SLR - June 2020 - Stephanie M. Kane

Cigarette Smoke Inhalation Impairs Angiogenesis in Early Bone Healing Processes and Delays Fracture Union

Reference: Chao-Jui Chang, I-Ming Jou, Tung-Tai Wu, Fong-Chin Su, Ta-Wei Tai, Cigarette Smoke Inhalation Impairs Angiogenesis in Early Bone Healing Processes and Delays Fracture Union. Bone Joint Res. 2020;9(3):99–107.

Scientific Literature review

Reviewed By: Stephanie M. Kane, DPM
Residency Program: Bethesda Hospital East/West – Boynton Beach, FL

Podiatric Relevance: It is common in podiatric surgery to encounter fractures and healing of osteotomies. When preforming a preoperative exam, smoking is a common cause of concern with patients and their healing. This article focuses on research which shows cigarette smoke inhalation may delay fracture healing and angiogenesis. This study aims to look at a laboratory example of the effects of exposure to inhalation of cigarette smoke on bone healing.

Methods: A total of 48 adult rats were divided into two groups, the smoking and the control group. The authors developed a custom-made chamber for rats with airflow to inhale cigarette smoke to simulate second hand smoke for two hours each day for one week before the osteotomy surgery was performed. Their hypothesis was tested with a femoral osteotomy made on the rats and a subsequent retrograde intramedullary nail. Both radiographs and microCT imaging studies were performed. Plain radiographs were used to evaluate the fracture union and confirmed with CT.  A cylindrical volume of interest (VOI) was created and encompassed the callus around the fracture site. The bone volume and the total volume of the whole callus were measured via CT. Biomechanical testing was performed after the rats were euthanized. The bone was put through a three-point bending test and the contralateral femur was used as a control. At weeks one, two and four, after the rats were anesthetized, callus was collected, and Western blot analysis was performed. Subsequently, histology and immunohistochemistry were performed and microvessel density was evaluated.

Results: The healing of the fractures was evaluated using the microCT and histological evaluation. Only four out of ten subjects in the smoking group reached union and eight out of ten in the non-smoking group. The smoking group had a lower ratio of bone to tissue volume compared to the control under microCT. The biomechanical tests revealed the bones in the smoking group were weaker than those in the control group. Western blot analysis was utilized to detect expression of vascular endothelial growth factors (VEGF) and von Willebrand factor (vWF) in the fracture calluses at week one, two and four and showed that in the smoking group these were lower and that cigarette inhalation reduced the expression of these angiogenic factors. The smoking group also showed significantly less microvessel density than the control group after only one week.

Conclusions: The authors revealed that cigarette smoke inhalation, in which they mentioned was comparative to second-hand smoke exposure, has showed an association with impaired bone healing, weaker fracture sites, and decreased in angiogenic markers (VEGF and vWF) early in the bone healing phases. This is important in the practice of podiatric surgery to understand how exposure to second hand smoke can effect a patient’s bone healing. It is important to discuss findings from studies like these with patients for evidence of decrease union rates, decreased bone strength, decrease in growth factors and angiogenic factors and less microvessel density if they are a smoker or exposed to smokers. Some limitations with this study were that there was no investigation into the individual substances in cigarettes that may have a negative effect on bone healing, however they focused on cigarette smoke exposure as a whole.  

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