Zoledronic acid inhibits osteoclastogenesis in vitro and in a mouse model of inflammatory osteolysis.
This study assessed effects of the bisphosphonate zoledronic acid (ZLNA) on osteoclastogenesis. To assess the effect of ZLNA on osteoclast formation in vitro, we cultured mouse bone marrow cells under conditions that promote osteoclastogenesis. Administered at concentrations from 10(-6) to 10(-9) mol/L, ZLNA led to a dose-dependent inhibition of osteoclastogenesis. Combined TUNEL staining and histochemical staining for tartrate-resistant acid phosphatase showed that ZLNA induced apoptosis in osteoclasts and monocytic precursor cells. To study the effects of ZLNA in vivo, we placed keratin particles onto the surface of the parietal bone of mice to induce localized inflammatory bone resorption. Three experimental groups received daily subcutaneous injections of ZLNA (1, 3, or 10 microg/kg body weight) from 4 days before surgery until 5 days after keratin implantation. The ZLNA significantly reduced osteoclast recruitment in a dose-dependent manner, but did not affect the degree of inflammation or the mineral apposition rate.
Sudhoff
Holger
H
Department of Otorhinolaryngology-Head and Neck Surgery, St Elisabeth Hospital, University of Bochum, Bochum, Germany.
Jung
Jae Y
JY
Ebmeyer
Jörg
J
Faddis
Brian T
BT
Hildmann
Henning
H
Chole
Richard A
RA
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D001862:Bone Resorption / Q000209:etiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007633:Keratins / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008903:Minerals / Q000378:metabolism; D010000:Osteitis / Q000150:complications*; D010010:Osteoclasts / Q000473:pathology*; D010014:Osteolysis / Q000209:etiology* / Q000473:pathology*; D010294:Parietal Bone / Q000473:pathology / Q000601:surgery; D010521:Periosteum / Q000378:metabolism; D019736:Prostheses and Implants / Q000009:adverse effects; D012886:Skull / Q000378:metabolism; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D008903:Minerals; D007633:Keratins; D000077211:Zoledronic Acid