Effect of a single botulinum toxin injection on bone development in growing rabbits

Intramuscular injections with botulinum toxin A (BTX-A) lead to a rapid decrease in muscle mass and force, but the effect of this drug on bone development is unclear. In the present pilot study we evaluated the effect of a one-time injection of BTXA in growing rabbits. Twelve young (weight 1.5 kg) New Zealand rabbits were randomly assigned to receive either BTX-A (total dose 8 units per kg body weight) or sodium chloride 0.9% injections into the left quadriceps and gastrocnemius muscles. Both groups continued to gain weight in a similar manner following the injection. However, when the animals were sacrificed at five weeks after the injection, the group receiving BTX-A had a significant deficit (of 10%) in gastrocnemius muscle mass on the injected side, whereas no significant side-difference was found for the quadriceps. BTX-A injections did not affect the length of the tibia. Nevertheless, bone mineral content of the whole tibia, as measured by dual-energy X-ray absorptiometry, was 7% lower in the BTX-A injected side than on the contralateral side. Peripheral quantitative computed tomography showed that this bone mass deficit was larger in the metaphysis than in the epiphysis or diaphysis. In the diaphysis, the bone mass deficit was due to a reduction in cross-sectional bone dimensions, which equally affected the cross-section of the entire bone, the cortical compartment and the marrow space. BTX-A injections did not have a detectable effect on cortical bone mineral density. The bone mass deficit in the diaphysis thus appeared to be caused by a lack of periosteal bone apposition rather than increased endocortical or intracortical resorption. These preliminary data suggest that intramuscular BTX-A injections can have a deleterious effect on the development of bones that are loaded by the injected muscles.