Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix

Pretreatment of a long bone explant with P-C-P can prevent the osteoclastic resorption of its mineralized matrix, when it is entirely dependent upon activation and accession of extra-osseous osteoclast precursors. When treatment of the explant is postponed until after the development of mature osteo...

Full description

Saved in:
Bibliographic Details
Published inBone and mineral Vol. 1; no. 1; p. 27
Main Authors Boonekamp, P M, van der Wee-Pals, L J, van Wijk-van Lennep, M M, Thesing, C W, Bijvoet, O L
Format Journal Article
LanguageEnglish
Published Ireland 1986
Subjects
Animals
Bone Matrix - anatomy & histology
Bone Matrix - drug effects
Bone Matrix - metabolism
Bone Resorption - drug effects
Diphosphonates - pharmacology
Fetus - cytology
Fetus - metabolism
In Vitro Techniques
Mice
Minerals - metabolism
Osteoclasts - cytology
Osteoclasts - drug effects
Osteoclasts - metabolism
Rats
Online AccessGet more information

Cover

More Information
Summary:Pretreatment of a long bone explant with P-C-P can prevent the osteoclastic resorption of its mineralized matrix, when it is entirely dependent upon activation and accession of extra-osseous osteoclast precursors. When treatment of the explant is postponed until after the development of mature osteoclasts, the P-C-P dose required for an inhibitory effect is increased 100-fold for the amino bisphosphonate APD, but not for EHDP and Cl2MDP. It is concluded that high doses of all P-C-Ps inhibit the resorbing osteoclast, but that low dose of the amino P-C-P can specifically inhibit the accession of osteoclast precursors to mineralized matrix. Both actions require P-C-P binding to the mineral. The relative potencies of the P-C-Ps in the precursor-dependent system correspond to their relative potencies in vivo. This suggests that inhibition of accession underlies the high potency which the aminobisphosphonate has in vivo.
ISSN:0169-6009