| Title | Risedronate directly inhibits osteoclast differentiation and inflammatory bone loss. | | Author(s) | Kwak HB, Kim JY, Kim KJ, Choi MK, Kim JJ, Kim KM, Shin YI, Lee MS, Kim HS, Kim JW, Chun CH, Cho HJ, Hong GY, Juhng SK, Yoon KH, Park BH, Bae JM, Han JK, Oh J | | Institution | Department of Anatomy, School of Medicine, Wonkwang University. | | Source | Biol Pharm Bull 2009 Jul; 32(7):1193-8. | | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19571384 |
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