Comparison of Anti-osteoporotic Medications and Alternatives

골다공증 치료의 의학약제와 대체 약물의 비교

Kang, Byung-Moon
강병문

  • Published : 20061200

Abstract

Osteoporosis becomes a serious health threat for aging postmenopausal women by predisposing them to an increased risk of fracture. Conventional pharmacological options are available for osteoporosis therapy, including bisphosphonates, the SERM raloxifene, estrogens, clacitonin, and parathyroid hormone. Although alternative treatment regimens, such as phytoestrogens, herbals, and dehydroepiandrosterone (DHEA) also show beneficial effect on bone density and health, further study to determine optional formulation is needed. Several new drugs are available or are in clinical development.

Keywords

References

  1. North American Menopause Society. Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society. Menopause 2006; 13: 340-67 https://doi.org/10.1097/01.gme.0000222475.93345.b3
  2. Liberman UA, Weiss SR, Broll JL. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 1995; 333: 1437-43 https://doi.org/10.1056/NEJM199511303332201
  3. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures: Fracture Intervention Trial Research Group. Lancet 1996; 348: 1531-41
  4. Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, 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 https://doi.org/10.1001/jama.280.24.2077
  5. Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA 1999; 282: 1344-52 https://doi.org/10.1001/jama.282.14.1344
  6. Reginster J, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, et al. for the Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporos Int 2000; 11: 83-91 https://doi.org/10.1007/s001980050010
  7. Chesnut CH III, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, et al. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res 2004; 19: 1241-9 https://doi.org/10.1359/JBMR.040325
  8. McClung M, Clemmesen B, Daifotis A, Gilchrist NL, Eisman J, Weinstein RS, et al. Alendronate prevents postmenopausal bone loss in women without osteoporosis: a double-blind, randomized controlled trial. Ann Intern Med 1998; 128: 253-61 https://doi.org/10.7326/0003-4819-128-4-199802150-00001
  9. McClung MR, Wasnich RD, Hosking DJ, Christiansen C, Ravn P, Wu M, et al. for the Early Postmenopausal Intervention Cohort Study. Prevention of postmenopausal bone loss: six-year results from the Early Postmenopausal Intervention Cohort Study. J Clin Endocrinol Metab 2004; 89: 4879-85 https://doi.org/10.1210/jc.2003-031672
  10. Liberman UA, Weiss SR, Broll JL. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 1995; 333: 1437-43 https://doi.org/10.1056/NEJM199511303332201
  11. Ensrud KE, Barrett-Connor EL, Schwartz A, for the Fracture Intervention Trial Long-Term Extension Research Group. Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the Fracture Intervention Trial long-term extension. J Bone Miner Res 2004; 19: 1259-69 https://doi.org/10.1359/JBMR.040326
  12. Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, et al. for the Alendronate Phase III Osteoporosis Treatment Study Group. Ten years' experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350: 1189-99 https://doi.org/10.1056/NEJMoa030897
  13. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures: Fracture Intervention Trial Research Group. Lancet 1996; 348: 1531-41
  14. Mortensen L, Charles P, Bekker PJ, Diggenaro J, Johnston CC Jr. Risedronate increases bone mass in an early postmenopausal population: two years of treatment plus one year of follow-up. J Clin Endocrinol Metab 1998; 83: 396-402 https://doi.org/10.1210/jc.83.2.396
  15. 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 https://doi.org/10.1056/NEJM200102013440503
  16. McClung MR, Wasnich RD, Recker R, Cauley JA, Chesnut CH 3rd, Ensrud KE, et al. for the Oral Ibandronate Study Group. Oral daily ibandronate prevents bone loss in early postmenopausal women without osteoporosis. J Bone Miner Res 2004; 19: 11-8 https://doi.org/10.1359/jbmr.0301202
  17. Mellstrom DD, Sorensen OH, Goemaere S, Roux C, Johnson TD, Chines AA. Seven years of treatment with risedronate in women with postmenopausal osteoporosis. Calcif Tissue Int 2004; 75: 462-8 https://doi.org/10.1007/s00223-004-0286-7
  18. Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 2005; 90: 1294-304 https://doi.org/10.1210/jc.2004-0952
  19. Ettinger B, Black DM, Mitlack BH, Knickerbocker RK, Nickelsen T, Genant HK, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999; 282: 637-45 https://doi.org/10.1001/jama.282.7.637
  20. Delmas PD, Ensrud KE, Adachi JD, Harper KD, Sarkar S, Gennari C, et al. for the Multiple Outcomes of Raloxifene Evaluation Investigators. Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab 2002; 87: 3609-17 https://doi.org/10.1210/jc.87.8.3609
  21. Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 1999; 281: 2189-97 https://doi.org/10.1001/jama.281.23.2189
  22. Martino S, Cauley JA, Barrett-Connor E, Powles TJ, Mershon J, Disch D, et al. for CORE Investigators. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 2004; 96: 1751-61 https://doi.org/10.1093/jnci/djh319
  23. Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006; 295: 2727-41 https://doi.org/10.1001/jama.295.23.joc60074
  24. Grady D, Ettinger B, Moscarelli E, Plouffe L Jr, Sarkar S, Ciaccia A, et al. for the Multiple Outcomes of Raloxifene Evaluation Investigators. Safety and adverse effects associated with raloxifene: multiple outcomes of raloxifene evaluation. Obstet Gynecol 2004; 104: 837-44 https://doi.org/10.1097/01.AOG.0000137349.79204.b8
  25. Barrett-Connor E, Mosca L, Collins P, Geiger MJ, Grady D, Kornitzer M, et al. Raloxifene Use for The Heart (RUTH) Trial Investigators. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 2006; 355: 125-37 https://doi.org/10.1056/NEJMoa062462
  26. Wells G, Tugwell P, Shea B, Guyatt G, Peterson J, Zytaruk N, et al. for the Osteoporosis Methodology Group and the Osteoporosis Research Advisor Group. Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Endocr Rev 2002; 23: 529-39 https://doi.org/10.1210/er.2001-5002
  27. Effects of hormone therapy on bone mineral density: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. The Writing Group for the PEPI. JAMA 1996; 276: 1389-96 https://doi.org/10.1001/jama.276.17.1389
  28. Cauley JA, Robbins J, Chen Z, for the Women's Health Initiative Investigators. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial. JAMA 2003; 290: 1729-38 https://doi.org/10.1001/jama.290.13.1729
  29. Lindsay R, Gallagher JC, Kleerekoper M, Pickar JH. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA 2002; 287: 2668-76 https://doi.org/10.1001/jama.287.20.2668
  30. Prestwood KM, Kenny AM, Kleppinger A, Kulldorff M. Ultralow-dose micronized 17beta-estradiol and bone density and bone metabolism in older women: a randomized controlled trial. JAMA 2003; 290: 1042-8 https://doi.org/10.1001/jama.290.8.1042
  31. Ettinger B, Ensrud KE, Wallace R, Johnson KC, Cummings SR, Yankov V, et al. Effects of ultralow-dose transdermal estradiol on bone mineral density: a randomized clinical trial. Obstet Gynecol 2004; 104: 443-51 https://doi.org/10.1097/01.AOG.0000137833.43248.79
  32. Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, et al. for the WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA 2003; 289: 3243-53 https://doi.org/10.1001/jama.289.24.3243
  33. Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G, Kooperberg C, Baird A, et al. for the WHI Investigators. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial. JAMA 2003; 289: 2673-84 https://doi.org/10.1001/jama.289.20.2673
  34. Manson JE, Hsia J, Hohnson KC, Rossouw JE, Assaf AR, Lasser NL, et al. for the Women's Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349: 523-34 https://doi.org/10.1056/NEJMoa030808
  35. Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, et al. for the Women's Health Initiative Investigators. Estrogen plus progestin and risk of venous thrombosis. JAMA 2004; 292: 1573-80 https://doi.org/10.1001/jama.292.13.1573
  36. The North American Menopause Society. Recommendations for estrogen and progestogen use in peri-and postmenopausal women: October 2004 position statement of The North American Menopause Society. Menopause 2004; 11: 589-600 https://doi.org/10.1097/01.gme.0000145876.76178.dc
  37. Chesnut CH III, Silverman S, Andriano K, Genant H, Gimona A, Harris S, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence of Osteoporotic Fractures Study. PROOF study group. Am J Med 2000; 109: 267-76 https://doi.org/10.1016/S0002-9343(00)00490-3
  38. Pun KK, Chan LW. Analgesic effect of intranasal salmon calcitonin in the treatment of osteoporotic vertebral fractures. Clin Ther 1989; 11: 205-9
  39. Lyritis GP, Ioannidis GV, Karachalios T, Roidis N, Kataxaki E, Papaioannou N, et al. Analgesic effect of salmon calcitonin suppositories in patients with acute pain due to recent osteoporotic vertebral crush fractures: a prospective double-blind, randomized, placebo-controlled clinical study. Clin J Pain 1999; 15: 284-9 https://doi.org/10.1097/00002508-199912000-00004
  40. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001; 344: 1434-41 https://doi.org/10.1056/NEJM200105103441904
  41. Bone HG, Greenspan SL, McKeever C, Bell N, Davidson M, Downs RW, et al. Alendronate and estrogen effect in postmenopausal women with low bone mineral density. Alendronate/Estrogen Study Group. J Clin Endocrinol Metab 2000; 85: 720-6 https://doi.org/10.1210/jc.85.2.720
  42. Harris ST, Eriksen EF, Davidson M, Ettinger MP, Moffett Jr AH Jr, Baylink DJ, et al. Effect of combined risedronate and hormone replacement therapies on bone mineral density in postmenopausal women. J Clin Endocrinol Metab 2001; 86: 1890-7 https://doi.org/10.1210/jc.86.5.1890
  43. Lindsay R, Nieves J, Formica C, Henneman E, Woelfert L, Shen V, et al. Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 1997; 350: 550-5 https://doi.org/10.1016/S0140-6736(97)02342-8
  44. Black DM, Bilezikian JP, Ensrud KE, et al. for the PaTH Study Investigators. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N Engl J Med 2005; 353: 555-65 https://doi.org/10.1056/NEJMoa050336
  45. Lydeking-Olsen E, Beck-Jensen J, Setchell KDR, Holm-Jensen T. Soy milk or progesterone for prevention of bone loss-a 2year randomized, placebo-controlled trial. Eur J Nutr 2004; 43: 246-57 https://doi.org/10.1007/s00394-004-0497-8
  46. Anderson JJ, Anthony MS, Cline JM, Washburn SA, Gardner SC. Health potential of soy isoflavones for menopausal women. Pub health Nutr 1999; 2: 489-504
  47. Greendale GA, FitzGerald G, Huang MH, Sternfeld B, Gold E, Seeman T, et al. Dietary soy isoflavones and bone mineral density: results from the study of women's health across the nation. Am J Epidemiol 2002; 155: 746-54 https://doi.org/10.1093/aje/155.8.746
  48. Potter SM, Baum J, Teng H, Stillman RJ, Shay NF, Erdman JW. Soy protein and isoflavones: ther effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 1998; 68(6suppl): 1375S-9S
  49. Clifton-Bligh PB, Baber RJ, Fulcher GR, Nery ML, Moreton T. The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism. Menopause 2001; 8: 4740-7
  50. Morabito N, Crisafulli A, Vegara C. Effects of genistein and hormone-replacement therapy on bone loss in early post-menopausal women: a randomized double-blind placebo controlled study. J Bone Miner Res 2002; 17: 1904-12 https://doi.org/10.1359/jbmr.2002.17.10.1904
  51. Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A, Lampe JW, et al. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. JAMA 2004; 292: 65-74 https://doi.org/10.1001/jama.292.1.65
  52. Chen Y, Ho SC, Lam SSH, Ho SSS, Woo JLF. Soy isoflavones have favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind randomized, controlled trial. J Clin Endocrinol Metab 2003; 88: 4740-7 https://doi.org/10.1210/jc.2003-030290
  53. Gallagher JC, Satpathy R, Rafferty K, Haynatzka V. The effect of soy protein isolate on bone metabolism. Menopause 2004; 11: 290-8 https://doi.org/10.1097/01.GME.0000097845.95550.71
  54. Uesugi T, Toda T, Okuhira T, Chen JT. Evidence of estrogenic effect by the three-month intervention of isoflavone on vaginal maturation and bone metabolism in early postmenopausal women. Endocr J 2003; 50: 613-9 https://doi.org/10.1507/endocrj.50.613
  55. Sassa S, Sakamoto S, Zhou YF, Mori T, Kikuchi T, Shinoda H. Preventive effects of a Chinese herbal medicine, hochu-ekki-to, on bone loss in ovariectomized rats. In Vivo 2001; 15: 25-8
  56. Sakamoto S, Sassa S, Kudo H, Suzuki S, Mitamura T, Shinoda H. Preventive effects of a herbal medicine on bone loss in rats treated with a GnRH agonist. Eur J Endocrinol 2000; 143: 139-42 https://doi.org/10.1530/eje.0.1430139
  57. Hidaka S, Okamoto Y, Yamada Y, Kon Y, Kimura T. A Japanese herbal medicine, Chujo-to, has a beneficial effect on osteoporosis in rats. Phytother Res 1999; 13: 14-9 https://doi.org/10.1002/(SICI)1099-1573(199902)13:1<14::AID-PTR375>3.0.CO;2-V
  58. Kim HJ, Bae YC, Park RW, Choi SW, Cho SH, Choi YS, et al. Bone protecting effect of safflower seeds in ovariectomized rats. Calcif Tissue Int 2002; 71: 88-94 https://doi.org/10.1007/s00223-001-1080-4
  59. Baulieu EE, Thomas G, Legrain S. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci USA 2000; 97: 4279-84 https://doi.org/10.1073/pnas.97.8.4279
  60. Pors Nielsen S. The biological role of strontium. Bone 2004; 35: 583-8 https://doi.org/10.1016/j.bone.2004.04.026
  61. Marie PJ, Ammann P, Boivin G, Rey C. Mechanisms of action and therapeutic potential of strontium in bone. Calcif Tissue Int 2001; 69: 121-9 https://doi.org/10.1007/s002230010055
  62. Baron R, Tsouderos Y. In vitro effects of S12911-2 on osteoclast function and bone marrow macrophage differentiation. Eur J Pharmacol 2002; 450: 11-7 https://doi.org/10.1016/S0014-2999(02)02040-X
  63. Canalis E, HottM, Deloffre P, Tsouderos Y, Marie PJ. The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro. Bone 1996; 18: 517-23 https://doi.org/10.1016/8756-3282(96)00080-4
  64. Ammann P, Shen V, Robin B, Mauras Y, Bonjour JP, Rizzoli R. Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J Bone Miner Res 2004; 19: 2012-20 https://doi.org/10.1359/jbmr.040906
  65. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 2004; 350: 459-68 https://doi.org/10.1056/NEJMoa022436
  66. Reginster JY, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C, et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of peripheral osteoporosis (TROPOS) study. J Clin Endocrinol Metab 2005; 90: 2816-22 https://doi.org/10.1210/jc.2004-1774
  67. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998; 93: 165-76 https://doi.org/10.1016/S0092-8674(00)81569-X
  68. Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 2004; 19: 1059-66 https://doi.org/10.1359/JBMR.040305
  69. McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, et al. for AMG 162 Bone Loss Study Group. Denosumab in postmenopausal women with low bone mineral density. 2006; 354: 821-31 https://doi.org/10.1056/NEJMoa044459