title: Risedronate directly inhibits osteoclast differentiation and inflammatory bone loss.
abstract: 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.
authors: Department of Anatomy, School of Medicine, Wonkwang University.
authors: Han Bok
authors: HB
authors: Kwak
authors: Jong Yun
authors: JY
authors: Kim
authors: Kwang Jin
authors: KJ
authors: Kim
authors: Min-Kye
authors: MK
authors: Choi
authors: Jeong-Joong
authors: JJ
authors: Kim
authors: Kwang Mee
authors: KM
authors: Kim
authors: Yong-Il
authors: YI
authors: Shin
authors: Myeung Su
authors: MS
authors: Lee
authors: Hun Soo
authors: HS
authors: Kim
authors: Jeung Woo
authors: JW
authors: Kim
authors: Chul Hong
authors: CH
authors: Chun
authors: Hae Joong
authors: HJ
authors: Cho
authors: Gi Youn
authors: GY
authors: Hong
authors: Seon Kwan
authors: SK
authors: Juhng
authors: Kwon Ha
authors: KH
authors: Yoon
authors: Byoung Hyun
authors: BH
authors: Park
authors: Ji Myung
authors: JM
authors: Bae
authors: Joung-Kyue
authors: JK
authors: Han
authors: Jaemin
authors: J
authors: Oh
mesh_terms: 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
chemical_list: 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