Skip to main content

Advertisement

Log in

Relevance of vitamin D in muscle health

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

This review will summarize the impact of vitamin D deficiency on muscle health. Mechanistic evidence regarding the presence of the specific vitamin D receptor in muscle tissue and muscle biopsy abnormalities observed with deficiency will be reviewed, as well as molecular and non-molecular effects of vitamin D in muscle tissue. At the clinical level, the evidence from randomized controlled trials of vitamin D supplementation on functional improvement and fall reduction will be summarized. Further, the manuscript will discuss whether vitamin D effects on fall prevention modulate in part its benefit on fracture prevention and why fall prevention is essential in fracture prevention at higher age. Finally, trial and epidemiological data will be reviewed to assess desirable serum 25-hydroxyvitamin D levels for optimal muscle health.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Al-Shoha A, Qiu S, Palnitkar S, Rao DS. Osteomalacia with bone marrow fibrosis due to severe vitamin D deficiency after a gastrointestinal bypass operation for severe obesity. Endocr Pract. 2009;15:528–33.

    Article  PubMed  Google Scholar 

  2. Schott GD, Wills MR. Muscle weakness in osteomalacia. Lancet. 1976;1:626–9.

    Article  PubMed  CAS  Google Scholar 

  3. Bischoff-Ferrari HA, Borchers M, Gudat F, Durmuller U, Stahelin HB, Dick W. Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res. 2004;19:265–9.

    Article  PubMed  CAS  Google Scholar 

  4. Ceglia L, da Silva Morais M, Park LK, Morris E, Harris SS, Bischoff-Ferrari HA, et al. Multi-step immunofluorescent analysis of vitamin D receptor loci and myosin heavy chain isoforms in human skeletal muscle. J Mol Histol. 2010;41:137–42.

    Article  PubMed  CAS  Google Scholar 

  5. Sorensen OH, Lund B, Saltin B, Andersen RB, Hjorth L, Melsen F, et al. Myopathy in bone loss of ageing: Improvement by treatment with 1 alpha-hydroxycholecalciferol and calcium. Clin Sci (Colch). 1979;56:157–61.

    CAS  Google Scholar 

  6. Freedman LP. Transcriptional targets of the vitamin D3 receptor-mediating cell cycle arrest and differentiation. J Nutr. 1999;129:581S–6S.

    PubMed  CAS  Google Scholar 

  7. Bouillon R, Bischoff-Ferrari H, Willett W. Vitamin D and health: Perspectives from mice and man. J Bone Miner Res. 2008;28:28.

    Google Scholar 

  8. Endo I, Inoue D, Mitsui T, Umaki Y, Akaike M, Yoshizawa T, et al. Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology. 2003;144:5138–44. Epub 2003 Aug 5113.

    Article  PubMed  CAS  Google Scholar 

  9. Wicherts IS, van Schoor NM, Boeke AJ, Visser M, Deeg DJ, Smit J, et al. Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrinol Metab. 2007;6:6.

    Google Scholar 

  10. Bischoff-Ferrari HA, Dietrich T, Orav EJ, Hu FB, Zhang Y, Karlson EW, 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 

  11. Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, et al. Effects of vitamin D and calcium supplementation on falls: A randomized controlled trial. J Bone Miner Res. 2003;18:343–51.

    Article  PubMed  CAS  Google Scholar 

  12. Pfeifer M, Begerow B, Minne HW, Suppan K, Fahrleitner-Pammer A, Dobnig H. Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals. Osteoporos Int. 2008;16:16.

    Google Scholar 

  13. Bischoff-Ferrari HA, Orav EJ, Dawson-Hughes B. Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: A 3-year randomized controlled trial. Arch Intern Med. 2006;166:424–30.

    Article  PubMed  CAS  Google Scholar 

  14. Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C. 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.

    Article  PubMed  CAS  Google Scholar 

  15. Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP. A higher dose of vitamin d reduces the risk of falls in nursing home residents: A randomized, multiple-dose study. J Am Geriatr Soc. 2007;55:234–9.

    Article  PubMed  Google Scholar 

  16. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, et al. Fall prevention with supplemental and active forms of vitamin D: A meta-analysis of randomised controlled trials. BMJ. 2009;339:339. b3692.

    Article  Google Scholar 

  17. Wang Y, DeLuca HF. Is the vitamin d receptor found in muscle? Endocrinology. 2011;152:354–63.

    Article  PubMed  CAS  Google Scholar 

  18. Bischoff HA, Borchers M, Gudat F, Duermueller U, Theiler R, Stahelin HB, et al. In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem J. 2001;33:19–24.

    Article  PubMed  CAS  Google Scholar 

  19. Boland R. Role of vitamin D in skeletal muscle function. Endocr Rev. 1986;7:434–48.

    Article  PubMed  CAS  Google Scholar 

  20. 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.

    Article  PubMed  CAS  Google Scholar 

  21. Simpson RU, Thomas GA, Arnold AJ. Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle. J Biol Chem. 1985;260:8882–91.

    PubMed  CAS  Google Scholar 

  22. Sorensen OH, Lund B, Saltin B, Andersen RB, Hjorth L, Melsen F, et al. Myopathy in bone loss of ageing: Improvement by treatment with 1 alpha-hydroxycholecalciferol and calcium. Clin Sci (Lond). 1979;56:157–61.

    CAS  Google Scholar 

  23. Sato Y, Iwamoto J, Kanoko T, Satoh K. Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: A randomized controlled trial. Cerebrovasc Dis. 2005;20:187–92.

    Article  PubMed  CAS  Google Scholar 

  24. de Boland AR, Boland RL. Rapid changes in skeletal muscle calcium uptake induced in vitro by 1,25-dihydroxyvitamin D3 are suppressed by calcium channel blockers. Endocrinology. 1987;120:1858–64.

    Article  PubMed  Google Scholar 

  25. Vazquez G, de Boland AR, Boland R. Stimulation of Ca2+ release-activated Ca2+ channels as a potential mechanism involved in non-genomic 1,25(OH)2-vitamin D3-induced Ca2+ entry in skeletal muscle cells. Biochem Biophys Res Commun. 1997;239:562–5.

    Article  PubMed  CAS  Google Scholar 

  26. Horst RL, Goff JP, Reinhardt TA. Advancing age results in reduction of intestinal and bone 1,25-dihydroxyvitamin D receptor. Endocrinology. 1990;126:1053–7.

    Article  PubMed  CAS  Google Scholar 

  27. Gonzalez Pardo V, Boland R, de Boland AR. Vitamin D receptor levels and binding are reduced in aged rat intestinal subcellular fractions. Biogerontology. 2008;9:109–18.

    Article  PubMed  CAS  Google Scholar 

  28. Bouillon R, Bischoff-Ferrari H, Willett W. Vitamin D and health: Perspectives from mice and man. J Bone Miner Res. 2008;23:974–9.

    Article  PubMed  CAS  Google Scholar 

  29. Li YC, Amling M, Pirro AE, Priemel M, Meuse J, Baron R, et al. Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice. Endocrinology. 1998;139:4391–6.

    Article  PubMed  CAS  Google Scholar 

  30. Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: Lessons from vitamin D receptor null mice. Endocr Rev. 2008;29:726–76.

    Article  PubMed  CAS  Google Scholar 

  31. Yoshikawa S, Nakamura T, Tanabe H, Imamura T. Osteomalacic myopathy. Endocrinol Jpn. 1979;26:65–72.

    Article  PubMed  CAS  Google Scholar 

  32. Bischoff-Ferrari HA, Willett WC, Orav EJ, Kiel DP, Dawson-Hughes B (2011) Re: Fall prevention with Vitamin D. Clarifications needed. http://www.bmj.com/content/339/bmj.b3692/reply

  33. Grimby G, Saltin B. The ageing muscle. Clin Physiol. 1983;3:209–18.

    Article  PubMed  CAS  Google Scholar 

  34. Zehnder D, Bland R, Williams MC, McNinch RW, Howie AJ, Stewart PM, et al. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab. 2001;86:888–94.

    Article  PubMed  CAS  Google Scholar 

  35. Somjen D, Weisman Y, Kohen F, Gayer B, Limor R, Sharon O, et al. 25-hydroxyvitamin D3-1alpha-hydroxylase is expressed in human vascular smooth muscle cells and is upregulated by parathyroid hormone and estrogenic compounds. Circulation. 2005;111:1666–71.

    Article  PubMed  CAS  Google Scholar 

  36. Malloy PJ, Feldman D. Genetic disorders and defects in vitamin d action. Endocrinol Metab Clin North Am, 39:333–346, table of contents.

  37. Delvin EE, Glorieux FH, Marie PJ, Pettifor JM. Vitamin D dependency: Replacement therapy with calcitriol? J Pediatr. 1981;99:26–34.

    Article  PubMed  CAS  Google Scholar 

  38. Al-Said YA, Al-Rached HS, Al-Qahtani HA, Jan MM. Severe proximal myopathy with remarkable recovery after vitamin D treatment. Can J Neurol Sci. 2009;36:336–9.

    PubMed  Google Scholar 

  39. Wicherts IS, van Schoor NM, Boeke AJ, Visser M, Deeg DJ, Smit J, et al. Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrinol Metab. 2007;92:2058–65.

    Article  PubMed  CAS  Google Scholar 

  40. LeBoff MS, Hawkes WG, Glowacki J, Yu-Yahiro J, Hurwitz S, Magaziner J. Vitamin D-deficiency and post-fracture changes in lower extremity function and falls in women with hip fractures. Osteoporos Int. 2008;19:1283–90.

    Article  PubMed  CAS  Google Scholar 

  41. Visser M, Deeg DJ, Puts MT, Seidell JC, Lips P. Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission. Am J Clin Nutr. 2006;84:616–22. quiz 671–612.

    PubMed  CAS  Google Scholar 

  42. Stockton KA, Mengersen K, Paratz JD, Kandiah D, Bennell KL. Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporos Int, 22:859–871.

  43. Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: A meta-analysis of randomized controlled trials. Arch Intern Med. 2009;169:551–61.

    Article  PubMed  CAS  Google Scholar 

  44. Glerup H, Mikkelsen K, Poulsen L, Hass E, Overbeck S, Andersen H, et al. Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement. Calcif Tissue Int. 2000;66:419–24.

    Article  PubMed  CAS  Google Scholar 

  45. Flicker L, MacInnis RJ, Stein MS, Scherer SC, Mead KE, Nowson CA, Thomas J, Lowndes C, Hopper JL, Wark JD. Should all older people in residential care receive vitamin D to prevent falls? Results of a randomized trial. JBMR, 2004;19(Suppl. 1), abstract F459, S99.

  46. Prince RL, Devine A, Dhaliwal SS, Dick IM. Effects of calcium supplementation on clinical fracture and bone structure: Results of a 5-year, double-blind, placebo-controlled trial in elderly women. Arch Intern Med. 2006;166:869–75.

    Article  PubMed  CAS  Google Scholar 

  47. Pfeifer M, Begerow B, Minne HW, Suppan K, Fahrleitner-Pammer A, Dobnig H. Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals. Osteoporos Int. 2009;20:315–22.

    Article  PubMed  CAS  Google Scholar 

  48. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. 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.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  50. Cummings SR, Nevitt MC. Non-skeletal determinants of fractures: The potential importance of the mechanics of falls. Study of Osteoporotic Fractures Research Group. Osteoporos Int. 1994;4 Suppl 1:67–70.

    Article  PubMed  Google Scholar 

  51. Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med. 1995;332:767–73.

    Article  PubMed  CAS  Google Scholar 

  52. Fatalities and injuries from falls among older adults–United States, 1993–2003 and 2001–2005. MMWR Morb Mortal Wkly Rep. 2006;55:1221–1224.

  53. Schwartz AV, Nevitt MC, Brown Jr BW, Kelsey JL. Increased falling as a risk factor for fracture among older women: The study of osteoporotic fractures. Am J Epidemiol. 2005;161:180–5.

    Article  PubMed  Google Scholar 

  54. Tinetti ME. Risk factors for falls among elderly persons living in the community. N Engl J Med. 1988;319:1701–7.

    Article  PubMed  CAS  Google Scholar 

  55. Nguyen ND, Frost SA, Center JR, Eisman JA, Nguyen TV. Development of a nomogram for individualizing hip fracture risk in men and women. Osteoporos Int. 2007;17:17.

    Google Scholar 

  56. Nevitt MC, Cummings SR. Type of fall and risk of hip and wrist fractures: The study of osteoporotic fractures. The Study of Osteoporotic Fractures Research Group. J Am Geriatr Soc. 1993;41:1226–34.

    PubMed  CAS  Google Scholar 

  57. Vellas BJ, Wayne SJ, Romero LJ, Baumgartner RN, Garry PJ. Fear of falling and restriction of mobility in elderly fallers. Age Ageing. 1997;26:189–93.

    Article  PubMed  CAS  Google Scholar 

  58. Arfken CL, Lach HW, Birge SJ, Miller JP. The prevalence and correlates of fear of falling in elderly persons living in the community. Am J Public Health. 1994;84:565–70.

    Article  PubMed  CAS  Google Scholar 

  59. McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, et al. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med. 2001;344:333–40.

    Article  PubMed  CAS  Google Scholar 

  60. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, et al. Effect of vitamin D on falls: A meta-analysis. JAMA. 2004;291:1999–2006.

    Article  PubMed  CAS  Google Scholar 

  61. Jackson C, Gaugris S, Sen SS, Hosking D. The effect of cholecalciferol (vitamin D3) on the risk of fall and fracture: A meta-analysis. Qjm. 2007;100:185–92.

    Article  PubMed  CAS  Google Scholar 

  62. Kalyani RR, Stein B, Valiyil R, Manno R, Maynard JW, Crews DC. Vitamin D treatment for the prevention of falls in older adults: systematic review and meta-analysis. J Am Geriatr Soc, 58, 1299–1310.

  63. O’Donnell S, Moher D, Thomas K, Hanley DA, Cranney A. Systematic review of the benefits and harms of calcitriol and alfacalcidol for fractures and falls. J Bone Miner Metab. 2008;26:531–42.

    Article  PubMed  Google Scholar 

  64. Richy F, Dukas L, Schacht E. Differential effects of D-hormone analogs and native vitamin D on the risk of falls: A comparative meta-analysis. Calcif Tissue Int. 2008;82:102–7.

    Article  PubMed  CAS  Google Scholar 

  65. Michael YL, Lin JS, Whitlock EP, Gold R, Fu R, O’Connor EA, Zuber SP, Beil TL, Lutz KW. Interventions to prevent falls in older adults: An updated systematic review. U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews, 2011

  66. Michael YL, Whitlock EP, Lin JS, Fu R, O’Connor EA, Gold R. Primary care-relevant interventions to prevent falling in older adults: A systematic evidence review for the U.S. Preventive services task force. Ann Intern Med. 2011;153:815–25.

    Google Scholar 

  67. Cameron ID, Murray GR, Gillespie LD, Robertson MC, Hill KD, Cumming RG, Kerse N. Interventions for preventing falls in older people in nursing care facilities and hospitals. Cochrane Database Syst Rev, CD005465

  68. AGS/BGS. (2010) AGS/BGS Guidelines on Fall Prevention in older Persons. http://www.americangeriatrics.org/files/documents/health_care_pros/Falls.Summary.Guide.pdf

  69. Dawson-Hughes B, Mithal A, Bonjour JP, Boonen S, Burckhardt P, Fuleihan GE, et al. IOF position statement: Vitamin D recommendations for older adults. Osteoporos Int. 2010;21:1151–4.

    Article  PubMed  CAS  Google Scholar 

  70. 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;96:1911–30.

    Article  PubMed  CAS  Google Scholar 

  71. Cummings SR, Nevitt MC, Kidd S. Forgetting falls. The limited accuracy of recall of falls in the elderly. J Am Geriatr Soc. 1988;36:613–6.

    PubMed  CAS  Google Scholar 

  72. Graafmans WC, Ooms ME, Hofstee HM, Bezemer PD, Bouter LM, Lips P. Falls in the elderly: A prospective study of risk factors and risk profiles. Am J Epidemiol. 1996;143:1129–36.

    PubMed  CAS  Google Scholar 

  73. Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, et al. 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. 2005;365:1621–8.

    Article  PubMed  CAS  Google Scholar 

  74. 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. 2003;326:469.

    Article  PubMed  CAS  Google Scholar 

  75. Latham NK, Anderson CS, Lee A, Bennett DA, Moseley A, Cameron ID. A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: The Frailty Interventions Trial in Elderly Subjects (FITNESS). J Am Geriatr Soc. 2003;51:291–9.

    Article  PubMed  Google Scholar 

  76. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: A meta-analysis of randomized controlled trials. Jama. 2005;293:2257–64.

    Article  PubMed  CAS  Google Scholar 

  77. Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM. Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Ann Intern Med. 1996;124:400–6.

    PubMed  CAS  Google Scholar 

  78. Meyer HE, Smedshaug GB, Kvaavik E, Falch JA, Tverdal A, Pedersen JI. Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. J Bone Miner Res. 2002;17:709–15.

    Article  PubMed  CAS  Google Scholar 

  79. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354:669–83.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Heike A. Bischoff-Ferrari.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bischoff-Ferrari, H.A. Relevance of vitamin D in muscle health. Rev Endocr Metab Disord 13, 71–77 (2012). https://doi.org/10.1007/s11154-011-9200-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11154-011-9200-6

Keywords

Navigation