PMID- 19571384
OWN - NLM
STAT- MEDLINE
DCOM- 20091008
LR  - 20240109
IS  - 0918-6158 (Print)
IS  - 0918-6158 (Linking)
VI  - 32
IP  - 7
DP  - 2009 Jul
TI  - Risedronate directly inhibits osteoclast differentiation and inflammatory bone 
      loss.
PG  - 1193-8
AB  - 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.
FAU - Kwak, Han Bok
AU  - Kwak HB
AD  - Department of Anatomy, School of Medicine, Wonkwang University.
FAU - Kim, Jong Yun
AU  - Kim JY
FAU - Kim, Kwang Jin
AU  - Kim KJ
FAU - Choi, Min-Kye
AU  - Choi MK
FAU - Kim, Jeong-Joong
AU  - Kim JJ
FAU - Kim, Kwang Mee
AU  - Kim KM
FAU - Shin, Yong-Il
AU  - Shin YI
FAU - Lee, Myeung Su
AU  - Lee MS
FAU - Kim, Hun Soo
AU  - Kim HS
FAU - Kim, Jeung Woo
AU  - Kim JW
FAU - Chun, Chul Hong
AU  - Chun CH
FAU - Cho, Hae Joong
AU  - Cho HJ
FAU - Hong, Gi Youn
AU  - Hong GY
FAU - Juhng, Seon Kwan
AU  - Juhng SK
FAU - Yoon, Kwon Ha
AU  - Yoon KH
FAU - Park, Byoung Hyun
AU  - Park BH
FAU - Bae, Ji Myung
AU  - Bae JM
FAU - Han, Joung-Kyue
AU  - Han JK
FAU - Oh, Jaemin
AU  - Oh J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nfatc1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (RANK Ligand)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - KM2Z91756Z (Risedronic Acid)
RN  - M2F465ROXU (Etidronic Acid)
SB  - IM
MH  - Animals
MH  - Bone Density Conservation Agents/pharmacology/*therapeutic use/toxicity
MH  - Bone Resorption/pathology/*prevention & control
MH  - Cell Differentiation/*drug effects
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Etidronic Acid/*analogs & derivatives/pharmacology/therapeutic use/toxicity
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/drug effects
MH  - Mice
MH  - Mice, Inbred ICR
MH  - NFATC Transcription Factors/antagonists & inhibitors/biosynthesis
MH  - Osteoclasts/cytology/*drug effects
MH  - Osteoporosis/*drug therapy/pathology
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-fos/antagonists & inhibitors/biosynthesis
MH  - RANK Ligand/pharmacology
MH  - Risedronic Acid
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2009/07/03 09:00
MHDA- 2009/10/09 06:00
CRDT- 2009/07/03 09:00
PHST- 2009/07/03 09:00 [entrez]
PHST- 2009/07/03 09:00 [pubmed]
PHST- 2009/10/09 06:00 [medline]
AID - JST.JSTAGE/bpb/32.1193 [pii]
AID - 10.1248/bpb.32.1193 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2009 Jul;32(7):1193-8. doi: 10.1248/bpb.32.1193.