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Maintaining Restored Bone with Bisphoshonate in the Ovariectomized Rat Skeleton: Dynamic Histomorphometry of Changes in Bone MassThis experiment contains the crucial data for the Lose, Restore and Maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses ovariectomy (ox) to lose bone, an anabolic agent to restore bone mass and then switches to an anti-resorptive agent to maintain bone mass. We ox'd or sham-ox'd rats for 150 days (Loss Phase), treated them with 6 mg PGE2/kg/d for 75 days to restore lost cancellous bone mass (Restore Phase) and then stopped PGE2 treatment and began treatment with 1 or 5 micro-g/kg Risedronate, a bisphosphonate twice a week for 60 days (Maintain Phase). During the Loss Phase, cancellous bone volumes of the proximal tibial metaphysis (PTM) in the ox'd rat fell to 19% of initial controls. During the Restore Phase, the PTM bone volume in ox'd rats doubled. However, when PGE2 treatment was stopped, the PGE2-induced cancellous bone disappeared. In contrast, 5 micro-g of Risedronate inhibited the bone loss and maintained it at the PGE2 treatment level. The key dynamic histomorphometry value for the restore (R) and maintenance (M) phases was the ratio of bone formation to resorption rates. The ratio was elevated to 5.8 in the R phase and depressed to 0.4 for no and 1 micro-g Risedronate treated M phase and to a ratio of near unity of 1.1 for the 5 micro-g Risedronate treatment. These findings indicate that we were successful in maintaining the new PTM bone induced by PGE2 after discontinuing PGE2 by administering enough Risedronate, a resorption inhibitor. We concluded that the LRM concept is correct and such an approach should be considered when employing anabolic agents or growth factors in the treatment of osteoporosis. Continued use of an anabolic agent may not be appropriate because of cost, potential adverse side effects and a loss of efficacy.
Document ID
19970001922
Acquisition Source
Ames Research Center
Document Type
Reprint (Version printed in journal)
Authors
Jee, W. S. S.
(Utah Univ. Salt Lake City, UT United States)
Tang, L.
(Creighton Univ. Omaha, NE United States)
Ke, H. Z.
(Creighton Univ. Omaha, NE United States)
Setterberg, R. B.
(Creighton Univ. Omaha, NE United States)
Kimmel, D. B.
(Creighton Univ. Omaha, NE United States)
Date Acquired
August 17, 2013
Publication Date
January 1, 1993
Publication Information
Publication: Bone
Volume: 14
ISSN: 8756-3282
Subject Category
Life Sciences (General)
Report/Patent Number
NASA-CR-202474
NAS 1.26:202474
Accession Number
97N70152
Funding Number(s)
CONTRACT_GRANT: DE-FG02-89ER-60764
CONTRACT_GRANT: AR-38346
CONTRACT_GRANT: NAG2-435
CONTRACT_GRANT: DE-AC02-76EV-00119
Distribution Limits
Public
Copyright
Public Use Permitted.
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