The pharmacology of bisphosphonates and new insights into their mechanisms of action

R G G Russell, M J Rogers, J C Frith, S P Luckman, Fraser Coxon, H L Benford, P I Croucher, C Shipman, H A Fleisch

Research output: Contribution to journalLiterature review

233 Citations (Scopus)

Abstract

Bisphosphonates are chemically stable analogs of inorganic pyrophosphate, which are resistant to breakdown by enzymatic hydrolysis, The biological effects of bisphosphonates on calcium metabolism were originally ascribed to their physico-chemical effects on hydroxyapatite crystals. Although such effects may contribute to their overall action, their effects on cells are probably of greater importance, particularly for the more potent compounds. Remarkable progress has been made in increasing the potency of bisphosphonates as inhibitors of bone resorption, and the most potent compounds in current use are characterized by the presence of a nitrogen atom at critical positions in the side chain which, together with the bisphosphonate moiety itself, seems to be essential for maximal activity, As a class the bisphosphonates offer a very effective means of treating Paget's disease.

Original languageEnglish
Pages (from-to)53-65
Number of pages13
JournalJournal of Bone and Mineral Research
Volume14
Issue numberSuppl. 2
Publication statusPublished - 1999

Keywords

  • mold dictyostelium-discoideum
  • cyclical etidronate therapy
  • GTP-binding protein
  • heterocycle-containing bisphosphonates
  • inhibit bone-resorption
  • acute-phase response
  • Pagets-Disease
  • in-vitro
  • dichlormethylene diphosphonate
  • postmenopausal osteoperosis

Cite this

Russell, R. G. G., Rogers, M. J., Frith, J. C., Luckman, S. P., Coxon, F., Benford, H. L., ... Fleisch, H. A. (1999). The pharmacology of bisphosphonates and new insights into their mechanisms of action. Journal of Bone and Mineral Research, 14(Suppl. 2), 53-65.

The pharmacology of bisphosphonates and new insights into their mechanisms of action. / Russell, R G G ; Rogers, M J ; Frith, J C ; Luckman, S P ; Coxon, Fraser; Benford, H L ; Croucher, P I ; Shipman, C ; Fleisch, H A .

In: Journal of Bone and Mineral Research, Vol. 14, No. Suppl. 2, 1999, p. 53-65.

Research output: Contribution to journalLiterature review

Russell, RGG, Rogers, MJ, Frith, JC, Luckman, SP, Coxon, F, Benford, HL, Croucher, PI, Shipman, C & Fleisch, HA 1999, 'The pharmacology of bisphosphonates and new insights into their mechanisms of action', Journal of Bone and Mineral Research, vol. 14, no. Suppl. 2, pp. 53-65.
Russell RGG, Rogers MJ, Frith JC, Luckman SP, Coxon F, Benford HL et al. The pharmacology of bisphosphonates and new insights into their mechanisms of action. Journal of Bone and Mineral Research. 1999;14(Suppl. 2):53-65.
Russell, R G G ; Rogers, M J ; Frith, J C ; Luckman, S P ; Coxon, Fraser ; Benford, H L ; Croucher, P I ; Shipman, C ; Fleisch, H A . / The pharmacology of bisphosphonates and new insights into their mechanisms of action. In: Journal of Bone and Mineral Research. 1999 ; Vol. 14, No. Suppl. 2. pp. 53-65.
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AU - Russell, R G G

AU - Rogers, M J

AU - Frith, J C

AU - Luckman, S P

AU - Coxon, Fraser

AU - Benford, H L

AU - Croucher, P I

AU - Shipman, C

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AB - Bisphosphonates are chemically stable analogs of inorganic pyrophosphate, which are resistant to breakdown by enzymatic hydrolysis, The biological effects of bisphosphonates on calcium metabolism were originally ascribed to their physico-chemical effects on hydroxyapatite crystals. Although such effects may contribute to their overall action, their effects on cells are probably of greater importance, particularly for the more potent compounds. Remarkable progress has been made in increasing the potency of bisphosphonates as inhibitors of bone resorption, and the most potent compounds in current use are characterized by the presence of a nitrogen atom at critical positions in the side chain which, together with the bisphosphonate moiety itself, seems to be essential for maximal activity, As a class the bisphosphonates offer a very effective means of treating Paget's disease.

KW - mold dictyostelium-discoideum

KW - cyclical etidronate therapy

KW - GTP-binding protein

KW - heterocycle-containing bisphosphonates

KW - inhibit bone-resorption

KW - acute-phase response

KW - Pagets-Disease

KW - in-vitro

KW - dichlormethylene diphosphonate

KW - postmenopausal osteoperosis

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JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

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