title: Simvastatin did not prevent nor restore ovariectomy-induced bone loss in adult rats.
abstract: Current published results on whether statins have beneficial effects on bone metabolism have been conflicting so far. In order to further investigate if statins were promising candidates for the treatment for osteoporosis, we conducted a study in which rats were ovariectomized (OVX) at 6 months of age, allowed to lose bone for 60 days and followed by oral administration of simvastatin at the dose levels of 0.3-10 mg/kg/d for 60 days. PGE2 (6 mg/kg) was used as a positive control. Study endpoints included bone histomorphometry on the proximal tibial metaphysis (PTM) and the tibial diaphysis (TX), dual-energy X-ray absorptiometry on the right femur and micro computed tomography (ICT) on the 5th lumbar vertebra (LV). After 120 days of OVX, cancellous bone lost by 80% in the PTM and 18% in the LV accompanied by increased bone formation and resorption. Simvastatin at all dose levels did not affect bone volume, bone formation rate and bone erosion surface when compared to 120 day ovariectomized animals at all bone sites studied. By contrast, PGE2 restored cancellous and cortical bone area to sham control levels. In conclusion, this study demonstrated that unlike PGE2, oral administration of simvastatin did not have effects on cancellous or cortical bone formation and resorption; and consequently was not able to prevent further bone loss or restore bone mass in the osteopenic, OVX rats.
authors.affiliation: Radiobiology Division, University of Utah, Salt Lake City, UT 84108-1218, USA.
authors.forename: W
authors.initials: W
authors.lastname: Yao
authors.forename: R
authors.initials: R
authors.lastname: Farmer
authors.forename: R
authors.initials: R
authors.lastname: Cooper
authors.forename: P A
authors.initials: PA
authors.lastname: Chmielewski
authors.forename: X Y
authors.initials: XY
authors.lastname: Tian
authors.forename: R B
authors.initials: RB
authors.lastname: Setterberg
authors.forename: W S S
authors.initials: WS
authors.lastname: Jee
authors.forename: M W
authors.initials: MW
authors.lastname: Lundy
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D002784:Cholesterol / Q000097:blood; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control*; D010052:Ovariectomy / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology*; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D002784:Cholesterol; D019821:Simvastatin