Effects of botulinum toxin A on fracture healing in rats: an experimental study

Aydın, Adem; Memişoğlu, Kaya; Cengiz, A. Tevfik; Atmaca, Halil; Müezzínoğlu, Bahar; Müezzinoğlu, Ü. Sefa

doi:10.1007/s00776-012-0269-x

Cited by 28 publications

(23 citation statements)

References 30 publications

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“…In contrary to the current study Aydin et al 5 reported statistically significant increase in union, spongious bone formation, and bone marrow organization scores as well as elastic modulus value of BTX-A injected sides. They concluded that BTX-A administration increases the healing power in a relatively fixated fracture and decreases the callus diameter as if rigid fixation had been performed.…”

contrasting

confidence: 99%

“…They concluded that BTX-A administration increases the healing power in a relatively fixated fracture and decreases the callus diameter as if rigid fixation had been performed. The main difference between the studies of Hao et al 1 and Aydin et al 5 was the shape and the mechanism of the fracture. Aydin et al 5 aimed to protect the vessels and periosteoum by using standard closed fracture in all rats while Hao et …”

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confidence: 90%

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The relation between Botulinum toxin‐A and fracture healing. Comment on Hao et al.: Short‐term muscle atrophy caused by Botulinum toxin‐A local injection impairs fracture healing in the rat femur

Atmaca

Memişoğlu

2013

Journal Orthopaedic Research

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confidence: 99%

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confidence: 90%

The relation between Botulinum toxin‐A and fracture healing. Comment on Hao et al.: Short‐term muscle atrophy caused by Botulinum toxin‐A local injection impairs fracture healing in the rat femur

Atmaca

Memişoğlu

2013

Journal Orthopaedic Research

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“…The simplicity of this model compared with a closed or open fracture model (eg, smaller and more confined callus formation, lack of gait defect) supports a direct role for muscle/bone crosstalk in fracture healing [12,19,21,28]. Previous studies using closed and open fracture models have reported conflicting findings over the potential benefit (or lack thereof) of muscle paralysis on fracture healing [3,13]. It has been postulated that variations in vascularity and soft tissue damage at the fracture site and the extent of neuromuscular inhibition have contributed to this variability [1,22].…”

Section: Discussionmentioning

confidence: 73%

“…Others have recently shown that transient paralysis of the quadriceps induced by botulinum toxin A (BTxA) inhibits periosteal osteogenesis and callus formation in a rat femur fracture model [3,13]. Given the known mechanism of action of BTxA (inhibition of neurotransmitter release), we therefore speculated that the blockade of neuromuscular signaling by BTxA inhibits neuromuscular interactions integral to the osteogenic response elicited by musculoskeletal trauma.…”

Section: Introductionmentioning

confidence: 99%

Botulinum Toxin-induced Muscle Paralysis Inhibits Heterotopic Bone Formation

Ausk

Gross

Bain

2015

Clinical Orthopaedics &Amp; Related Research

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Background Short-term muscle atrophy induced by botulinum toxin A (BTxA) has been observed to impair osteogenesis in a rat closed femur fracture model. However, it is unclear whether the underlying mechanism is a direct effect of BTxA on muscle-bone interactions or an indirect effect that is driven by skeletal unloading. Because skeletal trauma in the closed fracture model also leads to disuse atrophy, we sought to mitigate this confounding variable by examining BTxA effects on muscle-bone interactions in two complementary in vivo models in which osteogenesis is induced in the absence of skeletal unloading. The overall aim of this study was to identify a potential strategy to inhibit pathological bone formation and heterotopic ossification (HO). Questions/purposes (1) Does muscle paralysis inhibit periosteal osteogenesis induced by a transcortical defect? (2) Does muscle paralysis inhibit heterotopic bone formation stimulated by intramuscular bone morphogenetic protein (BMP) injection? Methods Focal osteogenesis was induced in the right hindlimb of mice through surgical initiation of a small transcortical defect in the tibia (fracture callus; n = 7/group) or intramuscular injection of BMP-2 (HO lesion; n = 6/group), both in the presence/absence of adjacent calf paralysis. High-resolution micro-CT images were obtained in all experimental groups 21 days postinduction and total volume (ie, perimeter of periosteal callus or HO lesion) and bone volume (calcified tissue within the total volume) were quantified as primary outcome measures. Finally, these outcome measures were compared to determine the effect of muscle paralysis on inhibition of local osteogenesis in both studies.Results After a transcortical defect, BTxA-treated mice showed profound inhibition of osteogenesis in the periosteal fracture callus 21 days postsurgery compared with saline-treated mice (total volume: 0.08 ± 0.06 versus 0.42 ± 0.11 mm 3 , p \ 0.001; bone volume: 0.07 ± 0.05 versus 0.32 ± 0.07 mm 3 , p \ 0.001). Similarly, BMP-2-induced HO formation was inhibited by adjacent muscle paralysis at the same time point (total volume: 1.42 ± 0.31 versus 3.42 ± 2.11 mm 3 , p = 0.034; bone volume: 0.68 ± 0.18 versus 1.36 ± 0.79 mm 3 , p = 0.045). Conclusions Our data indicate that BTxA-induced neuromuscular inhibition mitigated osteogenesis associated with both a transcortical defect and BMP-2-induced HO. Clinical Relevance Focal neuromuscular inhibition represents a promising new approach that may lead to a new clinical intervention to mitigate trauma-induced HO, a healthcare challenge that is severely debilitating for civilian and war-wounded populations, is costly to both the patient and the healthcare system, and currently lacks effective treatments.

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“…[14][15][16] According to the Wolff's law, narrow gap, rigid fixation and sustained dynamic compression are essential for bone healing. [17][18][19][20] In the earlier studies, researchers concluded that the dynamization technique should be performed by removing the most distal locking screw from the fracture site. Unfortunately, there is no mechanical evidence to prove the efficacy of such an approach.…”

mentioning

confidence: 99%

A new intramedullary sustained dynamic compression nail for the treatment of long bone fractures: a biomechanical study

Karakaşlı¹

2015

Eklem Hastalik Cerrahisi

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Effects of botulinum toxin A on fracture healing in rats: an experimental study

Cited by 28 publications

References 30 publications

The relation between Botulinum toxin‐A and fracture healing. Comment on Hao et al.: Short‐term muscle atrophy caused by Botulinum toxin‐A local injection impairs fracture healing in the rat femur

The relation between Botulinum toxin‐A and fracture healing. Comment on Hao et al.: Short‐term muscle atrophy caused by Botulinum toxin‐A local injection impairs fracture healing in the rat femur

Botulinum Toxin-induced Muscle Paralysis Inhibits Heterotopic Bone Formation

A new intramedullary sustained dynamic compression nail for the treatment of long bone fractures: a biomechanical study

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