Disodium 1-hydroxy-3-(1-pyrrolidinyl)-propylidene-1,1-bisphosphonate (EB-1053) is a potent inhibitor of bone resorption in vitro and in vivo.
The ability of the new nitrogen-containing bisphosphonate disodium-1-hydroxy-3-(1-pyrrolidinyl)-propylidene-1,1-bisphosphona te (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 45Ca release effectively and was found to be about 10 times more potent than pamidronate (ED50 = 2.5 x 10(-7) versus 2.5 x 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.
van der Pluijm
G
G
Department of Endocrinology, University Hospital, Leiden, The Netherlands.
Binderup
L
L
Bramm
E
E
van der Wee-Pals
L
L
De Groot
H
H
Binderup
E
E
Löwik
C
C
Papapoulos
S
S
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D000077268:Pamidronate; D010281:Parathyroid Hormone / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013977:Tibia
D004164:Diphosphonates; D010281:Parathyroid Hormone; D011759:Pyrrolidines; C078046:EB 1053; D000135:Acid Phosphatase; D000077268:Pamidronate; D002118:Calcium