading measures in Vitamin D analysis: a novel LC-MS/MS assay to account for epimers and isobars. Nutr J. 2011;10:46.
Krasowski MD. Pathology consultation on vitamin D testing. Am J Clin Pathol. 2011;136(4):507–14.
Carter GD, Berry JL, Gunter E, Jones G, Jones JC, Makin HL, et al. Proficiency testing of 25-hydroxyvitamin D (25-OHD) assays. J Steroid Biochem Mol Biol. 2010;121(1–2):176–9.
Taylor CL, Carriquiry AL, Bailey RL, Sempos CT, Yetley EA. Appropriateness of the probability approach with a nutrient status biomarker to assess population inadequacy: a study using vitamin D. Am J Clin Nutr. 2013;97(1):72–8.
Sai AJ, Walters RW, Fang X, Gallagher JC. Relationship between vitamin D, parathyroid hormone, and bone health. J Clin Endocrinol Metab. 2011;96(3):E436–46.
Szulc P, Delmas PD. Biochemical markers of bone turnover: potential use in the investigation and management of postmenopausal osteoporosis. Osteoporos Int. 2008;19(12):1683–704.
Woitge HW, Pecherstorfer M, Li Y, Keck AV, Horn E, Ziegler R, et al. Novel serum markers of bone resorption: clinical assessment and comparison with established urinary indices. J Bone Miner Res. 1999;14(5): 792–801.
Adams JE. Radiology of rickets and osteomalacia. In: Feldman D, Pike JW, Adams JS, editors. Vitamin D. 3rd ed. London: Academic; 2011. p. 861–89.
Pettifor JM. Vitamin D, deficiency and nutritional rickets in children. In: Feldman D, Pike JW, Adams JS, editors. Vitamin D. 3rd ed. London: Academic; 2011. p. 1107–28.
McKenna MJ, Kleerekoper M, Ellis BI, Rao DS, Parfitt AM, Frame B. Atypical insufficiency fractures confused with Looser zones of osteomalacia. Bone. 1987;8(2):71–8.
Imel EA, Econs MJ. Approach to the hypophosphatemic patient. J Clin Endocrinol Metab. 2012;97(3): 696–706.
Skingle L, Compston J, editors. Bone histomorphometry. 3rd ed. London: Academic; 2011.
Milat F, Wong P, Fuller P, Johnstone L, Kerr P, Doery J, et al. A case of hypophosphataemic osteomalacia secondary to deferasirox therapy. J Bone Miner Res. 2012;27:219–22.
Walton RJ, Bijvoet OL. A simple slide-rule method for the assessment of renal tubular reaborption of phosphate in man. Clin Chim Acta. 1977;81(3):273–6.
Lips P, van Schoor NM, Bravenboer N. Vitamin D-related disorders. In: Rosen CF, editor. Primer on metabolic bone diseases and disorders of mineral metabolism. Washington, DC: American Society of Bone and Mineral Research; 2008.
Aggarwal V, Seth A, Aneja S, Sharma B, Sonkar P, Singh S, et al. Role of calcium deficiency in development of nutritional rickets in Indian children: a case control study. J Clin Endocrinol Metab. 2012;97(10):3461–6.
Dhanwal DK, Sahoo S, Gautam VK, Saha R. Hip fracture patients in India have vitamin D deficiency and secondary hyperparathyroidism. Osteoporos Int. 2013;24(2):553–7.
Whyte MP. Enzyme defects and the skeleton. In: Rosen CJ, editor. Primer on metabolic bone diseases and disorders of mineral metabolism. Washington, DC: American Society of Bone and Mineral Research; 2008. p. 454–8.
McCarthy RA, McKenna MJ, Oyefeso O, Uduma O, Murray BF, Brady JJ, et al. Vitamin D nutritional status in preterm infants and response to supplementation. Br J Nutr. 2013;110(1):156–63.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(7):1191–930.
McKenna MJ, Murray BF. Vitamin D dose response is underestimated by Endocrine Society’s Clinical Practice Guideline. Endocr Connect. 2013;2:87–95.
Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18): 1815–22.
Manaseki-Holland S, Maroof Z, Bruce J, Mughal MZ, Masher MI, Bhutta ZA, et al. Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial. Lancet. 2012;379(9824): 1419–27.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this chapter
Cite this chapter
McKenna, M.J., Murray, B. (2014). Vitamin D Deficiency. In: Bandeira, F., Gharib, H., Golbert, A., Griz, L., Faria, M. (eds) Endocrinology and Diabetes. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8684-8_23
Download citation
DOI: https://doi.org/10.1007/978-1-4614-8684-8_23
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-8683-1
Online ISBN: 978-1-4614-8684-8
eBook Packages: MedicineMedicine (R0)