Oophorectomized (OVX) rats served for many years as a popular model for ‘postmenopausal’ osteoporosis in spite of the fact that the rat continues to grow during these experiments. We performed OVX in rats at 1, 3, 6 and 10 months of age and compared the histomorphometric (bone size, bone trabecular and cartilage volume in different areas) and chemical (ash, Ca, P and Mg content) parameters at 2, 6, 8 and 20 weeks post-OVX (2–20 weeks) to those of sham-operated rats. Significant differences were observed only in the animals that were OVX at a young or young-mature age, i.e. mainly at 1 and 3 months and some of the rats at 6 months of age. There were no changes in bone ash and mineral contents in the OVX animals in comparison to sham-operated rats, except 2 weeks post-OVX in the 1-month-old rats where these variables were reduced. The most significant finding was a reduction in the metaphyseal bone volume. This was observed in the rats OVX at 1, 3 and 6 months of age, but not in those OVX at 10 months. In the young OVX rats there was also an increase in epiphyseal cartilage volume. The epiphyseal and diaphyseal bone volumes were not different between the groups at any time postsurgery, explaining the lack of differences in bone ash and mineral contents. There were no significant changes in the results of the histomorphometric studies between OVX and sham-operated rats when surgery was performed at 10 months of age. Since OVX exerts significant changes only in young rapidly growing rats, this approach is an inappropriate model for postmenopausal osteoporosis, which occurs long after bone growth has ended.

Keywords:
Oophorectomy, Histomorphometry, Bone minerals, Metaphysis, Rat
1.
Aitken, J.M., E. Armstrong, J.B. Anderson (1972) Osteoporosis after oophorectomy in the mature female rat and the effect of estrogen and/or progesterone replacement therapy in its prevention. Endocrinology 55: 79–87.
2.
Bagi, C.M., P. Ammann, R. Rizzoli, S.C. Miller (1997) Effect of estrogen deficiency on cancellous and cortical bone structure and strength of the femoral neck in rats. Calcif Tissue Int 61: 336–344.
3.
Christiansen, C. (1992) Prevention and treatment of osteoporosis: A review of current modalities. Bone 13: S35–S39.
4.
Cohen, H., V. Solomon, I.S. Alferiev, E. Breuer, A. Ornoy, N. Patlas, N. Eidelman, G. Hagele, G. Golomb (1998) Bisphosphonates and tetracycline: Experimental models for their evaluation in calcium-related disorders. Pharm Res 15: 604–611.
5.
Durbridge, T.C., H.A. Morris, A.M. Parsons, I.H. Parkinson, R.J. Moore, S. Porter, A.G. Need, B.E. Nordin, B. Vernon-Roberts (1990) Progressive cancellous bone loss in rats after adrenalectomy and oophorectomy. Calcif Tissue Int 47: 383–387.
6.
Jahangiri, L., A. Kim, I. Nishimura (1997) Effect of ovariectomy on the local residual ridge remodeling. Prosthet Dent 77: 435–443.
7.
Kalu, D.N. (1991) The ovariectomized rat model of postmenopausal bone loss. Bone Miner 15: 175–191.
8.
Kalu, D.N., C.C. Liu, R.R Hardin, B.W. Hollis (1989) The aged rat model of ovarian hormone deficiency bone loss. Endocrinology 124: 7–16.
9.
Kanis, J.A., F.A. Pitt (1992) Epidemiology of osteoporosis. Bone 13: S7–S15.
10.
Lea, C.K., V. Moxham, M.J. Reed, A.M. Flanagan (1998) Androstenedione treatment reduces loss of cancellous bone volume in ovariectomized rats in a dose-responsive manner and the effect is not mediated by oestrogen. Endocrinology 156: 331–339.
11.
Li, M., Y. Shen, T.J. Wronski (1997) Time course of femoral neck osteopenia in ovariectomized rats. Bone 20: 55–61.
12.
Li, X.Q., L. Klein (1990) Age-related inequality between rates of formation and resorption in various whole bones of rats. Proc Soc Exp Biol Med 195: 350–355.
13.
Lutsky, I., F. Aizer, N. Mor (1984) The sabra rat: Definition of a laboratory animal. Isr J Med Sci 20: 603–612.
14.
Martin, R.B., S.L. Zissimos (1991) Relationship between marrow fat and bone turnover in ovariectomized and intact rats. Bone 12: 123–131.
15.
Notelovitz, M. (1989) Estrogen replacement therapy: Indications, contraindications, and agent selection. Am J Obstet Gynecol 161: 1832–1841.
16.
Ornoy, A., S. Geron, M. Goldstein, B.D. Boyan, Z. Schwartz (1994) Gender-dependent effects of testosterone and 17β-estradiol on bone growth and modelling in young mice. Bone Miner 24: 43–58.
17.
Ornoy, A., S. Katzburg (1995) Osteoporosis: Animal models for the human disease; in Ornoy, A. (ed): Animal Models for Human Related Calcium Metabolic Disorders. Boca Raton, CRC Press, pp 105–126.
18.
Patlas, N., P. Yaffe, A. Kimyagarov, G. Golomb, A. Ornoy (1997) Effects of continuous or cyclic administration of pamidronate on the skeleton in intact and oophorectomized young rats. Acta Anat 159: 42–47.
19.
Riggs, B.L., L.J. Melton (1983) Evidence for two distinct syndromes of involutional osteoporosis. Am J Med 75: 899–901.
20.
Saville, P.D. (1969) Changes in skeletal mass and fragility with castration in the rat: A model of osteoporosis. Am Geriatr Soc 17: 155–166.
21.
Stevenson, J.C., M.I. Whitehead (1982) Postmenopausal osteoporosis. Br Med J 285: 535–537.
22.
Tanaka, M., S. Ejiri, S. Kohno, H. Ozawa (1998) The effect of aging and ovariectomy on mandibular condyle in rats. Prosthet Dent 79: 685–690.
23.
Turner, R.T., K.S. Hannon, L.M. Demers, J. Buchanan, N.H. Bell (1989) Differential effects of gonadal function on bone histomorphometry in male and female rats. J Bone Miner Res 4: 557–563.
24.
Turnquist, J., A. Ornoy, D. Eini, Z. Schwartz (1992) The effects of 1α(OH)-vitamin D3 and 24,25(OH)2-vitamin D3 on long bones of glucorticoid treated mice. Acta Anat 145: 61–67.
25.
Wronski, T.J., L.M. Dann, S.L. Horner (1989) Time course of vertebral osteopenia in ovariectomized rats. Bone 10: 295–302.
26.
Wronski T.J., C.F. Yen (1991) The ovariectomized rat as an animal model for postmenopausal bone loss. Cells Mater suppl 1: 69–74.
27.
Yacobi, S. (1994) The Effect of Sex Hormones on Bone Structure in Gonadectomized and Ungonadectomized Male and Female Rats (in Hebrew); MSc thesis Hebrew University, Jerusalem.
28.
Yamazaki, I., H. Yamaguchi (1989) Characteristics of an ovariectomized osteopenic rats model. Bone Miner Res 4: 13–22.
© 2000 S. Karger AG, Basel
2000
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.