Tissue selective effects of bazedoxifene on the musculoskeletal system in female mice

Christine A. Cabelka, Cory W. Baumann, Angus Lindsay, Andrew Norton, Nick C. Blixt, Gengyun Le, Gordon L. Warren, Kim C. Mansky, Susan A. Novotny, Dawn A. Lowe

Research output: Contribution to journalArticlepeer-review

Abstract

The actions of selective estrogen receptor modulators are tissue dependent. The primary objective of the current study was to determine the tis sue selective effects of bazedoxifene (BZA) on the musculoskeletal system of ovariectomized (OVX) female mice, focusing on the strengths of muscle-bone pairs in the lower hindlimb. Treatment with BZA after ovariectomy (OVX+BZA) did not prevent body or fat mass gains (P < 0.05). In vivo plantarflexor muscle isometric torque was not affected by treatment with BZA (P = 0.522). Soleus muscle peak isometric, concentric and eccentric tetanic force production were greater in OVX+BZA mice compared to OVX+E2 mice (P ≤ 0.048) with no effect on maximal isometric specific force (P = 0.228). Tibia from OVX+BZA mice had greater cortical crosssectional area and moment of inertia than OVX mice treated with placebo (P < 0.001), but there was no impact of BZA treatment on cortical bone mineral density, cortical thickness, tibial bone ultimate load or stiffness (P ≥ 0.086). Overall, these results indicate that BZA may be an estrogen receptor agonist in skeletal muscle, as it has previously been shown in bone, providing minor benefits to the musculoskeletal system.

Original languageEnglish (US)
Pages (from-to)181-191
Number of pages11
JournalJournal of Endocrinology
Volume248
Issue number2
DOIs
StatePublished - Feb 2021
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grants R01-AG031743, T32-AR007612, T32-AR050938, T32-AG029796 and a Promotion of Doctoral Studies II Scholarship from the Foundation for Physical Therapy.

Publisher Copyright:
© 2021 Society for Endocrinology.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • Bone
  • Ovariectomy
  • Physical activity
  • SERM
  • Skeletal muscle

PubMed: MeSH publication types

  • Journal Article

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