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Optimal Vitamin D Status for the Prevention and Treatment of Osteoporosis

Abstract

Vitamin D3 (cholecalciferol) sufficiency is essential for maximising bone health. Vitamin D enhances intestinal absorption of calcium and phosphorus. The major source of vitamin D for both children and adults is exposure of the skin to sunlight. Season, latitude, skin pigmentation, sunscreen use, clothing and aging can dramatically influence the synthesis of vitamin D in the skin. Very few foods naturally contain vitamin D or are fortified with vitamin D. Serum 25-hydroxyvitamin D [25(OH)D; calcifediol] is the best measure of vitamin D status. Vitamin D deficiency [as defined by a serum 25(OH)D level of <50 nmol/L (<20 ng/mL)] is pandemic. This deficiency is very prevalent in osteoporotic patients. Vitamin D deficiency causes osteopenia, osteoporosis and osteomalacia, increasing the risk of fracture. Unlike osteoporosis, which is a painless disease, osteomalacia causes aching bone pain that is often misdiagnosed as fibromyalgia or chronic pain syndrome or is simply dismissed as depression. Vitamin D deficiency causes muscle weakness, increasing the risk of falls and fractures, and should be aggressively treated with pharmacological doses of vitamin D. Vitamin D sufficiency can be sustained by sensible sun exposure or ingesting at least 800–1000IU of vitamin D3 daily. Patients being treated for osteoporosis should be adequately supplemented with calcium and vitamin D to maximise the benefit of treatment.

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References

  1. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr 2004; 79: 362–71

    PubMed  CAS  Google Scholar 

  2. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 2006; 81(3): 353–73

    PubMed  Article  CAS  Google Scholar 

  3. Holick MF, Chen TC. Vitamin D deficiency pandemic and its health consequences. Am J Clin Nutr. In press

  4. Holick MF, Garabedian M. Vitamin D: photobiology, metabolism, mechanism of action, and clinical applications. In: Favus MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. 6th ed. Washington, DC: ASBMR, 2006: 106–14

    Google Scholar 

  5. Bouillon R. Vitamin D: from photosynthesis, metabolism, and action to clinical applications. In: DeGroot LJ, Jameson JL, editors. Endocrinology. Philadelphia (PA): WB Saunders, 2001: 1009–28

    Google Scholar 

  6. Christakos S, Dhawan P, Liu Y, et al. New insights into the mechanisms of vitamin D action. J Cell Biochem 2003; 88: 695–705

    PubMed  Article  CAS  Google Scholar 

  7. Holick MF. Vitamin D: a millennium perspective. J Cell Biochem 2003; 88: 296–307

    PubMed  Article  CAS  Google Scholar 

  8. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes Food and Nutrition Board Institute of Medicine. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, DC: National Academy Press, 1997: 146–89

    Google Scholar 

  9. Khosla S. The OPG/RANKL/RANK system. Endocrinology 2001; 142(12): 5050–5

    PubMed  Article  CAS  Google Scholar 

  10. Binkley N, Krueger D, Cowgill CS, et al. Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization. J Clin Endocrinol Metab 2004; 89: 3152–7

    PubMed  Article  CAS  Google Scholar 

  11. Lips P, Chapuy MC, Dawson-Hughes B, et al. An international comparison of serum 25-hydroxyvitamin D measurements. Osteoporos Int 1999; 9: 394–7

    PubMed  Article  CAS  Google Scholar 

  12. Glendenning P, Fraser WD. 25-OH-vitamin D assays [letter]. J Clin Endocrinol Metab 2005; 90: 3129

    PubMed  Article  CAS  Google Scholar 

  13. Dawson-Hughes B, Heaney RP, Holick MF, et al. Estimates of optimal vitamin D status (editorial). Osteoporos Int 2005; 16: 713–6

    PubMed  Article  CAS  Google Scholar 

  14. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet 1998; 351: 805–6

    PubMed  Article  CAS  Google Scholar 

  15. Chapuy MC, Preziosi P, Maaner M, et al. Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int 1997; 7: 439–43

    PubMed  Article  CAS  Google Scholar 

  16. Tangpricha V, Pearce EN, Chen TC, et al. Vitamin D insufficiency among free-living healthy young adults. Am J Med 2002; 112(8): 659–62

    PubMed  Article  CAS  Google Scholar 

  17. Holick MF, Siris ES, Binkley N, et al. Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab 2005; 90: 3215–24

    PubMed  Article  CAS  Google Scholar 

  18. Lips P, Duong T, Okeksik A, et al. A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the Multiple Outcomes of Raloxifene Evaluation Clinical Trial. J Clin Endocrinol Metab 2001; 86: 1212–21

    PubMed  Article  CAS  Google Scholar 

  19. Souberbielle J-C, Lawson-Body E, Hammadi B, et al. The use in clinical practice of parathyroid hormone normative values established in vitamin D-sufficient subjects. J Clin Endocrinol Metab 2003; 88(8): 3501–4

    PubMed  Article  CAS  Google Scholar 

  20. Heaney RP, Dowell MS, Hale CA, et al. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr 2003; 22(2): 142–6

    PubMed  CAS  Google Scholar 

  21. Adams JA, Clemens TL, Parrish JA, et al. Vitamin-D synthesis and metabolism after ultraviolet irradiation of normal and vitamin-D-deficient subjects. N Engl J Med 1982; 306: 722–5

    PubMed  Article  CAS  Google Scholar 

  22. Armas LAG, Hollis B, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 2004; 89: 5387–91

    PubMed  Article  CAS  Google Scholar 

  23. Bell NH, Green A, Epstein S, et al. Evidence for alteration of the vitamin D-endocrine system in blacks. J Pediatr 1985; 76: 470–3

    CAS  Google Scholar 

  24. Kyriakidou-Himonas M, Aloia JF, Yeh JK. Vitamin D supplementation in postmenopausal black women. J Clin Endocrinol Metab 1999; 84: 3988–90

    PubMed  Article  CAS  Google Scholar 

  25. Isaia G, Giorgino R, Rini GB, et al. Prevalence of hypovitaminosis D in elderly women in Italy: clinical consequences and risk factors. Osteoporos Int 2003; 14: 577–82

    PubMed  Article  CAS  Google Scholar 

  26. Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc 2003; 78: 1463–70

    PubMed  Article  Google Scholar 

  27. McKenna MJ. Differences in vitamin D status between countries in young adults and the elderly. Am J Med 1992; 93: 69–77

    PubMed  Article  CAS  Google Scholar 

  28. Bakhtiyarova S, Lesnyak O, Kyznesova N, et al. Vitamin D status among patients with hip fracture and elderly control subjects in Yekaterinburg, Russia. Osteoporos Int 2006; 17: 441–6

    PubMed  Article  CAS  Google Scholar 

  29. Gloth FM, Gundberg CM, Hollis BW, et al. Vitamin D deficiency in homebound elderly persons. JAMA 1995; 274: 1683–6

    PubMed  Article  Google Scholar 

  30. Boonen S, Bischoff-Ferrari A, Cooper C, et al. Addressing the musculoskeletal components of fracture risk with calcium and vitamin D: a review of the evidence. Calcif Tissue Int 2006; 78: 257–70

    PubMed  Article  CAS  Google Scholar 

  31. Gaugris S, Heaney RP, Boonen S, et al. Vitamin D inadequacy among post-menopausal women: a systematic review. QJM 2005; 98: 667–76

    PubMed  Article  CAS  Google Scholar 

  32. Beard MK, Lips P, Holick MF, et al. Vitamin D inadequacy is prevalent among postmenopausal osteoporotic women. Climacteric 2005; 8Suppl. 2: 199–200

    Google Scholar 

  33. Aaron JE, Gallagher JC, Anderson J, et al. Frequency of osteomalacia and osteoporosis in fractures of the proximal femur. Lancet 1974; I: 229–33

    Article  Google Scholar 

  34. Malabanan AO, Turner AK, Holick MF. Severe generalized bone pain and osteoporosis in a premenopausal black female: effect of vitamin D replacement. J Clin Densitom 1998; 1: 201–4

    Article  Google Scholar 

  35. Bhambri R, Naik V, Malhotra N, et al. Changes in bone mineral density following treatment of osteomalacia. J Clin Densitom 2006; 9(1): 120–7

    PubMed  Article  Google Scholar 

  36. Holick MF. Vitamin D deficiency: what a pain it is. Mayo Clin Proc 2003; 78(12): 1457–9

    PubMed  Article  Google Scholar 

  37. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992; 327: 1637–42

    PubMed  Article  CAS  Google Scholar 

  38. 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 1997; 337: 670–6

    PubMed  Article  CAS  Google Scholar 

  39. Larsen ER, Mosekilde L, Foldspang A. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. J Bone Miner Res 2004; 19: 370–8

    PubMed  Article  CAS  Google Scholar 

  40. Porthouse J, Cockayne S, King C, et al. Randomized controlled trial of supplementation with calcium and cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 2005; 330: 1003–6

    PubMed  Article  CAS  Google Scholar 

  41. Grant AM, Avenell A, Campbell MK, et al. Oral vitamin D3 and calcium for secondary prevention of low trauma fractures in elderly people (Randomized Evaluation of Calcium Or vitamin D, RECORD): a randomized placebo controlled trial. Lancet 2005; 365: 1621–8

    PubMed  Article  CAS  Google Scholar 

  42. Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006; 354(7): 669–83

    PubMed  Article  CAS  Google Scholar 

  43. Terris S, Lesser GT, Dawson-Hughes B. Calcium plus vitamin D and the risk of fractures. N Engl J Med 2006; 354(21): 2285–6

    PubMed  Article  CAS  Google Scholar 

  44. Bischoff-Ferrari HA, Giovannucci E, Willett WC, et al. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006; 84: 18–28

    PubMed  CAS  Google Scholar 

  45. 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: randomized double blind controlled trial. BMJ 2003; 326: 469–75

    PubMed  Article  CAS  Google Scholar 

  46. Heikinheima RJ, Inkovaara JA, Harju EJ, et al. Annual injection of vitamin D and fractures of aged bones. Calcif Tissue Int 1992; 51: 105–10

    Article  Google Scholar 

  47. Costa EM, Blau HM, Feldman D. 1,25-dihydroxyvitamin D3 receptors and hormonal responses in cloned human skeletal muscle cells. Endocrinology 1986; 119: 2214–20

    PubMed  Article  CAS  Google Scholar 

  48. Hess AF. Rickets including osteomalacia and tetany. Pennsylvania (PA): Lea J. Febiger, 1929

    Google Scholar 

  49. Schott G, Wills M. Muscle weakness in osteomalacia. Lancet 1976; II: 626–9

    Article  Google Scholar 

  50. Pfeifer M, Begerow B, Minne HW, et al. Vitamin D status, trunk muscle strength, body sway, falls, and fractures among 237 postmenopausal women with osteoporosis. Exp Clin Endocrinol Diabetes 2001; 109: 87–92

    PubMed  Article  CAS  Google Scholar 

  51. Pfeifer M, Begerow B, Minne H, et al. Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 2000; 15: 1113–8

    PubMed  Article  CAS  Google Scholar 

  52. Bischoff-Ferrari HA, Dietrich T, Orav EJ, et al. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged ≥60 y. Am J Clin Nutr 2004; 80: 752–8

    PubMed  CAS  Google Scholar 

  53. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al. Effect of vitamin D on falls: a meta-analysis. JAMA 2004; 291: 1999–2006

    PubMed  Article  CAS  Google Scholar 

  54. Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab 1988; 67: 373–8

    PubMed  Article  CAS  Google Scholar 

  55. Matsuoka LY, Ide L, Wortsman J, et al. Sunscreens suppress cutaneous vitamin D3 synthesis. J Clin Endocrinol Metab 1987; 64: 1165–8

    PubMed  Article  CAS  Google Scholar 

  56. Clemens TL, Henderson SL, Adams JS, et al. Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. Lancet 1982; I(8263): 74–6

    Article  Google Scholar 

  57. Lo CW, Paris PW, Holick MF. Serum vitamin D in response to ultraviolet irradiation in Asians. In: Norman AW, editor. Proceedings of sixth workshop on vitamin D, Merano, Italy. Berlin: Walter de Gruyter, 1985: 709–10

    Google Scholar 

  58. Holick MF, Matsuoka LY, Wortsman J. Age, vitamin D, and solar ultraviolet. Lancet 1989; II(8671): 1104–5

    Article  Google Scholar 

  59. Lu Z, Chen T, Kline L, et al. Photosynthesis of previtamin D3 in cities around the world. In: Holick M, Kligman A, editors. Biologic effects of light: proceedings, Berlin: Walter De Gruyter, 1992: 48–51

    Google Scholar 

  60. Lo CW, Paris PW, Clemens TL, et al. Vitamin D absorption in healthy subjects and in patients with intestinal malabsorption syndromes. Am J Clin Nutr 1985; 42: 644–9

    PubMed  CAS  Google Scholar 

  61. Bell NH, Epstein S, Greene A, et al. Evidence for alteration of the vitamin D-endocrine system in obese subjects. J Clin Invest 1985; 76: 370–3

    PubMed  Article  CAS  Google Scholar 

  62. Wortsman J, Matsuoka LY, Chen TC, et al. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000; 72: 690–3. Erratum Am J Clin Nutr 2003; 77: 1342

    PubMed  CAS  Google Scholar 

  63. Pascussi JM, Robert A, Nguyen M, et al. Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug induced osteomalacia. J Clin Invest 2005; 115: 177–86

    PubMed  CAS  Google Scholar 

  64. Zhou C, Assem M, Tay JC, et al. Steroid and xenobiotics receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia. J Clin Invest 2006; 116(6): 1703–12

    PubMed  Article  CAS  Google Scholar 

  65. Heaney RP, Davies KM, Chen TC, et al. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 2003; 77: 204–10

    PubMed  CAS  Google Scholar 

  66. Tangpricha V, Koutkia P, Rieke SM, et al. Fortification of orange juice with vitamin D: a novel approach to enhance vitamin D nutritional health. Am J Clin Nutr 2003; 77: 1478–83

    PubMed  CAS  Google Scholar 

  67. Chuck A, Todd J, Diffey B. Subliminal ultraviolet-B irradiation for the prevention of vitamin D deficiency in the elderly: a feasibility study. Photochem Photoimmun Photomed 2001; 17(4): 168–71

    CAS  Google Scholar 

  68. Tangpricha V, Turner A, Spina C, et al. Tanning is associated with optimal vitamin D status (serum 25-hydroxyvitamin D concentration) and higher bone mineral density. Am J Clin Nutr 2004; 80: 1645–9

    PubMed  CAS  Google Scholar 

  69. Chel VGM, Ooms ME, Popp-Snijders C, et al. Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly. J Bone Miner Res 1998; 13: 1238–42

    PubMed  Article  CAS  Google Scholar 

  70. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999; 69(5): 842–56

    PubMed  CAS  Google Scholar 

  71. Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med 2001; 345(1): 66–7

    PubMed  Article  CAS  Google Scholar 

  72. Adams JS, Gains LG. Bone mineral density with resolution of vitamin D intoxication. Ann Intern Med 1997; 127: 203–6

    PubMed  CAS  Google Scholar 

  73. Steingrimsdottir L, Gunnarsson O, Indridason OS, et al. Relationship between serum parathyroid hormone levels, vitamin D sufficiency and calcium intake. JAMA 2005; 294(18): 2335–41

    Article  Google Scholar 

  74. Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357(3): 266–81

    PubMed  Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by National Institutes of Health grants M01RR00533 and AR36963 and the UV Foundation. The author has acted as a consultant to Quest Diagnostics on assays for vitamin D metabolites.

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Correspondence to Michael F. Holick.

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Holick, M.F. Optimal Vitamin D Status for the Prevention and Treatment of Osteoporosis. Drugs Aging 24, 1017–1029 (2007). https://doi.org/10.2165/00002512-200724120-00005

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Keywords

  • Fibromyalgia
  • Osteomalacia
  • Hyperforin
  • Intestinal Calcium Absorption
  • Dietary Phosphorus