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Loss of Bone Strength is Dependent on Skeletal Site in Disuse Osteoporosis in Rats

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Abstract

Intramuscular injection with botulinum toxin A (BTX) leads to a transient paralysis of the muscles, resulting in a rapid loss of muscle mass and function as well as rapid bone loss (disuse osteoporosis). The purpose of this study was to investigate the temporal development and the site specificity of BTX-induced immobilization on bone strength at five skeletal sites. Three-month-old rats (n = 108) were randomized into nine groups: one served as baseline, while four were injected with BTX and four with saline in the right hind-limb musculature. Animals were killed after 1, 2, 3, or 4 weeks. BTX-induced a significant loss of rectus femoris muscle mass (−61%) and muscle cell cross-sectional area (−59%) as well as bone strength at the femoral neck (−31%), femoral diaphysis (−6%), distal femoral metaphysis (−17%), proximal tibial metaphysis (−31%), and tibial diaphysis (−13%) after 4 weeks. Muscle atrophy occurred in parallel with the bone loss at the femoral neck and proximal tibia, whereas it occurred earlier than the bone loss at the other skeletal sites. At the proximal tibial metaphysis BTX significantly decreased BV/TV (−10%), trabecular thickness (−13%), and bone formation (MS/BS −25%, BFR/BS −50%) and increased osteoclast covered surfaces (+97%) after 4 weeks. In conclusion, BTX-induced a time-dependent loss of bone strength. Moreover, the loss of bone strength differed significantly at the five tested skeletal sites.

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Acknowledgments

The authors are grateful for the excellent technical assistance of Jytte Utoft and Maj-Britt Lundorf. Dr. Kim Henriksen (Nordic Bioscience) is gratefully acknowledged for providing the biochemical analyses of serum. We thank Visiopharm for a contribution to the newCAST™ stereology software system. The μCT scanner was donated by the VELUX Foundation. The study was kindly supported by The A.P. Møller Foundation for the Advancement of Medical Science and Aarhus University Research Foundation. The Centre for Stochastic Geometry and Advanced Bioimaging is supported by the Villum Foundation.

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Authors and Affiliations

  1. Department of Biomedicine, Aarhus University, Aarhus, Denmark

    Jesper Skovhus Thomsen, Lisbeth Lydiksen Christensen, Jens Bay Vegger & Annemarie Brüel

  2. Stereology and Electron Microscopy Laboratory and Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Aarhus, Denmark

    Jens Randel Nyengaard

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  1. Jesper Skovhus Thomsen
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Correspondence to Jesper Skovhus Thomsen.

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Thomsen, J.S., Christensen, L.L., Vegger, J.B. et al. Loss of Bone Strength is Dependent on Skeletal Site in Disuse Osteoporosis in Rats. Calcif Tissue Int 90, 294–306 (2012). https://doi.org/10.1007/s00223-012-9576-7

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  • DOI: https://doi.org/10.1007/s00223-012-9576-7

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