Bone Loss after Temporarily Induced Muscle Paralysis by Botox Is Not Fully Recovered After 12 Weeks

Abstract

To study the effect of unloading followed by reloading on hindlimb bone mineral content (BMC), we used botulinum toxin A (Botox). We studied the timing and degree of recovery upon restoration of muscle function. We also tested to see if reaction to Botox injection occurred as a function of the degree of expression of connexin43 (Cx43). Sixteen mice were divided by gender and genotype; wild-type equivalent (Gja1(+/flox)) and heterozygous (Gja1(+/-)) mice were injected with a single dose of 2U/100 g Botox i.m. in the quadriceps, hamstrings, and posterior calf muscle groups (day 0). Regional BMC was monitored for 12 weeks in the injected and contralateral control limb. Significant bone loss was observed in the injected limb by week 2 in the Gja1(+/flox) mice, and by week 3-4 in the Gja1(+/-) mice. By week 12, BMC in the Botox-treated limb of both male and female wild-type and heterozygous mice was still at least 14% less than that of the noninjected limb. Cortical thickness and BV/TV were lower in the Botox femur compared to the noninjected femur. The heterozygous mice tended to show a slower response to Botox injection as reflected in a slower loss of BMC. Our results show that the rapid and profound bone loss following temporary muscle paralysis is not fully recovered upon restoration of muscle function within 12 weeks. These results underscore the significance of normal muscle function in the maintenance of bone mass.

Loss of Bone Strength is Dependent on Skeletal Site in Disuse Osteoporosis in Rats

“…Immobilization with BTX has been applied to a series of animals such as rats [20,[25][26][27][28][29], mice [30][31][32][33][34][35], and rabbits [36]. However, the effect of BTX on bone strength has not yet been investigated in any of these animal models.…”

The Role of Mechanobiology in the Attachment of Tendon to Bone

“…Connexin proteins assemble in the cell membrane to form hemichannels or gap junctions to enable direct cell-cell communication. Selective loss of connexin 43 from bone cells results in a loss of the mechanoresponsiveness of bone to both loading-induced bone formation and muscle paralysis-induced bone loss [103][104][105][106]. The mechanoresponsiveness of connexins and other molecules involved in direct cell-cell communication underlines the importance of cell-cell communication in the response to mechanical stimuli.…”

Clinical commentary: Systemic and subclinical adverse effects of repeated botulinum toxin a injections to decrease spasticity in adults affected by stroke undergoing rehabilitation

“…Repeated acute muscle paralysis from BTX disturbs the normal muscle bone homeostasis due to blockage of release or transport of certain biochemical factors; a process that leads to bone resorption and osteopenia [12][13] . Raphael et al (2014) reported that the paralytic action of BTX in rabbit's jaw muscles caused osteoporosis and negatively affected the overall jaw bone health 14 .…”

“…Subclinical changes in muscle and bone tissues may initially be undetected by clinical observation as it involves fatty infiltration in muscles, formation of atrophic muscle fibers and decrease in muscle mass [11][12][13] . A post-stroke patient with history of repeated BTX injections may develop gradual muscle atrophy not only of the injected muscles but also of adjacent or distant muscle groups.…”

“…Alternatives to longterm and repeated BTX injections for post-stroke spasticity is recommended as it is not known if muscle tissues will go back to pre-injection levels, or return to normal skeletal fibers if general activity level is resumed. [11][12][13] It will be a huge error if these AE are attributed as an extension of the stroke.…”