• 1
    Bussard KM, Gay CV, Mastro AM. The bone microenvironment in metastasis; what is special about bone?. Cancer Metastasis Rev. 2008; 27:4155.
  • 2
    Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001; 27:16576.
  • 3
    Kozlow W, Guise TA. Breast cancer metastasis to bone: mechanisms of osteolysis and implications for therapy. J Mammary Gland Biol Neoplasia. 2005; 10:16980.
  • 4
    Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002; 2:58493.
  • 5
    Bendre MS, Gaddy-Kurten D, Mon-Foote T, Akel NS, Skinner RA, Nicholas RW, Suva LJ. Expression of interleukin 8 and not parathyroid hormone-related protein by human breast cancer cells correlates with bone metastasis in vivo. Cancer Res. 2002; 62:55719.
  • 6
    Guise TA. The vicious cycle of bone metastases. J Musculoskelet Neuronal Interact. 2002; 2:5702.
  • 7
    Donaldson CL, Hulley SB, Vogel JM, Hattner RS, Bayers JH, McMillan DE. Effect of prolonged bed rest on bone mineral. Metabolism. 1970; 19:107184.
  • 8
    Vico L, Collet P, Guignandon A, Lafage-Proust MH, Thomas T, Rehaillia M, Alexandre C. Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts. Lancet. 2000 May 6; 355:160711.
  • 9
    Hillam RA, Skerry TM. Inhibition of bone resorption and stimulation of formation by mechanical loading of the modeling rat ulna in vivo. J Bone Miner Res. 1995; 10:6839.
  • 10
    Chow JW, Wilson AJ, Chambers TJ, Fox SW. Mechanical loading stimulates bone formation by reactivation of bone lining cells in 13-week-old rats. J Bone Miner Res. 1998; 13:17607.
  • 11
    Kerr D, Ackland T, Maslen B, Morton A, Prince R. Resistance training over 2 years increases bone mass in calcium-replete postmenopausal women. J Bone Miner Res. 2001; 16:17581.
  • 12
    Kohrt WM, Ehsani AA, Birge SJ Jr. Effects of exercise involving predominantly either joint-reaction or ground-reaction forces on bone mineral density in older women. J Bone Miner Res. 1997; 12:125361.
  • 13
    Milne HM, Wallman KE, Gordon S, Courneya KS. Effects of a combined aerobic and resistance exercise program in breast cancer survivors: a randomized controlled trial. Breast Cancer Res Treat. 2008; 108:27988.
  • 14
    Schwartz AL, Winters-Stone K, Gallucci B. Exercise effects on bone mineral density in women with breast cancer receiving adjuvant chemotherapy. Oncol Nurs Forum. 2007; 34:62733.
  • 15
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144:64674.
  • 16
    Mosley JR, Lanyon LE. Strain rate as a controlling influence on adaptive modeling in response to dynamic loading of the ulna in growing male rats. Bone. 1998; 23:3138.
  • 17
    Stengel SV, Kemmler W, Pintag R, Beeskow C, Weineck J, Lauber D, Kalender WA, Engelke K. Power training is more effective than strength training for maintaining bone mineral density in postmenopausal women. J Appl Physiol. 2005; 99:1818.
  • 18
    Fritton JC, Myers ER, Wright TM, van der Meulen MC. Bone mass is preserved and cancellous architecture altered due to cyclic loading of the mouse tibia after orchidectomy. J Bone Miner Res. 2008; 23:66371.
  • 19
    Lynch ME, Main RP, Xu Q, Schmicker TL, Schaffler MB, Wright TM, van der Meulen MC. Tibial compression is anabolic in the adult mouse skeleton despite reduced responsiveness with aging. Bone. 2011; 49:43946.
  • 20
    Main RP, Lynch ME, van der Meulen MC. In vivo tibial stiffness is maintained by whole bone morphology and cross-sectional geometry in growing female mice. J Biomech. 2010; 43:268994.
  • 21
    De Souza RL, Matsuura M, Eckstein F, Rawlinson SC, Lanyon LE, Pitsillides AA. Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element. Bone. 2005; 37:8108.
  • 22
    Berlin O, Samid D, Donthineni-Rao R, Akeson W, Amiel D, Woods VL Jr. Development of a novel spontaneous metastasis model of human osteosarcoma transplanted orthotopically into bone of athymic mice. Cancer Res. 1993; 53:48905.
  • 23
    Fritz V, Louis-Plence P, Apparailly F, Noël D, Voide R, Pillon A, Nicolas JC, Müller R, Jorgensen C. Micro-CT combined with bioluminescence imaging: a dynamic approach to detect early tumor-bone interaction in a tumor osteolysis murine model. Bone. 2007; 40:103240.
  • 24
    Park BK, Zhang H, Zeng Q, Dai J, Keller ET, Giordano T, Gu K, Shah V, Pei L, Zarbo RJ, McCauley L, Shi S, Chen S, Wang CY. NF-kappaB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF. Nat Med. 2007; 13:629.
  • 25
    Lanyon LE. Functional strain as a determinant for bone remodeling. Calcif Tissue Int. 1984; 36Suppl 1:S5661.
  • 26
    Fritton JC, Myers ER, Wright TM, van der Meulen MC. Loading induces site-specific increases in mineral content assessed by microcomputed tomography of the mouse tibia. Bone. 2005; 36:10308.
  • 27
    Pathi SP, Kowalczewski C, Tadipatri R, Fischbach C. A novel 3-D mineralized tumor model to study breast cancer bone metastasis. PLoS One. 2010; 5:e8849.
  • 28
    Fischbach C, Chen R, Matsumoto T, Schmelzle T, Brugge JS, Polverini PJ, Mooney DJ. Engineering tumors with 3D scaffolds. Nat Methods. 2007; 4:85560.
  • 29
    Pathi SP, Lin DD, Dorvee JR, Estroff LA, Fischbach C. Hydroxyapatite nanoparticle-containing scaffolds for the study of breast cancer bone metastasis. Biomaterials. 2011; 32:511222.
  • 30
    Ballyns JJ, Bonassar LJ. Dynamic compressive loading of image-guided tissue engineered meniscal constructs. J Biomech. 2011; 44:50916.
  • 31
    Sittichockechaiwut A, Scutt AM, Ryan AJ, Bonewald LF, Reilly GC. Use of rapidly mineralising osteoblasts and short periods of mechanical loading to accelerate matrix maturation in 3D scaffolds. Bone. 2009; 44:8229.
  • 32
    Sanchez C, Gabay O, Salvat C, Henrotin YE, Berenbaum F. Mechanical loading highly increases IL-6 production and decreases OPG expression by osteoblasts. Osteoarthritis Cartilage. 2009; 17:47381.
  • 33
    Minn AJ, Kang Y, Serganova I, Gupta GP, Giri DD, Doubrovin M, Ponomarev V, Gerald WL, Blasberg R, Massagué J. Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest. 2005; 115:4455.
  • 34
    Mancino AT, Klimberg VS, Yamamoto M, Manolagas SC, Abe E. Breast cancer increases osteoclastogenesis by secreting M-CSF and upregulating RANKL in stromal cells. J Surg Res. 2001; 100:1824.
  • 35
    Thomas RJ, Guise TA, Yin JJ, Elliott J, Horwood NJ, Martin TJ, Gillespie MT. Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinology. 1999; 140:44518.
  • 36
    Barnes GL, Hebert KE, Kamal M, Javed A, Einhorn TA, Lian JB, Stein GS, Gerstenfeld LC. Fidelity of Runx2 activity in breast cancer cells is required for the generation of metastases-associated osteolytic disease. Cancer Res. 2004; 64:450613.
  • 37
    Javed A, Barnes GL, Pratap J, Antkowiak T, Gerstenfeld LC, van Wijnen AJ, Stein JL, Lian JB, Stein GS. Impaired intranuclear trafficking of Runx2 (AML3/CBFA1) transcription factors in breast cancer cells inhibits osteolysis in vivo. Proc Natl Acad Sci U S A. 2005; 102:14549.
  • 38
    Bu G, Lu W, Liu CC, Selander K, Yoneda T, Hall C, Keller ET, Li Y. Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: implication for breast cancer osteolytic bone metastases. Int J Cancer. 2008; 123:103442.
  • 39
    Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008; 3:11018.
  • 40
    Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987; 162:1569.
  • 41
    Arrington SA, Schoonmaker JE, Damron TA, Mann KA, Allen MJ. Temporal changes in bone mass and mechanical properties in a murine model of tumor osteolysis. Bone. 2006; 38:35967.
  • 42
    Clohisy DR, Palkert D, Ramnaraine ML, Pekurovsky I, Oursler MJ. Human breast cancer induces osteoclast activation and increases the number of osteoclasts at sites of tumor osteolysis. J Orthop Res. 1996; 14:396402.
  • 43
    Mantila Roosa SM, Liu Y, Turner CH. Gene expression patterns in bone following mechanical loading. J Bone Miner Res. 2011; 26:10012.
  • 44
    Turner CH, Owan I, Alvey T, Hulman J, Hock JM. Recruitment and proliferative responses of osteoblasts after mechanical loading in vivo determined using sustained-release bromodeoxyuridine. Bone. 1998; 22:4639.
  • 45
    Forwood MR, Owan I, Takano Y, Turner CH. Increased bone formation in rat tibiae after a single short period of dynamic loading in vivo. Am J Physiol. 1996 Mar; 270:E41923.
  • 46
    Lynch ME, Main RP, Xu Q, Walsh DJ, Schaffler MB, Wright TM, van der Meulen MC. Cancellous bone adaptation to tibial compression is not sex dependent in growing mice. J Appl Physiol. 2010; 109:68591.
  • 47
    Weilbaecher KN, Guise TA, McCauley LK. Cancer to bone: a fatal attraction. Nat Rev Cancer. 2011; 11:41125.
  • 48
    Sugiyama T, Meakin LB, Galea GL, Jackson BF, Lanyon LE, Ebetino FH, Russell RG, Price JS. Risedronate does not reduce mechanical loading-related increases in cortical and trabecular bone mass in mice. Bone. 2011; 49:1339.
  • 49
    Klein-Nulend J, Veldhuijzen JP, van Strien ME, de Jong M, Burger EH. Inhibition of osteoclastic bone resorption by mechanical stimulation in vitro. Arthritis Rheum. 1990; 33:6672.
  • 50
    Kobayashi Y, Hashimoto F, Miyamoto H, Kanaoka K, Miyazaki-Kawashita Y, Nakashima T, Shibata M, Kobayashi K, Kato Y, Sakai H. Force-induced osteoclast apoptosis in vivo is accompanied by elevation in transforming growth factor beta and osteoprotegerin expression. J Bone Miner Res. 2000; 15:192434.
  • 51
    Boerckel JD, Uhrig BA, Willett NJ, Huebsch N, Guldberg RE. Mechanical regulation of vascular growth and tissue regeneration in vivo. Proc Natl Acad Sci U S A. 2011; 108:E67480.
  • 52
    Barnes GL, Javed A, Waller SM, Kamal MH, Hebert KE, Hassan MQ, Bellahcene A, Van Wijnen AJ, Young MF, Lian JB, Stein GS, Gerstenfeld LC. Osteoblast-related transcription factors Runx2 (Cbfa1/AML3) and MSX2 mediate the expression of bone sialoprotein in human metastatic breast cancer cells. Cancer Res. 2003; 63:26317.
  • 53
    Pratap J, Wixted JJ, Gaur T, Zaidi SK, Dobson J, Gokul KD, Hussain S, van Wijnen AJ, Stein JL, Stein GS, Lian JB. Runx2 transcriptional activation of Indian Hedgehog and a downstream bone metastatic pathway in breast cancer cells. Cancer Res. 2008; 68:7795802.
  • 54
    Mendoza-Villanueva D, Zeef L, Shore P. Metastatic breast cancer cells inhibit osteoblast differentiation through the Runx2/CBFbeta-dependent expression of the Wnt antagonist, sclerostin. Breast Cancer Res. 2011; 13:R106.
  • 55
    Kuperwasser C, Dessain S, Bierbaum BE, Garnet D, Sperandio K, Gauvin GP, Naber SP, Weinberg RA, Rosenblatt M. A mouse model of human breast cancer metastasis to human bone. Cancer Res. 2005; 65:61308.
  • 56
    Almeida M, Han L, Martin-Millan M, O'Brien CA, Manolagas SC. Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factor- to forkhead box O-mediated transcription. J Biol Chem. 2007; 282:27298305.
  • 57
    Romas E, Gillespie MT. Inflammation-induced bone loss: can it be prevented?. Rheum Dis Clin North Am. 2006; 32:75973.
  • 58
    Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow?. Lancet. 2001; 357:53945.
  • 59
    Frost HM. The regional acceleratory phenomenon: a review. Henry Ford Hosp Med J. 1983; 31:39.
  • 60
    Zheng Y, Zhou H, Brennan K, Blair JM, Modzelewski JR, Seibel MJ, Dunstan CR. Inhibition of bone resorption, rather than direct cytotoxicity, mediates the anti-tumour actions of ibandronate and osteoprotegerin in a murine model of breast cancer bone metastasis. Bone. 2007; 40:4718.
  • 61
    Schwartz AL, Mori M, Gao R, Nail LM, King ME. Exercise reduces daily fatigue in women with breast cancer receiving chemotherapy. Med Sci Sports Exerc. 2001; 33:71823.
  • 62
    Winters-Stone KM, Dobek J, Bennett JA, Nail LM, Leo MC, Schwartz A. The effect of resistance training on muscle strength and physical function in older, postmenopausal breast cancer survivors: a randomized controlled trial. J Cancer Surviv. 2012; 6:18999.
  • 63
    Vainionpää A, Korpelainen R, Leppäluoto J, Jämsä T. Effects of high-impact exercise on bone mineral density: a randomized controlled trial in premenopausal women. Osteoporos Int. 2005; 16:1917.
  • 64
    Ozcivici E, Luu YK, Rubin CT, Judex S. Low-level vibrations retain bone marrow's osteogenic potential and augment recovery of trabecular bone during reambulation. PLoS One. 2010; 5:e11178.
  • 65
    Parkinson DR, Dracopoli N, Petty BG, Compton C, Cristofanilli M, Deisseroth A, Hayes DF, Kapke G, Kumar P, Lee J, Liu MC, McCormack R, Mikulski S, Nagahara L, Pantel K, Pearson-White S, Punnoose EA, Roadcap LT, Schade AE, Scher HI, Sigman CC, Kelloff GJ. Considerations in the development of circulating tumor cell technology for clinical use. J Transl Med. 2012; 10:138.