title: Vertical ground reaction forces diminish in mice after botulinum toxin injection.
abstract: We examined changes in weight-bearing ability in mice after injection with botulinum toxin type A (BTX) to determine whether BTX can be used to isolate the effects of muscle on bone. As ambulation patterns were previously shown to improve within two weeks post-injection, we hypothesized that BTX injection to the posterior hindlimb would not significantly affect the mouse's ability to bear weight in the affected limb one week post-injection. Female BALB/c mice (N=13, 16-17 week old) were injected with either 20 μL of BTX (1U/100 g) or saline (SAL) in the left posterior hindlimb. Vertical ground reaction forces (GRF), hindlimb muscle cross-sectional area (MCSA), and tibial bone micro-architecture were assessed for 42 d following injection. Peak and average vertical GRF were 11±1% and 23±3% lower, respectively, in the BTX-injected hindlimb within 4d post-injection and remained lower than the SAL-injected hindlimb 14-21 d post-injection (15±4% and 10±2%, respectively). Time between forelimb and hindlimb peaks was 30-40% greater in the BTX-injected hindlimb than SAL-injected hindlimb 4-14 d post-injection. Peak vertical GRF recovered earlier following BTX injection than MCSA or bone volume fraction. These results indicate that weight-bearing ability recovered despite persistent muscle atrophy, and that weight-bearing alone was insufficient to maintain bone in the absence of muscle activity. We suggest that the absence of high-frequency signals typically associated with fast-twitch muscle activity may be contributing to the ongoing degradation of bone after BTX injection.
authors.affiliation: Faculty of Kinesiology, University of Calgary, Calgary, Canada.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Manske
authors.forename: Steven K
authors.initials: SK
authors.lastname: Boyd
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Zernicke
mesh_terms: D000818:Animals; D001905:Botulinum Toxins / Q000008:administration & dosage*; D005260:Female; D005528:Foot / Q000502:physiology*; D005684:Gait / Q000187:drug effects / Q000502:physiology*; D006614:Hindlimb / Q000187:drug effects / Q000502:physiology; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D013314:Stress, Mechanical; D016474:Weight-Bearing / Q000502:physiology*
chemical_list: D001905:Botulinum Toxins