Effect of nicotine and tobacco administration method on the mechanical properties of healing bone following closed fracture.
We previously showed different effects of tobacco and nicotine on fracture healing, but due to pump reservoir limits, maximum exposure period was 4 weeks. To allow flexibility in pre- and post-fracture exposure periods, the objective of this study was to compare a new oral administration route for nicotine to the established pump method. Four groups were studied: (1) pump saline, (2) pump saline + oral tobacco, (3) pump saline/nicotine + oral tobacco, and (4) pump saline + oral nicotine/tobacco. Sprague-Dawley rats (n = 84) received a transverse femoral fracture stabilized with an intramedullary pin 1 week after initiating dosing. After 3 weeks, no difference was found in torsional strength or stiffness between oral nicotine/tobacco or pump nicotine + tobacco, while energy absorption with oral nicotine/tobacco was greater than pump nicotine + tobacco (p < 0.05). Compared to saline control, strength for oral nicotine/tobacco was higher than control (p < 0.05), and stiffnesses for pump nicotine + tobacco and oral nicotine/tobacco were higher than control (p < 0.05). No differences in energy were found for either nicotine-tobacco group compared to saline control. Mean serum cotinine (stable nicotine metabolite) was different between pump and oral nicotine at 1 and 4 weeks, but all groups were in the range of 1-2 pack/day smokers. In summary, relevant serum cotinine levels can be reached in rats with oral nicotine, and, in the presence of tobacco, nicotine can influence mechanical aspects of fracture healing, dependent on administration method. Caution should be exercised when comparing results of fracture healing studies using different methods of nicotine administration.
Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Aarhus University Hospital, Norrebrogade 44, Building 1A, 8000 Aarhus C, Denmark. d022340@dadlnet.dk
Sidsel Gaarn
SG
Hastrup
Xinqian
X
Chen
Joan E
JE
Bechtold
Richard F
RF
Kyle
Ole
O
Rahbek
Daniel E
DE
Keyler
Martin
M
Skoett
Kjeld
K
Soeballe
D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D017102:Fracture Healing / Q000187:drug effects*; D005596:Fractures, Closed / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007260:Infusion Pumps; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D054159:Torsion, Mechanical; D014867:Water
D018722:Nicotinic Agonists; D010936:Plant Extracts; D014867:Water; D009538:Nicotine