Reduced gravitational loading does not account for the skeletal effect of botulinum toxin-induced muscle inhibition suggesting a direct effect of muscle on bone

Stuart J. Warden, Matthew R. Galley, Jeffrey S. Richard, Lydia A. George, Rachel C. Dirks, Elizabeth A. Guildenbecher, Ashley M. Judd, Alexander Robling, Robyn K. Fuchs

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Intramuscular injection of botulinum toxin (botox) into rodent hindlimbs has developed as a useful model for exploring muscle-bone interactions. Botox-induced muscle inhibition rapidly induces muscle atrophy and subsequent bone loss, with the latter hypothesized to result from reduced muscular loading of the skeleton. However, botox-induced muscle inhibition also reduces gravitational loading (as evident by reduced ground reaction forces during gait) which may account for its negative skeletal effects. The aim of this study was to investigate the skeletal effect of botox-induced muscle inhibition in cage control and tail suspended mice, with tail suspension being used to control for the reduced gravitational loading associated with botox. Female C57BL/6J mice were injected unilaterally with botox and contralaterally with vehicle, and subsequently exposed to tail suspension or normal cage activities for 6. weeks. Botox-induced muscle inhibition combined with tail suspension had the largest detrimental effect on the skeleton, causing the least gains in midshaft tibial bone mass, cortical area and cortical thickness, greatest gains in midshaft tibial medullary area, and lowest proximal tibial trabecular bone volume fraction. These data indicate botox-induced muscle inhibition has skeletal effects over and above any effect it has in altering gravitational loading, suggesting that muscle has a direct effect on bone. This effect may be relevant in the development of strategies targeting musculoskeletal health.

Original languageEnglish (US)
Pages (from-to)98-105
Number of pages8
JournalBone
Volume54
Issue number1
DOIs
StatePublished - May 2013

Fingerprint

Botulinum Toxins
Bone and Bones
Muscles
Hindlimb Suspension
Skeleton
Muscular Atrophy
Intramuscular Injections
Hindlimb
Gait
Inbred C57BL Mouse
Tail
Rodentia
Health

Keywords

  • Botox
  • Mechanical loading
  • Muscle-bone interaction
  • Myokines
  • Tail suspension

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Warden, S. J., Galley, M. R., Richard, J. S., George, L. A., Dirks, R. C., Guildenbecher, E. A., ... Fuchs, R. K. (2013). Reduced gravitational loading does not account for the skeletal effect of botulinum toxin-induced muscle inhibition suggesting a direct effect of muscle on bone. Bone, 54(1), 98-105. https://doi.org/10.1016/j.bone.2013.01.043

Reduced gravitational loading does not account for the skeletal effect of botulinum toxin-induced muscle inhibition suggesting a direct effect of muscle on bone. / Warden, Stuart J.; Galley, Matthew R.; Richard, Jeffrey S.; George, Lydia A.; Dirks, Rachel C.; Guildenbecher, Elizabeth A.; Judd, Ashley M.; Robling, Alexander; Fuchs, Robyn K.

In: Bone, Vol. 54, No. 1, 05.2013, p. 98-105.

Research output: Contribution to journalArticle

Warden, Stuart J. ; Galley, Matthew R. ; Richard, Jeffrey S. ; George, Lydia A. ; Dirks, Rachel C. ; Guildenbecher, Elizabeth A. ; Judd, Ashley M. ; Robling, Alexander ; Fuchs, Robyn K. / Reduced gravitational loading does not account for the skeletal effect of botulinum toxin-induced muscle inhibition suggesting a direct effect of muscle on bone. In: Bone. 2013 ; Vol. 54, No. 1. pp. 98-105.
@article{37b0ee4fdcbd4976b3132870663e7a8e,
title = "Reduced gravitational loading does not account for the skeletal effect of botulinum toxin-induced muscle inhibition suggesting a direct effect of muscle on bone",
abstract = "Intramuscular injection of botulinum toxin (botox) into rodent hindlimbs has developed as a useful model for exploring muscle-bone interactions. Botox-induced muscle inhibition rapidly induces muscle atrophy and subsequent bone loss, with the latter hypothesized to result from reduced muscular loading of the skeleton. However, botox-induced muscle inhibition also reduces gravitational loading (as evident by reduced ground reaction forces during gait) which may account for its negative skeletal effects. The aim of this study was to investigate the skeletal effect of botox-induced muscle inhibition in cage control and tail suspended mice, with tail suspension being used to control for the reduced gravitational loading associated with botox. Female C57BL/6J mice were injected unilaterally with botox and contralaterally with vehicle, and subsequently exposed to tail suspension or normal cage activities for 6. weeks. Botox-induced muscle inhibition combined with tail suspension had the largest detrimental effect on the skeleton, causing the least gains in midshaft tibial bone mass, cortical area and cortical thickness, greatest gains in midshaft tibial medullary area, and lowest proximal tibial trabecular bone volume fraction. These data indicate botox-induced muscle inhibition has skeletal effects over and above any effect it has in altering gravitational loading, suggesting that muscle has a direct effect on bone. This effect may be relevant in the development of strategies targeting musculoskeletal health.",
keywords = "Botox, Mechanical loading, Muscle-bone interaction, Myokines, Tail suspension",
author = "Warden, {Stuart J.} and Galley, {Matthew R.} and Richard, {Jeffrey S.} and George, {Lydia A.} and Dirks, {Rachel C.} and Guildenbecher, {Elizabeth A.} and Judd, {Ashley M.} and Alexander Robling and Fuchs, {Robyn K.}",
year = "2013",
month = "5",
doi = "10.1016/j.bone.2013.01.043",
language = "English (US)",
volume = "54",
pages = "98--105",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Reduced gravitational loading does not account for the skeletal effect of botulinum toxin-induced muscle inhibition suggesting a direct effect of muscle on bone

AU - Warden, Stuart J.

AU - Galley, Matthew R.

AU - Richard, Jeffrey S.

AU - George, Lydia A.

AU - Dirks, Rachel C.

AU - Guildenbecher, Elizabeth A.

AU - Judd, Ashley M.

AU - Robling, Alexander

AU - Fuchs, Robyn K.

PY - 2013/5

Y1 - 2013/5

N2 - Intramuscular injection of botulinum toxin (botox) into rodent hindlimbs has developed as a useful model for exploring muscle-bone interactions. Botox-induced muscle inhibition rapidly induces muscle atrophy and subsequent bone loss, with the latter hypothesized to result from reduced muscular loading of the skeleton. However, botox-induced muscle inhibition also reduces gravitational loading (as evident by reduced ground reaction forces during gait) which may account for its negative skeletal effects. The aim of this study was to investigate the skeletal effect of botox-induced muscle inhibition in cage control and tail suspended mice, with tail suspension being used to control for the reduced gravitational loading associated with botox. Female C57BL/6J mice were injected unilaterally with botox and contralaterally with vehicle, and subsequently exposed to tail suspension or normal cage activities for 6. weeks. Botox-induced muscle inhibition combined with tail suspension had the largest detrimental effect on the skeleton, causing the least gains in midshaft tibial bone mass, cortical area and cortical thickness, greatest gains in midshaft tibial medullary area, and lowest proximal tibial trabecular bone volume fraction. These data indicate botox-induced muscle inhibition has skeletal effects over and above any effect it has in altering gravitational loading, suggesting that muscle has a direct effect on bone. This effect may be relevant in the development of strategies targeting musculoskeletal health.

AB - Intramuscular injection of botulinum toxin (botox) into rodent hindlimbs has developed as a useful model for exploring muscle-bone interactions. Botox-induced muscle inhibition rapidly induces muscle atrophy and subsequent bone loss, with the latter hypothesized to result from reduced muscular loading of the skeleton. However, botox-induced muscle inhibition also reduces gravitational loading (as evident by reduced ground reaction forces during gait) which may account for its negative skeletal effects. The aim of this study was to investigate the skeletal effect of botox-induced muscle inhibition in cage control and tail suspended mice, with tail suspension being used to control for the reduced gravitational loading associated with botox. Female C57BL/6J mice were injected unilaterally with botox and contralaterally with vehicle, and subsequently exposed to tail suspension or normal cage activities for 6. weeks. Botox-induced muscle inhibition combined with tail suspension had the largest detrimental effect on the skeleton, causing the least gains in midshaft tibial bone mass, cortical area and cortical thickness, greatest gains in midshaft tibial medullary area, and lowest proximal tibial trabecular bone volume fraction. These data indicate botox-induced muscle inhibition has skeletal effects over and above any effect it has in altering gravitational loading, suggesting that muscle has a direct effect on bone. This effect may be relevant in the development of strategies targeting musculoskeletal health.

KW - Botox

KW - Mechanical loading

KW - Muscle-bone interaction

KW - Myokines

KW - Tail suspension

UR - http://www.scopus.com/inward/record.url?scp=84874385602&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874385602&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2013.01.043

DO - 10.1016/j.bone.2013.01.043

M3 - Article

VL - 54

SP - 98

EP - 105

JO - Bone

JF - Bone

SN - 8756-3282

IS - 1

ER -