From the American Academy of Orthopaedic Surgeons
It is well-established that conventional cigarette smoking causes delayed healing of fractures and results in higher rates of nonunion. Nicotine exposure through smoking cigarettes may be more harmful than nicotine exposure through oral administration or nicotine patches, due to other harmful chemicals in the smoke. However, little is known concerning the effects on fracture healing of electronic cigarettes (e-cigarettes) that contain nicotine.
A study presented at the AAOS 2023 Annual Meeting aimed to compare the effects of traditional cigarette smoke and e-cigarettes on fracture healing using a rodent model. The study found that although levels of cotinine (a nicotine metabolite) were lower in the e-cigarette group than in the group exposed to cigarette smoke, bone healing in the e-cigarette group was still compromised compared with the control (no nicotine) group.
In the study, 48 adult male Sprague Dawley rats were randomly allocated to exposure to ambient air (control), regular cigarettes, or e-cigarettes. Researchers placed the latter two groups in a smoking chamber for 20 minutes twice daily.
After 1 week of exposure, all animals were anesthetized and underwent surgery. The researchers created a transverse osteotomy in the midshaft of one femur, which was then stabilized surgically with an intramedullary Kirschner wire. All animals were treated with buprenorphine to reduce pain after surgery. Half of the animals were euthanized 3 weeks after fracture surgery, and the remaining animals were euthanized 6 weeks after surgery.
Serum obtained at the time of euthanasia was used to measure cotinine levels. Bilateral femurs were harvested and imaged with contact radiographs and microCT. An orthopaedic traumatologist used a modified Radiographic Union Score for Tibia Fractures (mRUST) scoring system to evaluate both the contact radiographs and the microCT images of the fractured femurs in a blinded fashion. That surgeon also made an assessment of whether each femur was healed. The microCT images were segmented into three density ranges (unmineralized callus, mineralized callus, and cortical bone) and analyzed with BoneJ (an open-source bone-analysis plug-in technology) to determine the volume of tissue present in the three density ranges.
Five animals (two in the control group, one in the cigarette group, and two in the e-cigarette group) were removed from analysis due to either inadequate fracture fixation or nontransverse fracture. Cotinine levels in the animals from the cigarette group were nearly twice the level of those in the e-cigarette group.
The mRUST scores from contact radiographs correlated modestly but significantly with most measures from the microCT image analysis (r values ranged from 0.312 for cross-sectional area moment of inertia to 0.570 for medium-density tissue volume). After 3 weeks, there were significantly more animals in the control group (42.9 percent) who were classified via microCT as healed than in either the cigarette (0 percent) or e-cigarette group (0 percent).
At 6 weeks, there were no differences among the three groups in terms of healing assessment, but the e-cigarette group had significantly higher measures of low-density tissue, indicating persistent soft callus volumes, explained Mark L. Prasarn, MD, FAAOS, of Memorial Hermann–Texas Medical Center, presenting author of the study. This finding raises the possibility that e-cigarette use “may be even more detrimental to fracture healing than conventional cigarettes,” Dr. Prasarn said.
Addressing limitations of the study, Dr. Prasarn explained that although the investigators attempted to equalize the amount of time animals were exposed to cigarette smoke or e-cigarette vapors in the chamber, the finding of lower serum levels of cotinine in the e-cigarette group is likely attributable to the device they chose to investigate. “It is possible that other e-cigarettes dispense higher or lower amounts of nicotine than the one we used or that individuals using them draw more from them during each use or use them more frequently than regular smokers light up,” he said. “Additional studies are warranted to compare the effects of the two types of nicotine exposure on bone metabolism and healing. Studies in humans would also be beneficial.”
Noting that e-cigarette use is increasing, especially among young people, and that the detrimental effects associated with nicotine use (whether from smoke or e-cigarette vapor) on bone healing are established, Dr. Prasarn said, “Physicians should counsel patients to discontinue using e-cigarettes after fractures, as well as conventional cigarettes, to avoid issues with healing.”
Dr. Prasarn’s coauthors of “The Effects of E-cigarettes on Fracture Healing” are Ryan Tyler Anthony, MD; James F. Kellam, MD, FAAOS; and Glenn R. Rechtine II, MD, FAAOS.
Visit aaos.org/ameducation to view an ePoster of this study or any AAOS 2023 Annual Meeting poster.
Terry Stanton is the senior medical writer for AAOS Now. He can be reached at tstanton@aaos.org.
