Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Risedronate Directly Inhibits Osteoclast Differentiation and Inflammatory Bone Loss
Han Bok Kwak, Jong Yun Kim, Kwang Jin Kim, Min-Kye Choi, Jeong-Joong Kim, Kwang Mee Kim, Yong-Il Shin, Myeung Su Lee, Hun Soo Kim, Jeung Woo Kim, Chul Hong Chun, Hae Joong Cho, Gi Youn Hong, Seon Kwan Juhng, Kwon Ha Yoon, Byoung Hyun Park, Ji Myung Bae, Joung-Kyue Han, Jaemin Oh
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Keywords: risedronate, osteoclast, osteoporosis, inflammation
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2009 Volume 32 Issue 7 Pages 1193-1198

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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)-κB 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.
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© 2009 The Pharmaceutical Society of Japan
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