Risedronate directly inhibits osteoclast differentiation and inflammatory bone loss.
Risedronate, a nitrogen-containing bisphosphonate, is widely used in the clinical field for the treatment of osteoporosis. Risedronate is known to exert its effects through binding to hydroxyapatite in bone tissue, inhibiting osteoclastic activity, and inducing apoptosis of osteoclasts. The purpose of this study was to determine the effects of risedronate on osteoclast differentiation in vitro and on an inflammatory bone loss model in vivo. Risedronate inhibited osteoclast differentiation in co-culture of bone marrow cells (BMCs) and osteoblasts, and suppressed receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-mediated osteoclast differentiation from bone marrow-derived macrophages (BMMs) in a dose-dependent manner without toxicity. Risedronate significantly inhibited expression of c-Fos and nuclear factor of activated T cells (NFAT) c1 induced by RANKL. To examine the effect of risedronate on bone loss in vivo, we used a mouse model of lipopolysaccharide (LPS)-mediated bone loss. Micro-CT analysis of the femurs showed that LPS treatment caused bone loss. However, bone loss was significantly attenuated in mice administered with risedronate. Taken together, we conclude that risedronate exerts beneficial effects on osteoporosis by inhibiting osteoclast differentiation both directly and indirectly. In infectious conditions, the inhibitory effect of risedronate on bone erosion was excellent. Thus risedronate could be a treatment option for osteoporosis caused by inflammatory and infectious conditions.
Kwak
Han Bok
HB
Department of Anatomy, School of Medicine, Wonkwang University.
Kim
Jong Yun
JY
Kim
Kwang Jin
KJ
Choi
Min-Kye
MK
Kim
Jeong-Joong
JJ
Kim
Kwang Mee
KM
Shin
Yong-Il
YI
Lee
Myeung Su
MS
Kim
Hun Soo
HS
Kim
Jeung Woo
JW
Chun
Chul Hong
CH
Cho
Hae Joong
HJ
Hong
Gi Youn
GY
Juhng
Seon Kwan
SK
Yoon
Kwon Ha
KH
Park
Byoung Hyun
BH
Bae
Ji Myung
JM
Han
Joung-Kyue
JK
Oh
Jaemin
J
D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D001862:Bone Resorption / Q000473:pathology / Q000517:prevention & control*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053245:RANK Ligand / Q000494:pharmacology; D000068296:Risedronic Acid; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D050071:Bone Density Conservation Agents; D008070:Lipopolysaccharides; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D048051:p38 Mitogen-Activated Protein Kinases; D000068296:Risedronic Acid; D012968:Etidronic Acid