• 1
    Van Beek ER, Pieterman E, Cohen L, Löwik CWGM, Papapoulos SE. Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates. Biochem Biophys Res Commun. 1999 Oct; 264(1): 10811.
  • 2
    Kavanagh KL, Guo K, Dunford JE, Wu X, Knapp S, Ebetino FH, Rogers MJ, Russell RGG, Opperman U. The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proc Natl Acad Sci USA. 2006 May; 103(20): 782934.
  • 3
    Fisher JE, Rogers MJ, Halasy JM, Luckman SP, Hughes DE, Masarachia PJ, Wesolowski G, Russell RGG, Rodan GA, Reszka AA. Mechanism of action of alendronate: geranylgeraniol, an intermediate of the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption and kinase activation in vitro. Proc Natl Acad Sci USA. 1999 Jan; 96(1): 1338.
  • 4
    Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ. 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 Feb; 296(2): 23542.
  • 5
    Russell RGG, Watts NB, Ebetino FH, Rogers MJ. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 2008 Jun; 19(6): 73359.
  • 6
    Ebetino FH, Hogan AM, Sun S, Tsoumpra MK, Duan X, Triffitt JT, Kwaasi AA, Dunford JE, Barnett BL, Opperman U, Lundy MW, Boyde A, Kashemirov BA, McKenna CE, Russell RGG. The relationship between the chemistry and biological activity of the bisphosphonates. Bone. 2011 Jul; 49(1): 2033.
  • 7
    Russell RGG, Rogers MJ. Bisphosphonates: from the laboratory to the clinic and back again. Bone. 1999 Jul; 25(1): 97106.
  • 8
    Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RGG, Ebetino FH. Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006 May; 38(5): 61727.
  • 9
    Henneman ZJ, Nancollas GH, Ebetino FH, Russell RGG, Phipps RJ. Bisphosphonate binding affinity as assessed by inhibition of carbonated apatite dissolution in vitro. J Biomed Mater Res A. 2008 Jun; 85(4): 9931000.
  • 10
    Lawson MA, Xia Z, Barnett BL, Triffitt JT, Phipps RJ, Dunford JE, Locklin RM, Ebetino FH, Russell RGG. Differences between bisphosphonates in binding affinities for hydroxyapatite. J Biomed Mater Res B Appl Biomater. 2010 Jan; 92(1): 14955.
  • 11
    Leu CT, Luegmayr E, Freedman LP, Rodan GA, Reszka AA. Relative binding affinities of bisphosphonates for human bone and relationship to antiresorptive efficacy. Bone. 2006 May; 38(5): 62836.
  • 12
    Mukherjee S, Song Y, Oldfield E. NMR investigations of the static and dynamic structures of bisphosphonates on human bone: a molecular model. J Am Chem Soc. 2008 Jan; 130(4): 126473.
  • 13
    Sato M, Grasser W, Endo N, Akins R, Simmons H, Thompson DD, Golub E, Rodan GA. Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest. 1991 Dec; 88(6): 2095105.
  • 14
    Azuma Y, Sato H, Oue Y, Okabe K, Ohta T, Tsuchimoto M, Kiyoki M. Alendronate distributed on bone surfaces inhibits osteoclastic bone resorption in vitro and in experimental hypercalcemia models. Bone. 1995 Feb; 16(2): 23545.
  • 15
    Masarachia P, Weinreb M, Balena R, Godan GA. Comparison of the distribution of 3H-alendronate and 3H-etidronate in rat and mouse bones. Bone. 1996 Sep; 19(3): 28190.
  • 16
    Kashemirov BA, Bala JLF, Chen X, Ebetino FH, Xia Z, Russell RGG, Coxon FP, Roelofs AJ, Rogers MJ, McKenna CE. Fluorescently labeled risedronate and related analogs: “magic linker” synthesis. Bioconjug Chem. 2008 Dec; 19(12): 230810.
  • 17
    Roelofs AJ, Coxon FP, Ebetino FH, Lundy MW, Henneman ZJ, Nancollas GH, Sun S, Blazewska KM, Bala JL, Kashemirov BA, Khalid AB, McKenna CE, Rogers MJ. Fluorescent risedronate analogues reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in vivo. J Bone Miner Res. 2010 Mar; 25(3): 60616.
  • 18
    Marma MS, Xia Z, Stewart C, Coxon FP, Dunford JE, Baron R, Kashemirov BA, Ebetino FH, Triffitt JT, Russell RGG, McKenna CE. Synthesis and biological evaluation of alpha-halogenated bisphosphonate and phosphonocarboxylate analogues of risedronate. J Med Chem. 2007 Nov 29; 50(24): 596775.
  • 19
    Coxon FP, Helfrich MH, Larijani B, Muzylak M, Dunford JE, Marshall D, McKinnon AD, Nesbitt SA, Horton MA, Seabra MC, Ebetino FH, Rogers MJ. Identification of a novel phosphonocarboxylate inhibitor of rab geranylgeranyl transferase that specifically prevents rab prenylation in osteoclasts and macrophages. J Biol Chem. 2001 Dec 21; 276(51): 4821322.
  • 20
    Coxon FP, Frith JC, Benford HL, Rogers MJ. Isolation and purification of rabbit osteoclasts. Methods Mol Med. 2003; 80: 8999.
  • 21
    Coxon FP, Thompson K, Roelofs AJ, Ebetino FH, Rogers MJ. Visualizing mineral binding and uptake of bisphosphonate by osteoclasts and non-resorbing cells. Bone. 2008 May; 42(5): 84660.
  • 22
    Mukherjee S, Huang C, Guerra F, Wang K, Oldfield E. Thermodynamics of bisphosphonates binding to human bone: a two-site model. J Am Chem Soc. 2009 Jun; 131(24): 83745.
  • 23
    Lin JH. Bisphosphonates: a review of their pharmacokinetic properties. Bone. 1996 Feb; 18(2): 7585.
  • 24
    Christiansen C, Phipps R, Burgio D, Sun L, Russell D, Keck B, Kuzmak B, Lindsay R. Comparison of risedronate and alendronate pharmacokinetics at clinical doses. Osteoporos Int. 2003; 14( suppl 7): S38.
  • 25
    Kozloff KM, Weissleder R, Mahmood U. Noninvasive optical detection of bone mineral. J Bone Miner Res. 2007 Aug; 22(8): 120816.
  • 26
    Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest. 1999 Nov; 104(10): 136374.
  • 27
    Follet H, Li J, Phipps RJ, Hui S, Condon K, Burr DB. Risedronate and alendronate suppress osteocyte apoptosis following cyclic fatigue loading. Bone. 2007 Apr; 40(4): 11727.
  • 28
    Plotkin LI, Manolagas SC, Bellido T. Dissociation of the pro-apoptotic effects of bisphosphonates on osteoclasts from their anti-apoptotic effects on osteoblasts/osteocytes with novel analogs. Bone. 2006 Sep; 39(3): 44352.
  • 29
    Plotkin LI, 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 Jul; 49(1): 1227.
  • 30
    Plotkin LI, Manolagas SC, Bellido T. Transduction of cell survival signals by connexin-43 hemichannels. J Biol Chem. 2002 Mar; 277(10): 864857.
  • 31
    Plotkin LI, Lezcano V, Thostenson J, Weinstein RS, Manolagas SC, Bellido T. Connexin 43 is required for the anti-apoptotic effect of bisphosphonates on osteocytes and osteoblasts in vivo. J Bone Miner Res. 2008 Nov; 23(11): 171221.
  • 32
    Aya-ay J, Athavale S, Morgan-Bagley S, Bian H, Bauss F, Kim HK. Retention, distribution, and effects of intraosseously administered ibandronate in the infarcted femoral head. J Bone Miner Res. 2007 Jan; 22(1): 93100.
  • 33
    Löwik CWGM, Van der Pluijm G, Van der Wee-Pals LJA, Van Treslong-De Groot HB, Bijvoet OLM. Migration and phenotypic transformation of osteoclast precursors into mature osteoclasts: the effect of a bisphosphonate. J Bone Miner Res. 1988 Apr; 3(2): 18592.
  • 34
    Hughes DE, MacDonald BR, Russell RGG, Gowen M. Inhibition of osteoclast-like cell formation by bisphosphonates in long-term cultures of human bone marrow. J Clin Invest. 1989 Jun; 83(6): 19305.
  • 35
    Van Beek ER, Löwik CWGM, Papapoulos SE. Bisphosphonates suppress bone resorption by a direct effect on early osteoclast precursors without affecting the osteoclastogenic capacity of osteogenic cells: the role of protein geranylgeranylation in the action of nitrogen-containing bisphosphonates on osteoclast precursors. Bone. 2002 Jan; 30(1): 6470.