Production of new trabecular bone in osteopenic ovariectomized rats by prostaglandin E2.
Serum chemistry and bone morphometry of the proximal tibial metaphysis were performed in 3-month-old double fluorescent-labeled, female Sprague-Dawley rats subjected to bilateral ovariectomy or sham surgery for 4 months prior to treatment with 0, 0.3, 1, 3, or 6 mg of prostaglandin E2 (PGE2)/kg/day subcutaneously for 30 days. The 4-month postovariectomized rats possessed an osteopenic proximal tibial metaphysis with 7% trabecular area compared with controls (19%). PGE2 treatment elevated osteocalcin levels and augmented proximal tibial metaphyseal bone area in ovariectomized and sham-operated rats. Osteopenic, ovariectomized rats treated with 6 mg PGE2/kg/day for 30 days restored bone area to levels of age-matched sham-operated rats. Morphometric analyses showed increased woven and lamellar bone area, fluorescent-labeled perimeter (osteoblastic recruitment), mineral apposition rate (osteoblastic activity), bone formation rate (BFR/BV), and longitudinal bone growth. These dramatic bone changes were all significantly increased at the dose-response manner. This study showed that in vivo PGE2 is a powerful activator of bone remodeling, it increases both bone resorption and bone formation, and produces an anabolic effect by shifting bone balance to the positive direction. Furthermore, PGE2-induced augmentation of metaphyseal bone area in ovariectomized rats was at least two times greater than in sham-operated rats.
Mori
S
S
Division of Radiobiology, University of Utah School of Medicine, Salt Lake City 84112.
Jee
W S
WS
Li
X J
XJ
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000503:physiopathology*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002130:Calcium Phosphates / Q000097:blood; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D008856:Microscopy, Fluorescence; D009929:Organ Size / Q000187:drug effects; D015675:Osteocalcin / Q000097:blood; D010052:Ovariectomy; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013977:Tibia
D002130:Calcium Phosphates; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D015675:Osteocalcin; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; D000469:Alkaline Phosphatase; D015232:Dinoprostone; C485829:calcium phosphate, dibasic, anhydrous