[en] 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.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Boonen, S.
Bischoff-Ferrari, H. A.
Cooper, C.
Lips, P.
Ljunggren, O.
Meunier, P. J.
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Language :
English
Title :
Addressing the musculoskeletal components of fracture risk with calcium and vitamin D: A review of the evidence
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 353:878-882
Melton LJ III, Chrischilles EA, Cooper C, Lane AW, Riggs BL (1992) Perspective. How many women have osteoporosis? J Bone Miner Res 7:1005-1010
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 149:2445-2448
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 79:942-946
Chrischilles EA, Butler CD, Davis CS, Wallace RB (1991) A model of lifetime osteoporosis impact. Arch Intern Med 151:2026-2032
Cooper C, Campion G, Melton LJ III (1992) Hip fractures in the elderly: a world-wide projection. Osteoporos Int 2:285-289
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 353:802-805
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 11:669-674
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 7:414-425
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 83:493-500
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 11:373-380
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 15:87-94
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 11:1935-1942
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 15:507-514
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 48:283-288
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 15:38-42
Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D (2000) Risk of mortality following clinical fractures. Osteoporos Int 11:556-561
Kanis JA, Oden A, Johnell O, De Laet C, Jonsson B (2004) Excess mortality after hospitalisation for vertebral fracture. Osteoporos Int 15:108-112
Cooper C (1997) The crippling consequences of fractures and their impact on quality of life. Am J Med 103:12S-17S
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 14:130-136
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 14:879-883
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 285:320-323
Gold DT (1996) The clinical impact of vertebral fractures: quality of life in women with osteoporosis. Bone 18:185S-189S
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 9:508-515
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 3:11
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 12:663-675
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 128:793-800
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 8:261-267
Melton LJ III, Atkinson EJ, Cooper C, O'Fallon WM, Riggs BL (1999) Vertebral fractures predict subsequent fractures. Osteoporos Int 10:214-221
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 12:85-90
Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137-1148
Colditz GA, Manson JE, Hankinson SE (1997) The Nurses' Health Study: 20-year contribution to the understanding of health among women. J Womens Health 6:49-62
Kiebzak GM, Beinart GA, Perser K, Ambrose CG, Siff SJ, Heggeness MH (2002) Undertreatment of osteoporosis in men with hip fracture. Arch Intern Med 162:2217-2222
Freedman KB, Kaplan FS, Bilker WB, Strom BL, Lowe RA (2000) Treatment of osteoporosis: are physicians missing an opportunity? J Bone Joint Surg Am 82:1063-1070
Port L, Center J, Briffa NK, Nguyen T, Cumming R, Eisman J (2003) Osteoporotic fracture: missed opportunity for intervention. Osteoporos Int 14:780-784
Gehlbach SH, Bigelow C, Heimisdottir M, May S, Walker M, Kirkwood JR (2000) Recognition of vertebral fracture in a clinical setting. Osteoporos Int 11:577-582
Gehlbach SH, Fournier M, Bigelow C (2002) Recognition of osteoporosis by primary care physicians. Am J Public Health 92:271-273
Bahl S, Coates PS, Greenspan SL (2003) The management of osteoporosis following hip fracture: have we improved our care? Osteoporos Int 14:884-888
Nguyen TV, Center JR, Eisman JA (2004) Osteoporosis: underrated, underdiagnosed and undertreated. Med J Aust 180:818-822
Panneman MJ, Lips P, Sen SS, Herings RM (2004) Undertreatment with anti-osteoporotic drugs after hospitalization for fracture. Osteoporos Int 15:120-124
Hauselmann HJ, Rizzoli R (2003) A comprehensive review of treatments for postmenopausal osteoporosis. Osteoporos Int 14:2-12
Boonen S, Haentjens P, Vandenput L, Vanderschueren D (2004) Preventing osteoporotic fractures with antiresorptive therapy: implications of microarchitectural changes. J Intern Med 255:1-12
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 15:511-519
Kamel HK (2004) Underutilization of calcium and vitamin D supplements in an academic long-term care facility. J Am Med Dir Assoc 5:98-100
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 18:1947-1954
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 112:281-289
Heaney RP (2003) Is the paradigm shifting? Bone 33:457-465
Bono CM, Einhorn TA (2003) Overview of osteoporosis: pathophysiology and determinants of bone strength. Eur Spine J 12(suppl 2):S90-S96
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 12:2119-2126
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 81:1129-1133
Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22:477-501
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 4:85-93
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 45:755-763
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 67:644-650
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 85:4023-4027
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 86:1212-1221
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 7:439-443
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 57:204-206
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 338:777-783
Malabanan A, Veronikis IE, Holick MF (1998) Redefining vitamin D insufficiency. Lancet 351:805-806
Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R (2005) Estimates of optimal vitamin D status. Osteoporosis Int 16:713-716
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 22:142-146
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 111-131
Campbell AJ, Reinken J, Allan BC, Martinez GS (1981) Falls in old age: a study of frequency and related clinical factors. Age Ageing 10:264-270
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-M119
Tinetti ME, Speechley M, Ginter SF (1988) Risk factors for falls among elderly persons living in the community. N Engl J Med 319:1701-1707
Tinetti ME, Williams CS (1997) Falls, injuries due to falls, and the risk of admission to a nursing home. N Engl J Med 337:1279-1284
Geusens P, Milisen K, Dejaeger E, Boonen S (2003) Falls and fractures in postmenopausal women: a review. J Br Menopause Soc 9:101-106
Englander F, Hodson TJ, Terregrossa RA (1996) Economic dimensions of slip and fall injuries. J Forensic Sci 41:733-746
Tinetti ME (1987) Factors associated with serious injury during falls by ambulatory nursing home residents. J Am Geriatr Soc 35:644-648
Nevitt MC, Cummings SR, Kidd S, Black D (1989) Risk factors for recurrent nonsyncopal falls. A prospective study. JAMA 261:2663-2668
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 81:1699-1703
Dawson-Hughes B, Harris SS, Krall EA, Dallai 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 61:1140-1145
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 67:644-650
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 80:1052-1058
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 13:1238-1242
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 327:1637-1642
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 10:1753-1761
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 52:701-706
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 80:1052-1058
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 84:2729-2730
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 6:314-319
Simpson RU, Thomas GA, Arnold AJ (1985) Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle. J Biol Chem 260:8882-8891
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 33:19-24
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) 56:157-161
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 19:265-269
Boland R (1986) Role of vitamin D in skeletal muscle function. Endocr Rev 7:434-448
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 66:419-424
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 80:54-58
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 18:343-351
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 15:1113-1118
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 51:291-299
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 80:752-758
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 52:230-236
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 143:1129-1136
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 330:1003
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 365:1621-1628
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 291:1999-2006
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 308:1081-1082
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 13:257-264
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 337:670-676
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 19:370-378
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 18:1051-1056
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 19:1250-1258
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 124:400-406
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 17:709-715
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 326:469
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 51:105-110
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:A1032
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 293:2257-2264
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 72:745-750
Steel SA, Albertazzi P, Howarth EM, Purdie DW (2003) Factors affecting long-term adherence to hormone replacement therapy after screening for osteoporosis. Climacteric 6:96-103
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) 42:769-772
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 16:245-251
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 24:1871-1886
