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Effects of Prostaglandin E2 and Risedronate Administration on Cancellous Bone in Older Female RatsThe effects of Prostaglandin E2 (PGE2) and Risedronate (Ris) both separately and in combination (PGE2 + Ris) were studied on the intact aged female rat skeleton to determine whether the combination of PGE2 with an antiresorptive agent is more effective anabolically than PGE2 alone. Nine month-old Sprague-Dawley rats were injected subcutaneously either with vehicle, 6 mg PGE2/kg per day, 1 or 5 microgram Ris/kg twice a week, or 6 mg PGE2/kg per day plus 1 or 5 microgram Ris/kg twice a week (PGE2 + 1 Ris or PGE2 + 5 Ris) for 60 days. After the treatment, we determined the longitudinal bone growth rate, the qualitative appearance of the primary spongiosa (PS), and the static and dynamic bone histomorphometry of the secondary spongiosa (SS) of the proximal tibial metaphysis (PTM) by examining undecalcified longitudinal sections after double fluorescent labeling. The relative effects of these treatments on longitudinal bone growth were ranked as follows: PGE2 + 5 Ris greater than PGE2 + 1 Ris = basal greater than PGE2 greater than 1 microgram Ris = 5 microgram Ris = aging. The density of the PS was ranked as follows: PGE2 + 5 Ris greater than PGE2 + 1 Ris = PGE2 = 5 microgram Ris = 1 microgram Ris greater than basal = aging. The increase in density of the PS was the result of stimulated longitudinal growth and the action of bisphosphonate. Bone mass in the SS was ranked as follows: PGE2 + 5 Ris = PGE2 + 1 Ris = PGE2 greater than 5 microgram Ris = 1 microgram Ris = aging = basal. However, PGE2 alone and its cotreatment with Ris accumulated bone by different tissue mechanisms. PGE2 alone created new bone by increasing activation frequency 8.3-fold and the formation to resorption ratio 1.3-fold from the controls. The combination of PGE2 and Ris depressed activation frequency (-54% to -74%), and bone formation rate (tissue-based -31%, and bone-based -42%) and eroded surface (-79% to -81%), so as to increase the formation to resorption ratio (three- to four-fold) over PGE2 alone. The increased ratio was due primarily to a greater decrease in eroded perimeter than in labeled perimeter. The major finding of this study is that the combination of PGE2 and a bisphosphonate (Ris) is more anabolic than PGE2 or Ris alone when endochondral ossification is active, but PGE2 + Ris is no more anabolic than PGE2 alone in old bone without endochondral ossification. However, the tissue mechanisms by which PGE2 alone and PGE2 + Ris treatments accumulated bone differed in that the latter allowed the same bone mass to accumulate with lower levels of cell recruitment and activity.
Document ID
19970004339
Acquisition Source
Ames Research Center
Document Type
Reprint (Version printed in journal)
Authors
Lin, B. Y.
(Utah Univ. Salt Lake City, UT United States)
Jee, W. S. S.
(Utah Univ. Salt Lake City, UT United States)
Ma, Y. F.
(Utah Univ. Salt Lake City, UT United States)
Ke, H. Z.
(Utah Univ. Salt Lake City, UT United States)
Kimmel, D. B.
(Creighton Univ. Omaha, NE United States)
Li, X. J.
(Utah Univ. Salt Lake City, UT United States)
Date Acquired
August 17, 2013
Publication Date
January 1, 1994
Publication Information
Publication: Bone
Publisher: Elsevier Science Ltd.
Volume: 15
Issue: 5
ISSN: 8756-3282
Subject Category
Life Sciences (General)
Report/Patent Number
NAS 1.26:202671
NASA-CR-202671
Accession Number
97N70308
Funding Number(s)
CONTRACT_GRANT: NAG2-435
CONTRACT_GRANT: DE-AC02-76EV-00119
CONTRACT_GRANT: NIH-AR-38346
Distribution Limits
Public
Copyright
Public Use Permitted.
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