International Journal of Oral Biology

  • 제44권1호
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  • Pages.1-7
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  • 2019
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  • 1226-7155(pISSN)
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  • 2287-6618(eISSN)
대한구강생물학회 (The Korean Academy of Oral Biology)
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Biological characteristics of osteoporosis drugs: the effect of osteoblast-osteoclast coupling

  • Kim, Sung-Jin (Department of Oral Biology, Yonsei University College of Dentistry) ;
  • Moon, Seok Jun (Department of Oral Biology, Yonsei University College of Dentistry) ;
  • Seo, Jeong Taeg (Department of Oral Biology, Yonsei University College of Dentistry)
  • 투고 : 2019.03.03
  • 심사 : 2019.03.27
  • 발행 : 2019.03.31
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초록

Osteoporosis is a common disease characterized by bone mass reduction, leading to an increased risk of bone fracture, and it is caused by an imbalance of osteoblastic bone formation and osteoclastic bone resorption. Current osteoporosis drugs aim to reduce the risk of bone fracture, either by increasing osteoblastic bone formation or decreasing osteoclastic bone resorption. However, osteoblasts and osteoclasts are closely coupled, such that any reagent altering the differentiation or activity of one eventually affects the other. This tight coupling between osteoblasts and osteoclasts not only limits the therapeutic efficacy but also threatens the safety of osteoporosis drugs. This review will discuss the biological mechanisms of action of currently approved medications for osteoporosis treatment, focusing on the osteoblast-osteoclast coupling.

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참고문헌

  1. Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R; National Osteoporosis Foundation. Clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int 2014;25:2359-81. doi: 10.1007/s00198-014-2794-2.
  2. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosisrelated fractures in the United States, 2005-2025. J Bone Miner Res 2007;22:465-75. doi: 10.1359/jbmr.061113.
  3. Chen X, Wang Z, Duan N, Zhu G, Schwarz EM, Xie C. Osteoblast-osteoclast interactions. Connect Tissue Res 2018;59:99-107. doi: 10.1080/03008207.2017.1290085.
  4. Cao X. Targeting osteoclast-osteoblast communication. Nat Med 2011;17:1344-6. doi: 10.1038/nm.2499.
  5. van Beek ER, Cohen LH, Leroy IM, Ebetino FH, Lowik CW, Papapoulos SE. Differentiating the mechanisms of antiresorptive action of nitrogen containing bisphosphonates. Bone 2003;33:805-11. doi: 10.1016/j.bone.2003.07.007.
  6. Amin D, Cornell SA, Gustafson SK, Needle SJ, Ullrich JW, Bilder GE, Perrone MH. Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis. J Lipid Res 1992;33:1657-63. https://doi.org/10.1016/S0022-2275(20)41388-4
  7. Itzstein C, Coxon FP, Rogers MJ. The regulation of osteoclast function and bone resorption by small GTPases. Small GT-Pases 2011;2:117-30. doi: 10.4161/sgtp.2.3.16453.
  8. van beek E, Lowik C, van der Pluijm G, Papapoulos S. The role of geranylgeranylation in bone resorption and its suppression by bisphosphonates in fetal bone explants in vitro: a clue to the mechanism of action of nitrogen-containing bisphosphonates. J Bone Miner Res 1999;14:722-9. doi: 10.1359/jbmr.1999.14.5.722.
  9. Wei W, Schwaid AG, Wang X, Wang X, Chen S, Chu Q, Saghatelian A, Wan Y. Ligand activation of $ERR{\alpha}$ by cholesterol mediates statin and bisphosphonate effects. Cell Metab 2016;23:479-91. doi: 10.1016/j.cmet.2015.12.010.
  10. McClung M, Harris ST, Miller PD, Bauer DC, Davison KS, Dian L, Hanley DA, Kendler DL, Yuen CK, Lewiecki EM. Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med 2013;126:13-20. doi: 10.1016/j.amjmed.2012.06.023.
  11. Maruotti N, Corrado A, Neve A, Cantatore FP. Bisphosphonates: effects on osteoblast. Eur J Clin Pharmacol 2012;68:1013-8. doi: 10.1007/s00228-012-1216-7.
  12. Naylor KE, Bradburn M, Paggiosi MA, Gossiel F, Peel NFA, McCloskey EV, Walsh JS, Eastell R. Effects of discontinuing oral bisphosphonate treatments for postmenopausal osteoporosis on bone turnover markers and bone density. Osteoporos Int 2018;29:1407-17. doi: 10.1007/s00198-018-4460-6.
  13. Pederson L, Ruan M, Westendorf JJ, Khosla S, Oursler MJ. Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. Proc Natl Acad Sci U S A 2008;105:20764-9. doi: 10.1073/pnas.0805133106.
  14. Baron R, Ferrari S, Russell RG. Denosumab and bisphosphonates: different mechanisms of action and effects. Bone 2011;48:677-92. doi: 10.1016/j.bone.2010.11.020.
  15. McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ; AMG 162 Bone Loss Study Group. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006;354:821-31. doi: 10.1056/NEJMoa044459.
  16. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756-65. doi: 10.1056/NEJMoa0809493.
  17. Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet 2019;393:364-76. doi: 10.1016/S0140-6736(18)32112-3.
  18. Khan SA, Kanis JA, Vasikaran S, Kline WF, Matuszewski BK, McCloskey EV, Beneton MN, Gertz BJ, Sciberras DG, Holland SD, Orgee J, Coombes GM, Rogers SR, Porras AG. Elimination and biochemical responses to intravenous alendronate in postmenopausal osteoporosis. J Bone Miner Res 1997;12:1700-7. doi: 10.1359/jbmr.1997.12.10.1700.
  19. Watts NB, Roux C, Modlin JF, Brown JP, Daniels A, Jackson S, Smith S, Zack DJ, Zhou L, Grauer A, Ferrari S. Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association? Osteoporos Int 2012;23:327-37. doi: 10.1007/s00198-011-1755-2.
  20. Finkelstein JS, Brockwell SE, Mehta V, Greendale GA, Sowers MR, Ettinger B, Lo JC, Johnston JM, Cauley JA, Danielson ME, Neer RM. Bone mineral density changes during the menopause transition in a multiethnic cohort of women. J Clin Endocrinol Metab 2008;93:861-8. doi: 10.1210/jc.2007-1876.
  21. Khosla S, Oursler MJ, Monroe DG. Estrogen and the skeleton. Trends Endocrinol Metab 2012;23:576-81. doi: 10.1016/j.tem.2012.03.008.
  22. Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, Harada Y, Azuma Y, Krust A, Yamamoto Y, Nishina H, Takeda S, Takayanagi H, Metzger D, Kanno J, Takaoka K, Martin TJ, Chambon P, Kato S. Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell 2007;130:811-23. doi: 10.1016/j.cell.2007.07.025.
  23. Martin-Millan M, Almeida M, Ambrogini E, Han L, Zhao H, Weinstein RS, Jilka RL, O'Brien CA, Manolagas SC. The estrogen receptor-alpha in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone. Mol Endocrinol 2010;24:323-34. doi: 10.1210/me.2009-0354.
  24. Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest 2003;111:1221-30. doi: 10.1172/JCI17215.
  25. Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL. Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 1999;140:4367-70. doi: 10.1210/endo.140.9.7131.
  26. Kousteni S, Bellido T, Plotkin LI, O'Brien CA, Bodenner DL, Han L, Han K, DiGregorio GB, Katzenellenbogen JA, Katzenellenbogen BS, Roberson PK, Weinstein RS, Jilka RL, Manolagas SC. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 2001;104:719-30. doi: 10.1016/S0092-8674(01)00268-9.
  27. Almeida M, Iyer S, Martin-Millan M, Bartell SM, Han L, Ambrogini E, Onal M, Xiong J, Weinstein RS, Jilka RL, O'Brien CA, Manolagas SC. Estrogen receptor-${\alpha}$ signaling in osteoblast progenitors stimulates cortical bone accrual. J Clin Invest 2013;123:394-404. doi: 10.1172/JCI65910.
  28. Chlebowski RT, Anderson GL, Sarto GE, Haque R, Runowicz CD, Aragaki AK, Thomson CA, Howard BV, Wactawski- Wende J, Chen C, Rohan TE, Simon MS, Reed SD, Manson JE. Continuous combined estrogen plus progestin and endometrial cancer: the Women's Health Initiative randomized trial. J Natl Cancer Inst. 2015;108:djv350. doi: 10.1093/jnci/djv350.
  29. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, LeBoff M, Lewis CE, McGowan J, Neuner J, Pettinger M, Stefanick ML, Wactawski-Wende J, Watts NB; 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. doi: 10.1001/jama.290.13.1729.
  30. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-33. doi: 10.1001/jama.288.3.321.
  31. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O'Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S; Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004;291:1701-12. doi: 10.1001/jama.291.14.1701.
  32. The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause 2017;24:728-53. doi: 10.1097/GME.0000000000000921.
  33. Pickar JH, Boucher M, Morgenstern D. Tissue selective estrogen complex (TSEC): a review. Menopause 2018;25:1033-45. doi: 10.1097/GME.0000000000001095.
  34. Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, Norton L, Nickelsen T, Bjarnason NH, Morrow M, Lippman ME, Black D, Glusman JE, Costa A, Jordan VC. 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. doi: 10.1001/jama.281.23.2189.
  35. Musa MA, Khan MO, Cooperwood JS. Medicinal chemistry and emerging strategies applied to the development of selective estrogen receptor modulators (SERMs). Curr Med Chem 2007;14:1249-61. doi: 10.2174/092986707780598023.
  36. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Gluer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR. 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. doi: 10.1001/jama.282.7.637.
  37. Silverman SL, Christiansen C, Genant HK, Vukicevic S, Zanchetta JR, de Villiers TJ, Constantine GD, Chines AA. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial. J Bone Miner Res 2008;23:1923-34. doi: 10.1359/jbmr.080710.
  38. Aslan D, Andersen MD, Gede LB, de Franca TK, Jorgensen SR, Schwarz P, Jorgensen NR. Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans. Scand J Clin Lab Invest 2012;72:14-22. doi: 10.3109/00365513.2011.624631.
  39. Locklin RM, Khosla S, Turner RT, Riggs BL. Mediators of the biphasic responses of bone to intermittent and continuously administered parathyroid hormone. J Cell Biochem 2003;89:180-90. doi: 10.1002/jcb.10490.
  40. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. 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. doi: 10.1056/NEJM200105103441904.
  41. Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, Alexandersen P, Zerbini CA, Hu MY, Harris AG, Fitzpatrick LA, Cosman F, Christiansen C; ACTIVE Study Investigators. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA 2016;316:722-33. doi: 10.1001/jama.2016.11136.
  42. Vahle JL, Sato M, Long GG, Young JK, Francis PC, Engelhardt JA, Westmore MS, Linda Y, Nold JB. Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety. Toxicol Pathol 2002;30:312-21. doi: 10.1080/01926230252929882.
  43. Pleiner-Duxneuner J, Zwettler E, Paschalis E, Roschger P, Nell-Duxneuner V, Klaushofer K. Treatment of osteoporosis with parathyroid hormone and teriparatide. Calcif Tissue Int 2009;84:159-70. doi: 10.1007/s00223-009-9218-x.
  44. Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med 2017;377:1417-27. doi: 10.1056/NEJMoa1708322.