Differential effects of nicotine and smoke condensate on bone cell metabolic activity.
OBJECTIVE
Delayed or impaired healing of skeletal trauma in patients who smoke has been attributed to vascular responses of nicotine absorption and/or a direct effect of nicotine or other smoke components on bone cells. In vivo studies indicate variability in osteosynthetic response to nicotine versus smoke inhalation. We tested the hypothesis that components of cigarette smoke other than nicotine may be responsible for the adverse skeletal effects of smoking.


METHODS
In vitro cultures of MC3T3-E1 osteoblastlike cells were exposed to varying doses of nicotine or condensates of cigarette smoke. Metabolic assays included alkaline phosphatase activity, collagen synthesis, and total protein synthesis as well as cell proliferation.


RESULTS
Variations in the degree of response were noted between bone cell preparations. Nicotine elicited a significant dose-dependent stimulation of bone cell metabolism in all studies. This was detected as increases in alkaline phosphatase activity and increases in total protein and collagen synthesis. Responses were noted with nicotine doses as low as 12.5 ng/mL (half the nicotine level circulating in smokers). In one study, maximum stimulation occurred at 250 ng/mL with levels reaching 74% (total protein) and 104% (collagen) greater than control cultures. In a second study, 222% and 627% stimulation of protein and collagen synthesis over controls was noted using 100 ng/mL. Addition of the nicotine receptor antagonist mecamylamine reduced the nicotine stimulation. Preparations of smoke condensate with equivalent nicotine concentrations reduced all indices of metabolic activity. Cell proliferation was stimulated by both nicotine (20-25%) and smoke condensate (38-46%).


CONCLUSIONS
The data suggest that nicotine acts as a direct stimulant of bone cell metabolic activity. Smoke condensate containing equivalent levels of nicotine elicits an inhibitory effect. A probable speculation is that the delay in clinical healing of skeletal trauma in smoking patients may in part be a result of absorption of components of smoke other than nicotine.
Gullihorn
Leslie
L
Division of Orthopaedic Surgery, Maricopa Medical Center, Phoenix, AZ, USA.
Karpman
Robert
R
Lippiello
Louis
L
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D017102:Fracture Healing / Q000187:drug effects; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects*
D012906:Smoke; D009538:Nicotine