[ NEWS - SPINE ]
Can a Drug Reduce a Smoker ’ s Risk of Pseudoarthrosis ?
Could using the drug varenicline cut the risk of pseudarthrosis for those patients who smoke ?
New work , a mouse model , from Rothman Institute and Thomas Jefferson University delivered promising data . The study , “ Varenicline mitigates the increased risk of pseudarthrosis associated with nicotine ,” was published in the September 2023 edition of The Spine Journal .
Lead author Brian Karamian , M . D . told OTW , “ One of the most significant concerns for smokers undergoing spinal fusion is the increased risk of pseudarthrosis . In clinic , we do everything we can to help patients quit smoking . Despite counseling , long-term abstinence remains difficult for patients increasing the risk profile for patients requiring non-elective spine surgery who are unable to abstain from nicotine .”
“ One of the most successful pharmaceutical adjuncts for smoking cessation is varenicline , a partial agonist that outcompetes nicotine at the α4β2 nicotinic acetylcholine receptor within the central nervous system . The α4β2 receptor is the primary receptor targeted by nicotine inhaled from smoke . With a greater binding affinity than nicotine , varenicline decreases dopaminergic tone in the mesolimbic pathway , reducing habit reinforcing symptoms helping patients abstain from smoking .”
Using a rodent model ( n = 60 ), the researchers set up four groups : control , nicotine , varenicline , and nicotine combined with varenicline . out-competing nicotine and limiting the downstream activation of nicotinic pathways known to decrease trabecular bone volume , thickness , formation , and mineralizing rate .”
“ This is the first validation of a non-instrumented nicotine-nonunion model using the rodent lumbar spine , providing a novel addition to the basic science approach to studying the clinically important topic of nicotine and pseudarthrosis after spine surgery .”
“ Additionally , this is the first investigation to evaluate pharmaceutical smoking cessations agents and their role in fusion biology , both alone and in the presence of nicotine .”
“ There is a dearth of literature investigating the role of these drugs in musculoskeletal tissue , despite evidence that the target receptors for these drugs are also responsible in regulating bone metabolism . We used a novel approach to established research methodology to quantify changes in fusion morphology . Histomorphometry via fluorochrome labeling has previously been used to study bone mineralization in many different settings . However , to our knowledge , this is the first application of fluorochrome labeling in the setting of bone fusion .”
When OTW asked for details about the research methodology , Dr . Karamian said , “ We delivered pharmaceuticals through subcutaneous osmotic pumps to achieve more consistent delivery and maintain target serum concentrations .”
“ Targeted concentrations were selected based on the serum concentrations of a heavy smoker and recom-
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They found that the fusion rate in the control ( 93.3 %) and combined ( 93.3 %) groups were significantly greater than that of the nicotine group ( 33.3 %). They documented greater bone volume fraction and bone mineral density in the control and combined groups compared to the nicotine group ; there was also a greater mineral apposition rate in the combined group compared to the nicotine group .
“ The role of the central nervous system as a regulator of bone mass has recently come to light with the discovery that all components of the cholinergic system are present in mammalian non-neuronal cells ,” stated Dr . Karamian , to OTW .
“ This means all necessary enzymes , transporters , and receptors for acetylcholine synthesis and recycling are in mesenchymal cells . As a partial agonist of the same receptors activated during smoking , it begs the question if varenicline is able to mitigate the harmful effects of nicotine on bone metabolism by
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