Different Effects of Agonistic vs. Antagonistic GnRH-Analogues (Triptorelin vs. Cetrorelix) on Bone Modeling and Remodeling in Peripubertal Female Rats

C. L. Roth; C. Neu; H. Jarry; E. Schoenau

doi:10.1055/s-2005-865710

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2005; 113(8): 451-456
DOI: 10.1055/s-2005-865710

Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Different Effects of Agonistic vs. Antagonistic GnRH-Analogues (Triptorelin vs. Cetrorelix) on Bone Modeling and Remodeling in Peripubertal Female Rats

C. L. Roth¹ , C. Neu² , H. Jarry³ , E. Schoenau²

¹Department of Pediatrics, University of Bonn, Germany
²Children's Hospital, University of Cologne, Germany
³Division of Clinical & Experimental Endocrinology, University of Göttingen, Germany

Abstract

Little is known about the effects of antagonistic GnRH analogues vs. agonists on bone strength, specifically in context of treating precocious puberty. Peripubertal female rats were treated from postnatal day 25 - 36 with either the GnRH agonist triptorelin (TRIP) or the antagonist cetrorelix (CET). Using peripherial quantitative computerized tomography (pQCT) we investigated effects on bone parameters. Onset of puberty was retarded by both analogues as measured by prevention of vaginal opening at 36 d of age and reduced uterine weights. In the tibia, cortical content, cortical area related to body weight, and periosteal circumference related to weight were significantly reduced in CET-treated rats - indicating reduced bone modeling and reduced bone strength (cortical circumference related to body weight: CET 0.066 ± 0.001 vs. TRIP 0.068 ± 0.001 vs. controls 0.071 ± 0.001 mm/g, mean ± SEM, p < 0.05 CET vs. controls; cortical area related to body weight: CET 3.87 ± 0.46 vs. TRIP 6.80 ± 0.63 vs. controls 8.07 ± 1.13, × 10^-3 mm²/g, p < 0.001 CET vs. controls; cortical content: CET 0.316 ± 0.038 vs. TRIP 0.546 ± 0.051 vs. controls 0.624 ± 0.089 mg/mm, p < 0.01 CET vs. controls). In conclusion, although both CET and TRIP inhibit puberty in rats, cortical thinning was only seen in CET-treated rats. This indicates that GnRH antagonist treatment might cause reduced bone strength which is partly comparable to postmenopausal bone loss. When using new GnRH antagonists for treating precocious puberty in humans, parameters for bone strength and mineralization should be monitored.

Key words

Puberty - GnRH-analogues - bone mineralization - bone modeling and remodeling

Full Text

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PD Dr. med. Christian L. Roth

Department of Pediatrics
University of Bonn

Adenauerallee 119

53113 Bonn

Email: croth@uni-bonn.de