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 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.
D000818:Animals; D001857:Bone Matrix / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D001862:Bone Resorption / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008903:Minerals / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D004164:Diphosphonates; D008903:Minerals