In vivo rat assay: bone remodeling and steroid effects on juvenile bone by pQCT quantification in 7 days.
Anesthetized Sprague-Dawley weanling rats were scanned for bone mineral density (BMD) values after 7 days of treatment to determine whether resorption/growth at the proximal tibia can be quantified by peripheral quantitative computed tomography scanning techniques. Because the weanling rat is in a rapid growth stage, all groups showed significant increases in change from baseline values of BMD. Bisphosphonate treatment produced significant dose-related changes in BMD with average increases of 195 and 241% (10 and 20 microg/kg) vs. 86% in control rats. We further characterized this model to determine effects of steroids on growing bone. Graded doses of glucocorticoid (3.5, 7.0, 10.5, 14.0, 28.0, and 42.0 mg x kg(-1) x wk(-1)) caused no significant differences in trabecular BMD in 7 days between control and treated rats. Significant decreases in growth (weights) and increases in cortical bone area were observed, indicating that this model may be useful in comparing effects of nonsteroid, anti-inflammatory alternatives on juvenile bone. Although the relevance of this model to adult disease remains to be elucidated, it also provides a tool for mechanistic evaluation of therapeutic modalities or efficacy assessment for dose selection for longerterm models.
McHugh
Nansie A
NA
Allergy, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA. nansie.mchugh@spcorp.com
Vercesi
Haydee M
HM
Egan
Robert W
RW
Hey
John A
JA
D000375:Aging; D019386:Alendronate / Q000008:administration & dosage; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000033:anatomy & histology; D005938:Glucocorticoids / Q000494:pharmacology; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013256:Steroids / Q000494:pharmacology*; D014057:Tomography, X-Ray Computed / Q000379:methods*
D005938:Glucocorticoids; D013256:Steroids; D019386:Alendronate; D008775:Methylprednisolone