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Review Article

骨质疏松症：药物发展的机制、分子目标及现状

卷 28, 期 8, 2021

发表于: 30 March, 2020

页: [1489 - 1507] 页: 19

弟呕挨: 10.2174/0929867327666200330142432

价格: $65

摘要

骨质疏松症是由于骨重塑失衡导致的骨质病理改变，破骨细胞介导的骨吸收超过了成骨细胞介导的骨形成，导致骨骼脆弱和骨折。 抗吸收剂，例如双膦酸盐和SERM，以及刺激骨形成的合成代谢药物，包括PTH类似物和硬化蛋白抑制剂，是目前治疗骨质疏松症的方法。 尽管具有疗效，但严重的副作用和药效下降可能会限制单一药物的长期使用。 当前药物的顺序和组合使用，例如从合成代谢药物转换为抗吸收药物，可能会提供另一种方法。 此外，正在开发针对新兴目标的新药，例如组织蛋白酶K和17β-HSD2，它们的副作用可能较小。 这篇综述将总结骨质疏松症的分子机制，目前用于骨质疏松症治疗的药物以及新药开发策略。

关键词: 骨质疏松症，骨骼重塑，破骨细胞，成骨细胞，骨细胞，抗吸收药物，合成代谢药物。

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[1]
Armas, L.A.; Recker, R.R. Pathophysiology of osteoporosis: new mechanistic insights. Endocrinol. Metab. Clin. North Am., 2012, 41(3), 475-486.
[http://dx.doi.org/10.1016/j.ecl.2012.04.006] [PMID: 22877425]
[2]
Reid, I.R. Short-term and long-term effects of osteoporosis therapies. Nat. Rev. Endocrinol., 2015, 11(7), 418-428.
[http://dx.doi.org/10.1038/nrendo.2015.71] [PMID: 25963272]
[3]
Burge, R.; Dawson-Hughes, B.; Solomon, D.H.; Wong, J.B.; King, A.; Tosteson, A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J. Bone Miner. Res., 2007, 22(3), 465-475.
[http://dx.doi.org/10.1359/jbmr.061113] [PMID: 17144789]
[4]
Coughlan, T.; Dockery, F. Osteoporosis and fracture risk in older people. Clin. Med. (Lond.), 2014, 14(2), 187-191.
[http://dx.doi.org/10.7861/clinmedicine.14-2-187] [PMID: 24715132]
[5]
Ström, O.; Borgström, F.; Kanis, J.A.; Compston, J.; Cooper, C.; McCloskey, E.V.; Jönsson, B. Osteoporosis: burden, health care provision and opportunities in the EU: a report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch. Osteoporos., 2011, 6, 59-155.
[http://dx.doi.org/10.1007/s11657-011-0060-1] [PMID: 22886101]
[6]
Brown, C. Osteoporosis: Staying strong. Nature, 2017, 550(7674), S15-S17.
[http://dx.doi.org/10.1038/550S15a] [PMID: 28976955]
[7]
Chen, H.; Senda, T.; Kubo, K.Y. The osteocyte plays multiple roles in bone remodeling and mineral homeostasis. Med. Mol. Morphol., 2015, 48(2), 61-68.
[http://dx.doi.org/10.1007/s00795-015-0099-y] [PMID: 25791218]
[8]
Raggatt, L.J.; Partridge, N.C. Cellular and molecular mechanisms of bone remodeling. J. Biol. Chem., 2010, 285(33), 25103-25108.
[http://dx.doi.org/10.1074/jbc.R109.041087] [PMID: 20501658]
[9]
Canalis, E. Wnt signalling in osteoporosis: mechanisms and novel therapeutic approaches. Nat. Rev. Endocrinol., 2013, 9(10), 575-583.
[http://dx.doi.org/10.1038/nrendo.2013.154] [PMID: 23938284]
[10]
Alexandre, C.; Vico, L. Pathophysiology of bone loss in disuse osteoporosis. Joint Bone Spine, 2011, 78(6), 572-576.
[http://dx.doi.org/10.1016/j.jbspin.2011.04.007] [PMID: 21664854]
[11]
Doty, S.B.; DiCarlo, E.F. Pathophysiology of immobilization osteoporosis. Curr. Opin. Orthop., 1995, 6(5), 45-49.
[http://dx.doi.org/10.1097/00001433-199510000-00008] [PMID: 11541523]
[12]
Sibonga, J.D. Spaceflight-induced bone loss: is there an osteoporosis risk? Curr. Osteoporos. Rep., 2013, 11(2), 92-98.
[http://dx.doi.org/10.1007/s11914-013-0136-5] [PMID: 23564190]
[13]
Mazziotti, G.; Formenti, A.M.; Adler, R.A.; Bilezikian, J.P.; Grossman, A.; Sbardella, E.; Minisola, S.; Giustina, A. Glucocorticoid-induced osteoporosis: pathophysiological role of GH/IGF-I and PTH/VITAMIN D axes, treatment options and guidelines. Endocrine, 2016, 54(3), 603-611.
[http://dx.doi.org/10.1007/s12020-016-1146-8] [PMID: 27766553]
[14]
Whittier, X.; Saag, K.G. Glucocorticoid-induced Osteoporosis. Rheum. Dis. Clin. North Am., 2016, 42(1), 177-189. x.
[http://dx.doi.org/10.1016/j.rdc.2015.08.005] [PMID: 26611558]
[15]
Kim, H.Y.; Kim, Y. Associations of obesity with osteoporosis and metabolic syndrome in Korean postmenopausal women: a cross-sectional study using national survey data. Arch. Osteoporos., 2019, 14(1), 64.
[http://dx.doi.org/10.1007/s11657-019-0615-0] [PMID: 31218525]
[16]
Xiao, W.; Li, S.; Pacios, S.; Wang, Y.; Graves, D.T. Bone remodeling under pathological conditions. Front. Oral Biol., 2016, 18, 17-27.
[http://dx.doi.org/10.1159/000351896] [PMID: 26599114]
[17]
Guo, L.; Xu, J.; Qi, J.; Zhang, L.; Wang, J.; Liang, J.; Qian, N.; Zhou, H.; Wei, L.; Deng, L. MicroRNA-17-92a upregulation by estrogen leads to Bim targeting and inhibition of osteoblast apoptosis. J. Cell Sci., 2013, 126(Pt 4), 978-988.
[http://dx.doi.org/10.1242/jcs.117515] [PMID: 23264746]
[18]
Yuan, F.L.; Xu, R.S.; Jiang, D.L.; He, X.L.; Su, Q.; Jin, C.; Li, X. Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF-κB and PI3K/Akt signaling pathways. Bone, 2015, 75, 128-137.
[http://dx.doi.org/10.1016/j.bone.2015.02.017] [PMID: 25708053]
[19]
Suchacki, K.J.; Cawthorn, W.P.; Rosen, C.J. Bone marrow adipose tissue: formation, function and regulation. Curr. Opin. Pharmacol., 2016, 28, 50-56.
[http://dx.doi.org/10.1016/j.coph.2016.03.001] [PMID: 27022859]
[20]
Aspray, T.J.; Hill, T.R. Osteoporosis and the ageing skeleton. Subcell. Biochem., 2019, 91, 453-476.
[http://dx.doi.org/10.1007/978-981-13-3681-2_16] [PMID: 30888662]
[21]
Khosla, S.; Hofbauer, L.C. Osteoporosis treatment: recent developments and ongoing challenges. Lancet Diabetes Endocrinol., 2017, 5(11), 898-907.
[http://dx.doi.org/10.1016/S2213-8587(17)30188-2] [PMID: 28689769]
[22]
Hasegawa, T.; Amizuka, N. [Bone remodeling and modeling/mini-modeling]. Clin. Calcium, 2017, 27(12), 1713-1722.
[PMID: 29179165]
[23]
Sølling, A.S.K.; Harsløf, T.; Langdahl, B. Current status of bone-forming therapies for the management of osteoporosis. Drugs Aging, 2019, 36(7), 625-638.
[http://dx.doi.org/10.1007/s40266-019-00675-8] [PMID: 31066015]
[24]
Cano, A.; Chedraui, P.; Goulis, D.G.; Lopes, P.; Mishra, G.; Mueck, A.; Senturk, L.M.; Simoncini, T.; Stevenson, J.C.; Stute, P.; Tuomikoski, P.; Rees, M.; Lambrinoudaki, I. Calcium in the prevention of postmenopausal osteoporosis: EMAS clinical guide. Maturitas, 2018, 107, 7-12.
[http://dx.doi.org/10.1016/j.maturitas.2017.10.004] [PMID: 29169584]
[25]
Paschalis, E.P.; Gamsjaeger, S.; Hassler, N.; Fahrleitner-Pammer, A.; Dobnig, H.; Stepan, J.J.; Pavo, I.; Eriksen, E.F.; Klaushofer, K. Vitamin D and calcium supplementation for three years in postmenopausal osteoporosis significantly alters bone mineral and organic matrix quality. Bone, 2017, 95, 41-46.
[http://dx.doi.org/10.1016/j.bone.2016.11.002] [PMID: 27826025]
[26]
Weaver, C.M.; Alexander, D.D.; Boushey, C.J.; Dawson-Hughes, B.; Lappe, J.M.; LeBoff, M.S.; Liu, S.; Looker, A.C.; Wallace, T.C.; Wang, D.D. Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos. Int., 2016, 27(1), 367-376.
[http://dx.doi.org/10.1007/s00198-015-3386-5] [PMID: 26510847]
[27]
Pagnotti, G.M.; Styner, M.; Uzer, G.; Patel, V.S.; Wright, L.E.; Ness, K.K.; Guise, T.A.; Rubin, J.; Rubin, C.T. Combating osteoporosis and obesity with exercise: leveraging cell mechanosensitivity. Nat. Rev. Endocrinol., 2019, 15(6), 339-355.
[http://dx.doi.org/10.1038/s41574-019-0170-1] [PMID: 30814687]
[28]
Feng, X.; McDonald, J.M. Disorders of bone remodeling. Annu. Rev. Pathol., 2011, 6, 121-145.
[http://dx.doi.org/10.1146/annurev-pathol-011110-130203] [PMID: 20936937]
[29]
Drake, M.T.; Clarke, B.L.; Khosla, S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin. Proc., 2008, 83(9), 1032-1045.
[http://dx.doi.org/10.4065/83.9.1032] [PMID: 18775204]
[30]
Levin, V.A.; Jiang, X.; Kagan, R. Estrogen therapy for osteoporosis in the modern era. Osteoporos. Int., 2018, 29(5), 1049-1055.
[http://dx.doi.org/10.1007/s00198-018-4414-z] [PMID: 29520604]
[31]
Ellis, A.J.; Hendrick, V.M.; Williams, R.; Komm, B.S. Selective estrogen receptor modulators in clinical practice: a safety overview. Expert Opin. Drug Saf., 2015, 14(6), 921-934.
[http://dx.doi.org/10.1517/14740338.2015.1014799] [PMID: 25936229]
[32]
Guañabens, N.; Moro-Álvarez, M.J.; Casado, E.; Blanch-Rubió, J.; Gómez-Alonso, C.; Díaz-Guerra, G.M.; Del Pino-Montes, J.; Valero Díaz de Lamadrid, C.; Peris, P.; Muñoz-Torres, M.; Group, S.W. The next step after anti-osteoporotic drug discontinuation: an up-to-date review of sequential treatment. Endocrine, 2019, 64(3), 441-455.
[http://dx.doi.org/10.1007/s12020-019-01919-8] [PMID: 30963388]
[33]
Xu, Z.; Fan, C.; Zhao, X.; Tao, H. Treatment of osteoporosis with eldecalcitol, a new vitamin D analog: a comprehensive review and meta-analysis of randomized clinical trials. Drug Des. Devel. Ther., 2016, 10, 509-517.
[http://dx.doi.org/10.2147/dddt.s84264] [PMID: 26869769]
[34]
Noguchi, Y.; Kawate, H.; Nomura, M.; Takayanagi, R. Eldecalcitol for the treatment of osteoporosis. Clin. Interv. Aging, 2013, 8, 1313-1321.
[http://dx.doi.org/10.2147/cia.s49825] [PMID: 24101867]
[35]
Iba, K.; Sonoda, T.; Takada, J.; Dohke, T.; Yamashita, T. Further significant effects of eldecalcitol on bone resorption markers and bone mineral density in postmenopausal osteoporosis patients having undergone long-term bisphosphonate treatment. J. Bone Miner. Metab., 2017, 35(2), 171-176.
[http://dx.doi.org/10.1007/s00774-016-0738-y] [PMID: 26832388]
[36]
Cornish, J.; Callon, K.E.; Bava, U.; Kamona, S.A.; Cooper, G.J.; Reid, I.R. Effects of calcitonin, amylin, and calcitonin gene-related peptide on osteoclast development. Bone, 2001, 29(2), 162-168.
[http://dx.doi.org/10.1016/S8756-3282(01)00494-X] [PMID: 11502478]
[37]
Cosman, F.; Crittenden, D.B.; Adachi, J.D.; Binkley, N.; Czerwinski, E.; Ferrari, S.; Hofbauer, L.C.; Lau, E.; Lewiecki, E.M.; Miyauchi, A.; Zerbini, C.A.; Milmont, C.E.; Chen, L.; Maddox, J.; Meisner, P.D.; Libanati, C.; Grauer, A. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N. Engl. J. Med., 2016, 375(16), 1532-1543.
[http://dx.doi.org/10.1056/NEJMoa1607948] [PMID: 27641143]
[38]
Khosla, S.; Shane, E. A crisis in the treatment of osteoporosis. J. Bone Miner. Res., 2016, 31(8), 1485-1487.
[http://dx.doi.org/10.1002/jbmr.2888] [PMID: 27335158]
[39]
Komori, T. Functions of the osteocyte network in the regulation of bone mass. Cell Tissue Res., 2013, 352(2), 191-198.
[http://dx.doi.org/10.1007/s00441-012-1546-x] [PMID: 23329124]
[40]
Heino, T.J.; Hentunen, T.A.; Väänänen, H.K. Osteocytes inhibit osteoclastic bone resorption through transforming growth factor-beta: enhancement by estrogen. J. Cell. Biochem., 2002, 85(1), 185-197.
[http://dx.doi.org/10.1002/jcb.10109] [PMID: 11891862]
[41]
Katsimbri, P. The biology of normal bone remodelling. Eur. J. Cancer Care (Engl.), 2017, 26(6)
[http://dx.doi.org/10.1111/ecc.12740] [PMID: 28786518]
[42]
McHugh, K.P.; Hodivala-Dilke, K.; Zheng, M.H.; Namba, N.; Lam, J.; Novack, D.; Feng, X.; Ross, F.P.; Hynes, R.O.; Teitelbaum, S.L. Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts. J. Clin. Invest., 2000, 105(4), 433-440.
[http://dx.doi.org/10.1172/JCI8905] [PMID: 10683372]
[43]
Ono, T.; Nakashima, T. Recent advances in osteoclast biology. Histochem. Cell Biol., 2018, 149(4), 325-341.
[http://dx.doi.org/10.1007/s00418-018-1636-2] [PMID: 29392395]
[44]
Martin, T.J.; Sims, N.A. Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol. Med., 2005, 11(2), 76-81.
[http://dx.doi.org/10.1016/j.molmed.2004.12.004] [PMID: 15694870]
[45]
Tang, Y.; Wu, X.; Lei, W.; Pang, L.; Wan, C.; Shi, Z.; Zhao, L.; Nagy, T.R.; Peng, X.; Hu, J.; Feng, X.; Van Hul, W.; Wan, M.; Cao, X. TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat. Med., 2009, 15(7), 757-765.
[http://dx.doi.org/10.1038/nm.1979] [PMID: 19584867]
[46]
Lind, M.; Deleuran, B.; Thestrup-Pedersen, K.; Søballe, K.; Eriksen, E.F.; Bünger, C. Chemotaxis of human osteoblasts. Effects of osteotropic growth factors. APMIS, 1995, 103(2), 140-146.
[http://dx.doi.org/10.1111/j.1699-0463.1995.tb01089.x] [PMID: 7748538]
[47]
Bala, Y.; Farlay, D.; Delmas, P.D.; Meunier, P.J.; Boivin, G. Time sequence of secondary mineralization and microhardness in cortical and cancellous bone from ewes. Bone, 2010, 46(4), 1204-1212.
[http://dx.doi.org/10.1016/j.bone.2009.11.032] [PMID: 19969115]
[48]
Pettit, A.R.; Chang, M.K.; Hume, D.A.; Raggatt, L.J. Osteal macrophages: a new twist on coupling during bone dynamics. Bone, 2008, 43(6), 976-982.
[http://dx.doi.org/10.1016/j.bone.2008.08.128] [PMID: 18835590]
[49]
Mellis, D.J.; Itzstein, C.; Helfrich, M.H.; Crockett, J.C. The skeleton: a multi-functional complex organ: the role of key signalling pathways in osteoclast differentiation and in bone resorption. J. Endocrinol., 2011, 211(2), 131-143.
[http://dx.doi.org/10.1530/JOE-11-0212] [PMID: 21903860]
[50]
Kwon, O.H.; Lee, C.K.; Lee, Y.I.; Paik, S.G.; Lee, H.J. The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors. Biochem. Biophys. Res. Commun., 2005, 335(2), 437-446.
[http://dx.doi.org/10.1016/j.bbrc.2005.07.092] [PMID: 16083856]
[51]
Boyce, B.F. Advances in the regulation of osteoclasts and osteoclast functions. J. Dent. Res., 2013, 92(10), 860-867.
[http://dx.doi.org/10.1177/0022034513500306] [PMID: 23906603]
[52]
Thu, Y.M.; Richmond, A. NF-κB inducing kinase: a key regulator in the immune system and in cancer. Cytokine Growth Factor Rev., 2010, 21(4), 213-226.
[http://dx.doi.org/10.1016/j.cytogfr.2010.06.002] [PMID: 20685151]
[53]
Yamashita, T.; Yao, Z.; Li, F.; Zhang, Q.; Badell, I.R.; Schwarz, E.M.; Takeshita, S.; Wagner, E.F.; Noda, M.; Matsuo, K.; Xing, L.; Boyce, B.F. NF-kappaB p50 and p52 regulate receptor activator of NF-kappaB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1. J. Biol. Chem., 2007, 282(25), 18245-18253.
[http://dx.doi.org/10.1074/jbc.M610701200] [PMID: 17485464]
[54]
Matsumoto, M.; Kogawa, M.; Wada, S.; Takayanagi, H.; Tsujimoto, M.; Katayama, S.; Hisatake, K.; Nogi, Y. Essential role of p38 mitogen-activated protein kinase in cathepsin K gene expression during osteoclastogenesis through association of NFATc1 and PU.1. J. Biol. Chem., 2004, 279(44), 45969-45979.
[http://dx.doi.org/10.1074/jbc.M408795200] [PMID: 15304486]
[55]
Irie, A.; Yamamoto, K.; Miki, Y.; Murakami, M. Phosphatidylethanolamine dynamics are required for osteoclast fusion. Sci. Rep., 2017, 7, 46715.
[http://dx.doi.org/10.1038/srep46715] [PMID: 28436434]
[56]
McGill, G.G.; Horstmann, M.; Widlund, H.R.; Du, J.; Motyckova, G.; Nishimura, E.K.; Lin, Y.L.; Ramaswamy, S.; Avery, W.; Ding, H.F.; Jordan, S.A.; Jackson, I.J.; Korsmeyer, S.J.; Golub, T.R.; Fisher, D.E. Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. Cell, 2002, 109(6), 707-718.
[http://dx.doi.org/10.1016/S0092-8674(02)00762-6] [PMID: 12086670]
[57]
Hikita, A.; Yana, I.; Wakeyama, H.; Nakamura, M.; Kadono, Y.; Oshima, Y.; Nakamura, K.; Seiki, M.; Tanaka, S. Negative regulation of osteoclastogenesis by ectodomain shedding of receptor activator of NF-kappaB ligand. J. Biol. Chem., 2006, 281(48), 36846-36855.
[http://dx.doi.org/10.1074/jbc.M606656200] [PMID: 17018528]
[58]
Nakashima, T.; Hayashi, M.; Fukunaga, T.; Kurata, K.; Oh-Hora, M.; Feng, J.Q.; Bonewald, L.F.; Kodama, T.; Wutz, A.; Wagner, E.F.; Penninger, J.M.; Takayanagi, H. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat. Med., 2011, 17(10), 1231-1234.
[http://dx.doi.org/10.1038/nm.2452] [PMID: 21909105]
[59]
Bucay, N.; Sarosi, I.; Dunstan, C.R.; Morony, S.; Tarpley, J.; Capparelli, C.; Scully, S.; Tan, H.L.; Xu, W.; Lacey, D.L.; Boyle, W.J.; Simonet, W.S. osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev., 1998, 12(9), 1260-1268.
[http://dx.doi.org/10.1101/gad.12.9.1260] [PMID: 9573043]
[60]
Cummings, S.R.; San Martin, J.; McClung, M.R.; Siris, E.S.; Eastell, R.; Reid, I.R.; Delmas, P.; Zoog, H.B.; 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(8), 756-765.
[http://dx.doi.org/10.1056/NEJMoa0809493] [PMID: 19671655]
[61]
Komori, T. Regulation of osteoblast differentiation by transcription factors. J. Cell. Biochem., 2006, 99(5), 1233-1239.
[http://dx.doi.org/10.1002/jcb.20958] [PMID: 16795049]
[62]
Komori, T. Regulation of osteoblast differentiation by Runx2. Adv. Exp. Med. Biol., 2010, 658, 43-49.
[http://dx.doi.org/10.1007/978-1-4419-1050-9_5] [PMID: 19950014]
[63]
Nakashima, K.; Zhou, X.; Kunkel, G.; Zhang, Z.; Deng, J.M.; Behringer, R.R.; de Crombrugghe, B. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell, 2002, 108(1), 17-29.
[http://dx.doi.org/10.1016/S0092-8674(01)00622-5] [PMID: 11792318]
[64]
Gaur, T.; Lengner, C.J.; Hovhannisyan, H.; Bhat, R.A.; Bodine, P.V.; Komm, B.S.; Javed, A.; van Wijnen, A.J.; Stein, J.L.; Stein, G.S.; Lian, J.B. Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J. Biol. Chem., 2005, 280(39), 33132-33140.
[http://dx.doi.org/10.1074/jbc.M500608200] [PMID: 16043491]
[65]
Hill, T.P.; Später, D.; Taketo, M.M.; Birchmeier, W.; Hartmann, C. Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev. Cell, 2005, 8(5), 727-738.
[http://dx.doi.org/10.1016/j.devcel.2005.02.013] [PMID: 15866163]
[66]
Hu, H.; Hilton, M.J.; Tu, X.; Yu, K.; Ornitz, D.M.; Long, F. Sequential roles of hedgehog and Wnt signaling in osteoblast development. Development, 2005, 132(1), 49-60.
[http://dx.doi.org/10.1242/dev.01564] [PMID: 15576404]
[67]
Maruyama, Z.; Yoshida, C.A.; Furuichi, T.; Amizuka, N.; Ito, M.; Fukuyama, R.; Miyazaki, T.; Kitaura, H.; Nakamura, K.; Fujita, T.; Kanatani, N.; Moriishi, T.; Yamana, K.; Liu, W.; Kawaguchi, H.; Nakamura, K.; Komori, T. Runx2 determines bone maturity and turnover rate in postnatal bone development and is involved in bone loss in estrogen deficiency. Dev. Dyn., 2007, 236(7), 1876-1890.
[http://dx.doi.org/10.1002/dvdy.21187] [PMID: 17497678]
[68]
Liu, W.; Toyosawa, S.; Furuichi, T.; Kanatani, N.; Yoshida, C.; Liu, Y.; Himeno, M.; Narai, S.; Yamaguchi, A.; Komori, T. Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures. J. Cell Biol., 2001, 155(1), 157-166.
[http://dx.doi.org/10.1083/jcb.200105052] [PMID: 11581292]
[69]
Xiao, Z.S.; Hjelmeland, A.B.; Quarles, L.D. Selective deficiency of the “bone-related” Runx2-II unexpectedly preserves osteoblast-mediated skeletogenesis. J. Biol. Chem., 2004, 279(19), 20307-20313.
[http://dx.doi.org/10.1074/jbc.M401109200] [PMID: 15007057]
[70]
Xiao, Z.; Awad, H.A.; Liu, S.; Mahlios, J.; Zhang, S.; Guilak, F.; Mayo, M.S.; Quarles, L.D. Selective Runx2-II deficiency leads to low-turnover osteopenia in adult mice. Dev. Biol., 2005, 283(2), 345-356.
[http://dx.doi.org/10.1016/j.ydbio.2005.04.028] [PMID: 15936013]
[71]
Adhami, M.D.; Rashid, H.; Chen, H.; Clarke, J.C.; Yang, Y.; Javed, A. Loss of runx2 in committed osteoblasts impairs postnatal skeletogenesis. J. Bone Miner. Res., 2015, 30(1), 71-82.
[http://dx.doi.org/10.1002/jbmr.2321] [PMID: 25079226]
[72]
Adhami, M.D.; Rashid, H.; Chen, H.; Javed, A. Runx2 activity in committed osteoblasts is not essential for embryonic skeletogenesis. Connect. Tissue Res., 2014, 55(Suppl. 1), 102-106.
[http://dx.doi.org/10.3109/03008207.2014.923873] [PMID: 25158191]
[73]
Komori, T. Runx2, an inducer of osteoblast and chondrocyte differentiation. Histochem. Cell Biol., 2018, 149(4), 313-323.
[http://dx.doi.org/10.1007/s00418-018-1640-6] [PMID: 29356961]
[74]
Vimalraj, S.; Arumugam, B.; Miranda, P.J.; Selvamurugan, N. Runx2: Structure, function, and phosphorylation in osteoblast differentiation. Int. J. Biol. Macromol., 2015, 78, 202-208.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.04.008] [PMID: 25881954]
[75]
Pacifici, R. T cells, osteoblasts, and osteocytes: interacting lineages key for the bone anabolic and catabolic activities of parathyroid hormone. Ann. N. Y. Acad. Sci., 2016, 1364, 11-24.
[http://dx.doi.org/10.1111/nyas.12969] [PMID: 26662934]
[76]
Kramer, I.; Halleux, C.; Keller, H.; Pegurri, M.; Gooi, J.H.; Weber, P.B.; Feng, J.Q.; Bonewald, L.F.; Kneissel, M. Osteocyte Wnt/beta-catenin signaling is required for normal bone homeostasis. Mol. Cell. Biol., 2010, 30(12), 3071-3085.
[http://dx.doi.org/10.1128/MCB.01428-09] [PMID: 20404086]
[77]
Monroe, D.G.; McGee-Lawrence, M.E.; Oursler, M.J.; Westendorf, J.J. Update on Wnt signaling in bone cell biology and bone disease. Gene, 2012, 492(1), 1-18.
[http://dx.doi.org/10.1016/j.gene.2011.10.044] [PMID: 22079544]
[78]
Robinson, J.A.; Chatterjee-Kishore, M.; Yaworsky, P.J.; Cullen, D.M.; Zhao, W.; Li, C.; Kharode, Y.; Sauter, L.; Babij, P.; Brown, E.L.; Hill, A.A.; Akhter, M.P.; Johnson, M.L.; Recker, R.R.; Komm, B.S.; Bex, F.J. Wnt/beta-catenin signaling is a normal physiological response to mechanical loading in bone. J. Biol. Chem., 2006, 281(42), 31720-31728.
[http://dx.doi.org/10.1074/jbc.M602308200] [PMID: 16908522]
[79]
Liu, C.; Li, Y.; Semenov, M.; Han, C.; Baeg, G.H.; Tan, Y.; Zhang, Z.; Lin, X.; He, X. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell, 2002, 108(6), 837-847.
[http://dx.doi.org/10.1016/S0092-8674(02)00685-2] [PMID: 11955436]
[80]
Chen, Q.; Shou, P.; Zheng, C.; Jiang, M.; Cao, G.; Yang, Q.; Cao, J.; Xie, N.; Velletri, T.; Zhang, X.; Xu, C.; Zhang, L.; Yang, H.; Hou, J.; Wang, Y.; Shi, Y. Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? Cell Death Differ., 2016, 23(7), 1128-1139.
[http://dx.doi.org/10.1038/cdd.2015.168] [PMID: 26868907]
[81]
Behrens, J.; von Kries, J.P.; Kühl, M.; Bruhn, L.; Wedlich, D.; Grosschedl, R.; Birchmeier, W. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature, 1996, 382(6592), 638-642.
[http://dx.doi.org/10.1038/382638a0] [PMID: 8757136]
[82]
Bennett, C.N.; Longo, K.A.; Wright, W.S.; Suva, L.J.; Lane, T.F.; Hankenson, K.D.; MacDougald, O.A. Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc. Natl. Acad. Sci. USA, 2005, 102(9), 3324-3329.
[http://dx.doi.org/10.1073/pnas.0408742102] [PMID: 15728361]
[83]
Baron, R.; Gori, F. Targeting WNT signaling in the treatment of osteoporosis. Curr. Opin. Pharmacol., 2018, 40, 134-141.
[http://dx.doi.org/10.1016/j.coph.2018.04.011] [PMID: 29753194]
[84]
Tatsumi, S.; Ishii, K.; Amizuka, N.; Li, M.; Kobayashi, T.; Kohno, K.; Ito, M.; Takeshita, S.; Ikeda, K. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab., 2007, 5(6), 464-475.
[http://dx.doi.org/10.1016/j.cmet.2007.05.001] [PMID: 17550781]
[85]
Schaffler, M.B.; Cheung, W.Y.; Majeska, R.; Kennedy, O. Osteocytes: master orchestrators of bone. Calcif. Tissue Int., 2014, 94(1), 5-24.
[http://dx.doi.org/10.1007/s00223-013-9790-y] [PMID: 24042263]
[86]
Bonewald, L.F.; Johnson, M.L. Osteocytes, mechanosensing and Wnt signaling. Bone, 2008, 42(4), 606-615.
[http://dx.doi.org/10.1016/j.bone.2007.12.224] [PMID: 18280232]
[87]
Yee, C.S.; Manilay, J.O.; Chang, J.C.; Hum, N.R.; Murugesh, D.K.; Bajwa, J.; Mendez, M.E.; Economides, A.E.; Horan, D.J.; Robling, A.G.; Loots, G.G. Conditional Deletion of Sost in MSC-Derived Lineages Identifies Specific Cell-Type Contributions to Bone Mass and B-Cell Development. J. Bone Miner. Res., 2018, 33(10), 1748-1759.
[http://dx.doi.org/10.1002/jbmr.3467] [PMID: 29750826]
[88]
Witcher, P.C.; Miner, S.E.; Horan, D.J.; Bullock, W.A.; Lim, K.E.; Kang, K.S.; Adaniya, A.L.; Ross, R.D.; Loots, G.G.; Robling, A.G. Sclerostin neutralization unleashes the osteoanabolic effects of Dkk1 inhibition. JCI Insight, 2018, 3(11), 98673.
[http://dx.doi.org/10.1172/jci.insight.98673] [PMID: 29875318]
[89]
Colditz, J.; Thiele, S.; Baschant, U.; Niehrs, C.; Bonewald, L.F.; Hofbauer, L.C.; Rauner, M. Postnatal skeletal deletion of dickkopf-1 increases bone formation and bone volume in male and female mice, despite increased sclerostin expression. J. Bone Miner. Res., 2018, 33(9), 1698-1707.
[http://dx.doi.org/10.1002/jbmr.3463] [PMID: 29734465]
[90]
Xiao, Z.; Baudry, J.; Cao, L.; Huang, J.; Chen, H.; Yates, C.R.; Li, W.; Dong, B.; Waters, C.M.; Smith, J.C.; Quarles, L.D. Polycystin-1 interacts with TAZ to stimulate osteoblastogenesis and inhibit adipogenesis. J. Clin. Invest., 2018, 128(1), 157-174.
[http://dx.doi.org/10.1172/JCI93725] [PMID: 29202470]
[91]
Xiao, Z.; Dallas, M.; Qiu, N.; Nicolella, D.; Cao, L.; Johnson, M.; Bonewald, L.; Quarles, L.D. Conditional deletion of Pkd1 in osteocytes disrupts skeletal mechanosensing in mice. FASEB J., 2011, 25(7), 2418-2432.
[http://dx.doi.org/10.1096/fj.10-180299] [PMID: 21454365]
[92]
Temiyasathit, S.; Tang, W.J.; Leucht, P.; Anderson, C.T.; Monica, S.D.; Castillo, A.B.; Helms, J.A.; Stearns, T.; Jacobs, C.R. Mechanosensing by the primary cilium: deletion of Kif3A reduces bone formation due to loading. PLoS One, 2012, 7(3), e33368.
[http://dx.doi.org/10.1371/journal.pone.0033368] [PMID: 22428034]
[93]
Chen, J.C.; Hoey, D.A.; Chua, M.; Bellon, R.; Jacobs, C.R. Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism. FASEB J., 2016, 30(4), 1504-1511.
[http://dx.doi.org/10.1096/fj.15-276402] [PMID: 26675708]
[94]
Malone, A.M.; Anderson, C.T.; Tummala, P.; Kwon, R.Y.; Johnston, T.R.; Stearns, T.; Jacobs, C.R. Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism. Proc. Natl. Acad. Sci. USA, 2007, 104(33), 13325-13330.
[http://dx.doi.org/10.1073/pnas.0700636104] [PMID: 17673554]
[95]
Phillips, J.A.; Almeida, E.A.; Hill, E.L.; Aguirre, J.I.; Rivera, M.F.; Nachbandi, I.; Wronski, T.J.; van der Meulen, M.C.; Globus, R.K. Role for beta1 integrins in cortical osteocytes during acute musculoskeletal disuse. Matrix Biol., 2008, 27(7), 609-618.
[http://dx.doi.org/10.1016/j.matbio.2008.05.003] [PMID: 18619537]
[96]
Grimston, S.K.; Brodt, M.D.; Silva, M.J.; Civitelli, R. Attenuated response to in vivo mechanical loading in mice with conditional osteoblast ablation of the connexin43 gene (Gja1). J. Bone Miner. Res., 2008, 23(6), 879-886.
[http://dx.doi.org/10.1359/jbmr.080222] [PMID: 18282131]
[97]
Xiao, Z.; Quarles, L.D. Physiological mechanisms and therapeutic potential of bone mechanosensing. Rev. Endocr. Metab. Disord., 2015, 16(2), 115-129.
[http://dx.doi.org/10.1007/s11154-015-9313-4] [PMID: 26038304]
[98]
Russell, R.G. Bisphosphonates: the first 40 years. Bone, 2011, 49(1), 2-19.
[http://dx.doi.org/10.1016/j.bone.2011.04.022] [PMID: 21555003]
[99]
Russell, R.G. Bisphosphonates: from bench to bedside. Ann. N. Y. Acad. Sci., 2006, 1068, 367-401.
[http://dx.doi.org/10.1196/annals.1346.041] [PMID: 16831938]
[100]
Dunford, J.E.; Thompson, K.; Coxon, F.P.; Luckman, S.P.; Hahn, F.M.; Poulter, C.D.; Ebetino, F.H.; Rogers, M.J. Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J. Pharmacol. Exp. Ther., 2001, 296(2), 235-242.
[PMID: 11160603]
[101]
Kavanagh, K.L.; Guo, K.; Dunford, J.E.; Wu, X.; Knapp, S.; Ebetino, F.H.; Rogers, M.J.; Russell, R.G.; Oppermann, U. The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proc. Natl. Acad. Sci. USA, 2006, 103(20), 7829-7834.
[http://dx.doi.org/10.1073/pnas.0601643103] [PMID: 16684881]
[102]
Khan, S.A.; Kanis, J.A.; Vasikaran, S.; Kline, W.F.; Matuszewski, B.K.; McCloskey, E.V.; Beneton, M.N.; Gertz, B.J.; Sciberras, D.G.; Holland, S.D.; Orgee, J.; Coombes, G.M.; Rogers, S.R.; Porras, A.G. Elimination and biochemical responses to intravenous alendronate in postmenopausal osteoporosis. J. Bone Miner. Res., 1997, 12(10), 1700-1707.
[http://dx.doi.org/10.1359/jbmr.1997.12.10.1700] [PMID: 9333131]
[103]
Chen, L.R.; Ko, N.Y.; Chen, K.H. Medical treatment for osteoporosis: from molecular to clinical opinions. Int. J. Mol. Sci., 2019, 20(9), 2213.
[http://dx.doi.org/10.3390/ijms20092213] [PMID: 31064048]
[104]
Boskey, A.L.; Spevak, L.; Ma, Y.; Wang, H.; Bauer, D.C.; Black, D.M.; Schwartz, A.V. Insights into the bisphosphonate holiday: a preliminary FTIRI study. Osteoporos. Int., 2018, 29(3), 699-705.
[http://dx.doi.org/10.1007/s00198-017-4324-5] [PMID: 29204959]
[105]
Woo, S.B.; Hellstein, J.W.; Kalmar, J.R. Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann. Intern. Med., 2006, 144(10), 756-761.
[http://dx.doi.org/10.7326/0003-4819-144-10-200605160-00009] [PMID: 16702591]
[106]
Khosla, S.; Burr, D.; Cauley, J.; Dempster, D.W.; Ebeling, P.R.; Felsenberg, D.; Gagel, R.F.; Gilsanz, V.; Guise, T.; Koka, S.; McCauley, L.K.; McGowan, J.; McKee, M.D.; Mohla, S.; Pendrys, D.G.; Raisz, L.G.; Ruggiero, S.L.; Shafer, D.M.; Shum, L.; Silverman, S.L.; Van Poznak, C.H.; Watts, N.; Woo, S.B.; Shane, E. 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(10), 1479-1491.
[http://dx.doi.org/10.1359/jbmr.0707onj] [PMID: 17663640]
[107]
Watts, N.B.; Diab, D.L. Long-term use of bisphosphonates in osteoporosis. J. Clin. Endocrinol. Metab., 2010, 95(4), 1555-1565.
[http://dx.doi.org/10.1210/jc.2009-1947] [PMID: 20173017]
[108]
Burr, D.B.; Miller, L.; Grynpas, M.; Li, J.; Boyde, A.; Mashiba, T.; Hirano, T.; Johnston, C.C. Tissue mineralization is increased following 1-year treatment with high doses of bisphosphonates in dogs. Bone, 2003, 33(6), 960-969.
[http://dx.doi.org/10.1016/j.bone.2003.08.004] [PMID: 14678856]
[109]
Shane, E.; Burr, D.; Ebeling, P.R.; Abrahamsen, B.; Adler, R.A.; Brown, T.D.; Cheung, A.M.; Cosman, F.; Curtis, J.R.; Dell, R.; Dempster, D.; Einhorn, T.A.; Genant, H.K.; Geusens, P.; Klaushofer, K.; Koval, K.; Lane, J.M.; McKiernan, F.; McKinney, R.; Ng, A.; Nieves, J.; O’Keefe, R.; Papapoulos, S.; Sen, H.T.; van der Meulen, M.C.; Weinstein, R.S.; Whyte, M. 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(11), 2267-2294.
[http://dx.doi.org/10.1002/jbmr.253] [PMID: 20842676]
[110]
Hofbauer, L.C.; Schoppet, M. Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA, 2004, 292(4), 490-495.
[http://dx.doi.org/10.1001/jama.292.4.490] [PMID: 15280347]
[111]
Rossouw, J.E.; Anderson, G.L.; Prentice, R.L.; LaCroix, A.Z.; Kooperberg, C.; Stefanick, M.L.; Jackson, R.D.; Beresford, S.A.; Howard, B.V.; Johnson, K.C.; Kotchen, J.M.; Ockene, J. 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(3), 321-333.
[http://dx.doi.org/10.1001/jama.288.3.321] [PMID: 12117397]
[112]
Ettinger, B.; Black, D.M.; Mitlak, B.H.; Knickerbocker, R.K.; Nickelsen, T.; Genant, H.K.; Christiansen, C.; Delmas, P.D.; Zanchetta, J.R.; Stakkestad, J.; Glüer, C.C.; Krueger, K.; Cohen, F.J.; Eckert, S.; Ensrud, K.E.; Avioli, L.V.; Lips, P.; Cummings, S.R. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA, 1999, 282(7), 637-645.
[http://dx.doi.org/10.1001/jama.282.7.637] [PMID: 10517716]
[113]
Naylor, K.E.; Clowes, J.A.; Finigan, J.; Paggiosi, M.A.; Peel, N.F.; Eastell, R. The effect of cessation of raloxifene treatment on bone turnover in postmenopausal women. Bone, 2010, 46(3), 592-597.
[http://dx.doi.org/10.1016/j.bone.2009.10.043] [PMID: 19897063]
[114]
Anastasilakis, A.D.; Polyzos, S.A.; Efstathiadou, Z.A.; Savvidis, M.; Sakellariou, G.T.; Papatheodorou, A.; Kokkoris, P.; Makras, P. Denosumab in treatment-naïve and pre-treated with zoledronic acid postmenopausal women with low bone mass: effect on bone mineral density and bone turnover markers. Metabolism, 2015, 64(10), 1291-1297.
[http://dx.doi.org/10.1016/j.metabol.2015.06.018] [PMID: 26198440]
[115]
Tsourdi, E.; Langdahl, B.; Cohen-Solal, M.; Aubry-Rozier, B.; Eriksen, E.F.; Guañabens, N.; Obermayer-Pietsch, B.; Ralston, S.H.; Eastell, R.; Zillikens, M.C. Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS. Bone, 2017, 105, 11-17.
[http://dx.doi.org/10.1016/j.bone.2017.08.003] [PMID: 28789921]
[116]
Khan, M.; Cheung, A.M.; Khan, A.A. Drug-Related Adverse Events of Osteoporosis Therapy. Endocrinol. Metab. Clin. North Am., 2017, 46(1), 181-192.
[http://dx.doi.org/10.1016/j.ecl.2016.09.009] [PMID: 28131131]
[117]
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(3), 159-170.
[http://dx.doi.org/10.1007/s00223-009-9218-x] [PMID: 19189037]
[118]
Dean, T.; Vilardaga, J.P.; Potts, J.T., Jr; Gardella, T.J. Altered selectivity of parathyroid hormone (PTH) and PTH-related protein (PTHrP) for distinct conformations of the PTH/PTHrP receptor. Mol. Endocrinol., 2008, 22(1), 156-166.
[http://dx.doi.org/10.1210/me.2007-0274] [PMID: 17872377]
[119]
Hattersley, G.; Dean, T.; Corbin, B.A.; Bahar, H.; Gardella, T.J. Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling. Endocrinology, 2016, 157(1), 141-149.
[http://dx.doi.org/10.1210/en.2015-1726] [PMID: 26562265]
[120]
Vahle, J.L.; Long, G.G.; Sandusky, G.; Westmore, M.; Ma, Y.L.; Sato, M. Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose. Toxicol. Pathol., 2004, 32(4), 426-438.
[http://dx.doi.org/10.1080/01926230490462138] [PMID: 15204966]
[121]
Leder, B.Z. Optimizing Sequential and Combined Anabolic and Antiresorptive Osteoporosis Therapy. JBMR Plus, 2018, 2(2), 62-68.
[http://dx.doi.org/10.1002/jbm4.10041] [PMID: 30283892]
[122]
Bandeira, L.; Lewiecki, E.M.; Bilezikian, J.P. Romosozumab for the treatment of osteoporosis. Expert Opin. Biol. Ther., 2017, 17(2), 255-263.
[http://dx.doi.org/10.1080/14712598.2017.1280455] [PMID: 28064540]
[123]
Wijenayaka, A.R.; Kogawa, M.; Lim, H.P.; Bonewald, L.F.; Findlay, D.M.; Atkins, G.J. Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS One, 2011, 6(10), e25900.
[http://dx.doi.org/10.1371/journal.pone.0025900] [PMID: 21991382]
[124]
Ominsky, M.S.; Niu, Q.T.; Li, C.; Li, X.; Ke, H.Z. Tissue-level mechanisms responsible for the increase in bone formation and bone volume by sclerostin antibody. J. Bone Miner. Res., 2014, 29(6), 1424-1430.
[http://dx.doi.org/10.1002/jbmr.2152] [PMID: 24967455]
[125]
Saag, K.G.; Petersen, J.; Brandi, M.L.; Karaplis, A.C.; Lorentzon, M.; Thomas, T.; Maddox, J.; Fan, M.; Meisner, P.D.; Grauer, A. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N. Engl. J. Med., 2017, 377(15), 1417-1427.
[http://dx.doi.org/10.1056/NEJMoa1708322] [PMID: 28892457]
[126]
Ferrari, S. Future directions for new medical entities in osteoporosis. Best Pract. Res. Clin. Endocrinol. Metab., 2014, 28(6), 859-870.
[http://dx.doi.org/10.1016/j.beem.2014.08.002] [PMID: 25432357]
[127]
Shen, Y.; Gray, D.L.; Martinez, D.S. Combined pharmacologic therapy in postmenopausal osteoporosis. Endocrinol. Metab. Clin. North Am., 2017, 46(1), 193-206.
[http://dx.doi.org/10.1016/j.ecl.2016.09.008] [PMID: 28131133]
[128]
Leder, B.Z.; Tsai, J.N.; Uihlein, A.V.; Wallace, P.M.; Lee, H.; Neer, R.M.; Burnett-Bowie, S.A. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet, 2015, 386(9999), 1147-1155.
[http://dx.doi.org/10.1016/S0140-6736(15)61120-5] [PMID: 26144908]
[129]
Eastell, R.; Nickelsen, T.; Marin, F.; Barker, C.; Hadji, P.; Farrerons, J.; Audran, M.; Boonen, S.; Brixen, K.; Gomes, J.M.; Obermayer-Pietsch, B.; Avramidis, A.; Sigurdsson, G.; Glüer, C.C. Sequential treatment of severe postmenopausal osteoporosis after teriparatide: final results of the randomized, controlled European Study of Forsteo (EUROFORS). J. Bone Miner. Res., 2009, 24(4), 726-736.
[http://dx.doi.org/10.1359/jbmr.081215] [PMID: 19049337]
[130]
Cosman, F.; Miller, P.D.; Williams, G.C.; Hattersley, G.; Hu, M.Y.; Valter, I.; Fitzpatrick, L.A.; Riis, B.J.; Christiansen, C.; Bilezikian, J.P.; Black, D. Eighteen months of treatment with subcutaneous abaloparatide followed by 6 months of treatment with alendronate in postmenopausal women with osteoporosis: results of the ACTIVExtend Trial. Mayo Clin. Proc., 2017, 92(2), 200-210.
[http://dx.doi.org/10.1016/j.mayocp.2016.10.009] [PMID: 28160873]
[131]
Black, D.M.; Bilezikian, J.P.; Ensrud, K.E.; Greenspan, S.L.; Palermo, L.; Hue, T.; Lang, T.F.; McGowan, J.A.; Rosen, C.J.; Pa, T.H.S.I. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N. Engl. J. Med., 2005, 353(6), 555-565.
[http://dx.doi.org/10.1056/NEJMoa050336] [PMID: 16093464]
[132]
Recker, R.R.; Benson, C.T.; Matsumoto, T.; Bolognese, M.A.; Robins, D.A.; Alam, J.; Chiang, A.Y.; Hu, L.; Krege, J.H.; Sowa, H.; Mitlak, B.H.; Myers, S.L. A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density. J. Bone Miner. Res., 2015, 30(2), 216-224.
[http://dx.doi.org/10.1002/jbmr.2351] [PMID: 25196993]
[133]
Recknor, C.P.; Recker, R.R.; Benson, C.T.; Robins, D.A.; Chiang, A.Y.; Alam, J.; Hu, L.; Matsumoto, T.; Sowa, H.; Sloan, J.H.; Konrad, R.J.; Mitlak, B.H.; Sipos, A.A. The effect of discontinuing treatment with blosozumab: follow-up results of a phase 2 randomized clinical trial in postmenopausal women with low bone mineral density. J. Bone Miner. Res., 2015, 30(9), 1717-1725.
[http://dx.doi.org/10.1002/jbmr.2489] [PMID: 25707611]
[134]
Vuorinen, A.; Engeli, R.T.; Leugger, S.; Kreutz, C.R.; Schuster, D.; Odermatt, A.; Matuszczak, B. Phenylbenzenesulfonates and -sulfonamides as 17β-hydroxysteroid dehydrogenase type 2 inhibitors: synthesis and SAR-analysis. Bioorg. Med. Chem. Lett., 2017, 27(13), 2982-2985.
[http://dx.doi.org/10.1016/j.bmcl.2017.05.005] [PMID: 28506753]
[135]
Perspicace, E.; Cozzoli, L.; Gargano, E.M.; Hanke, N.; Carotti, A.; Hartmann, R.W.; Marchais-Oberwinkler, S. Novel, potent and selective 17β-hydroxysteroid dehydrogenase type 2 inhibitors as potential therapeutics for osteoporosis with dual human and mouse activities. Eur. J. Med. Chem., 2014, 83, 317-337.
[http://dx.doi.org/10.1016/j.ejmech.2014.06.036] [PMID: 24974351]
[136]
Gargano, E.M.; Perspicace, E.; Carotti, A.; Marchais-Oberwinkler, S.; Hartmann, R.W. Addressing cytotoxicity of 1,4-biphenyl amide derivatives: Discovery of new potent and selective 17β-hydroxysteroid dehydrogenase type 2 inhibitors. Bioorg. Med. Chem. Lett., 2016, 26(1), 21-24.
[http://dx.doi.org/10.1016/j.bmcl.2015.11.047] [PMID: 26615885]
[137]
Abdelsamie, A.S.; Herath, S.; Biskupek, Y.; Börger, C.; Siebenbürger, L.; Salah, M.; Scheuer, C.; Marchais-Oberwinkler, S.; Frotscher, M.; Pohlemann, T.; Menger, M.D.; Hartmann, R.W.; Laschke, M.W.; van Koppen, C.J. Targeted endocrine therapy: design, synthesis, and proof-of-principle of 17β-Hydroxysteroid dehydrogenase type 2 inhibitors in bone fracture healing. J. Med. Chem., 2019, 62(3), 1362-1372.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01493] [PMID: 30645111]
[138]
Fu, H.J.; Zhou, Y.R.; Bao, B.H.; Jia, M.X.; Zhao, Y.; Zhang, L.; Li, J.X.; He, H.L.; Zhou, X.M. Tryptophan hydroxylase 1 (Tph-1)-targeted bone anabolic agents for osteoporosis. J. Med. Chem., 2014, 57(11), 4692-4709.
[http://dx.doi.org/10.1021/jm5002293] [PMID: 24844139]
[139]
Cummings, S.R.; McClung, M.; Reginster, J.Y.; Cox, D.; Mitlak, B.; Stock, J.; Amewou-Atisso, M.; Powles, T.; Miller, P.; Zanchetta, J.; Christiansen, C. Arzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women. J. Bone Miner. Res., 2011, 26(2), 397-404.
[http://dx.doi.org/10.1002/jbmr.191] [PMID: 20658564]
[140]
Kendler, D.L.; Palacios, S.; Cox, D.A.; Stock, J.; Alam, J.; Dowsett, S.A.; Zanchetta, J. Arzoxifene versus raloxifene: effect on bone and safety parameters in postmenopausal women with osteoporosis. Osteoporos. Int., 2012, 23(3), 1091-1101.
[http://dx.doi.org/10.1007/s00198-011-1587-0] [PMID: 21374068]
[141]
Cummings, S.R.; Ensrud, K.; Delmas, P.D.; LaCroix, A.Z.; Vukicevic, S.; Reid, D.M.; Goldstein, S.; Sriram, U.; Lee, A.; Thompson, J.; Armstrong, R.A.; Thompson, D.D.; Powles, T.; Zanchetta, J.; Kendler, D.; Neven, P.; Eastell, R.; Investigators, P.S. Lasofoxifene in postmenopausal women with osteoporosis. N. Engl. J. Med., 2010, 362(8), 686-696.
[http://dx.doi.org/10.1056/NEJMoa0808692] [PMID: 20181970]
[142]
de Villiers, T.J. The quest for new drugs to prevent osteoporosis-related fractures. Climacteric, 2017, 20(2), 103-106.
[http://dx.doi.org/10.1080/13697137.2017.1289659] [PMID: 28286990]
[143]
Mei, Y.Y.H.T.J.; Wei, L.; Xiang, H.; Hao, W.; Ming, Z.X.; An, L.X. Abstract P1-18-03: phase I trial to assess the safety, pharmacokinetics and pharmacodynamics of receptor activator of nuclear factor-βB ligand inhibitor (TK006) in patients with bone metastases from breast cancer.Proceedings of the 2018 San Antonio Breast Cancer Symposium; San Antonio, TX, 2019, 79, p. (4 Suppl.)P1-18-03.
[http://dx.doi.org/10.1158/1538-7445.SABCS18-P1-18-03]
[144]
Vahe, C.; Benomar, K.; Espiard, S.; Coppin, L.; Jannin, A.; Odou, M.F.; Vantyghem, M.C. Diseases associated with calcium-sensing receptor. Orphanet J. Rare Dis., 2017, 12(1), 19.
[http://dx.doi.org/10.1186/s13023-017-0570-z] [PMID: 28122587]
[145]
Goltzman, D.; Hendy, G.N. The calcium-sensing receptor in bone--mechanistic and therapeutic insights. Nat. Rev. Endocrinol., 2015, 11(5), 298-307.
[http://dx.doi.org/10.1038/nrendo.2015.30] [PMID: 25752283]
[146]
Berencsi, K.; Sami, A.; Ali, M.S.; Marinier, K.; Deltour, N.; Perez-Gutthann, S.; Pedersen, L.; Rijnbeek, P.; Van der Lei, J.; Lapi, F.; Simonetti, M.; Reyes, C.; Sturkenboom, M.C.J.M.; Prieto-Alhambra, D. Impact of risk minimisation measures on the use of strontium ranelate in Europe: a multi-national cohort study in 5 EU countries by the EU-ADR Alliance. Osteoporos. Int., 2019.
[http://dx.doi.org/10.1007/s00198-019-05181-6] [PMID: 31696274]
[147]
Saftig, P.; Hunziker, E.; Wehmeyer, O.; Jones, S.; Boyde, A.; Rommerskirch, W.; Moritz, J.D.; Schu, P.; von Figura, K. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc. Natl. Acad. Sci. USA, 1998, 95(23), 13453-13458.
[http://dx.doi.org/10.1073/pnas.95.23.13453] [PMID: 9811821]
[148]
Allen, J.G.; Fotsch, C.; Babij, P. Emerging targets in osteoporosis disease modification. J. Med. Chem., 2010, 53(11), 4332-4353.
[http://dx.doi.org/10.1021/jm9018756] [PMID: 20218623]
[149]
Rizzoli, R.; Benhamou, C.L.; Halse, J.; Miller, P.D.; Reid, I.R.; Rodríguez Portales, J.A.; DaSilva, C.; Kroon, R.; Verbruggen, N.; Leung, A.T.; Gurner, D. Continuous treatment with odanacatib for up to 8 years in postmenopausal women with low bone mineral density: a phase 2 study. Osteoporos. Int., 2016, 27(6), 2099-2107.
[http://dx.doi.org/10.1007/s00198-016-3503-0] [PMID: 26879200]
[150]
Boggild, M.K.; Gajic-Veljanoski, O.; McDonald-Blumer, H.; Ridout, R.; Tile, L.; Josse, R.; Cheung, A.M. Odanacatib for the treatment of osteoporosis. Expert Opin. Pharmacother., 2015, 16(11), 1717-1726.
[http://dx.doi.org/10.1517/14656566.2015.1064897] [PMID: 26149759]
[151]
Chappard, D.; Libouban, H.; Mindeholm, L.; Baslé, M.F.; Legrand, E.; Audran, M. The cathepsin K inhibitor AAE581 induces morphological changes in osteoclasts of treated patients. Microsc. Res. Tech., 2010, 73(7), 726-732.
[http://dx.doi.org/10.1002/jemt.20813] [PMID: 20025055]
[152]
Peroni, A.; Zini, A.; Braga, V.; Colato, C.; Adami, S.; Girolomoni, G. Drug-induced morphea: report of a case induced by balicatib and review of the literature. J. Am. Acad. Dermatol., 2008, 59(1), 125-129.
[http://dx.doi.org/10.1016/j.jaad.2008.03.009] [PMID: 18410981]
[153]
Eastell, R.; Nagase, S.; Ohyama, M.; Small, M.; Sawyer, J.; Boonen, S.; Spector, T.; Kuwayama, T.; Deacon, S. Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis: the OCEAN study. J. Bone Miner. Res., 2011, 26(6), 1303-1312.
[http://dx.doi.org/10.1002/jbmr.341] [PMID: 21312264]
[154]
Murphy, M.G.; Cerchio, K.; Stoch, S.A.; Gottesdiener, K.; Wu, M.; Recker, R.; Group, L.S. Effect of L-000845704, an alphaVbeta3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J. Clin. Endocrinol. Metab., 2005, 90(4), 2022-2028.
[http://dx.doi.org/10.1210/jc.2004-2126] [PMID: 15687321]
[155]
El-Gamal, M.I.; Al-Ameen, S.K.; Al-Koumi, D.M.; Hamad, M.G.; Jalal, N.A.; Oh, C.H. Recent Advances of Colony-Stimulating Factor-1 Receptor (CSF-1R) Kinase and Its Inhibitors. J. Med. Chem., 2018, 61(13), 5450-5466.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00873] [PMID: 29293000]
[156]
Vuorinen, A.; Engeli, R.; Meyer, A.; Bachmann, F.; Griesser, U.J.; Schuster, D.; Odermatt, A. Ligand-based pharmacophore modeling and virtual screening for the discovery of novel 17β-hydroxysteroid dehydrogenase 2 inhibitors. J. Med. Chem., 2014, 57(14), 5995-6007.
[http://dx.doi.org/10.1021/jm5004914] [PMID: 24960438]
[157]
Lavoie, B.; Lian, J.B.; Mawe, G.M. Regulation of bone metabolism by serotonin. Adv. Exp. Med. Biol., 2017, 1033, 35-46.
[http://dx.doi.org/10.1007/978-3-319-66653-2_3] [PMID: 29101650]
[158]
Kontulainen, S.; Sievänen, H.; Kannus, P.; Pasanen, M.; Vuori, I. Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: a peripheral quantitative computed tomography study between young and old starters and controls. J. Bone Miner. Res., 2002, 17(12), 2281-2289.
[http://dx.doi.org/10.1359/jbmr.2002.17.12.2281] [PMID: 12469923]
[159]
Jiang, M.; Peng, L.; Yang, K.; Wang, T.; Yan, X.; Jiang, T.; Xu, J.; Qi, J.; Zhou, H.; Qian, N.; Zhou, Q.; Chen, B.; Xu, X.; Deng, L.; Yang, C. development of small-molecules targeting receptor activator of nuclear factor-κB ligand (RANKL)-receptor activator of nuclear factor-κB (RANK) Protein-protein interaction by structure-based virtual screening and hit optimization. J. Med. Chem., 2019, 62(11), 5370-5381.
[http://dx.doi.org/10.1021/acs.jmedchem.8b02027] [PMID: 31082234]
[160]
Pativada, T.; Kim, M.H.; Lee, J.H.; Hong, S.S.; Choi, C.W.; Choi, Y.H.; Kim, W.J.; Song, D.W.; Park, S.I.; Lee, E.J.; Seo, B.Y.; Kim, H.; Kim, H.K.; Lee, K.H.; Ahn, S.K.; Ku, J.M.; Park, G.H. Benzylideneacetone derivatives inhibit osteoclastogenesis and activate osteoblastogenesis independently based on specific structure-activity relationship. J. Med. Chem., 2019, 62(13), 6063-6082.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00270] [PMID: 31257875]
[161]
Saito, K.; Shinozuka, T.; Nakao, A.; Kiho, T.; Kunikata, T.; Shiiki, T.; Nagai, Y.; Naito, S. Synthesis and structure-activity relationship of 4-alkoxy-thieno[2,3-b]pyridine derivatives as potent alkaline phosphatase enhancers for osteoporosis treatment. Bioorg. Med. Chem. Lett., 2019, 29(14), 1769-1773.
[http://dx.doi.org/10.1016/j.bmcl.2019.05.014] [PMID: 31101474]
[162]
Zhao, C.; Huang, D.; Li, R.; Xu, Y.; Su, S.; Gu, Q.; Xu, J. Identifying novel anti-osteoporosis leads with a chemotype-assembly approach. J. Med. Chem., 2019, 62(12), 5885-5900.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00517] [PMID: 31125222]
[163]
Lindsay, R.; Cosman, F.; Zhou, H.; Bostrom, M.P.; Shen, V.W.; Cruz, J.D.; Nieves, J.W.; Dempster, D.W. A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest bone biopsy: early actions of teriparatide. J. Bone Miner. Res., 2006, 21(3), 366-373.
[http://dx.doi.org/10.1359/JBMR.051109] [PMID: 16491283]

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