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Strontium ranelate does not stimulate bone formation in ovariectomized rats

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Abstract

Introduction

Strontium ranelate (SrR) is suggested to function as a dual-acting agent in the treatment of postmenopausal osteoporosis with anti-resorptive and anabolic skeletal benefits. We evaluated the effects of SrR on the skeleton in ovariectomized (OVX) rats and evaluated the influence of dietary calcium.

Methods

Three-month old virgin female rats underwent ovariectomy (OVX, n = 50) or SHAM surgery (SHAM, n = 10). Four weeks post-surgery, rats were treated daily by oral gavage with distilled water (10 ml/kg/day) or SrR (25 or 150 mg/kg/day) for 90 days. Separate groups of animals for each dose of SrR were fed a low (0.1%) or normal (1.19%) calcium (Ca) diet. Static and dynamic histomorphometry, DXA, μ-CT, mechanical testing, and serum and skeletal concentrations of strontium were assessed.

Results

SrR at doses of 25 and 150 mg/kg/day did not increase bone formation on trabecular or periosteal bone surfaces, and failed to inhibit bone resorption of trabecular bone regardless of Ca intake. There were no improvements in bone mass, volume or strength with either dose of SrR given normal Ca.

Conclusion

These findings demonstrate that SrR at dosages of 25 and 150 mg/kg/day did not stimulate an anabolic bone response, and failed to improve the bone biomechanical properties of OVX rats.

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Acknowledgements

We thank Lauren Waugh and Logan Vaught for their help in preparing the bone tissue for histological analysis and Antonio Lanzirotti for X-ray fluorescence data analysis. The Alliance for Better Bone Health (Procter & Gamble Pharmaceuticals and Sanofi-Aventis) provided the strontium ranelate drug substance and financial support for the study. The study was also funded by an NIH Musculoskeletal Training Grant T32 AR-7581–09. The National Synchrotron Light Source is funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract No. DE-AC02–98CH10886. Portions of this work were performed at Beamline X26A, NSLS, Brookhaven National Laboratory, which is supported by the DOE-Basic Energy Sciences, Geosciences Division (DE-FG02–92ER14244 to the University of Chicago-CARS) and DOE-Office of Biological and Environmental Research, Environmental Remediation Sciences Division (DE-FC09–96-SR18546 to the University of Georgia).

Disclaimers/Funding Source

The Alliance for Better Bone Health (Procter & Gamble Pharmaceuticals and Sanofi-Aventis), NIH Musculoskeletal Training Grant T32 AR-7581–09, National Synchrotron Light Source funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences (No. DE-AC02–98CH10886), Geosciences Division (No. DE-FG02–92ER14244 to the University of Chicago-CARS) and Department of Energy, Office of Biological and Environmental Research, Environmental Remediation Sciences Division (No. DE-FC09–96-SR18546 to the University of Georgia).

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA

    R. K. Fuchs, M. R. Allen, K. W. Condon, S. Reinwald & D. B. Burr

  2. Department of Physical Therapy, School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, IN, USA

    R. K. Fuchs

  3. National Synchrotron Light Source, Brookhaven National Laboratory, Upton, NY, USA

    L. M. Miller

  4. Procter and Gamble Pharmaceuticals, Mason, OH, USA

    D. McClenathan, B. Keck & R. J. Phipps

  5. Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

    D. B. Burr

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  1. R. K. Fuchs
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Correspondence to R. K. Fuchs.

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Fuchs, R.K., Allen, M.R., Condon, K.W. et al. Strontium ranelate does not stimulate bone formation in ovariectomized rats. Osteoporos Int 19, 1331–1341 (2008). https://doi.org/10.1007/s00198-008-0602-6

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  • DOI: https://doi.org/10.1007/s00198-008-0602-6

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