Bone Abstracts

Transient paralysis by a single injection of botulinum toxin type A (Botox) in rodents has been shown to cause local bone loss of the affected leg. The animals regain function of the leg within 3–4 weeks and bone loss slowly recovers. The duration of the paralysis is dose-dependent. However, higher doses of Botox cause weight loss and decreased activity level.

Aim of study was to investigate whether repeated injections of low-dose Botox could induce prolonged paralysis in rats in vivo, without additional adverse effects. Furthermore, the effect of prolonged Botox-induced paralysis on bone was assessed.

Fifteen-week-old female rats were randomized into three groups. During anaesthesia, the Botox-1 group received Botox-injections at week 0 (2.5 U) and week 4 (2 U), the Botox-2 group received Botox-injections at week 0 (2.5 U), week 3 (2 U), and week 6 (1.5 U). The control group received saline-injections. Animals were sacrificed after 8 weeks. Paralysis score, body weight, DEXA-bone mineral density (BMD), and mechanical bone strength were evaluated. Botox-groups were pooled for bone analysis.

Paralysis was induced and reached maximum 3–4 days after injection of Botox, followed by a decline in paralysis score until re-injection of Botox. At week 8, body weight was significantly lower in the Botox groups (P<0.05). All groups increased body weight significantly over time (P<0.05). At week 2, BMD of the total femur (−14%; P=0.001) and total tibia (−11%; P=0.001) of the Botox-injected leg was significantly reduced compared to controls. At week 8, BMD was further reduced in the Botox group compared to controls (tibia: −20% and femur: −29%). Maximum load of the femoral neck (P=0.044) and femoral shaft (P<0.001) was significantly lower in the Botox-injected leg compared to controls (−23%).

In conclusion, repeated injections of low-dose Botox in rats can be used to induce prolonged paralysis resulting in a time-dependent loss of BMD.