The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
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Management of Osteoporosis: Who to Treat, What to Use, and for How Long?

골다공증 치료의 최신 지견: 누구를, 무엇으로, 얼마 동안 치료할 것인가?

  • Kim, Sang Wan (Department of Internal Medicine, Seoul National University College of Medicine, Division of Endocrinology and Metabolism Seoul Metropolitan Government Borame Medical Center)
  • 김상완 (서울대학교 의과대학 내과학교실, 서울특별시보라매병원 내분비대사내과)
  • Published : 2013.10.01
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Abstract

Osteoporosis is a huge global problem both socially and economically- in the South Korea alone, in 2011 66 million dollar was spent on treatment and social care of the 773,000 osteoporotic patients- and therefore variable preventative and therapeutic approaches are keys to managing this problem within the aging population of today. This review discusses the main issues- who should be treated, what pharmacological agents should be used, and how long they should be administered-surrounding current osteoporosis management. Identifying patients at risk is challenging before they develop a fracture. Probability of fracture based on the Korea-adapted WHO algorithm should be used in making decision of treatment. Though bisphosphonates are the most commonly used drugs for the treatment of osteoporosis, the majority of data on fracture effect is from studies of 3 or 4 years. The long-term treatment should balance fracture efficacy against the risk of adverse events. Although evidence is limited regarding the risk of fracture with the continuation of bisphosphonate therapy, it might be useful to continue treat osteoporosis up to 10 years, to prevent vertebral fractures in the high risk elderly. There are currently no data to guide clinicians in determining who should continue treatment after 5 years. The duration of treatment and the agent selected should be based on individual assessment of risks and benefits and on patient preference.

Keywords

References

  1. Choi YJ, Oh HJ, Kim DJ, Lee Y, Chung YS. The prevalence of osteoporosis in Korean adults aged 50 years or older and the higher diagnosis rates in women who were beneficiaries of a national screening program: the Korea National Health and Nutrition Examination Survey 2008-2009. J Bone Miner Res 2012;27:1879-1886.
  2. Shin CS, Choi HJ, Kim MJ, et al. Prevalence and risk factors of osteoporosis in Korea: a community-based cohort study with lumbar spine and hip bone mineral density. Bone 2010; 47:378-387. https://doi.org/10.1016/j.bone.2010.03.017
  3. Lee YK, Yoon BH, Koo KH. Epidemiology of Osteoporosis and Osteoporotic Fractures in South Korea. Endocrinol Metab 2012;28:90-93.
  4. Health Insurance Review & Assessment Service. Report [Internet]. Seoul: Health Insurance Review & Assessment Service, c2013 [cited 2013 Sep 1]. Available from: http:// www.hira.or.kr/dummy.do?pgmid=HIRAA020041000000 & cmsurl=/cms/notice/02/1316013_13390.html.
  5. National Osteoporosis Foundation. Clinician's guide to prevention and treatment of osteoporosis [Internet]. Washington, DC: National Osteoporosis Foundation, c2013 [cited 2013 Sep 1]. Available from: http://www.nof.org/hcp/clinicians-guide.
  6. Kanis JA, Oden A, Johansson H, Borgström F, Ström O, McCloskey E. FRAX and its applications to clinical practice. Bone 2009;44:734-743. https://doi.org/10.1016/j.bone.2009.01.373
  7. Dunford JE, Thompson K, Coxon FP, et al. Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogencontaining bisphosphonates. J Pharmacol Exp Ther 2001;296: 235-242.
  8. Van Beek E, Pieterman E, Cohen L, Löwik C, Papapoulos S. Nitrogen-containing bisphosphonates inhibit isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo. Biochem Biophys Res Commun 1999;255:491-494. https://doi.org/10.1006/bbrc.1999.0224
  9. Fisher JE, Rogers MJ, Halasy JM, et al. Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci U S A 1999;96:133-138. https://doi.org/10.1073/pnas.96.1.133
  10. Luckman SP, Hughes DE, Coxon FP, Graham R, Russell G, Rogers MJ. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 1998;13:581-589. https://doi.org/10.1359/jbmr.1998.13.4.581
  11. Welton JL, Morgan MP, Marti S, et al. Monocytes and $\gamma\delta$ T cells control the acute-phase response to intravenous zoledronate: insights from a phase IV safety trial. J Bone Miner Res 2013;28:464-471. https://doi.org/10.1002/jbmr.1797
  12. Khosla S, Burr D, Cauley J, et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007;22:1479-1491. https://doi.org/10.1359/jbmr.0707onj
  13. Rizzoli R. Zoledronic Acid for the treatment and prevention of primary and secondary osteoporosis. Ther Adv Musculoskelet Dis 2010;2:3-16. https://doi.org/10.1177/1759720X09352920
  14. Assael LA. Oral bisphosphonates as a cause of bisphosphonate- related osteonecrosis of the jaws: clinical findings, assessment of risks, and preventive strategies. J Oral Maxillofac Surg 2009;67(5 Suppl):35-43.
  15. Fleisher KE, Jolly A, Venkata UD, Norman RG, Saxena D, Glickman RS. Osteonecrosis of the jaw onset times are based on the route of bisphosphonate therapy. J Oral Maxillofac Surg 2013;71:513-519. https://doi.org/10.1016/j.joms.2012.07.049
  16. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate- induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 2005;63:1567-1575. https://doi.org/10.1016/j.joms.2005.07.010
  17. Shane E, Burr D, Ebeling PR, et al. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2010;25:2267-2294. https://doi.org/10.1002/jbmr.253
  18. Abrahamsen B, Einhorn TA. Beyond a reasonable doubt? b isphosphonates and atypical femur fractures. Bone 2012;50: 1196-1200. https://doi.org/10.1016/j.bone.2012.02.009
  19. Davey RA, Findlay DM. Calcitonin: physiology or fantasy? J Bone Miner Res 2013;28:973-979. https://doi.org/10.1002/jbmr.1869
  20. Shlossman M, Brown M, Shapiro E, Dziak R. Calcitonin effects on isolated bone cells. Calcif Tissue Int 1982;34: 190-196. https://doi.org/10.1007/BF02411232
  21. European Medicines Agency. Questions and answers on the review of calcitonin containing medicines: outcome of a procedure under article 31 of directive 2001/83/EC [Internet]. London: European Medicines Agency, c2012 [accessed 2013 Apr 18]. Available from: http://www.ema.europa.eu/docs/en_GB/ document_library/Press_release/2012/07/WC500130122.pdf
  22. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer: Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1997;350:1047-1059. https://doi.org/10.1016/S0140-6736(97)08233-0
  23. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-333. https://doi.org/10.1001/jama.288.3.321
  24. Delmas PD, Bjarnason NH, Mitlak BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997;337:1641-1647. https://doi.org/10.1056/NEJM199712043372301
  25. Recker RR, Kendler D, Recknor CP, et al. Comparative effects of raloxifene and alendronate on fracture outcomes in postmenopausal women with low bone mass. Bone 2007;40: 843-851. https://doi.org/10.1016/j.bone.2006.11.001
  26. Barrett-Connor E, Mosca L, Collins P, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 2006;355:125-137. https://doi.org/10.1056/NEJMoa062462
  27. Lee WL, Chao HT, Cheng MH, Wang PH. Rationale for using raloxifene to prevent both osteoporosis and breast cancer in postmenopausal women. Maturitas 2008;60:92-107. https://doi.org/10.1016/j.maturitas.2008.04.009
  28. Ming LG, Chen KM, Xian CJ. Functions and action mechanisms of flavonoids genistein and icariin in regulating bone remodeling. J Cell Physiol 2013;228:513-521. https://doi.org/10.1002/jcp.24158
  29. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756-765. https://doi.org/10.1056/NEJMoa0809493
  30. Seeman E, Delmas PD, Hanley DA, et al. Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res 2010;25: 1886-1894. https://doi.org/10.1002/jbmr.81
  31. Malan J, Ettinger K, Naumann E, Beirne OR. The relationship of denosumab pharmacology and osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:671-676. https://doi.org/10.1016/j.oooo.2012.08.439
  32. Watson PH, Hanley DA. Parathyroid hormone: regulation of synthesis and secretion. Clin Invest Med 1993;16:58-77.
  33. Reeve J, Meunier PJ, Parsons JA, et al. Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial. Br Med J 1980;280:1340-1344. https://doi.org/10.1136/bmj.280.6228.1340
  34. Finkelstein JS, Wyland JJ, Lee H, Neer RM. Effects of teriparatide, alendronate, or both in women with postmenopausal osteoporosis. J Clin Endocrinol Metab 2010;95: 1838-1845. https://doi.org/10.1210/jc.2009-1703
  35. Saag KG, Shane E, Boonen S, et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med 2007;357:2028-2039. https://doi.org/10.1056/NEJMoa071408
  36. Yamamoto T, Tsujimoto M, Hamaya E, Sowa H. Assessing the effect of baseline status of serum bone turnover markers and vitamin D levels on efficacy of teriparatide 20 $\mu{g}$/day administered subcutaneously in Japanese patients with osteoporosis. J Bone Miner Metab 2013;31:199-205. https://doi.org/10.1007/s00774-012-0403-z
  37. Jilka RL. Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone 2007;40:1434-1446. https://doi.org/10.1016/j.bone.2007.03.017
  38. Black DM, Greenspan SL, Ensrud KE, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 2003;349: 1207-1215. https://doi.org/10.1056/NEJMoa031975
  39. Miller PD, Delmas PD, Lindsay R, et al. Early responsiveness of women with osteoporosis to teriparatide after therapy with alendronate or risedronate. J Clin Endocrinol Metab 2008;93: 3785-3793. https://doi.org/10.1210/jc.2008-0353
  40. Tsai JN, Uihlein AV, Lee H, et al. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet 2013;382:50-56. https://doi.org/10.1016/S0140-6736(13)60856-9
  41. Andrews EB, Gilsenan AW, Midkiff K, et al. The US postmarketing surveillance study of adult osteosarcoma and teriparatide: study design and findings from the first 7 years. J Bone Miner Res 2012;27:2429-2437. https://doi.org/10.1002/jbmr.1768
  42. Watanabe A, Yoneyama S, Nakajima M, et al. Osteosarcoma in Sprague-Dawley rats after long-term treatment with teriparatide (human parathyroid hormone [1-34]). J Toxicol Sci 2012;37:617-629. https://doi.org/10.2131/jts.37.617
  43. Shiraki M, Sugimoto T, Nakamura T. Effects of a single injection of teriparatide on bone turnover markers in postmenopausal women. Osteoporos Int 2013;24:219-226. https://doi.org/10.1007/s00198-012-2159-7
  44. Devogelaer JP, Boutsen Y, Manicourt DH. Biologicals in osteoporosis: teriparatide and parathyroid hormone in women and men. Curr Osteoporos Rep 2010;8:154-161. https://doi.org/10.1007/s11914-010-0024-1
  45. Farra R, Sheppard NF Jr, McCabe L, et al. First-in-human testing of a wirelessly controlled drug delivery microchip. Sci Transl Med 2012;4:122ra121.
  46. Inaoka T, Bilbe G, Ishibashi O, Tezuka K, Kumegawa M, Kokubo T. Molecular cloning of human cDNA for cathepsin K: novel cysteine proteinase predominantly expressed in bone. Biochem Biophys Res Commun 1995;206:89-96. https://doi.org/10.1006/bbrc.1995.1013
  47. Li YP, Alexander M, Wucherpfennig AL, Yelick P, Chen W, Stashenko P. Cloning and complete coding sequence of a novel human cathepsin expressed in giant cells of osteoclastomas. J Bone Miner Res 1995;10:1197-1202.
  48. Gelb BD, Shi GP, Chapman HA, Desnick RJ. Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science 1996;273:1236-1238. https://doi.org/10.1126/science.273.5279.1236
  49. Saftig P, Hunziker E, Wehmeyer O, et al. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc Natl Acad Sci U S A 1998;95:13453-13458. https://doi.org/10.1073/pnas.95.23.13453
  50. Gauthier JY, Chauret N, Cromlish W, et al. The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett 2008;18:923-928. https://doi.org/10.1016/j.bmcl.2007.12.047
  51. Perez-Castrillon JL, Pinacho F, De Luis D, Lopez-Menendez M, Duenas Laita A. Odanacatib, a new drug for the treatment of osteoporosis: review of the results in postmenopausal women. J Osteoporos 2010;2010. pii: 401581.
  52. Ng KW. Potential role of odanacatib in the treatment of osteoporosis. Clin Interv Aging 2012;7:235-247.
  53. Balemans W, Ebeling M, Patel N, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 2001;10:537-543. https://doi.org/10.1093/hmg/10.5.537
  54. Lin C, Jiang X, Dai Z, et al. Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res 2009;24:1651-1661. https://doi.org/10.1359/jbmr.090411
  55. Spatz JM, Ellman R, Cloutier AM, et al. Sclerostin antibody inhibits skeletal deterioration due to reduced mechanical loading. J Bone Miner Res 2013;28:865-874. https://doi.org/10.1002/jbmr.1807
  56. Costa AG, Bilezikian JP. Sclerostin: therapeutic horizons based upon its actions. Curr Osteoporos Rep 2012;10:64-72. https://doi.org/10.1007/s11914-011-0089-5
  57. Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 2011;26: 19-26. https://doi.org/10.1002/jbmr.173
  58. Steinert AF, Rackwitz L, Gilbert F, Nöth U, Tuan RS. Concise review: the clinical application of mesenchymal stem cells for musculoskeletal regeneration: current status and perspectives. Stem Cells Transl Med 2012;1:237-247. https://doi.org/10.5966/sctm.2011-0036
  59. Guan M, Yao W, Liu R, et al. Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass. Nat Med 2012;18:456-462. https://doi.org/10.1038/nm.2665
  60. Ettinger B, Black DM, Mitlak BH, 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;282:637-645. https://doi.org/10.1001/jama.282.7.637
  61. Delmas PD, Ensrud KE, Adachi JD, et al. 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; 87:3609-3617. https://doi.org/10.1210/jcem.87.8.8750
  62. Cummings SR, Ensrud K, Delmas PD, et al. Lasofoxifene in postmenopausal women with osteoporosis. N Engl J Med 2010;362:686-696. https://doi.org/10.1056/NEJMoa0808692
  63. De Villiers TJ, Chines AA, Palacios S, et al. Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial. Osteoporos Int 2011;22:567-576. https://doi.org/10.1007/s00198-010-1302-6
  64. Silverman SL, Chines AA, Kendler DL, et al. Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study. Osteoporos Int 2012; 23:351-363. https://doi.org/10.1007/s00198-011-1691-1
  65. Siris ES, Harris ST, Eastell R, et al. Skeletal effects of raloxifene after 8 years: results from the continuing outcomes relevant to Evista (CORE) Study. J Bone Miner Res 2005; 20:1514-1524. https://doi.org/10.1359/JBMR.050509
  66. Lippman ME, Cummings SR, Disch DP, et al. Effect of raloxifene on the incidence of invasive breast cancer in postmenopausal women with osteoporosis categorized by breast cancer risk. Clin Cancer Res 2006;12:5242-5247. https://doi.org/10.1158/1078-0432.CCR-06-0688
  67. Martino S, Cauley JA, Barrett-Connor E, et al. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 2004;96:1751-1761. https://doi.org/10.1093/jnci/djh319
  68. Whitaker M, Guo J, Kehoe T, Benson G. Bisphosphonates for osteoporosis: where do we go from here? N Engl J Med 2012;366:2048-2051. https://doi.org/10.1056/NEJMp1202619
  69. Sorensen OH, Crawford GM, Mulder H, et al. Long-term efficacy of risedronate: a 5-year placebo-controlled clinical experience. Bone 2003;32:120-126. https://doi.org/10.1016/S8756-3282(02)00946-8
  70. Black DM, Schwartz AV, Ensrud KE, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 2006;296:2927-2938. https://doi.org/10.1001/jama.296.24.2927
  71. Ensrud KE, Barrett-Connor EL, Schwartz A, et al. 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;19:1259-1269. https://doi.org/10.1359/JBMR.040326
  72. Black DM, Bauer DC, Schwartz AV, Cummings SR, Rosen CJ. Continuing bisphosphonate treatment for osteoporosis: for whom and for how long? N Engl J Med 2012;366: 2051-2053. https://doi.org/10.1056/NEJMp1202623
  73. Bone HG, Hosking D, Devogelaer JP, et al. Ten years' experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 2004;350:1189-1199. https://doi.org/10.1056/NEJMoa030897
  74. Mellström 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;75:462-468. https://doi.org/10.1007/s00223-004-0286-7
  75. Devogelaer JP, Brown JP, Burckhardt P, et al. Zoledronic acid efficacy and safety over five years in postmenopausal osteoporosis. Osteoporos Int 2007;18:1211-1218. https://doi.org/10.1007/s00198-007-0367-3
  76. Papapoulos S, Chapurlat R, Libanati C, et al. Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension. J Bone Miner Res 2012;27:694-701. https://doi.org/10.1002/jbmr.1479
  77. Miller PD, Bolognese MA, Lewiecki EM, et al. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone 2008;43:222-229. https://doi.org/10.1016/j.bone.2008.04.007
  78. Miller PD, Wagman RB, Peacock M, et al. Effect of denosumab on bone mineral density and biochemical markers of bone turnover: six-year results of a phase 2 clinical trial. J Clin Endocrinol Metab 2011;96:394-402. https://doi.org/10.1210/jc.2010-1805

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