Source:http://linkedlifedata.com/resource/pubmed/id/16006205
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2005-8-22
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| pubmed:abstractText |
Disuse induces rapid and severe bone loss in larger mammals as a result of greatly elevated osteoclastic resorption. In this study, we tested whether risedronate (RIS), a potent inhibitor of osteoclastic activity, would effectively prevent cancellous bone loss in female beagles (5-7 years old, N = 28) subjected to single forelimb immobilization (IM) for 12 months. Age-matched, non-IM dogs served as controls (Con). Half the animals from each group received RIS 1 mg/kg p.o. daily (Con + RIS, IM + RIS). Remaining dogs received sterile water (Con, IM). Histomorphometry showed that IM caused a dramatic reduction in cancellous bone mass (-71%) of distal 2nd metacarpals, characterized by marked decreases in trabecular width (-51%) and number (-41%), and 4-fold increases in the indices of bone resorption (eroded surface, osteoclast number, and surface). Bone formation indices (calcein-labeled surface, osteoid surface, and bone formation rate) were also significantly higher in IM than in controls. Activation frequency in IM increased about 4-fold beyond control level. RIS treatment reduced, but did not abolish cancellous bone loss due to immobilization. IM animals treated with RIS lost nearly 50% of cancellous bone mass, while trabecular width and number were reduced by 31% and 25%, respectively. In both RIS-treated control and IM animals, overall bone formation parameters (mineralized bone surface fraction and bone formation rate) remained roughly at intact control levels; however, mineral apposition rate relative to intact control was reduced 40% in RIS-treated control and 86% in RIS-treated IM animals. These results indicate that high-dose RIS treatment might suppress osteoblastic function, especially under long-term disuse. Interestingly, bone resorption parameters in RIS-treated IM animals reached levels even higher than in vehicle-treated IM animals; values for eroded surface, osteoclast number, and surface were 84%, 53%, and 83% above vehicle-treated IM values, respectively. Our data indicate that risedronate treatment is partially effective in preventing cancellous bone loss during long-term disuse. Moreover, our results suggest that bisphosphonates can impair the ability of mature osteoclasts to resorb bone, but cannot overcome the strong stimulus for osteoclast recruitment caused by long-term disuse.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
8756-3282
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
37
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
287-95
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading | |
| pubmed:year |
2005
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| pubmed:articleTitle |
High-dose risedronate treatment partially preserves cancellous bone mass and microarchitecture during long-term disuse.
|
| pubmed:affiliation |
Leni and Peter W. May Department of Orthopaedics, Mount Sinai School of Medicine, Box 1188, One Gustave L. Levy Place, New York, NY 10029, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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