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Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants

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Abstract

Summary

Treatment of adult ovariectomized (OVX) rats with strontium ranelate prevented vertebral biomechanics degradation as a result of the prevention of bone loss and micro-architecture deterioration associated to an effect on intrinsic bone material quality. Strontium ranelate influenced the determinants of bone strength by prevention of ovariectomy-induced changes which contribute to explain strontium ranelate antifracture efficacy.

Introduction

Strontium ranelate effects on the determinants of bone strength in OVX rats were evaluated.

Methods

Adult female Sprague–Dawley rats were OVX, then treated daily for 52 weeks with 125, 250, or 625 mg strontium ranelate/kg. Bone strength, mass, micro-architecture, turnover, and intrinsic quality were assessed.

Results

Strontium ranelate prevented ovariectomy-induced deterioration in mechanical properties with energy necessary for fracture completely maintained vs. SHAM at 625 mg/kg/day, which corresponds to the clinical dose. This was related to a dose-dependent effect on bone volume, higher trabeculae number, and lower trabecular separation in strontium ranelate vs. OVX. Load and energy required to induce lamella deformation were higher with strontium ranelate than in OVX and in SHAM, indicating that the bone formed with strontium ranelate is able to withstand greater damage before fracture. Bone formation was maintained high or even increased in strontium ranelate as shown by mineralizing surfaces and alkaline phosphatase while strontium ranelate led to reductions in deoxypyridinoline.

Conclusion

Strontium ranelate administered at 625 mg/kg/day for 52 weeks prevented OVX-induced biomechanical properties deterioration by influencing the determinants of bone strength: it prevented bone loss and micro-architecture degradation in association with an effect on intrinsic bone quality. These beneficial effects on bone contribute to explain strontium ranelate antifracture efficacy.

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Acknowledgements

The authors would like to acknowledge Craig Bailey, Matt Heggem, Ryan Leininger, and Debbie Puerner for their contributions to the study management and mechanical testing procedures, Tina Bailey for her performance and analysis of the bone biomarker assays, Hellen Zheng and Chung Liu for the performance of the bone histomorphometry, and Isabelle Badoud for performing the nano-indentation tests and μCT analysis.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department Orthopaedics/Sports Medicine, University of Washington, Washington, USA

    S. D. Bain

  2. Think Bone Consulting, Inc., P.O. Box 1611, Langley, WA, 98260, USA

    C. Jerome

  3. MDS Pharma Services, 22011 30th Dr. SE, Bothell, WA, 98021-4444, USA

    V. Shen

  4. Institut de Recherches Internationales Servier, Courbevoie, France

    I. Dupin-Roger

  5. Service of Bone Diseases (WHO Collaborating Center for Osteoporosis Prevention), Hopital Cantonal, rue Micheli du Crest, 1211, Geneva 14, Switzerland

    P. Ammann

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  1. S. D. Bain
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  2. C. Jerome
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  3. V. Shen
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  4. I. Dupin-Roger
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  5. P. Ammann
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Correspondence to P. Ammann.

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Bain, S.D., Jerome, C., Shen, V. et al. Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants. Osteoporos Int 20, 1417–1428 (2009). https://doi.org/10.1007/s00198-008-0815-8

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  • DOI: https://doi.org/10.1007/s00198-008-0815-8

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