Smoking and impaired bone healing: will activation of cholinergic anti-inflammatory pathway be the bridge?

Purpose: This review was written to analyse the potential role of the cholinergic anti-inflammatory pathway in smoking-induced impairment of the bone healing process.
Methods: Literature in PubMed was reviewed by entering the following keywords "smoking AND bone healing", "cholinergic anti-inflammatory pathway AND tumour necrosis factor", "tumour necrosis factor AND bone healing". All the related papers were recruited and carefully selected according to the content of this paper.
Results: Literature review indicated that tumour necrosis factor alpha (TNF-α) plays a pivotal role in the fracture healing process. In brief, TNF-α may accelerate the endochondral ossification process by increasing matrix metalloproteinases (MMPs) level, chondrocyte apoptosis, as well as osteoclast formation, therefore reducing the cartilaginous stage leading to the acceleration of fracture healing. Nicotine is the main effective ingredient of tobacco, which has been found to inhibit the secretion of TNF-α through activation of the cholinergic anti-inflammatory pathway.
Conclusions: It is reasonable to believe that the nicotine in tobacco at least partly contributes to the delayed fracture healing by inhibiting TNF-α secretion through the activation of the cholinergic anti-inflammatory pathway. An in-depth study of this issue will contribute to the clinical treatment of nonunion, as well as the development of new therapies to accelerate bone healing.