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Sex steroids during bone growth: a comparative study between mouse models for hypogonadal and senile osteoporosis

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Abstract

Summary

In this study, the role of disturbed bone mineral acquisition during puberty in the pathogenesis of osteoporosis was studied. To this end, a mouse model for senile and hypogonadal osteoporosis was used. Longitudinal follow-up showed that bone fragility in both models results from deficient bone build-up during early puberty.

Introduction

Male osteoporosis may result from impaired bone growth. This study characterizes the mechanisms of deficient peak bone mass acquisition in models for senile (SAMP6) and hypogonadal (orchidectomized SAMR1) osteoporosis.

Methods

Bone mineral acquisition was investigated longitudinally in SAMP6 and orchidectomized SAMR1 mice (eight to ten animals per group) using peripheral quantitative computed tomography and histomorphometry. Additionally, the effects of long-term 5α-dihydrotestosterone (DHT) and 17β-estradiol (E2) replacement were studied. Statistical analysis was performed using ANOVA and Student’s t test.

Results

SAMP6 mice showed an early (4 weeks) medullary expansion of the cortex due to impaired endocortical bone formation (−43%). Despite compensatory periosteal bone formation (+47%), cortical thickness was severely reduced in 20-week-old SAMP6 versus SAMR1. Orchidectomy reduced periosteal apposition between 4 and 8 weeks of age and resulted in high bone turnover and less trabecular bone gain in SAMP6 and SAMR1. DHT and E2 stimulated periosteal expansion and trabecular bone in orchidectomized SAMP6 and SAMR1. E2 stimulated endocortical apposition in SAMP6. Moreover, sex steroid action occurred between 4 and 8 weeks of age.

Conclusion

Bone fragility in both models resulted from deficient bone build-up during early puberty. DHT and E2 improved bone mass acquisition in orchidectomized animals, suggesting a role for AR and ER in male skeletal development.

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Acknowledgments

The authors thank Erik Van Herck, Ivo Jans, Karen Moermans, and Riet Van Looveren for excellent technical assistance. This study was supported by grant OT/05/53 from the Katholieke Universiteit Leuven and grant G.0417.03 from the Fund for Scientific Research-Flanders, Belgium (F.W.O.-Vlaanderen). Steven Boonen and Dirk Vanderschueren are Senior Clinical Researchers of the Fund for Scientific Research (F.W.O.-Vlaanderen). Katrien Venken is a postdoctoral fellow of the Fund for Scientific Research-Flanders (F.W.O.-Vlaanderen).

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Authors and Affiliations

  1. Bone Research Unit, Laboratory for Experimental Medicine and Endocrinology, Department of Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium

    J. Ophoff, K. Venken, F. Callewaert, S. Boonen, R. Bouillon & D. Vanderschueren

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  1. J. Ophoff
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  2. K. Venken
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  3. F. Callewaert
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  4. S. Boonen
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  5. R. Bouillon
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  6. D. Vanderschueren
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Correspondence to D. Vanderschueren.

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Ophoff, J., Venken, K., Callewaert, F. et al. Sex steroids during bone growth: a comparative study between mouse models for hypogonadal and senile osteoporosis. Osteoporos Int 20, 1749–1757 (2009). https://doi.org/10.1007/s00198-009-0851-z

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  • DOI: https://doi.org/10.1007/s00198-009-0851-z

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