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Calcified Tissue International

, Volume 78, Issue 5, pp 257–270 | Cite as

Addressing the Musculoskeletal Components of Fracture Risk with Calcium and Vitamin D: A Review of the Evidence

  • S. Boonen
  • H. A. Bischoff-Ferrari
  • C. Cooper
  • P. Lips
  • O. Ljunggren
  • P. J. Meunier
  • J.-Y. Reginster
Review

Abstract

Osteoporotic fractures are an extremely common and serious health problem in the elderly. This article presents the rationale for calcium and vitamin D supplementation in the prevention and treatment of osteoporotic fractures and reviews the literature evidence on the efficacy of this strategy. Two musculoskeletal risk factors are implicated in osteoporotic fractures in the elderly: the loss of bone mass due to secondary hyperparathyroidism and the increased propensity to falls. Calcium and vitamin D reverse secondary hyperparathyroidism with resultant beneficial effects on bone mineral density (BMD). Additionally, calcium and vitamin D supplementation significantly improves body sway and lower extremity strength, reducing the risk of falls. The effects of combined calcium and vitamin D on parathyroid function and BMD provide a strong rationale for the use of this therapy in the prevention and treatment of osteoporosis and osteoporotic fractures. There is general agreement that, in patients with documented osteoporosis, calcium and vitamin D supplementation should be an integral component of the management strategy, along with antiresorptive or anabolic treatment. Frail elderly individuals constitute another major target population for calcium and vitamin D because evidence from randomized studies in institutionalized elderly subjects demonstrates that these supplements reduce osteoporotic fracture risk, particularly in the presence of dietary deficiencies. However, the results of trials in community-dwelling subjects have been equivocal. Within the primary-care setting, further research is required to establish appropriate target subgroups for calcium and vitamin D supplementation; overall, the data are consistent with a benefit individuals with insufficient calcium and/or vitamin D, although patients with documented osteoporosis will derive further benefit in terms of fracture prevention from the addition of an antiresorptive agent.

Keywords

Osteoporosis Vitamin D Calcium Fracture Fall 

Notes

Acknowledgments

S. B. is a senior clinical investigator of the Fund for Scientific Research–Flanders, Belgium (F.W.O.– Vlaanderen) and holder of the Leuven University Chair in Metabolic Bone Diseases. This work was supported by grant G.0171.03 from the Fund for Scientific Research–Flanders, to S. B.

References

  1. 1.
    Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA (1999) Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353:878–882CrossRefPubMedGoogle Scholar
  2. 2.
    Melton LJ III, Chrischilles EA, Cooper C, Lane AW, Riggs BL (1992) Perspective. How many women have osteoporosis? J Bone Miner Res 7:1005–1010PubMedGoogle Scholar
  3. 3.
    Cummings SR, Black DM, Rubin SM (1989) Lifetime risks of hip, Colles’, or vertebral fracture and coronary heart disease among white postmenopausal women. Arch Intern Med 149:2445–2448CrossRefPubMedGoogle Scholar
  4. 4.
    Reginster JY, Gillet P, Gosset C (2001) Secular increase in the incidence of hip fractures in Belgium between 1984 and 1996; need for a concerted public health strategy. Bull World Health Org 79:942–946PubMedGoogle Scholar
  5. 5.
    Chrischilles EA, Butler CD, Davis CS, Wallace RB (1991) A model of lifetime osteoporosis impact. Arch Intern Med 151:2026–2032CrossRefPubMedGoogle Scholar
  6. 6.
    Cooper C, Campion G, Melton LJ III (1992) Hip fractures in the elderly: a world-wide projection. Osteoporos Int 2:285–289CrossRefPubMedGoogle Scholar
  7. 7.
    Kannus P, Niemi S, Parkkari J, Palvanen M, Vuori I, Jarvinen M (1999) Hip fractures in Finland between 1970 and 1997 and predictions for the future. Lancet 353:802–805CrossRefPubMedGoogle Scholar
  8. 8.
    Kanis JA, Johnell O, Oden A, Sembo I, Redlund-Johnell I, Dawson A, De Laet C, Jonsson B (2000) Long-term risk of osteoporotic fracture in Malmo. Osteoporos Int 11:669–674CrossRefPubMedGoogle Scholar
  9. 9.
    Lippuner K, von Overbeck J, Perrelet R, Bosshard H, Jaeger P (1997) Incidence and direct medical costs of hospitalizations due to osteoporotic fractures in Switzerland. Osteoporos Int 7:414–425CrossRefPubMedGoogle Scholar
  10. 10.
    Haentjens P, Autier P, Barette M, Boonen S (2001) The economic cost of hip fractures among elderly women. A one-year, prospective, observational cohort study with matched-pair analysis. Belgian Hip Fracture Study Group. J Bone Joint Surg Am 83:493–500PubMedGoogle Scholar
  11. 11.
    Autier P, Haentjens P, Bentin J, Baillon JM, Grivegnee AR, Closon MC, Boonen S (2000) Costs induced by hip fractures: a prospective controlled study in Belgium. Belgian Hip Fracture Study Group. Osteoporos Int 11:373–380CrossRefPubMedGoogle Scholar
  12. 12.
    Boonen S, Autier P, Barette M, Vanderschueren D, Lips P, Haentjens P (2004) Functional outcome and quality of life following hip fracture in elderly women: a prospective controlled study. Osteoporos Int 15:87–94CrossRefPubMedGoogle Scholar
  13. 13.
    Schurch MA, Rizzoli R, Mermillod B, Vasey H, Michel JP, Bonjour JP (1996) A prospective study on socioeconomic aspects of fracture of the proximal femur. J Bone Miner Res 11:1935–1942PubMedGoogle Scholar
  14. 14.
    Reginster JY, Gillet P, Ben Sedrine W, Brands G, Ethgen O, de Froidmont C, Gosset C (1999) Direct costs of hip fractures in patients over 60 years of age in Belgium. Pharmacoeconomics 15:507–514CrossRefPubMedGoogle Scholar
  15. 15.
    Cree M, Soskolne CL, Belseck E, Hornig J, McElhaney JE, Brant R, Suarez-Almazor M (2000) Mortality and institutionalization following hip fracture. J Am Geriatr Soc 48:283–288PubMedGoogle Scholar
  16. 16.
    Johnell O, Kanis JA, Oden A, Sernbo I, Redlund-Johnell I, Petterson C, De Laet C, Jonsson B (2004) Mortality after osteoporotic fractures. Osteoporos Int 15:38–42CrossRefPubMedGoogle Scholar
  17. 17.
    Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D (2000) Risk of mortality following clinical fractures. Osteoporos Int 11:556–561CrossRefPubMedGoogle Scholar
  18. 18.
    Kanis JA, Oden A, Johnell O, De Laet C, Jonsson B (2004) Excess mortality after hospitalisation for vertebral fracture. Osteoporos Int 15:108–112CrossRefPubMedGoogle Scholar
  19. 19.
    Cooper C (1997) The crippling consequences of fractures and their impact on quality of life. Am J Med 103:12S–17SCrossRefPubMedGoogle Scholar
  20. 20.
    Chapurlat RD, Bauer DC, Nevitt M, Stone K, Cummings SR (2003) Incidence and risk factors for a second hip fracture in elderly women. The study of osteoporotic fractures. Osteoporos Int 14:130–136PubMedGoogle Scholar
  21. 21.
    Colon-Emeric C, Kuchibhatla M, Pieper C, Hawkes W, Fredman L, Magaziner J, Zimmerman S, Lyles KW (2003) The contribution of hip fracture to risk of subsequent fractures: data from two longitudinal studies. Osteoporos Int 14:879–883CrossRefPubMedGoogle Scholar
  22. 22.
    Lindsay R, Silverman SL, Cooper C, Hanley DA, Barton I, Broy SB, Licata A, Benhamou L, Geusens P, Flowers K, Stracke H, Seeman E (2001) Risk of new vertebral fracture in the year following a fracture. JAMA 285:320–323CrossRefPubMedGoogle Scholar
  23. 23.
    Gold DT (1996) The clinical impact of vertebral fractures: quality of life in women with osteoporosis. Bone 18:185S–189SCrossRefPubMedGoogle Scholar
  24. 24.
    Hall SE, Criddle RA, Comito TL, Prince RL (1999) A case-control study of quality of life and functional impairment in women with long-standing vertebral osteoporotic fracture. Osteoporos Int 9:508–515CrossRefPubMedGoogle Scholar
  25. 25.
    Adachi JD, Ioannidis G, Olszynski WP, Brown JP, Hanley DA, Sebaldt RJ, Petrie A, Tenenhouse A, Stephenson GF, Papaioannou A, Guyatt GH, Goldsmith CH (2002) The impact of incident vertebral and non-vertebral fractures on health related quality of life in postmenopausal women. BMC Musculoskelet Disord 3:11CrossRefPubMedGoogle Scholar
  26. 26.
    Leidig-Bruckner G, Minne HW, Schlaich C, Wagner G, Scheidt-Nave C, Bruckner T, Gebest HJ, Ziegler R (1997) Clinical grading of spinal osteoporosis: quality of life components and spinal deformity in women with chronic low back pain and women with vertebral osteoporosis. J Bone Miner Res 12:663–675CrossRefPubMedGoogle Scholar
  27. 27.
    Nevitt MC, Ettinger B, Black DM, Stone K, Jamal SA, Ensrud K, Segal M, Genant HK, Cummings SR (1998) The association of radiographically detected vertebral fractures with back pain and function: a prospective study. Ann Intern Med 128:793–800PubMedGoogle Scholar
  28. 28.
    Schlaich C, Minne HW, Bruckner T, Wagner G, Gebest HJ, Grunze M, Ziegler R, Leidig-Bruckner G (1998) Reduced pulmonary function in patients with spinal osteoporotic fractures. Osteoporos Int 8:261–267CrossRefPubMedGoogle Scholar
  29. 29.
    Melton LJ III, Atkinson EJ, Cooper C, O’Fallon WM, Riggs BL (1999) Vertebral fractures predict subsequent fractures. Osteoporos Int 10:214–221CrossRefPubMedGoogle Scholar
  30. 30.
    Ismail AA, Cockerill W, Cooper C, Finn JD, Abendroth K, Parisi G, Banzer D, Benevolenskaya LI, Bhalla AK, Armas JB, Cannata JB, Delmas PD, Dequeker J, Dilsen G, Eastell R, Ershova O, Falch JA, Felsch B, Havelka S, Hoszowski K, Jajic I, Kragl U, Johnell O, Lopez VA, Lorenc R, Lyritis G, Marchand F, Masaryk P, Matthis C, Miazgowski T, Pols HA, Poor G, Rapado A, Raspe HH, Reid DM, Reisinger W, Janott J, Scheidt-Nave C, Stepan J, Todd C, Weber K, Woolf AD, Ambrecht G, Gowin W, Felsenberg D, Lunt M, Kanis JA, Reeve J, Silman AJ, O’Neill TW (2001) Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study. Osteoporos Int 12:85–90CrossRefPubMedGoogle Scholar
  31. 31.
    Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148PubMedGoogle Scholar
  32. 32.
    Colditz GA, Manson JE, Hankinson SE (1997) The Nurses’ Health Study: 20-year contribution to the understanding of health among women. J Womens Health 6:49–62PubMedCrossRefGoogle Scholar
  33. 33.
    Kiebzak GM, Beinart GA, Perser K, Ambrose CG, Siff SJ, Heggeness MH (2002) Undertreatment of osteoporosis in men with hip fracture. Arch Intern Med 162:2217–2222CrossRefPubMedGoogle Scholar
  34. 34.
    Freedman KB, Kaplan FS, Bilker WB, Strom BL, Lowe RA (2000) Treatment of osteoporosis: are physicians missing an opportunity? J Bone Joint Surg Am 82:1063–1070PubMedGoogle Scholar
  35. 35.
    Port L, Center J, Briffa NK, Nguyen T, Cumming R, Eisman J (2003) Osteoporotic fracture: missed opportunity for intervention. Osteoporos Int 14:780–784CrossRefPubMedGoogle Scholar
  36. 36.
    Gehlbach SH, Bigelow C, Heimisdottir M, May S, Walker M, Kirkwood JR (2000) Recognition of vertebral fracture in a clinical setting. Osteoporos Int 11:577–582CrossRefPubMedGoogle Scholar
  37. 37.
    Gehlbach SH, Fournier M, Bigelow C (2002) Recognition of osteoporosis by primary care physicians. Am J Public Health 92:271–273PubMedGoogle Scholar
  38. 38.
    Bahl S, Coates PS, Greenspan SL (2003) The management of osteoporosis following hip fracture: have we improved our care? Osteoporos Int 14:884–888CrossRefPubMedGoogle Scholar
  39. 39.
    Nguyen TV, Center JR, Eisman JA (2004) Osteoporosis: underrated, underdiagnosed and undertreated. Med J Aust 180:S18–S22PubMedGoogle Scholar
  40. 40.
    Panneman MJ, Lips P, Sen SS, Herings RM (2004) Undertreatment with anti-osteoporotic drugs after hospitalization for fracture. Osteoporos Int 15:120–124CrossRefPubMedGoogle Scholar
  41. 41.
    Hauselmann HJ, Rizzoli R (2003) A comprehensive review of treatments for postmenopausal osteoporosis. Osteoporos Int 14:2–12CrossRefPubMedGoogle Scholar
  42. 42.
    Boonen S, Haentjens P, Vandenput L, Vanderschueren D (2004) Preventing osteoporotic fractures with antiresorptive therapy: implications of microarchitectural changes. J Intern Med 255:1–12CrossRefPubMedGoogle Scholar
  43. 43.
    Boonen S, Rizzoli R, Meunier PJ, Stone M, Nuki G, Syversen U, Lehtonen-Veromaa M, Lips P, Johnell O, Reginster JY (2004) The need for clinical guidance in the use of calcium and vitamin D in the management of osteoporosis: a consensus report. Osteoporos Int 15:511–519CrossRefPubMedGoogle Scholar
  44. 44.
    Kamel HK (2004) Underutilization of calcium and vitamin D supplements in an academic long-term care facility. J Am Med Dir Assoc 5:98–100CrossRefPubMedGoogle Scholar
  45. 45.
    Stone KL, Seeley DG, Lui LY, Cauley JA, Ensrud K, Browner WS, Nevitt MC, Cummings SR (2003) BMD at multiple sites and risk of fracture of multiple types: long-term results from the Study of Osteoporotic Fractures. J Bone Miner Res 18:1947–1954CrossRefPubMedGoogle Scholar
  46. 46.
    Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, Black DM (2002) Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 112:281–289CrossRefPubMedGoogle Scholar
  47. 47.
    Heaney RP (2003) Is the paradigm shifting? Bone 33:457–465CrossRefPubMedGoogle Scholar
  48. 48.
    Bono CM, Einhorn TA (2003) Overview of osteoporosis: pathophysiology and determinants of bone strength. Eur Spine J 12(suppl 2):S90–S96CrossRefPubMedGoogle Scholar
  49. 49.
    Boonen S, Vanderschueren D, Cheng XG, Verbeke G, Dequeker J, Geusens P, Broos P, Bouillon R (1997) Age-related (type II) femoral neck osteoporosis in men: biochemical evidence for both hypovitaminosis D- and androgen deficiency-induced bone resorption. J Bone Miner Res 12:2119–2126CrossRefPubMedGoogle Scholar
  50. 50.
    Chapuy MC, Schott AM, Garnero P, Hans D, Delmas PD, Meunier PJ (1996) Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. EPIDOS Study Group. J Clin Endocrinol Metab 81:1129–1133CrossRefPubMedGoogle Scholar
  51. 51.
    Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22:477–501CrossRefPubMedGoogle Scholar
  52. 52.
    Lips P, Netelenbos JC, Jongen MJ, van Ginkel FC, Althuis AL, van Schaik CL, van der Vijgh WJ, Vermeiden JP, van der MC (1982) Histomorphometric profile and vitamin D status in patients with femoral neck fracture. Metab Bone Dis Relat Res 4:85–93CrossRefPubMedGoogle Scholar
  53. 53.
    Bouillon RA, Auwerx JH, Lissens WD, Pelemans WK (1987) Vitamin D status in the elderly: seasonal substrate deficiency causes 1,25-dihydroxycholecalciferol deficiency. Am J Clin Nutr 45:755–763PubMedGoogle Scholar
  54. 54.
    Lips P, Wiersinga A, van Ginkel FC, Jongen MJ, Netelenbos JC, Hackeng WH, Delmas PD, van der Vijgh WJ (1988) The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects. J Clin Endocrinol Metab 67:644–650PubMedGoogle Scholar
  55. 55.
    Pattanaungkul S, Riggs BL, Yergey AL, Vieira NE, O’Fallon WM, Khosla S (2000) Relationship of intestinal calcium absorption to 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in young versus elderly women: evidence for age-related intestinal resistance to 1,25(OH)2D action. J Clin Endocrinol Metab 85:4023–4027CrossRefPubMedGoogle Scholar
  56. 56.
    Lips P, Duong T, Oleksik A, Black D, Cummings S, Cox D, Nickelsen T (2001) 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 86:1212–1221CrossRefPubMedGoogle Scholar
  57. 57.
    Chapuy MC, Preziosi P, Maamer M, Arnaud S, Galan P, Hercberg S, Meunier PJ (1997) Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int 7:439–443CrossRefPubMedGoogle Scholar
  58. 58.
    Lips P, Hackeng WH, Jongen MJ, van Ginkel FC, Netelenbos JC (1983) Seasonal variation in serum concentrations of parathyroid hormone in elderly people. J Clin Endocrinol Metab 57:204–206PubMedCrossRefGoogle Scholar
  59. 59.
    Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS (1998) Hypovitaminosis D in medical inpatients. N Engl J Med 338:777–783CrossRefPubMedGoogle Scholar
  60. 60.
    Malabanan A, Veronikis IE, Holick MF (1998) Redefining vitamin D insufficiency. Lancet 351:805–806CrossRefPubMedGoogle Scholar
  61. 61.
    Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R (2005) Estimates of optimal vitamin D status. Osteoporosis Int 16:713–716CrossRefGoogle Scholar
  62. 62.
    Heaney RP, Dowell MS, Hale CA, Bendich A (2003) Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr 22:142–146PubMedGoogle Scholar
  63. 63.
    Melton LJI, Chao EYS, Lane J (1998) Biomechanical aspects of fractures. In: Riggs BL, Melton LJ (eds), Osteoporosis: Etiology, Diagnosis, and Management. Raven Press, New York, pp 111–131Google Scholar
  64. 64.
    Campbell AJ, Reinken J, Allan BC, Martinez GS (1981) Falls in old age: a study of frequency and related clinical factors. Age Ageing 10:264–270PubMedGoogle Scholar
  65. 65.
    Tinetti ME, Williams CS (1998) The effect of falls and fall injuries on functioning in community-dwelling older persons. J Gerontol A Biol Sci Med Sci 53:M112–M119PubMedGoogle Scholar
  66. 66.
    Tinetti ME, Speechley M, Ginter SF (1988) Risk factors for falls among elderly persons living in the community. N Engl J Med 319:1701–1707PubMedCrossRefGoogle Scholar
  67. 67.
    Tinetti ME, Williams CS (1997) Falls, injuries due to falls, and the risk of admission to a nursing home. N Engl J Med 337:1279–1284CrossRefPubMedGoogle Scholar
  68. 68.
    Geusens P, Milisen K, Dejaeger E, Boonen S (2003) Falls and fractures in postmenopausal women: a review. J Br Menopause Soc 9:101–106CrossRefPubMedGoogle Scholar
  69. 69.
    Englander F, Hodson TJ, Terregrossa RA (1996) Economic dimensions of slip and fall injuries. J Forensic Sci 41:733–746PubMedGoogle Scholar
  70. 70.
    Tinetti ME (1987) Factors associated with serious injury during falls by ambulatory nursing home residents. J Am Geriatr Soc 35:644–648PubMedGoogle Scholar
  71. 71.
    Nevitt MC, Cummings SR, Kidd S, Black D (1989) Risk factors for recurrent nonsyncopal falls. A prospective study. JAMA 261:2663–2668CrossRefPubMedGoogle Scholar
  72. 72.
    McKane WR, Khosla S, Egan KS, Robins SP, Burritt MF, Riggs BL (1996) Role of calcium intake in modulating age-related increases in parathyroid function and bone resorption. J Clin Endocrinol Metab 81:1699–1703CrossRefPubMedGoogle Scholar
  73. 73.
    Dawson-Hughes B, Harris SS, Krall EA, Dallal GE, Falconer G, Green CL (1995) Rates of bone loss in postmenopausal women randomly assigned to one of two dosages of vitamin D. Am J Clin Nutr 61:1140–1145PubMedGoogle Scholar
  74. 74.
    Lips P, Wiersinga A, van Ginkel FC, Jongen MJ, Netelenbos JC, Hackeng WH, Delmas PD, van der Vijgh WJ (1988) The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects. J Clin Endocrinol Metab 67:644–650PubMedGoogle Scholar
  75. 75.
    Ooms ME, Roos JC, Bezemer PD, van der Vijgh WJ, Bouter LM, Lips P (1995) Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial. J Clin Endocrinol Metab 80:1052–1058CrossRefPubMedGoogle Scholar
  76. 76.
    Chel VG, Ooms ME, Popp-Snijders C, Pavel S, Schothorst AA, Meulemans CC, Lips P (1998) Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly. J Bone Miner Res 13:1238–1242CrossRefPubMedGoogle Scholar
  77. 77.
    Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ (1992) Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 327:1637–1642PubMedCrossRefGoogle Scholar
  78. 78.
    Brazier M, Kamel S, Maamer M, Agbomson F, Elesper I, Garabedian M, Desmet G, Sebert JL (1995) Markers of bone remodeling in the elderly subject: effects of vitamin D insufficiency and its correction. J Bone Miner Res 10:1753–1761PubMedCrossRefGoogle Scholar
  79. 79.
    Himmelstein S, Clemens TL, Rubin A, Lindsay R (1990) Vitamin D supplementation in elderly nursing home residents increases 25(OH)D but not 1,25(OH)2D. Am J Clin Nutr 52:701–706PubMedGoogle Scholar
  80. 80.
    Ooms ME, Roos JC, Bezemer PD, van der Vijgh WJ, Bouter LM, Lips P (1995) Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial. J Clin Endocrinol Metab 80:1052–1058CrossRefPubMedGoogle Scholar
  81. 81.
    Adams JS, Kantorovich V, Wu C, Javanbakht M, Hollis BW (1999) Resolution of vitamin D insufficiency in osteopenic patients results in rapid recovery of bone mineral density. J Clin Endocrinol Metab 84:2729–2730CrossRefPubMedGoogle Scholar
  82. 82.
    Prestwood KM, Pannullo AM, Kenny AM, Pilbeam CC, Raisz LG (1996) The effect of a short course of calcium and vitamin D on bone turnover in older women. Osteoporos Int 6:314–319CrossRefPubMedGoogle Scholar
  83. 83.
    Simpson RU, Thomas GA, Arnold AJ (1985) Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle. J Biol Chem 260:8882–8891PubMedGoogle Scholar
  84. 84.
    Bischoff HA, Borchers M, Gudat F, Duermueller U, Theiler R, Stahelin HB, Dick W (2001) In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem J 33:19–24CrossRefPubMedGoogle Scholar
  85. 85.
    Sorensen OH, Lund B, Saltin B, Lund B, Andersen RB, Hjorth L, Melsen F, Mosekilde L (1979) Myopathy in bone loss of ageing: improvement by treatment with 1 alpha-hydroxycholecalciferol and calcium. Clin Sci (Colch) 56:157–161Google Scholar
  86. 86.
    Bischoff-Ferrari HA, Borchers M, Gudat F, Durmuller U, Stahelin HB, Dick W (2004) Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res 19:265–269CrossRefPubMedGoogle Scholar
  87. 87.
    Boland R (1986) Role of vitamin D in skeletal muscle function. Endocr Rev 7:434–448PubMedCrossRefGoogle Scholar
  88. 88.
    Glerup H, Mikkelsen K, Poulsen L, Hass E, Overbeck S, Andersen H, Charles P, Eriksen EF (2000) Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement. Calcif Tissue Int 66:419–424CrossRefPubMedGoogle Scholar
  89. 89.
    Bischoff HA, Stahelin HB, Urscheler N, Ehrsam R, Vonthein R, Perrig-Chiello P, Tyndall A, Theiler R (1999) Muscle strength in the elderly: its relation to vitamin D metabolites. Arch Phys Med Rehabil 80:54–58CrossRefPubMedGoogle Scholar
  90. 90.
    Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, Nebiker M, Theiler R, Pfeifer M, Begerow B, Lew RA, Conzelmann M (2003) Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 18:343–351CrossRefPubMedGoogle Scholar
  91. 91.
    Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C (2000) Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 15:1113–1118CrossRefPubMedGoogle Scholar
  92. 92.
    Latham NK, Anderson CS, Lee A, Bennett DA, Moseley A, Cameron ID (2003) 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 51:291–299CrossRefPubMedGoogle Scholar
  93. 93.
    Bischoff-Ferrari HA, Dietrich T, Orav EJ, Hu FB, Zhang Y, Karlson EW, Dawson-Hughes B (2004) 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 80:752–758PubMedGoogle Scholar
  94. 94.
    Dukas L, Bischoff HA, Lindpaintner LS, Schacht E, Birkner-Binder D, Damm TN, Thalmann B, Stahelin HB (2004) Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily. J Am Geriatr Soc 52:230–236CrossRefPubMedGoogle Scholar
  95. 95.
    Graafmans WC, Ooms ME, Hofstee HM, Bezemer PD, Bouter LM, Lips P (1996) Falls in the elderly: a prospective study of risk factors and risk profiles. Am J Epidemiol 143:1129–1136PubMedGoogle Scholar
  96. 96.
    Porthouse J, Cockayne S, King C, Saxon L, Steele E, Aspray T, Baverstock M, Birks Y, Dumville J, Francis R, Iglesias C, Puffer S, Sutcliffe A, Watt I, Torgerson DJ (2005) Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 330:1003CrossRefPubMedGoogle Scholar
  97. 97.
    RECORD Trial Group (2005) 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 365:1621–1628CrossRefGoogle Scholar
  98. 98.
    Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, Wong JB (2004) Effect of vitamin D on falls: a meta-analysis. JAMA 291:1999–2006CrossRefPubMedGoogle Scholar
  99. 99.
    Chapuy MC, Arlot ME, Delmas PD, Meunier PJ (1994) Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. BMJ 308:1081–1082PubMedGoogle Scholar
  100. 100.
    Chapuy MC, Pamphile R, Paris E, Kempf C, Schlichting M, Arnaud S, Garnero P, Meunier PJ (2002) Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study. Osteoporos Int 13:257–264CrossRefPubMedGoogle Scholar
  101. 101.
    Dawson-Hughes B, Harris SS, Krall EA, Dallal GE (1997) Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 337:670–676CrossRefPubMedGoogle Scholar
  102. 102.
    Larsen ER, Mosekilde L, Foldspang A (2004) 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 19:370–378CrossRefPubMedGoogle Scholar
  103. 103.
    Eastell R, Barton I, Hannon RA, Chines A, Garnero P, Delmas PD (2003) Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 18:1051–1056CrossRefPubMedGoogle Scholar
  104. 104.
    Bauer DC, Black DM, Garnero P, Hochberg M, Ott S, Orloff J, Thompson DE, Ewing SK, Delmas PD (2004) Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. J Bone Miner Res 19:1250–1258CrossRefPubMedGoogle Scholar
  105. 105.
    Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM (1996) Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Ann Intern Med 124:400–406PubMedGoogle Scholar
  106. 106.
    Meyer HE, Smedshaug GB, Kvaavik E, Falch JA, Tverdal A, Pedersen JI (2002) Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. J Bone Miner Res 17:709–715CrossRefPubMedGoogle Scholar
  107. 107.
    Trivedi DP, Doll R, Khaw KT (2003) 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 326:469CrossRefPubMedGoogle Scholar
  108. 108.
    Heikinheimo RJ, Inkovaara JA, Harju EJ, Haavisto MV, Kaarela RH, Kataja JM, Kokko AM, Kolho LA, Rajala SA (1992) Annual injection of vitamin D and fractures of aged bones. Calcif Tissue Int 51:105–110CrossRefPubMedGoogle Scholar
  109. 109.
    Smith H, Anderson F, Raphael H, Crozier S, Cooper C (2004) Annual intramuscular vitamin D and fractures in the elderly. J Bone Miner Res 19:A1032CrossRefGoogle Scholar
  110. 110.
    Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B (2005) Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 293:2257–2264CrossRefPubMedGoogle Scholar
  111. 111.
    Dawson-Hughes B, Harris SS, Krall EA, Dallal GE (2000) Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women. Am J Clin Nutr 72:745–750PubMedGoogle Scholar
  112. 112.
    Steel SA, Albertazzi P, Howarth EM, Purdie DW (2003) Factors affecting long-term adherence to hormone replacement therapy after screening for osteoporosis. Climacteric 6:96–103PubMedGoogle Scholar
  113. 113.
    Patel S, Ogunremi L, Chinappen U (2003) Acceptability and compliance with hip protectors in community-dwelling women at high risk of hip fracture. Rheumatology (Oxford) 42:769–772CrossRefGoogle Scholar
  114. 114.
    Rees TP, Howe I (2001) A randomised, single-blind, crossover comparison of the acceptability of the calcium and vitamin D3 supplements Calcichew D3 Forte and Ad Cal D3 in elderly patients. Curr Med Res Opin 16:245–251CrossRefPubMedGoogle Scholar
  115. 115.
    Simon JA, Lewiecki EM, Smith ME, Petruschke RA, Wang L, Palmisano JJ (2002) Patient preference for once-weekly alendronate 70 mg versus once-daily alendronate 10 mg: a multicenter, randomized, open-label, crossover study. Clin Ther 24:1871–1886CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • S. Boonen
    • 1
  • H. A. Bischoff-Ferrari
    • 2
  • C. Cooper
    • 3
  • P. Lips
    • 4
  • O. Ljunggren
    • 5
  • P. J. Meunier
    • 6
  • J.-Y. Reginster
    • 7
  1. 1.Leuven University Center for Metabolic Bone Diseases and Division of Geriatric MedicineKatholieke Universiteit LeuvenLeuvenBelgium
  2. 2.Division of Aging and Division of Rheumatology, Immunology and AllergyThe Robert B. Brigham Arthritis and Musculoskeletal Diseases Clinical Research Center, Brigham and Women’s HospitalBostonUSA
  3. 3.MRC Environmental Epidemiology Unit and University of Southampton School of MedicineSouthampton General HospitalSouthamptonUK
  4. 4.Department of EndocrinologyVrije Universiteit University Medical CenterAmsterdamThe Netherlands
  5. 5.Institution for Medical Sciences and Surgical SciencesUniversity HospitalUppsalaSweden
  6. 6.Université Paris-Descartes, Faculty de Medecine R. LlaennecLyonFrance
  7. 7.Unité d’Exploration de l’Os et du CartilageLiègeBelgium

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