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Effect of Strontium Ranelate on the Muscle and Vertebrae of Ovariectomized Rats

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Abstract

Osteoporosis is often accompanied by sarcopenia. The effect of strontium ranelate (SR) on muscle tissue has not been investigated sufficiently. In this study, the effect of different SR treatments on muscle was studied. Additionally, the lumbar vertebrae were analyzed. Three-month-old female rats were divided into five groups (n = 12): Group 1: untreated (NON-OVX); Group 2: ovariectomized and left untreated (OVX); Group 3: SR after OVX until the study ended (13 weeks, SR prophylaxis and therapy = pr+th); Group 4: OVX and SR for 8 weeks (SR prophylaxis = pr); Group 5: SR for 5 weeks from the 8 week after OVX (SR therapy = SR th). SR was applied in food (630 mg/kg body weight). The size of muscle fibers, capillary density, metabolic enzymes, and mRNA expression were assessed in soleus, gastrocnemius, and longissimus muscles. The vertebral bodies underwent micro-CT, biomechanical, and ashing analyses. In general, SR did not alter the muscle histological parameters. The changes in fiber size and capillary ratio were related to the body weight. Myostatin mRNA was decreased in Sr pr+th; protein expression was not changed. SR th led to increase in mRNA expression of vascular endothelial growth factor (Vegf-B). In lumbar spine, SR pr+th enhanced biomechanical properties, bone mineral density, trabecular area, density, and thickness and cortical density. The reduced calcium/phosphate ratio in the SR pr+th group indicates the replacement of calcium by strontium ions. SR has no adverse effects on muscle tissue and it shows a favorable time-dependent effect on vertebrae. A functional analysis of muscles could verify these findings.

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Acknowledgements

We wish to express our gratitude to Elsbeth Bonhoff Stiftung for providing the financial support for the present study (Grant N70). Moreover, we are grateful to R. Wigger, R. Castro-Machguth, and A. Witt for the technical support they provided.

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Authors and Affiliations

  1. Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Goettingen, Robert-Koch Str. 40, 37075, Göettingen, Germany

    D. Saul, B. Harlas, A. Ahrabi, D. B. Hoffmann, K. O. Böker, S. Sehmisch & M. Komrakova

  2. Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075, Göettingen, Germany

    R. L. Kosinsky

  3. Medical Institute of General Hygiene and Environmental Health, University of Goettingen, 37075, Göettingen, Germany

    M. Wassmann

  4. Department of Animal Science, University of Goettingen, 37075, Göettingen, Germany

    R. Wigger

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Authors D. Saul, B. Harlas, A. Ahrabi, R. L. Kosinsky, D. B. Hoffmann, M. Wassmann, R. Wigger, K. O. Böker, S. Sehmisch, and M. Komrakova declare that they have no conflicts of interest.

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223_2017_374_MOESM1_ESM.eps

ATPase analysis of M. gastrocnemius, M. longissimus and M. soleus. area: cross sectional area of muscle fibers; dia: mean diameter of muscle fibers; oxi: oxidative and intermittent muscle fibers (I and IIa); gly: glycolytic muscle fibers (IIb). Data corrected by body weight (g). A,B, G-J,: Dunn´s test; C-F: Tukey-test. *p < 0.05, **p < 0.01, ***p < 0.001. (EPS 3448 KB)

223_2017_374_MOESM2_ESM.eps

Activity of lactate dehydrogenase (LDH), citrate synthase (CS) and Complex I was measured in M. gastrocnemius, M. longissimus and M. soleus. There were no significant differences between the groups (p > 0.05). A, H: Dunn´s test; B-G, I: Tukey-test (EPS 3226 KB)

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Saul, D., Harlas, B., Ahrabi, A. et al. Effect of Strontium Ranelate on the Muscle and Vertebrae of Ovariectomized Rats. Calcif Tissue Int 102, 705–719 (2018). https://doi.org/10.1007/s00223-017-0374-0

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