2 MODES OF ACTION OF BISPHOSPHONATES ON OSTEOCLASTIC RESORPTION OF MINERALIZED MATRIX

  • 1 February 1986
    • journal article
    • research article
    • Vol. 1  (1) , 27-39
Abstract
Pretreatment of a long bone explant with P.sbd.C.sbd.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.sbd.C.sbd.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.sbd.C.sbd.Ps inhibit the resorbing osteoclast, but that low dose of the amino P.sbd.C.sbd.P can specifically inhibit the accession of osteoclast precursors to mineralized matrix. Both actions require P.sbd.C.sbd.P binding to the mineral. The relative potencies of the P.sbd.C.sbd.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.