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Preventing Fractures in Postmenopausal Women with Osteoporosis

A Review of Recent Controlled Trials of Antiresorptive Agents

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Abstract

The evidence from randomised, controlled trials of the ability of antiresorptive treatments to reduce the risk of fractures in postmenopausal women with osteoporosis is reviewed and summarised. The aminobisphosphonates, alendronic acid and risedronic acid, and the selective estrogen receptor modulator raloxifene have all been shown to reduce the incidence of radiographic vertebral fractures. Only alendronic acid and risedronic acid have been shown to reduce the incidence of non-spine fractures in women with postmenopausal osteoporosis. There is evidence of antifracture efficacy for calcium plus vitamin D, primarily in a nursing home setting or in people with low intakes of these nutrients. Furthermore, since both the placebo and active treatment groups received calcium and vitamin D in most controlled trials of antiresorptive agents, it appears that the other agents provide benefits beyond those of calcium and vitamin D alone. There is insufficient published evidence from randomised controlled trials to convincingly support the antifracture efficacy of other agents, including calcitonin, estrogen and etidronic acid, at this time. Data from observational studies suggest, however, that estrogen and etidronic acid may have antifracture efficacy in this population.

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References

  1. Cooper C, Campion G, Melton LJ III. Hip fractures in the elderly: a world-wide projection. Osteoporosis Int 1992; 2: 285–9

    Article  CAS  Google Scholar 

  2. Guyatt GH. Evidence-based management of patients with osteoporosis. J Clin Densitom 1998; 1: 395–402

    Article  PubMed  CAS  Google Scholar 

  3. Seeman E. Osteoporosis: trials and tribulations. Am J Med 1997; 103Suppl. 2A: 74S–89S

    Article  PubMed  CAS  Google Scholar 

  4. Meunier PJ. Evidence-based medicine and osteoporosis: a comparison of fracture risk reduction data from osteoporosis randomised clinical trials. Int J Clin Pract 1999; 53(2): 122–9

    PubMed  CAS  Google Scholar 

  5. Torgerson DJ, Roberts C. Randomisation methods: concealment. BMJ 1999; 319: 375–6

    Article  PubMed  CAS  Google Scholar 

  6. Black DM, Reiss TF, Nevitt MC, et al. Design of the Fracture Intervention Trial. Osteoporos Int 1993; Suppl. 3: S29–39

    Google Scholar 

  7. Windeier J, Lange S. Events perperson year: a dubious concept. BMJ 1995; 310: 454–6

    Article  Google Scholar 

  8. Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996; 348: 1535–41

    Article  PubMed  CAS  Google Scholar 

  9. Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 1998; 280: 2077–82

    Article  PubMed  CAS  Google Scholar 

  10. Ensrud DE, Black DM, Palermo L, et al. Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial. Arch Intern Med 1997; 157: 2617–24

    Article  PubMed  CAS  Google Scholar 

  11. Hochberg MC, Ross PD, Black D, et al. Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Arthritis Rheum 1999; 42(6): 1246–54

    Article  PubMed  CAS  Google Scholar 

  12. Liberman UA, Weiss SR, Bröil J, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 1995; 333: 1437–43

    Article  PubMed  CAS  Google Scholar 

  13. Karpf DB, Shapiro DR, Seeman E, et al. Prevention of non-vertebral fractures by alendronate: a meta-analysis. JAMA 1997; 277: 1159–64

    Article  PubMed  CAS  Google Scholar 

  14. Pols HAP, Felsenberg D, Hanley DA, et al. Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study. Osteoporos Int 1999; 9: 461–8

    Article  PubMed  CAS  Google Scholar 

  15. Nevitt MC, Thompson DE, Black DM, et al. Effect of alendronate on limited-activity days and bed-disability days caused by back pain in postmenopausal women with existing vertebral fractures. Arch Intern Med 2000; 160: 77–85

    Article  PubMed  CAS  Google Scholar 

  16. Musliner T, Thompson D, Vandormael K, et al. Consistency of effect of alendronate on reduction in risk of nonvertebral fractures [abstract]. Bone 1998; 23Suppl. 5: S478

    Google Scholar 

  17. Black DM, Thompson D, Bauer D, et al. Antifracture efficacy of alendronate in women at high risk of fracture: results from the Fracture Intervention Trial [abstract]. Osteoporos Int 1998; 8Suppl. 3: 107

    Google Scholar 

  18. Scott J, Thompson D, Schneider DL, et al. Alendronate reduces the risk of multiple clinical fractures: results from FIT [abstract]. Calcif Tissue Int 1999; 64Suppl. 1: S82

    Google Scholar 

  19. Nevitt MC, Ettinger B, Black DM, et al. The association of radiographically detected vertebral fractures with back pain and function: a prospective study. Ann Intern Med 1998; 128(10): 793–800

    PubMed  CAS  Google Scholar 

  20. Huang C, Ross PD, Wasnich RD. Vertebral fractures and other predictors of back pain among older women. J Bone Miner Res 1996; 11(7): 1026–32

    Article  PubMed  CAS  Google Scholar 

  21. Huang C, Ross PD, Wasnich RD. Vertebral fracture and other predictors of physical impairment and health care utilization. Arch Intern Med 1996; 156: 2469–75

    Article  PubMed  CAS  Google Scholar 

  22. Chrischilles EA, Dasbach EJ, Rubenstein LM, et al. The effect of alendronate on fracture-related healthcare utilization and costs: the Fracture Intervention Trial [abstract]. Bone 1998; 23Suppl. 5:S182

    Google Scholar 

  23. Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. JAMA 1999; 282: 1344–52

    Article  PubMed  CAS  Google Scholar 

  24. Reginster JY, Minne HW, Sorensen OH, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporosis Int 2000; 11:83–91

    Article  CAS  Google Scholar 

  25. Miller P, Roux C, McClung M, et al. Risedronate reduces hip fractures in patients with low femoral neck bone mineral density [abstract]. Arthritis Rheum 1999; 42 Suppl.: S287

    Google Scholar 

  26. McClung MR, Eastell R, Benhamouu L, et al. Risedronate reduces hip fractures in elderly postmenopausal women.

  27. Watts NB, Harris ST, Genant HK, et al. Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med 1990; 323(2): 73–9

    Article  PubMed  CAS  Google Scholar 

  28. Storm T, Thamsborg G, Steiniche T, et al. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med 1990; 322: 1265–71

    Article  PubMed  CAS  Google Scholar 

  29. Harris ST, Watts NB, Jackson RD, et al. Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: three years of blinded therapy followed by one year of open therapy. Am J Med 1993; 95: 557–67

    Article  PubMed  CAS  Google Scholar 

  30. Cardona JM, Pastor E. Calcitonin versus etidronate for the treatment of postmenopausal osteoporosis: a meta-analysis of published clinical trials. Osteoporos Int 1997; 7: 165–74

    Article  PubMed  CAS  Google Scholar 

  31. Wimalawansa SJ. A four-year randomized controlled trial of hormone replacement and bisphosphonate, alone or in combination, in women with postmenopausal osteoporosis. Am J Med 1998; 104: 219–26

    Article  PubMed  CAS  Google Scholar 

  32. van Staa TP, Abenhaim L, Cooper C. Use of cyclical etidronate and prevention of non-vertebral fractures. Br J Rheumatol 1998; 37: 87–94

    Article  PubMed  Google Scholar 

  33. Reid IR, Wattie DJ, Evans MC, et al. Continuous therapy with pamidronate, a potent bisphosphonate, in postmenopausal osteoporosis. J Clin Endocrinol Metab 1994; 79: 1595–9

    Article  PubMed  CAS  Google Scholar 

  34. Genant HK, Chesnut CH III, Eisman JA, et al. Chronic intermittent cyclical administration of tiludronate in postmenopausal osteoporosis: report of two multicenter studies in 2316 patients [abstract]. Bone 1998; 23 Suppl.: S175

    Google Scholar 

  35. Reginster JY, Roux C, Christiansen C, et al. Intermittent cyclical low dose tiludronate in treatment of postmenopausal osteoporosis: report of two phase III European studies (2305 patients) [abstract]. Bone 1998; 23 Suppl.: S594

    Google Scholar 

  36. McCloskey E, Selby P, Davies M, et al. Clodronate decreases vertebral fracture incidence in men and women with established osteoporosis [abstract]. Calcif Tissue Int 1999; 64Suppl. 1:S82

    Google Scholar 

  37. O’Connell D, Robertson J, Henry D, et al. A systematic review of the skeletal effects of estrogen therapy in postmenopausal women. II. An assessment of treatment effects. Climacteric 1998; 1: 112–23

    Article  PubMed  Google Scholar 

  38. Bush TL, Wells HB, James MK, et al. Effects of hormone therapy on bone mineral density: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. JAMA 1996; 276(17): 1389–96

    Article  Google Scholar 

  39. Komulainen MH, Kroger H, Tuppurainen MT, et al. HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial. Maturitas 1998; 31: 45–54

    Article  PubMed  CAS  Google Scholar 

  40. Lufkin EG, Wahner HW, O’Fallon WM, et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med 1992; 117: 1–9

    PubMed  CAS  Google Scholar 

  41. Nachtigall LE, Nachtigall RH, Nachtigall RD, et al. Estrogen replacement therapy. I. Ten year prospective study in the relationship to osteoporosis. Obstet Gynecol 1979; 53: 277–81

    PubMed  CAS  Google Scholar 

  42. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280: 605–13

    Article  PubMed  CAS  Google Scholar 

  43. Cauley JA, Black DM, Barrett-Connor E, et al. The effect of HRT on fracture risk: results of a 4-year randomized trial of 2,763 postmenopausal women [abstract]. Bone 1998; 23 Suppl.: S294

    Google Scholar 

  44. Kiel DP, Felson DT, Anderson JJ, et al. Hip fracture and the use of estrogens in postmenopausal women: the Framingham Study. N Engl J Med 1987; 317: 1169–74

    Article  PubMed  CAS  Google Scholar 

  45. Cauley JA, Seeley DG, Ensrud K, et al. Estrogen replacement therapy and fractures in older women. Ann Intern Med 1995; 122: 9–16

    PubMed  CAS  Google Scholar 

  46. Paganini-Hill A, Chao A, Ross RK, et al. Exercise and other factors in the prevention of hip fracture: the Leisure World Study. Epidemiology 1991; 2: 16–25

    Article  PubMed  CAS  Google Scholar 

  47. Schneider DL, Barrett-Connor EL, Morton DJ. Timing of postmenopausal estrogen for optimal bone mineral density: the Rancho Bernardo study. JAMA 1997; 277(7): 543–7

    Article  PubMed  CAS  Google Scholar 

  48. Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med 1992; 117(12): 1016–37

    PubMed  CAS  Google Scholar 

  49. Michaelsson K, Baron JA, Farahmand BY, et al. Hormone replacement therapy and risk of hip fracture: population-based case-control study. BMJ 1998; 316: 1858–63

    Article  PubMed  CAS  Google Scholar 

  50. Colson F, Conrozier T, Tebib JG, et al. Hormonal replacement therapy (HRT): which duration is effective to reduce the incidence of fracture in postmenopausal women? [abstract] Bone 1998; 23 Suppl.: S496

    Google Scholar 

  51. Matthews KA, Kuller LH, Wing RR, et al. Prior to use of estrogen replacement therapy, are users healthier than nonusers? Am J Epidemiol 1996; 143: 971–8

    Article  PubMed  CAS  Google Scholar 

  52. Barrett-Connor E. Hormone replacement therapy. BMJ 1998; 317:457–61

    Article  PubMed  CAS  Google Scholar 

  53. Khaw K-T. Hormone replacement therapy again. BMJ 1998; 316: 1842–4

    Article  PubMed  CAS  Google Scholar 

  54. Ettinger B, Black D, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene. JAMA 1999; 282: 637–45

    Article  PubMed  CAS  Google Scholar 

  55. Lufkin EG, Whitaker MD, Nickelsen T, et al. Treatment of established postmenopausal osteoporosis with raloxifene: a randomized trial. J Bone Miner Res 1998; 13: 1747–54

    Article  PubMed  CAS  Google Scholar 

  56. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-l Study. J Natl Cancer Inst 1998; 90: 1371–88

    Article  PubMed  CAS  Google Scholar 

  57. Overgaard K, Hansen MA, Jensen SB, et al. Effect of salcatonin given intranasally on bone mass and fracture rates in established osteoporosis: a dose-response study. BMJ 1992; 305: 556–61

    Article  PubMed  CAS  Google Scholar 

  58. Gennari C, Chierichetti SM, Bigazzi S, et al. Comparative effects on bone mineral content of calcium and calcium plus salmon calcitonin given in two different regimens in postmenopausal osteoporosis. Curr Ther Res 1985; 38: 455–64

    Google Scholar 

  59. Rico H, Revilla M, Hernandez ER, et al. Total and regional bone mineral content and fracture rate in postmenopausal osteoporosis treated with salmon calcitonin: a prospective study. Calcif Tissue Res 1995; 56: 181–5

    Article  CAS  Google Scholar 

  60. Rico H, Hernandez ER, Revilla M, et al. Salmon calcitonin reduces vertebral fracture rate in postmenopausal crash fracture syndrome. Bone Miner 1992; 16: 131–8

    Article  PubMed  CAS  Google Scholar 

  61. Kanis JA, McCloskey EV. Effect of calcitonin on vertebral and other fractures. Q J Med 1999; 92: 143–9

    Article  CAS  Google Scholar 

  62. Lyritis GP, Tsakalakos N, Magiasis B, et al. Analgesic effect of salmon calcitonin in osteoporotic vertebral fractures: a double-blind placebo-controlled clinical study. Calcif Tissue Int 1991; 49: 369–72

    Article  PubMed  CAS  Google Scholar 

  63. Pun KK, Chan LWL. Analgesic effect of intranasal salmon calcitonin in the treatment of osteoporotic vertebral fractures. Clin Ther 1989; 11:205–9

    PubMed  CAS  Google Scholar 

  64. Ljunghall S, Gardsell P, Johnell O, et al. Synthetic human calcitonin in postmenopausal osteoporosis: a placebo-controlled, double-blind study. Calcif Tissue Int 1991; 49: 17–9

    Article  PubMed  CAS  Google Scholar 

  65. Combe B, Cohen C, Aubin F. Equivalence of nasal spray and subcutaneous formulations of salmon calcitonin. Calcif Tissue Int 1997; 61: 10–5

    Article  PubMed  CAS  Google Scholar 

  66. Silverman SL, Moniz C, Andriano K, et al. Salmon-calcitonin nasal spray prevents vertebral fractures in established osteoporosis: final world wide results of the ‘PROOF’ study [abstract]. Calcif Tissue Int 1999; 64Suppl. 1: S43

    Google Scholar 

  67. Chapuy MC, Arlot ME, Delmas PD, et al. Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. BMJ 1994; 308: 1081–2

    Article  PubMed  CAS  Google Scholar 

  68. 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

    Article  PubMed  CAS  Google Scholar 

  69. Chevalley T, Rizzoli R, Nydegger V, et al. Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitamin-D-replete elderly patients. Osteoporosis Int 1994; 4: 245–52

    Article  CAS  Google Scholar 

  70. Recker RR, Hinders S, Davies KM, et al. Correcting calcium deficiency prevents spine fractures in elderly women. J Bone Miner Res 1996; 11: 1961–6

    Article  PubMed  CAS  Google Scholar 

  71. Reid IR, Ames RW, Evans MC, et al. Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial. 1995; 98: 331–5

  72. Lips P, Graafmans WC, Ooms ME, et al. 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 

  73. Ott SM, Chesnut CH III. Calcitriol treatment is not effective in postmenopausal osteoporosis. Ann Intern Med 1989; 110(4): 267–74

    PubMed  CAS  Google Scholar 

  74. Gallagher JC, Goldgar D. Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol. Ann Intern Med 1990; 113(9): 649–55

    PubMed  CAS  Google Scholar 

  75. Aloia JF, Vaswani A, Yeh JK, et al. Calcitriol in the treatment of postmenopausal osteoporosis. Am J Med 1988; 84: 401–8

    Article  PubMed  CAS  Google Scholar 

  76. Tilyard MW, Spears GFS, Thomson J, et al. Treatment of postmenopausal osteoporosis with calcitriol or calcium. N Engl J Med 1992; 326(6): 357–62

    Article  PubMed  CAS  Google Scholar 

  77. Gallagher JC, Riggs BL. Action of 1,25-dihydroxyvitamin D3 on calcium balance and bone turnover and its effect on vertebral fracture rate. Metabolism 1990; 39: 30–4

    Article  PubMed  CAS  Google Scholar 

  78. Shiraki M, Kushida K, Yamazaki K, et al. Effects of 2 years’ treatment of osteoporosis with lα-hydroxy vitamin D3 on bone mineral density and incidence of fracture: a placebo-controlled, double-blind prospective study. Endocr J 1996; 43:211–20

    Article  CAS  Google Scholar 

  79. Orimo H, Shiraki M, Hayashi Y, et al. Effects of lα-hydroxy-vitamin D3 on lumbar bone mineral density and vertebral fractures in patients with postmenopausal osteoporosis. Calcif Tissue Int 1994; 54: 370–6

    Article  PubMed  CAS  Google Scholar 

  80. Itami Y, Fujita T, Inoue T, et al. Effect of alphacalcidiol on osteoporosis: multicenter double-blind study. J Clin Exp Med 1982; 123: 958–73

    Google Scholar 

  81. Wasnich RD, Miller PD. Antifracture efficacy of antiresorptive agents are related to changes in bone density. J Clin Endocr Metab 2000; 85: 231–6

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The author would like to thank Philip D. Ross, Ph.D. for his assistance in the preparation of this manuscript.

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  1. Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, 10 South Pine St, MSTF 8-34, Baltimore, Maryland, 21201, USA

    Marc Hochberg

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Hochberg, M. Preventing Fractures in Postmenopausal Women with Osteoporosis. Drugs & Aging 17, 317–330 (2000). https://doi.org/10.2165/00002512-200017040-00007

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