Different effects of agonistic vs. antagonistic gnrh-analogues (triptorelin vs. cetrorelix) on bone modeling and remodeling in peripubertal female rats.
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, x 10 (-3) mm (2)/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.
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Department of Pediatrics, University of Bonn, Germany. croth@uni-bonn.de
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Jarry
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Schoenau
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D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006727:Hormone Antagonists / Q000008:administration & dosage*; D006801:Humans; D008186:Luteolytic Agents / Q000008:administration & dosage*; D011629:Puberty, Precocious / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011967:Receptors, Gonadotropin / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012741:Sexual Maturation / Q000187:drug effects* / Q000502:physiology; D017329:Triptorelin Pamoate / Q000008:administration & dosage*
D006727:Hormone Antagonists; D008186:Luteolytic Agents; D011967:Receptors, Gonadotropin; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; C062876:cetrorelix