title: Bisphosphonate tiludronate increases bone strength by improving mass and structure in established osteopenia after ovariectomy in rats.
abstract: We examined the mechanical properties of bone in ovariectomized rats treated with tiludronate. 186 Sprague-Dawley (SD) rats, 6 months of age, were assigned to 13 groups and were maintained for 3-9 months after surgery. Ovariectomy (ovx) groups were given tiludronate orally at the respective doses of 0 (vehicle), 12.5 (low), 25 (medium), and 50 (high) mg/kg body weight daily for 3 months beginning 3 months after surgery. Rats were killed at 0 (start), 3, 6, and 9 months. Whereas bone mineral density (BMD) values of the midfemur did not increase after ovx, the values in the sham-operated groups increased age-dependently. Bending moment to failure of the femur in the sham group was larger than that of the ovx control group at 9 months. In the ovx control groups, the ultimate compressive load values of the third lumbar body were reduced compared with those in the sham groups at 3 months and thereafter. Although serum osteocalcin levels were decreased in the medium- and high-dose tiludronate groups, both serum PTH and 1,25(OH)2D levels were increased only in the high-dose group. Femoral BMD, mechanical properties, and the cortical bone area were increased by the high dose at 9 months. Lumbar ultimate compressive load and the circumscribing cortical shell area in the high-dose group were increased at 6 months and thereafter. The trabecular number values were maintained at 6 and 9 months by the high dose. These data demonstrate that tiludronate administration increased the mechanical properties of bone by preserving the age-dependent increases in the cortical bone mass and three-dimensional structure of trabecular bone. These effects seemed to be due to reduced bone turnover by the agent.
authors.affiliation: Department of Orthopedic Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ohnishi
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Narusawa
authors.forename: H
authors.initials: H
authors.lastname: Murakami
authors.forename: M
authors.initials: M
authors.lastname: Abe
authors.forename: A
authors.initials: A
authors.lastname: Barbier
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects*; D002116:Calcitonin / Q000097:blood; D002117:Calcitriol / Q000097:blood; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005269:Femur / Q000187:drug effects / Q000473:pathology; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004164:Diphosphonates; D010281:Parathyroid Hormone; D015675:Osteocalcin; C058651:tiludronic acid; D002116:Calcitonin; D002117:Calcitriol