• 1
    Lombardo LJ, Lee FY, Chen P, et al. Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem. 2004; 47: 66586661.
  • 2
    Melnick JS, Janes J, Kim S, et al. An efficient rapid system for profiling the cellular activities of molecular libraries. Proc Natl Acad Sci USA. 2006; 103: 31533158.
  • 3
    Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. 2004; 305: 399401.
  • 4
    O'Hare T, Walters DK, Stoffregen EP, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005; 65: 45004505.
  • 5
    Hochhaus A, Kantarjian HM, Baccarani M, et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood. 2007; 109: 23032309.
  • 6
    Tokarski JS, Newitt JA, Chang CY, Cheng JD, Wittekind M, Kiefer SE, Kish K, Lee FY, Borzillerri R, Lombardo LJ, Xie D, Zhang Y, Klei HE. The structure of Dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants. Cancer Res. 2006; 66: 57905797.
  • 7
    Vandyke K, Dewar AL, Farrugia AN, Fitter S, Bik To L, Hughes TP, Zannettino ACW. Therapeutic concentrations of dasatinib inhibit in vitro osteoclastogenesis. Leukemia. 2009; 23: 994997.
  • 8
    Brownlow N, Mol C, Hayford C, Ghaem-Maghami S, Dibb NJ. Dasatinib is a potent inhibitor of tumour-associated macrophages, osteoclasts and the FMS receptor. Leukemia. 2009; 23: 590594.
  • 9
    Wiktor-Jedrzejczak W, Bartocci A, Ferrante AW Jr, Ahmed-Ansari A, Sell KW, Pollard JW, Stanley ER. Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. Proc Natl Acad Sci USA. 1990; 87: 48284832.
  • 10
    Yoshida H, Hayashi S, Kunisada T, Ogawa M, Nishikawa S, Okamura H, Sudo T, Shultz LD, Nishikawa S. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature. 1990; 345: 442444.
  • 11
    Dai XM, Ryan GR, Hapel AJ, Dominguez MG, Russell RG, Kapp S, Sylvestre V, Stanley ER. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood. 2002; 99: 111120.
  • 12
    Yang M, Mailhot G, MacKay CA, Mason-Savas A, Aubin J, Odgren PR. Chemokine and chemokine receptor expression during colony stimulating factor-1-induced osteoclast differentiation in the toothless osteopetrotic rat: a key role for CCL9 (MIP-1gamma) in osteoclastogenesis in vivo and in vitro. Blood. 2006; 107: 22622270.
  • 13
    Hock JM, Canalis E. Platelet-derived growth factor enhances bone cell replication, but not differentiated function of osteoblasts. Endocrinology. 1994; 134: 14231428.
  • 14
    Kubota K, Sakikawa C, Katsumata M, Nakamura T, Wakabayashi K. Platelet-derived growth factor BB secreted from osteoclasts acts as an osteoblastogenesis inhibitory factor. J Bone Miner Res. 2002; 17: 257265.
  • 15
    Chaudhary LR, Hofmeister AM, Hruska KA. Differential growth factor control of bone formation through osteoprogenitor differentiation. Bone. 2004; 34: 402411.
  • 16
    Tokunaga A, Oya T, Ishii Y, Motomura H, Nakamura C, Ishizawa S, Fujimori T, Nabeshima Y, Umezawa A, Kanamori M, Kimura T, Sasahara M. PDGF receptor beta is a potent regulator of mesenchymal stromal cell function. J Bone Miner Res. 2008; 23: 15191528.
  • 17
    Fitter S, Dewar AL, Kostakis P, To LB, Hughes TP, Roberts MM, Lynch K, Vernon-Roberts B, Zannettino ACW. Long-term imatinib therapy promotes bone formation in CML patients. Blood. 2008; 111: 25382547.
  • 18
    Fierro F, Illmer T, Jing D, Schleyer E, Ehninger G, Boxberger S, Bornhäuser M. Inhibition of platelet-derived growth factor receptorb by imatinib mesylate suppresses proliferation and alters differentiation of human mesenchymal stem cells in vitro. Cell Prolif. 2007; 40: 355366.
  • 19
    O'Sullivan S, Naot D, Callon K, Porteous F, Horne A, Wattie D, Watson M, Cornish J, Browett P, Grey A. Imatinib promotes osteoblast differentiation by inhibiting PDGFR signaling and inhibits osteoclastogenesis by both direct and stromal cell-dependent mechanisms. J Bone Miner Res. 2007; 22: 16791689.
  • 20
    Wihlidal P, Karlic H, Pfeilstocker M, Klaushofer K, Varga F. Imatinib mesylate (IM)-induced growth inhibition is associated with production of spliced osteocalcin-mRNA in cell lines. Leuk Res. 2008; 32: 437443.
  • 21
    Tibullo D, Giallongo C, La Cava P, Berretta S, Stagno F, Chiarenza A, Conticello C, Palumbo GA, Di Raimondo F. Effects of imatinib mesylate in osteoblastogenesis. Exp Hematol. 2009; 37: 461468.
  • 22
    Wani MR, Fuller K, Kim NS, Choi Y, Chambers T. Prostaglandin E2 cooperates with TRANCE in osteoclast induction from hemopoietic precursors: synergistic activation of differentiation, cell spreading, and fusion. Endocrinology. 1999; 140: 19271935.
  • 23
    Vandyke K, Dewar AL, Fitter S, Menicanin D, To LB, Hughes TP, Zannettino AC. Imatinib mesylate causes growth plate closure in vivo. Leukemia. 2009; 23: 21552159.
  • 24
    Dewar AL, Cambareri AC, Zannettino ACW, Miller BL, Doherty KV, Hughes TP, Lyons AB. Macrophage colony-stimulating factor receptor c-fms is a novel target of imatinib. Blood. 2005; 105: 31273132.
  • 25
    Sawyers CL. Chronic myeloid leukemia. N Engl J Med. 1999; 340: 13301340.
  • 26
    Labrinidis A, Hay S, Liapis V, Ponomarev V, Findlay DM, Evdokiou A. Zoledronic acid inhibits both the osteolytic and osteoblastic components of osteosarcoma lesions in a mouse model. Clin Cancer Res. 2009; 15: 34513461.
  • 27
    Perilli E, Baruffaldi F, Bisi MC, Cristofolini L, Cappello A. A physical phantom for the calibration of three-dimensional X-ray microtomography examination. J Microsc. 2006; 222: 124134.
  • 28
    McNeil PJ, Durbridge TC, Parkinson IH, Moore RJ. Simple method for the simultaneous demonstration of formation and resorption in undecalcified bone embedded in methyl methacrylate. J Histotechnol. 1997; 20: 307311.
  • 29
    Vanderkerken K, Asosingh K, Willems A, De Raeve H, Couck P, Gorus F, Croucher P, Van Camp B. The 5TMM murine model of multiple myeloma. In: BrownRD, HoPJ, eds. Multiple Myeloma: Methods and Protocols vol. 113. Humana Press, Totowa, NJ, USA: 2005; pp. 191205.
  • 30
    Cecchini MG, Dominguez MG, Mocci S, Wetterwald A, Felix R, Fleisch H, Chisholm O, Hofstetter W, Pollard JW, Stanley ER. Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse. Development. 1994; 120: 13571372.
  • 31
    Grey A, Chen Y, Paliwal I, Carlberg K, Insogna K. Evidence for a functional association between phosphatidylinositol 3-kinase and c-src in the spreading response of osteoclasts to colony-stimulating factor-1. Endocrinology. 2000; 141: 21292138.
  • 32
    Insogna KL, Sahni M, Grey AB, Tanaka S, Horne WC, Neff L, Mitnick M, Levy JB, Baron R. Colony-stimulating factor-1 induces cytoskeletal reorganization and c-src-dependent tyrosine phosphorylation of selected cellular proteins in rodent osteoclasts. J Clin Invest. 1997; 100: 24762485.
  • 33
    Glantschnig H, Fisher JE, Wesolowski G, Rodan GA, Reszka AA. M-CSF, TNFa and RANK ligand promote osteoclast survival by signaling through mTOR/S6 kinase. Cell Death Differ. 2003; 10: 11651177.
  • 34
    Cappellen D, Luong-Nguyen NH, Bongiovanni S, Grenet O, Wanke C, Šuša M. Transcriptional program of mouse osteoclast differentiation governed by the macrophage colony-stimulating factor and the ligand for the receptor activator of NFkappa B. J Biol Chem. 2002; 277: 2197121982.
  • 35
    Xing L, Venegas AM, Chen A, Garrett-Beal L, Boyce BF, Varmus HE, Schwartzberg PL. Genetic evidence for a role for Src family kinases in TNF family receptor signaling and cell survival. Genes Dev. 2001; 15: 241253.
  • 36
    Lowe C, Yoneda T, Boyce BF, Chen H, Mundy GR, Soriano P. Osteopetrosis in Src-deficient mice is due to an autonomous defect of osteoclasts. Proc Natl Acad Sci U S A. 1993; 90: 44854489.
  • 37
    Soriano P, Montgomery C, Geske R, Bradley A. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell. 1991; 64: 693702.
  • 38
    Boyce BF, Yoneda T, Lowe C, Soriano P, Mundy GR. Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice. J Clin Invest. 1992; 90: 16221627.
  • 39
    Vandyke K, Fitter S, Dewar AL, Hughes TP, Zannettino AC. Dysregulation of bone remodelling by imatinib mesylate. Blood. 2009; Published online 4 November,. 2009; doi: 10.1182/blood-2009-08-237404.
  • 40
    Jönsson S, Olsson B, Ohlsson C, Lorentzon M, Mellström D, Wadenvik H. Increased cortical bone mineralization in imatinib treated patients with chronic myelogenous leukemia. Haematologica. 2008; 93: 11011103.
  • 41
    O'Sullivan S, Horne A, Wattie D, Porteous F, Callon K, Gamble G, Ebeling P, Browett P, Grey A. Decreased bone turnover despite persistent secondary hyperparathyroidism during prolonged treatment with imatinib. J Clin Endocrinol Metab. 2009; 94: 11311136.
  • 42
    Joensuu H, Reichardt P. Imatinib and altered bone and mineral metabolism. N Engl J Med. 2006; 355: 628.
  • 43
    Grey A, O'Sullivan S, Reid IR, Browett P. Imatinib mesylate, increased bone formation, and secondary hyperparathyroidism. N Engl J Med. 2006; 355: 24942495.
  • 44
    Osorio S, Noblejas AG, Durán A, Steegmann JL. Imatinib mesylate induces hypophosphatemia in patients with chronic myeloid leukemia in late chronic phase, and this effect is associated with response. Am J Hematol. 2007; 82: 394395.
  • 45
    Berman E, Nicolaides M, Maki RG, Fleisher M, Chanel S, Scheu K, Wilson BA, Heller G, Sauter NP. Altered bone and mineral metabolism in patients receiving imatinib mesylate. N Engl J Med. 2006; 354: 20062013.
  • 46
    Owen S, Hatfield A, Letvak L. Imatinib and altered bone and mineral metabolism. N Engl J Med. 2006; 355: 627.
  • 47
    Carpiuc KT, Stephens JM, Botteman SYL, MF. Incidence of grade 3/4 adverse events in imatinib resistant/intolerant chronic phase CML (CP-CML): A comparison of nilotinib and dasatinib [abstract]. Journal of Clinical Oncology. 2007; 25: 17501.
  • 48
    Mori S, Burr DB. Increased intracortical remodeling following fatigue damage. Bone. 1993; 14: 103109.
  • 49
    Bentolila V, Boyce TM, Fyhrie DP, Drumb R, Skerry TM, Schaffler MB. Intracortical remodeling in adult rat long bones after fatigue loading. Bone. 1998; 23: 275281.
  • 50
    Burr DB, Forwood MR, Fyhrie DP, Martin RB, Schaffler MB, Turner CH. Bone microdamage and skeletal fragility in osteoporotic and stress fractures. J Bone Miner Res. 1997; 12: 615.
  • 51
    Mashiba T, Turner CH, Hirano T, Forwood MR, Johnston CC, Burr DB. Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles. Bone. 2001; 28: 524531.
  • 52
    Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res. 2000; 15: 613620.
  • 53
    Komatsubara S, Mori S, Mashiba T, Ito M, Li J, Kaji Y, Akiyama T, Miyamoto K, Cao Y, Kawanishi J, Norimatsu H. Long-term treatment of incadronate disodium accumulates microdamage but improves the trabecular bone microarchitecture in dog vertebra. J Bone Miner Res. 2003; 18: 512520.
  • 54
    Teo JCM, Si-Hoe KM, Keh JEL, Keh JEL, S. H. T. Correlation of cancellous bone microarchitectural parameters from microCT to CT number and bone mechanical properties. Mat Sci Eng C. 2007; 27: 333339.
  • 55
    Ikeda S, Morishita Y, Tsutsumi H, Ito M, Shiraishi A, Arita S, Akahoshi S, Narusawa K, Nakamura T. Reductions in bone turnover, mineral, and structure associated with mechanical properties of lumbar vertebra and femur in glucocorticoid-treated growing minipigs. Bone. 2003; 33: 779787.
  • 56
    Kleerekoper M, Villanueva AR, Stanciu J, Rao DS, Parfitt AM. The role of three-dimensional trabecular microstructure in the pathogenesis of vertebral compression fractures. Calcif Tissue Int. 1985; 37: 594597.
  • 57
    Coleman RE. Bisphosphonates: clinical experience. Oncologist. 2004; 9: 1427.
  • 58
    Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH., Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann NY Acad Sci. 2007; 1117: 209257.