BoneKEy Reports | BoneKEy Watch
The link between smoking, osteoporosis and fracture risk
DOI:10.1038/bonekey.2013.219
Smoking is a known risk factor for osteoporosis-related fractures, but which toxins in smoke are responsible and how they impact on bone remodeling is not well understood. This study investigated two likely candidates; benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Both bind the aryl hydrocarbon receptor (Ahr), activating cytochrome P450 1a/1b (Cyp1), which stimulates bone resorption by osteoclasts. When used at low doses BaP and TCDD were able to stimulate osteoclast formation in vitro and in vivo, an effect that was due to interaction with Ahr.
Cyp1 inhibitors reduced osteoclastogenesis in cells treated with RANKL, TCDD or BaP. Furthermore, cells lacking Cyp1a1/1a2 or Cyp1a1/1a2/1b1 treated with TCDD showed lower levels of osteoclast differentiation than cells in which the genes encoding these proteins were functional, demonstrating that the Cyp enzymes are downstream of Ahr.
In vivo studies using knockout mice unable to express any of the Cyp enzyme genes showed that the resulting mice had a high bone mass due to lower levels of bone resorption. The authors propose that this mechanism goes some way to explaining why chronic smokers have a high risk of osteoporosis and bone fracture, and suggest that blocking Ahr could be a potential therapeutic avenue worth exploring.
Editor’s comment: Smoking is a modest risk factor for fractures, and it is used as an independent risk factor in the fracture risk assessment tool FRAX. This association is now further supported by the demonstration of the pathophysiological mechanism linking smoke toxins to bone resorption.
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