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Disodium 1‐hydroxy‐3‐(1‐pyrrolidinyl)‐propylidene‐1,1‐bisphosphonate (EB‐1053) is a potent inhibitor of bone resorption in vitro and in vivo
Author(s) -
van der Pluijm Gabri,
Binderup Lise,
Bramm Erik,
van derWeePals Lianne,
de Groot Henny,
Binderup Ernst,
Löwik Clemens,
Papapoulos Socrates
Publication year - 1992
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650070815
Subject(s) - bisphosphonate , bone resorption , in vivo , resorption , endocrinology , osteoclast , medicine , chemistry , in vitro , osteoporosis , pharmacology , biology , biochemistry , microbiology and biotechnology
The ability of the new nitrogen‐containing bisphosphonate disodium‐1‐hydroxy‐3‐(1‐pyrrolidinyl)‐propylidene‐1,1‐bisphosphonate (EB‐1053) to inhibit osteoclastic resorption was examined in vitro and in vivo. Results were compared to those obtained with 3‐amino‐1‐hydroxypropylidene‐1,1‐bisphosphonate (pamidronate or APD). In vitro, when tested in osteoclast precursor‐dependent systems (fetal mouse metacarpals and a coculture system), EB‐1053 suppressed 45 Ca release effectively and was found to be about 10 times more potent than pamidronate (ED 50 = 2.5 × 10 −7 versus 2.5 × 10 −6 M, respectively). The EB‐1053‐inhibited osteoclastic resorption could be reversed by treatment with parathyroid hormone (PTH). In vivo, daily subcutaneous injections of EB‐1053 to young growing rats for 7 days increased metaphyseal bone mass in tibiae dose dependently. In these experiments EB‐1053 was about 50 times more potent than pamidronate. These studies show that EB‐1053 is a very potent bisphosphonate that has potential use in the treatment of skeletal disorders.