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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Osteoporosis: Mechanism, Molecular Target and Current Status on Drug Development

Author(s): Hanxuan Li, Zhousheng Xiao, L. Darryl Quarles* and Wei Li*

Volume 28, Issue 8, 2021

Published on: 30 March, 2020

Page: [1489 - 1507] Pages: 19

DOI: 10.2174/0929867327666200330142432

Price: $65

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Abstract

Osteoporosis is a pathological loss of bone mass due to an imbalance in bone remodeling where osteoclast-mediated bone resorption exceeds osteoblast-mediated bone formation resulting in skeletal fragility and fractures. Anti-resorptive agents, such as bisphosphonates and SERMs, and anabolic drugs that stimulate bone formation, including PTH analogues and sclerostin inhibitors, are current treatments for osteoporosis. Despite their efficacy, severe side effects and loss of potency may limit the long term usage of a single drug. Sequential and combinational use of current drugs, such as switching from an anabolic to an anti-resorptive agent, may provide an alternative approach. Moreover, there are novel drugs being developed against emerging new targets such as Cathepsin K and 17β-HSD2 that may have less side effects. This review will summarize the molecular mechanisms of osteoporosis, current drugs for osteoporosis treatment, and new drug development strategies.

Keywords: Osteoporosis, bone remodeling, osteoclasts, osteoblasts, osteocytes, antiresorptive drugs, anabolic drugs.

[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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