eCM (Eur Cell Mater / e Cells & Materials) Not-for-profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2001   Volume No 1 - pages 18-26

Title: The bisphosphonate zoledronate prevents vertebral bone loss in mature estrogen-deficient rats as assessed by micro-computed tomography

Authors: M. Glatt

Address: Novartis Pharma AG, Arthritis and Bone Metabolism Unit, Basel, Switzerland

E-mail: markus.glatt at pharma.novartis.com

Key Words: Bisphosphonate, zoledronate, vertebrae, rat, ovariectomy, estrogen-deficiency, microcomputed tomography, bone architecture, bone, morphometry.

Publication date: 10th January 2001

Abstract: The effect of long-term treatment with the bisphosphonate zoledronate on vertebral bone architecture was investigated in estrogen-deficient mature rats. 4-month-old rats were ovariectomized and development of cancellous osteopenia was assessed after 1 year. The change of bone architectural parameters was determined with a microtomographic instrument of high resolution. After 1 year of estrogen-deficiency, animals lost 55% of vertebral trabecular bone in comparison to sham operated control animals. Trabecular number (Tb.N) and trabecular thickness (Tb.Th) were significantly reduced in ovariectomized animals, whereas trabecular separation (Tb.Sp), bone surface to volume fraction (BS/BV) and trabecular bone pattern factor (TBPf) were significantly increased, indicating a loss of architectural integrity throughout the vertebral body. 3 groups of animals were treated subcutaneously with zoledronate for 1 year with 0.3, 1.5 and 7.5 microgram/kg/week to inhibit osteoclastic bone degradation. Administration started immediately after ovariectomy and treatment dose-dependently prevented the architectural bone deterioration and completely suppressed the effects of estrogen deficiency at the higher doses. The results show that microtomographic determination of static morphometric parameters can be used to quantitate the effects of drugs on vertebral bone architecture in small laboratory animals and that zoledronate is highly effective in this rat model.

Article download: Pages 18-26 (PDF file)
DOI: 10.22203/eCM.v001a03