Vitamin D Deficiency and Related Disorders Workup
- Author: Vin Tangpricha, MD, PhD; Chief Editor: George T Griffing, MD more...
Approach Considerations
Serum 25(OH)D
This is the best test to determine vitamin D status. The circulating half-life of 25(OH)D is 2 weeks. A 25(OH)D level of less than 30 ng/mL is considered vitamin D insufficient.[47] A 25(OH)D level of less than 15 or 20 ng/mL have been used to define vitamin D deficiency. Intestinal calcium absorption is optimized at levels above 30-32 ng/mL.[2, 27] Parathyroid hormone levels start to rise at 25(OH)D levels below 31 ng/mL,[48] which is another marker of vitamin D insufficiency.
Parathyroid hormone
Although not always required for the diagnosis of vitamin D insufficiency, a serum PTH may be used to help establish the diagnosis of vitamin D insufficiency. Often, patients with vitamin D insufficiency have a corresponding elevated PTH, indicating secondary hyperparathyroidism. An inverse relationship exists between PTH and 25(OH)D levels.[48] Usually, PTH levels decrease after the correction of a vitamin D insufficiency.
Holick MF. Vitamin D deficiency: what a pain it is. Mayo Clin Proc. Dec 2003;78(12):1457-9. [Medline].
Heaney RP, Dowell MS, Hale CA, et al. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr. Apr 2003;22(2):142-6. [Medline]. [Full Text].
Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. Nov 2004;89(11):5387-91. [Medline]. [Full Text].
Trang HM, Cole DE, Rubin LA, et al. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. Oct 1998;68(4):854-8. [Medline]. [Full Text].
Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. Mar 2008;93(3):677-81. [Medline].
Liu BA, Gordon M, Labranche JM, et al. Seasonal prevalence of vitamin D deficiency in institutionalized older adults. J Am Geriatr Soc. May 1997;45(5):598-603. [Medline].
Tangpricha V, Luo M, Fernández-Estívariz C, et al. Growth hormone favorably affects bone turnover and bone mineral density in patients with short bowel syndrome undergoing intestinal rehabilitation. J Parenter Enteral Nutr. Nov-Dec 2006;30:480-6. [Medline].
Koutkia P, Lu Z, Chen TC, Holick MF. Treatment of vitamin D deficiency due to Crohn's disease with tanning bed ultraviolet B radiation. Gastroenterology. Dec 2001;121(6):1485-8. [Medline].
Gartner LM, Greer FR. Prevention of rickets and vitamin D deficiency: new guidelines for vitamin D intake. Pediatrics. Apr 2003;111(4 Pt 1):908-10. [Medline]. [Full Text].
Elliott ME, Binkley NC, Carnes M, et al. Fracture risks for women in long-term care: high prevalence of calcaneal osteoporosis and hypovitaminosis D. Pharmacotherapy. Jun 2003;23(6):702-10. [Medline].
Thomas MK, Lloyd-Jones DM, Thadhani RI, et al. Hypovitaminosis D in medical inpatients. N Engl J Med. Mar 19 1998;338(12):777-83. [Medline]. [Full Text].
Tangpricha V, Pearce EN, Chen TC, et al. Vitamin D insufficiency among free-living healthy young adults. Am J Med. Jun 1 2002;112(8):659-62. [Medline].
Shoben AB, Kestenbaum B, Levin G, Hoofnagle AN, Psaty BM, Siscovick DS, et al. Seasonal variation in 25-hydroxyvitamin d concentrations in the cardiovascular health study. Am J Epidemiol. Dec 15 2011;174(12):1363-72. [Medline].
van der Wielen RP, Löwik MR, van den Berg H, et al. Serum vitamin D concentrations among elderly people in Europe. Lancet. Jul 22 1995;346(8969):207-10. [Medline].
Gannagé-Yared MH, Chemali R, Yaacoub N, et al. Hypovitaminosis D in a sunny country: relation to lifestyle and bone markers. J Bone Miner Res. Sep 2000;15(9):1856-62. [Medline].
Looker AC, Gunter EW. Hypovitaminosis D in medical inpatients. N Engl J Med. Jul 30 1998;339(5):344-5; author reply 345-6. [Medline].
Fuleihan GE, Deeb M. Hypovitaminosis D in a sunny country. N Engl J Med. Jun 10 1999;340(23):1840-1. [Medline].
Mishal AA. Effects of different dress styles on vitamin D levels in healthy young Jordanian women. Osteoporos Int. 2001;12(11):931-5. [Medline].
Clemens TL, Adams JS, Henderson SL, et al. Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. Lancet. Jan 9 1982;1(8263):74-6. [Medline].
Harris SS, Soteriades E, Coolidge JA, et al. Vitamin D insufficiency and hyperparathyroidism in a low income, multiracial, elderly population. J Clin Endocrinol Metab. Nov 2000;85(11):4125-30. [Medline]. [Full Text].
Nesby-O'Dell S, Scanlon KS, Cogswell ME, et al. 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. Jul 2002;76(1):187-92. [Medline]. [Full Text].
Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. Mar 2004;79(3):362-71. [Medline]. [Full Text].
Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med. Dec 3 1992;327(23):1637-42. [Medline].
Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. Mar 1 2003;326(7387):469. [Medline]. [Full Text].
Boonen S, Lips P, Bouillon R, et al. Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab. Apr 2007;92(4):1415-23. [Medline]. [Full Text].
[Best Evidence] Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. Mar 23 2009;169(6):551-61. [Medline].
Heaney RP. Vitamin D depletion and effective calcium absorption. J Bone Miner Res. Jul 2003;18(7):1342; author reply 1343. [Medline].
Dawson-Hughes B, Harris SS, Krall EA, et al. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med. Sep 4 1997;337(10):670-6. [Medline]. [Full Text].
Harwood RH, Sahota O, Gaynor K, et al. A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study. Age Ageing. Jan 2004;33(1):45-51. [Medline]. [Full Text].
Bischoff-Ferrari HA, Dietrich T, Orav EJ, et al. Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults. Am J Med. May 1 2004;116(9):634-9. [Medline].
Bischoff HA, Stahelin HB, Dick W, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res. Feb 2003;18(2):343-51. [Medline].
Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ. Oct 1 2009;339:b3692. [Medline].
Muir SW, Montero-Odasso M. Effect of vitamin d supplementation on muscle strength, gait and balance in older adults: a systematic review and meta-analysis. J Am Geriatr Soc. Dec 2011;59(12):2291-300. [Medline].
[Best Evidence] Lappe JM, Travers-Gustafson D, Davies KM, et al. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. Jun 2007;85(6):1586-91. [Medline]. [Full Text].
Chen TC, Holick MF. Vitamin D and prostate cancer prevention and treatment. Trends Endocrinol Metab. Nov 2003;14(9):423-30. [Medline].
Garland CF, Comstock GW, Garland FC, et al. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet. Nov 18 1989;2(8673):1176-8. [Medline].
Garland CF, Garland FC, Gorham ED. Calcium and vitamin D. Their potential roles in colon and breast cancer prevention. Ann N Y Acad Sci. 1999;889:107-19. [Medline].
Garland FC, Garland CF, Gorham ED, et al. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med. Nov 1990;19(6):614-22. [Medline].
Chen TC, Wang L, Whitlatch LW, et al. Prostatic 25-hydroxyvitamin D-1alpha-hydroxylase and its implication in prostate cancer. J Cell Biochem. Feb 1 2003;88(2):315-22. [Medline].
Freedman DM, Rajaraman P, Fuhrman B, et al. Sunlight, hormone replacement status and colorectal cancer risk in post-menopausal women. Int J Cancer. Sep 30 2009;[Medline].
Tangpricha V, Flanagan JN, Whitlatch LW, et al. 25-hydroxyvitamin D-1alpha-hydroxylase in normal and malignant colon tissue. Lancet. May 26 2001;357(9269):1673-4. [Medline].
Mathieu C, Gysemans C, Giulietti A, et al. Vitamin D and diabetes. Diabetologia. Jul 2005;48(7):1247-57. [Medline].
Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey. Am J Hypertens. Jul 2007;20(7):713-9. [Medline].
Joergensen C, Hovind P, Schmedes A, Parving HH, Rossing P. Vitamin d levels, microvascular complications, and mortality in type 1 diabetes. Diabetes Care. May 2011;34(5):1081-5. [Medline].
[Best Evidence] Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. Sep 10 2007;167(16):1730-7. [Medline].
Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. Jul 6 2011;CD007470. [Medline].
Hollis BW, Wagner CL. Normal serum vitamin D levels. N Engl J Med. Feb 3 2005;352(5):515-6; author reply 515-6. [Medline].
Chapuy MC, Preziosi P, Maamer M, et al. Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int. 1997;7(5):439-43. [Medline].
Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. Jun 6 2011;[Medline].
Haddad JG, Matsuoka LY, Hollis BW, Hu YZ, Wortsman J. Human plasma transport of vitamin D after its endogenous synthesis. J Clin Invest. Jun 1993;91(6):2552-5. [Medline]. [Full Text].
Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. Apr 2008;87(4):1080S-6S. [Medline].
Lu Z, Chen TC, Zhang A, et al. An evaluation of the vitamin D3 content in fish: is the vitamin D content adequate to satisfy the dietary requirement for vitamin D?. J Steroid Biochem Mol Biol. Mar 2007;103(3-5):642-4. [Medline].
Holick MF, Shao Q, Liu WW, et al. The vitamin D content of fortified milk and infant formula. N Engl J Med. Apr 30 1992;326(18):1178-81. [Medline].
Tangpricha V, Koutkia P, Rieke SM, et al. Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health. Am J Clin Nutr. Jun 2003;77(6):1478-83. [Medline]. [Full Text].
Hollis BW. Short-term and long-term consequences and concerns regarding valid assessment of vitamin D deficiency: comparison of recent food supplementation and clinical guidance reports. Curr Opin Clin Nutr Metab Care. Nov 2011;14(6):598-604. [Medline].
Bischoff H, Stahelin HB, Vogt P, et al. Immobility as a major cause of bone remodeling in residents of a long-stay geriatric ward. Calcif Tissue Int. Jun 1999;64(6):485-9. [Medline].
Elidrissy AT, Sedrani SH, Lawson DE. Vitamin D deficiency in mothers of rachitic infants. Calcif Tissue Int. May 1984;36(3):266-8. [Medline].
Heaney RP. Vitamin D, nutritional deficiency, and the medical paradigm. J Clin Endocrinol Metab. Nov 2003;88(11):5107-8. [Medline]. [Full Text].
Holick MF. Vitamin D deficiency. N Engl J Med. Jul 19 2007;357(3):266-81. [Medline].
Holick MF. Vitamin D: a millenium perspective. J Cell Biochem. Feb 1 2003;88(2):296-307. [Medline].
Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet. Mar 14 1998;351(9105):805-6. [Medline].
Suda T, Ueno Y, Fujii K, et al. Vitamin D and bone. J Cell Biochem. Feb 1 2003;88(2):259-66. [Medline].

