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The Impact of Strontium Ranelate on Metaphyseal Bone Healing in Ovariectomized Rats

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Abstract

The following questions were addressed: whether therapy with strontium ranelate (SR) should be continued or interrupted if the fractures occur during SR treatment and whether SR could be applied directly after fracture to improve bone healing. Sprague–Dawley rats (3 month old) were ovariectomized (Ovx, n = 48) or left intact (n = 12). After 8 weeks, a bilateral transverse osteotomy of the tibia metaphysis was created in all rats. Ovx rats were divided into four groups: Ovx; SR applied directly after Ovx until osteotomy (prophylaxis, SR pr, 8 weeks); SR applied after osteotomy (therapy, SR th, 5 weeks); SR applied during the whole experiment (pr + th, 13 weeks). SR dosage was 625 mg/kg body weight/day, administered in the feed. Five weeks later, tibiae were analyzed by biomechanical, histological, micro-CT, and gene expression analyses. The SR pr + th treatment increased total bone mineral density (BMD), bone volume fraction, cortical BMD and volume, callus area and density, serum alkaline phosphatase, tartrate-resistant acid phosphatase mRNA, accelerated osteotomy bridging, and callus formation at weeks 2 and 3 of healing and decreased the osteoprotegerin/receptor activator of nuclear factor kB ligand mRNA ratio. SR th enlarged callus area and improved callus formation during the 5th week of healing. SR pr improved cortical BMD preserving bone after SR discontinuation (5-week rest); the bone healing was not affected. SR content in the tibia metaphysis was the highest in SR pr + th group and was not different between SR pr and SR th. SR has a positive effect on osteoporotic bone healing in rat and SR treatment can be continued after the fracture occurs or applied directly after the fracture.

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Acknowledgments

The present study was supported by the Elsbeth–Bonhoff Foundation (N 70). We are thankful to R. Castro-Machguth and A. Witt for technical support.

Conflict of Interest

Authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

The animal study protocol was approved by the local regional government (G 11.560, Oldendurg, Germany) in accordance with German animal-protection laws prior to performing the study.

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Authors and Affiliations

  1. Department of Trauma Surgery and Reconstructive Surgery, University Medical Center Göttingen, Robert-Koch St. 40, 37075, Göttingen, Germany

    Marina Komrakova, Anna Weidemann, Mohammad Tezval, Klaus Michael Stuermer & Stephan Sehmisch

  2. Department of Radiology, University of Göttingen, Robert-Koch 40, 37075, Göttingen, Germany

    Christian Dullin

  3. Department of Medical Microbiology, Subdivision of General Hygiene and Environmental Health, University of Göttingen, Humboldallee 34a, 37073, Göttingen, Germany

    Joachim Ebert

Authors
  1. Marina Komrakova
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  2. Anna Weidemann
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  3. Christian Dullin
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  4. Joachim Ebert
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  5. Mohammad Tezval
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  6. Klaus Michael Stuermer
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  7. Stephan Sehmisch
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Correspondence to Marina Komrakova.

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Komrakova, M., Weidemann, A., Dullin, C. et al. The Impact of Strontium Ranelate on Metaphyseal Bone Healing in Ovariectomized Rats. Calcif Tissue Int 97, 391–401 (2015). https://doi.org/10.1007/s00223-015-0019-0

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  • DOI: https://doi.org/10.1007/s00223-015-0019-0

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