title: Maintaining restored bone with bisphosphonate in the ovariectomized rat skeleton: dynamic histomorphometry of changes in bone mass.
abstract: This 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 antiresorptive 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 micrograms/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 micrograms 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 microgram Risedronate treated M phase and to a ratio of near unity of 1.1 for the 5 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Radiobiology, University of Utah School of Medicine, Salt Lake City 84112.
authors.forename: W S
authors.initials: WS
authors.lastname: Jee
authors.forename: L
authors.initials: L
authors.lastname: Tang
authors.forename: H Z
authors.initials: HZ
authors.lastname: Ke
authors.forename: R B
authors.initials: RB
authors.lastname: Setterberg
authors.forename: D B
authors.initials: DB
authors.lastname: Kimmel
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000473:pathology; D001861:Bone Regeneration / Q000187:drug effects*; D015232:Dinoprostone / Q000494:pharmacology; D004164:Diphosphonates / Q000494:pharmacology*; D012968:Etidronic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068296:Risedronic Acid
chemical_list: D004164:Diphosphonates; D015232:Dinoprostone; D000068296:Risedronic Acid; D012968:Etidronic Acid