[1]
Fleisch, H. Development of bisphosphonates. Breast Cancer Res., 2002, 4, 30-34.
[2]
Papapoulos, S.E. Bisphosphonate actions: Physical chemistry revisited. Bone, 2006, 38, 613-616.
[3]
Drake, M.T.; Clarke, B.L.; Khosla, S. Bisphosphonates: Mechanism of action and role in clinical practice. Mayo Clin. Proc., 2008, 83, 1032-1045.
[4]
Widler, L.; Jahnke, W.; Green, J.R. The chemistry of bisphosphonates: From antiscaling agents to clinical therapeutics. Anticancer. Agents Med. Chem., 2012, 12, 95-101.
[5]
Russell, R.G. Bisphosphonates: Mode of action and pharmacology. Pediatrics, 2007, 119, S150-S162.
[6]
Lehenkari, P.P.; Kellinsalmi, M.; Näpänkangas, J.P.; Ylitalo, K.V.; Mönkkönen, J.; Rogers, M.J.; Azhayev, A.; Väänänen, H.K.; Hassinen, I.E. Further insight into mechanism of action of clodronate: Inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite. Mol. Pharmacol., 2002, 61, 1255-1262.
[7]
Russell, R.G.; Watts, N.B.; Ebetino, F.H.; Rogers, M.J. Mechanisms of action of bisphosphonates: Similarities and differences and their potential influence on clinical efficacy. Osteoporos. Int., 2008, 19, 733-759.
[8]
Rogers, M.J.; Gordon, S.; Benford, H.L.; Coxon, F.P.; Luckman, S.P.; Monkkonen, J.; Frith, J.C. Cellular and molecular mechanisms of action of bisphosphonates. Cancer, 2000, 88, 2961-2978.
[9]
Nancollas, G.H.; Tang, R.; Phipps, R.J.; Henneman, Z.; Gulde, S.; Wu, W.; Mangood, A.; Russell, R.G.; Ebetino, F.H. Novel insights into actions of bisphosphonates on bone: Differences in interactions with hydroxyapatite. Bone, 2006, 38, 617-627.
[10]
Benford, H.L.; Frith, J.C.; Auriola, S.; Monkkonen, J.; Rogers, M.J. Farnesol and geranylgeraniol prevent activation of caspases by aminobisphosphonates: Biochemical evidence for two distinct pharmacological classes of bisphosphonate drugs. Mol. Pharmacol., 1999, 56, 131-140.
[11]
Roelofs, A.J.; Stewart, C.A.; Sun, S.; Błażewska, K.M.; Kashemirov, B.A.; McKenna, C.E.; Russell, R.G.; Rogers, M.J.; Lundy, M.W.; Ebetino, F.H.; Coxon, F.P. Influence of bone affinity on the skeletal distribution of fluorescently labeled bisphosphonates in vivo. J. Bone Miner. Res., 2012, 27, 835-847.
[12]
Rogers, M.J.; Frith, J.C.; Luckman, S.P.; Coxon, F.P.; Benford, H.L.; Monkkonen, J.; Auriola, S.; Chilton, K.M.; Russell, R.G. Molecular mechanisms of action of bisphosphonates. Bone, 1999, 24, S73S-S79.
[13]
Sims, N.A.; Martin, T.J. Coupling the activities of bone formation and resorption: A multitude of signals within the basic multicellular unit. Bonekey Rep., 2014, 3, 481.
[14]
Tolia, M.; Zygogianni, A.; Kouvaris, J.R.; Meristoudis, C.; Margari, N.; Karakitsos, P.; Kokakis, I.; Kardamakis, D.; Papadimitriou, C.; Mystakidou, K.; Tsoukalas, N.; Kyrgias, G.; Armonis, B.; Filippiadis, D.K.; Kelekis, A.D.; Kelekis, N.; Kouloulias, V. The key role of bisphosphonates in the supportive care of cancer patients. Anticancer Res., 2014, 34, 23-37.
[15]
Fontana, A.; Delmas, P.D. Markers of bone turnover in bone metastases. Cancer, 2000, 88, 2952-2960.
[16]
Datta, H.K.; Ng, W.F.; Walker, J.A.; Tuck, S.P.; Varanasi, S.S. The cell biology of bone metabolism. J. Clin. Pathol., 2008, 61, 577-587.
[17]
Bhatt, R.N.; Hibbert, S.A.; Munns, C.F. The use of bisphosphonates in children: Review of the literature and guidelines for dental management. Aust. Dent. J., 2014, 59, 9-19.
[18]
Karlic, H.; Thaler, R.; Gerner, C.; Grunt, T.; Proestling, K.; Haider, F.; Varga, F. Inhibition of the mevalonate pathway affects epigenetic regulation in cancer cells. Cancer Genet., 2015, 208, 241-252.
[19]
Cremers, S.C.; Pillai, G.; Papapoulos, S.E. Pharmacokinetics/ pharmacodynamics of bisphosphonates: Use for optimisation of intermittent therapy for osteoporosis. Clin. Pharmacokinet., 2005, 44, 551-570.
[20]
Fogelman, I.; Smith, L.; Mazess, R.; Wilson, M.A.; Bevan, J.A. Absorption of oral diphosphonate in normal subjects. Clin. Endocrinol. (Oxf.), 1986, 24, 57-62.
[21]
Pazianas, M.; Abrahamsen, B.; Ferrari, S.; Russell, R.G. Eliminating the need for fasting with oral administration of bisphosphonates. Ther. Clin. Risk Manag., 2013, 9, 395-402.
[22]
Russell, R.G. Bisphosphonates: The first 40 years. Bone, 2011, 49, 2-19.
[23]
Mariotti, A. Bisphosphonates and osteonecrosis of the jaws. J. Dent. Educ., 2008, 72, 919-929.
[24]
Smith, H.S. Painful Osseous Metastases. Pain Physician, 2011, 14, 373-403.
[25]
Tolia, M.; Zygogianni, A.; Kouvaris, J.R.; Meristoudis, C.; Margari, N.; Karakitsos, P.; Kokakis, I.; Kardamakis, D.; Papadimitriou, C.; Mystakidou, K.; Tsoukalas, N.; Kyrgias, G.; Armonis, B.; Filippiadis, D.K.; Kelekis, A.D.; Kelekis, N.; Kouloulias, V. The key role of bisphosphonates in the supportive care of cancer patients. Anticancer Res., 2014, 34, 23-37.
[26]
Vepsalainen, J.J. Bisphosphonate prodrugs. Curr. Med. Chem., 2002, 9, 1201-1208.
[27]
Mönkkönen, H.; Auriola, S.; Lehenkari, P.; Kellinsalmi, M.; Hassinen, I.E.; Vepsäläinen, J.; Mönkkönen, J. A new endogenous ATP analog (ApppI) inhibits the mitochondrial adenine nucleotide translocase (ANT) and is responsible for the apoptosis induced by nitrogen-containing bisphosphonates. Br. J. Pharmacol., 2006, 147, 437-445.
[28]
Thompson, K.; Rogers, M.J.; Coxon, F.P.; Crockett, J.C. Cytosolic entry of bisphosphonate drugs requires acidification of vesicles after fluid-phase endocytosis. Mol. Pharmacol., 2006, 69, 1624-1632.
[29]
Rogers, M.J.; Crockett, J.C.; Coxon, F.P.; Mönkkönen, J. Biochemical and molecular mechanisms of action of bisphosphonates. Bone, 2011, 49, 34-41.
[30]
Roelofs, A.J.; Thompson, K.; Gordon, S.; Rogers, M.J. Molecular mechanisms of action of bisphosphonates: Current status. Clin. Cancer Res., 2006, 12, 6222s-6230s.
[31]
Green, J.R. Bisphosphonates: Preclinical review. Oncologist, 2004, 9, 3-13.
[32]
Benford, H.L.; McGowan, N.W.; Helfrich, M.H.; Nuttall, M.E.; Rogers, M.J. Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro. Bone, 2001, 28, 465-473.
[33]
Fournier, P.G.; Stresing, V.; Ebetino, F.H.; Clézardin, P. How do bisphosphonates inhibit bone metastasis in vivo? Neoplasia, 2010, 12, 571-578.
[34]
Marra, M.; Santini, D.; Tonini, G.; Meo, G.; Zappavigna, S.; Facchini, G.; Morabito, A.; Abbruzzese, A.; Cartenì, G.; Budillon, A.; Caraglia, M. Molecular and preclinical models enhancing anti-tumour activity of zoledronic acid. EJC Suppl., 2008, 6, 79-85.
[35]
Knight, L.A.; Kurbacher, C.M.; Glaysher, S.; Fernando, A.; Reichelt, R.; Dexel, S.; Reinhold, U.; Cree, I.A. Activity of mevalonate pathway inhibitors against breast and ovarian cancers in the ATP-based tumour chemosensitivity assay. BMC Cancer, 2009, 9, 38.
[36]
Xu, X.L.; Gou, W.L.; Wang, A.Y.; Wang, Y.; Guo, Q.Y.; Lu, Q.; Lu, S.B.; Peng, J. Basic research and clinical applications of bisphosphonates in bone disease: What have we learned over the last 40 years? J. Transl. Med., 2013, 11, 303.
[37]
Clezardin, P. Bisphosphonates’ antitumor activity: An unravelled side of a multifaceted drug class. Bone, 2011, 48, 71-79.
[38]
Koopmans, S.J.; van der Wee-Pals, L.; Lowik, C.W.; Papapoulos, S.E. Use of a rat model for the simultaneous assessment of pharmacokinetic and pharmacodynamic aspects of bisphosphonate treatment: Application to the study of intravenous 14C-labeled 1-hydroxy-3-(1-pyrrolidinyl)-propylidene-1,1-bisphosphonate. J. Bone Miner. Res., 1994, 9, 241-246.
[39]
Israel, O.; Front, D.; Hardoff, R.; Ish-Shalom, S.; Jerushalmi, J.; Kolodny, G.M. In vivo SPECT quantitation of bone metabolism in hyperparathyroidism and thyrotoxicosis. J. Nucl. Med., 1991, 32, 1157-1161.
[40]
Carnevale, V.; Dicembrino, F.; Frusciante, V.; Chiodini, I.; Minisola, S.; Scillitani, A. Different patterns of global and regional skeletal uptake of 99mTc-methylene diphosphonate with age: Relevance to the pathogenesis of bone loss. J. Nucl. Med., 2000, 41, 1478-1483.
[41]
Porras, A.G.; Holland, S.D.; Gertz, B.J. Pharmacokinetics of alendronate. Clin. Pharmacokinet., 1999, 36, 315-328.
[42]
Boskey, A.L.; Coleman, R. Aging and bone. J. Dent. Res., 2010, 89, 1333-1348.
[43]
Sato, M.; Grasser, W.; Endo, N.; Akins, R.; Simmons, H.; Thompson, D.D.; Golub, E.; Rodan, G.A. Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. J. Clin. Invest., 1991, 88, 2095-2105.
[44]
Allen, M.R.; Burr, D.B. Bisphosphonate effects on bone turnover, microdamage, and mechanical properties: What we think we know and what we know that we don’t know. Bone, 2011, 49, 56-65.
[45]
Plotkin, L.I.; Bivi, N.; Bellido, T. A bisphosphonate that does not affect osteoclasts prevents osteoblast and osteocyte apoptosis and the loss of bone strength induced by glucocorticoids in mice. Bone, 2011, 49, 122-127.
[46]
Bellido, T.; Plotkin, L.I. Novel actions of bisphosphonates in bone: Preservation of osteoblast and osteocyte viability. Bone, 2011, 49, 50-55.
[47]
Boland, R.L.; Morelli, S.; Santillan, G.; Scodelaro, P.; Colicheo, A.; de Boland, A.R.; Vyas, K.; Plotkin, L.I.; Bellido, T. Connexin 43 Is required for bisphosphonate-induced survival of osteoblastic cells but not for bisphosphonate binding. J. Bone Miner. Res., 2006, 21, S339.
[48]
Escudero, N.D.; Mandalunis, P.M. Influence of bisphosphonate treatment on medullary macrophages and osteoclasts: An experimental study. Bone Marrow Res., 2012, 2012526236
[49]
Weivoda, M.M.; Oursler, M.J. The roles of small GTPases in osteoclast biology. Orthop. Muscular Syst., 2014, 31000161
[50]
Taylor, A.; Mules, E.H.; Seabra, M.C.; Helfrich, M.H.; Rogers, M.J.; Coxon, F.P. Impaired prenylation of rab GTPases in the gunmetal mouse causes defects in bone cell function. Small GTPases, 2011, 2, 131-142.
[51]
Zekri, J.; Mansour, M.; Karim, S.M. The anti-tumour effects of zoledronic acid. J. Bone Oncol., 2003, 1, 25-35.
[52]
Einav, S.; Glenn, J.S. Prenylation inhibitors: A novel class of antiviral agents. J. Antimicrob. Chemother., 2003, 52, 883-886.
[53]
Jordão, F.M.; Saito, A.Y.; Miguel, D.C.; de Jesus Peres, V.; Kimura, E.A.; Katzin, A.M. In vitro and in vivo antiplasmodial activities of risedronate and its interference with protein prenylation in Plasmodium falciparum. Antimicrob. Agents Chemother., 2011, 55, 2026-2031.
[54]
Roelofs, A.J.; Thompson, K.; Ebetino, F.H.; Rogers, M.J.; Coxon, F.P. Bisphosphonates: Molecular mechanisms of action and effects on bone cells, monocytes and macrophages. Curr. Pharm. Des., 2010, 16, 2950-2960.
[55]
Sanders, J.M.; Song, Y.; Chan, J.M.W.; Zhang, Y.; Jennings, S.; Kosztowski, T.; Odeh, S.; Flessner, R.; Schwerdtfeger, C.; Kotsikorou, E.; Meints, G.A.; Gómez, A.O.; González-Pacanowska, F.; Raker, A.M.; Wang, H.; van Beek, E.R.; Papapoulos, S.E.; Morita, C.T.; Oldfield, E. Pyridinium-1-yl bisphosphonates are potent inhibitors of farnesyl diphosphate synthase and bone resorption. J. Med. Chem., 2005, 48, 2957-2963.
[56]
Liu, J.; Huang, W.; Zhou, R.; Jia, S.; Tang, W.; Luo, Y.; Zhang, J. Bisphosphonates in the treatment of patients with metastatic breast, lung, and prostate cancer - A meta-analysis. Medicine (Baltimore), 2015, 94e2014
[57]
Santini, D.; Stumbo, L.; Spoto, C.; D’Onofrio, L.; Pantano, F.; Iuliani, M.; Fioramonti, M.; Zoccoli, A.; Ribelli, G.; Virzì, V.; Vincenzi, B.; Tonini, G. Bisphosphonates as anticancer agents in early breast cancer: Preclinical and clinical evidence. Breast Cancer Res., 2015, 17, 121.
[58]
Costa-Rodrigues, J.; Moniz, K.A.; Teixeira, M.R.; Fernandes, M.H. Variability of the paracrine-induced osteoclastogenesis by human breast cancer cell lines. J. Cell. Biochem., 2012, 113, 1069-1079.
[59]
Costa-Rodrigues, J.; Teixeira, C.A.; Fernandes, M.H. Paracrine-mediated osteoclastogenesis by the osteosarcoma MG63 cell line: Is RANKL/RANK signalling really important? Clin. Exp. Metastasis, 2011, 28, 505-514.
[60]
Costa-Rodrigues, J.; Fernandes, A.; Fernandes, M.H. Reciprocal osteoblastic and osteoclastic modulation in co-cultured MG63 osteosarcoma cells and human osteoclast precursors. J. Cell. Biochem., 2011, 112, 3704-3713.
[61]
Guise, T.A. Molecular mechanisms of osteolytic bone metastases. Cancer, 2000, 88, 2892-2898.
[62]
Mathew, A.; Brufsky, A.M. The use of adjuvant bisphosphonates in the treatment of early-stage breast cancer. Clin. Adv. Hematol. Oncol., 2014, 12, 749-756.
[63]
Paterson, A.H. The potential role of bisphosphonates as adjuvant therapy in the prevention of bone metastases. Cancer, 2000, 88, 3038-3046.
[64]
Brufsky, A.; Mathew, A. Bisphosphonates, bone, and breast cancer recurrence. Lancet, 2015, 386, 1319-1320.
[65]
Wood, J.; Bonjean, K.; Ruetz, S.; Bellahcène, A.; Devy, L.; Foidart, J.M.; Castronovo, V.; Green, J.R. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J. Pharmacol. Exp. Ther., 2002, 302, 1055-1061.
[66]
Coxon, J.P.; Oades, G.M.; Kirby, R.S.; Colston, K.W. Zoledronic acid induces apoptosis and inhibits adhesion to mineralized matrix in prostate cancer cells via inhibition of protein prenylation. BJU Int., 2004, 94, 164-170.
[67]
Dedes, P.G.; Gialeli, C.H.; Tsonis, A.I.; Kanakis, I.; Theocharis, A.D.; Kletsas, D.; Tzanakakis, G.N.; Karamanos, N.K. Expression of matrix macromolecules and functional properties of breast cancer cells are modulated by the bisphosphonate zoledronic acid. Biochim. Biophys. Acta, 2012, 1820, 1926-1939.
[68]
Insalaco, L.; Di Gaudio, F.; Terrasi, M.; Amodeo, V.; Caruso, S.; Corsini, L.R.; Fanale, D.; Margarese, N.; Santini, D.; Bazan, V.; Russo, A. Analysis of molecular mechanisms and anti-tumoural effects of zoledronic acid in breast cancer cells. J. Cell. Mol. Med., 2012, 16, 2186-2195.
[69]
Senaratne, S.G.; Mansi, J.L.; Colston, K.W. The bisphosphonate zoledronic acid impairs membrane localisation and induces cytochrome c release in breast cancer cells. Br. J. Cancer, 2002, 86, 1479-1486.
[70]
Yuen, T.; Stachnik, A.; Iqbal, J.; Sgobba, M.; Gupta, Y.; Lu, P.; Colaianni, G.; Ji, Y.; Zhu, L.; Kim, S.; Li, J.; Liu, P.; Izadmehr, S.; Sangodkar, J.; Bailey, J.; Latif, Y.; Mujtaba, S.; Epstein, S.; Davies, T.F.; Bian, Z.; Zallone, A.; Aggarwal, A.K.; Haider, S.; New, M.I.; Sun, L.; Narla, G.; Zaidi, M. Bisphosphonates inactivate human EGFRs to exert antitumor actions. Proc. Natl. Acad. Sci. USA, 2014, 111, 17989-17994.
[71]
Gober, H.J.; Kistowska, M.; Angman, L.; Jenö, P.; Mori, L.; De Libero, G. Human T cell receptor γδ cells recognize endogenous mevalonate metabolites in tumor cells. J. Exp. Med., 2003, 197, 163-168.
[72]
Rogers, T.L.; Holen, I. Tumour macrophages as potential targets of bisphosphonates. J. Transl. Med., 2011, 9, 177.
[73]
Rüegg, C.; Mariotti, A. Vascular integrins: Pleiotropic adhesion and signaling molecules in vascular homeostasis and angiogenesis. Cell. Mol. Life Sci., 2003, 60, 1135-1157.
[74]
Scavelli, C.; Di Pietro, G.; Cirulli, T.; Coluccia, M.; Boccarelli, A.; Giannini, T.; Mangialardi, G.; Bertieri, R.; Coluccia, A.M.L.; Ribatti, D.; Dammacco, F.; Vacca, A. Zoledronic acid affects over-angiogenic phenotype of endothelial cells in patients with multiple myeloma. Mol. Cancer Ther., 2007, 6, 3256-3262.
[75]
Bezzi, M.; Hasmim, M.; Bieler, G.; Dormond, O.; Rüegg, C. Zoledronate sensitizes endothelial cells to tumor necrosis factor-induced programmed cell death. J. Biol. Chem., 2003, 278, 43603-43614.
[76]
Pécheur, I.; Peyruchaud, O.; Serre, C.M.; Guglielmi, J.; Voland, C.; Bourre, F.; Margue, C.; Cohen-Solal, M.; Buffet, A.; Kieffer, N.; Clézardin, P. Integrin αvβ3 expression confers on tumor cells a greater propensity to metastasize to bone. FASEB J., 2002, 16, 1266-1268.
[77]
Jagdev, S.P.; Coleman, R.E.; Shipman, C.M.; Rostami, H.A.; Croucher, P.I. The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: Evidence for synergy with paclitaxel. Br. J. Cancer, 2001, 84, 1126-1134.
[78]
Terpos, E.; Kleber, M.; Engelhardt, M.; Zweegman, S.; Gay, F.; Kastritis, E.; van de Donk, N.W.; Bruno, B.; Sezer, O.; Broijl, A.; Bringhen, S.; Beksac, M.; Larocca, A.; Hajek, R.; Musto, P.; Johnsen, H.E.; Morabito, F.; Ludwig, H.; Cavo, M.; Einsele, H.; Sonneveld, P.; Dimopoulos, M.A.; Palumbo, A. European myeloma network guidelines for the management of multiple myeloma-related complications. Haematologica, 2015, 100, 1254-1266.
[79]
Qian, Y.; Bhowmik, D.; Kachru, N.; Hernandez, R.K. Longitudinal patterns of bone-targeted agent use among patients with solid tumors and bone metastases in the United States. Support. Care Cancer, 2017, 25, 1845-1851.
[80]
Trémollieres, F.A.; Ceausu, I.; Depypere, H.; Lambrinoudaki, I.; Mueck, A.; Pérez-López, F.R.; van der Schouw, Y.T.; Senturk, L.M.; Simoncini, T.; Stevenson, J.C.; Stute, P.; Rees, M. Osteoporosis management in patients with breast cancer: EMAS position statement. Maturitas, 2017, 95, 65-71.
[81]
Miller, P.D.; Jamal, S.A.; Evenepoel, P.; Eastell, R.; Boonen, S. Renal safety in patients treated with bisphosphonates for osteoporosis: A review. J. Bone Miner. Res., 2013, 28, 2049-2059.
[82]
Saita, Y.; Ishijima, M.; Kaneko, K. Atypical femoral fractures and bisphosphonate use: Current evidence and clinical implications. Ther. Adv. Chronic Dis., 2015, 6, 185-193.
[83]
Maalouf, N.M.; Heller, H.J.; Odvina, C.V.; Kim, P.J.; Sakhaee, K. Bisphosphonate-induced hypocalcemia: Report of 3 cases and review of literature. Endocr. Pract., 2006, 12, 48-53.
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