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Ibandronate for prevention and treatment of glucocorticoid-induced osteoporosis in rabbits.

Abstract
The objective of this study is to evaluate the efficacy of ibandronate (IBN) in prevention and treatment of glucocorticoid-induced osteoporosis in rabbits. A total of 60 New Zealand white rabbits were randomly allocated into six groups. Twenty rabbits in the control group were injected with saline. Forty rabbits received dexamethasone (DX) treatment at a dose of 3 mg/kg twice weekly during the first 6 weeks, while 10 of these rabbits (group IBN&DX) were injected additionally with IBN at a dose of 2 mg/kg before DX treatment. At week 6, the rabbits from IBN&DX group, 10 rabbits from control group (group CNTR-1) and 10 rabbits treated with DX (group DX6) were killed. Half (10) of the remaining rabbits in DX group were continued for DX treatment at a dose of 3 mg/kg once weekly (group DX12), while the other half (10) rabbits (group DX&IBN) additionally received IBN injection (2 mg/kg) once before continuing DX treatment. The remaining rabbits (10) in an additional of control group (group CNTR-2) continuously received saline. At week 12, all rabbits were killed for bone biomechanical analysis and histological examination. At week 6, the analysis of bone biomechanical and histological results of group CNTR-1 and DX6 showed that GIOP rabbit models were successfully established. Compared with group DX6, bone volume/tissue volume (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th) of lumbar spine in group IBN&DX were increased by 100, 45.74 and 40.55%, respectively (P < 0.01). Meanwhile, BV/TV and Tb.N of femoral neck were increased by 30.29 and 16.86%, respectively (P < 0.01). The maximum compressive load, the maximum bending stress and the maximum torque were increased by 24.19, 29.91 and 37.24%, respectively (P < 0.01). At week 12, in comparison of the results between group DX12 and group DX6, the histomorphometric and mechanical analysis demonstrated that prolonged DX treatment could lead to further loss of bone mass and strength. Compared with group DX12, BV/TV, Tb.N and Tb.Th of lumbar spine in group DX&IBN were increased by 73.34, 39.02 and 23.87%, respectively (P < 0.05), the parameters of femoral neck were increased by 88.75, 31.29 and 42.01%, respectively (P < 0.01), and the biomechanical parameters were increased by 54.36, 21.38 and 105.75%, respectively (P < 0.05). IBN could effectively prevent and treat high-dosing glucocorticoid-induced loss of bone mass and strength in rabbits.
AuthorsKun-Juan Zhang, Jian Zhang, Ze-Kun Kang, Xiao-Mei Xue, Jing-Fen Kang, Yan-Wei Li, Hai-Ning Dong, Dong-Gang Liu
JournalRheumatology international (Rheumatol Int) Vol. 32 Issue 11 Pg. 3405-11 (Nov 2012) ISSN: 1437-160X [Electronic] Germany
PMID22057134 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Bone Density Conservation Agents
  • Diphosphonates
  • Glucocorticoids
  • Ibandronic Acid
Topics
  • Animals
  • Bone Density (drug effects, physiology)
  • Bone Density Conservation Agents (pharmacology, therapeutic use)
  • Diphosphonates (pharmacology, therapeutic use)
  • Femur Neck (drug effects, pathology)
  • Glucocorticoids
  • Ibandronic Acid
  • Lumbar Vertebrae (drug effects, pathology)
  • Osteoporosis (chemically induced, drug therapy, pathology, prevention & control)
  • Rabbits
  • Weight-Bearing

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