Differentiating the mechanisms of antiresorptive action of nitrogen containing bisphosphonates

Bone

Volumn 33, Issue 5, 2003, Pages 805-811

  Van Beek, E R ^a   Cohen, L H ^b   Leroy, I M ^b   Ebetino, F H ^c   Lowik C W G M ^a   Papapoulos, S E ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^b TNO   (Netherlands)

^c PROCTER AND GAMBLE PHARMACEUTICALS   (United States)

Author keywords

Bisphosphonates; Bone resorption; FPP synthase; Geranylgeranylation; Osteoclasts

Indexed keywords

ALENDRONIC ACID; BISPHOSPHONIC ACID DERIVATIVE; ETIDRONIC ACID; GERANYLGERANIOL; GERANYLTRANSFERASE; ISOPENTENYL DIPHOSPHATE DELTA ISOMERASE; NE 10575; NE 11808; NE 21650; NE 58086; NITROGEN; PAMIDRONIC ACID; RISEDRONIC ACID; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG EFFECT; DRUG MECHANISM; DRUG POTENCY; ENZYME ACTIVITY; ENZYME REPRESSION; FEMALE; FETUS; NONHUMAN; OSTEOCLAST; OSTEOLYSIS; STRUCTURAL HOMOLOGY;

EID: 0242610812     PISSN: 87563282     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bone.2003.07.007     Document Type: Article

References (27)

1. Fleisch H. Bisphosphonates mechanisms of action . Endocr Rev. 19:1998;80-100.
2. Rodan G.A. Mechanisms of action of bisphosphonates. Ann Rev Pharmacol Toxicol. 38:1998;375-388.
3. 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. 15, 88:(12 Suppl):2000;2961-2978.
4. Pelorgeas S., Martin J.B., Satre M. Cytotoxicity of dichloromethane diphosphonate and of 1-hydroxyethane-1, 1-diphosphonate in the amoebae of the slime mould Dictyostelium discoideum. A 31P NMR study. Biochem Pharmacol. 44:1992;2157-2163.
5. Frith J.C., Monkkonen J., Blackburn G.M., Russell R.G., Rogers M.J. Clodronate and liposome-encapsulated clodronate are metabolized to a toxic ATP analog, adenosine 5′-(beta, gamma-dichloromethylene) triphosphate, by mammalian cells in vitro. J Bone Miner Res. 12:1997;1358-1367.
6. van Beek E.R., Pieterman E., Cohen L., Löwik C., Papapoulos S. Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates. Biochem Bioph Res Comm. 264:1999;108-111.
7. Bergstrom J.D., Bostedor R.G., Masarachia P.J., Reszka A.A., Rodan G. Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase. Arch Biochem Biophys. 373:2000;231-241.
8. Grove J.E., Brown R.J., Watts D.J. The intracellular target for the antiresorptive aminobisphosphonate drugs in Dictyostelium discoideum is the enzyme farnesyl diphosphate synthase. J Bone Miner Res. 15:2000;971-981.
9. 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. 296:2001;235-242.
10. Russell R.G., Rogers M.J., Frith J.C., Luckman S.P., Coxon F.P., Benford H.I., Croucher P.I., Shipman C., Fleisch H.A. The pharmacology of bisphosphonates and new insights into their mechanisms of action. J Bone Miner Res. 14:(Suppl 2):1999;53-65.
11. van Beek E., Löwik C., van der Pluijm G., Papapoulos S. The role of protein geranylgeranylation in bone resorption and its suppression by bisphosphonates in fetal bone explants in vitro; a clue to the mechanism of action of nitrogen-containing bisphosphonates. J Bone Miner Res. 14:1999;722-729.
12. Fisher J.E., Rogers M.J., Halasy J.M., Luckman S.P., Hughes D.E., Masarachia P.J., Wesolowski G., Russell R.G., Rodan G.A., Reszka A.A. Alendronate mechanism of action geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro . Proc Natl Acad Sci USA. 5:(96):1999;133-138.
13. Sato M., Grasser W. Effects of bisphosphonates on isolated rat osteoclasts as examined by reflected light microscopy. J Bone Miner Res. 5:1990;31-40.
14. Ito M., Amizuka N., Nakajima T., Ozawa H. Ultrastructural and cytochemical studies on cell death of osteoclasts induced by bisphosphonate treatment. Bone. 25:1999;447-452.
15. Hughes D.E., Wright K.R., Uy H.L., Sasaki A., Yoneda T., Roodman G.D., Mundy G.R., Boyce B.F. Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res. 10:1995;1478-1487.
16. van Beek E.R., Pieterman E., Cohen L., Löwik C., Papapoulos S. Nitrogen-containing bisphosphonates inhibit isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo. Biochem Biophys Res Commun. 16:(255):1999;491-494.
17. Reinholz G.G., Getz B., Sanders E.S., Karpeisky M.Y., Padyukova N.S.H., Mikhailov S.N., Ingle J.N., Spelsberg T.C. Distinct mechanisms of bisphosphonate action between osteoblasts and breast cancer cells identity of a potent new bisphosphonate analogue . Breast Cancer Res Treat. 71:(3):2002;256-257.
18. Suri S., Monkkonen J., Taskinen M., Pesonen J., Blank M.A., Phipps R.J., Rogers M.J. Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway a model of bisphosphonate-induced gastrointestinal toxicity . Bone. 29:(4):2001;336-343.
19. Van Beek E., Lowik C., Que I., Papapoulos S. Dissociation of binding and antiresorptive properties of hydroxybisphosphonates by substitution of the hydroxyl with an amino group. J Bone Miner Res. 11:(10):1996;1492-1497.
20. 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. 56:(1):1999;131-140.
21. Luckman S.P., Coxon F.P., Ebetino F.H., Russell R.G., Rogers M.J. Heterocycle-containing bisphosphonates cause apoptosis and inhibit bone resorption by preventing protein prenylation evidence from structure-activity relationships in J774 macrophages . J Bone Miner Res. 13:(11):1998;1668-1678.
22. Rogers M.J., Chilton K.M., Coxon F.P., Lawry J., Smith M.O., Suri S., Russell R.G. Bisphosphonates induce apoptosis in mouse macrophage-like cells in vitro by a nitric oxide-independent mechanism. J Bone Miner Res. 11:(10):1996;1482-1491.
23. van Beek E.R., Lowik C.W., Ebetino F.H., Papapoulos S.E. Binding and antiresorptive properties of heterocycle-containing bisphosphonate analogs structure-activity relationships . Bone. 23:(5):1998;437-442.
24. Thompson K., Dunford J.E., Ebetino F.H., Rogers M.J. Identification of a bisphosphonate that inhibits isopentenyl diphosphate isomerase and farnesyl diphosphate synthase. Biochem Bioph Res Comm. 290:2002;869-873.
25. Schmidt A., Rutledge S.J., Endo N., Opas E.E., Tanaka H., Wesolowski G., Leu C.T., Huang Z., Ramachandaran C., Rodan S.B., Rodan G.A. Protein-tyrosine phosphatase activity regulates osteoclast formation and function inhibition by alendronate . Proc Natl Acad Sci USA. 2; 93:(7):1996;3068-3073.
26. Murakami H., Takahashi N., Tanaka S., Nakamura I., Udagawa N., Nakajo S., Nakaya K., Abe M., Yuda Y., Konno F., Barbier A., Suda T. Tiludronate inhibits protein tyrosine phosphatase activity in osteoclasts. Bone. 20:(5):1997;399-404.
27. Coxon F.P., Helfrich M.H., Larijani B., Muzylak M., Dunford J.E., Marshall D., McKinnon A.D., Nesbitt S.A., Horton M.A., Seabra M.C., Ebetino F.H., Rogers M.J. Identification of a novel phosphonocarboxylate inhibitor of Rab geranylgeranyl transferase that specifically prevents Rab prenylation in osteoclasts and macrophages. J Biol Chem. 21; 276:(51):1997;48213-48222.