Smoking is thought to be a risk factor for osteoporosis development; however, the consequences of stopping smoking for bone homeostasis remain unknown. Here we conducted two separate human studies and show that bone mineral density was significantly lower in smokers than in non-smokers. The first was an observational study of pre- and post-menopausal healthy female smokers and non-smokers; the second included 139 current smokers determined to stop smoking. In the second study, levels of bone formation markers such as osteocalcin and uncarboxylated osteocalcin significantly increased after successful smoking cessation, as verified by significantly reduced levels of serum cotinine, a nicotine metabolite. Moreover, nicotine administration to mice reduced bone mineral density and significantly increased the number of osteoclasts in bone. Reduced bone mass phenotypes seen in nicotine-treated mice were significantly increased following nicotine withdrawal, an outcome accompanied by significantly reduced serum levels of tartrate-resistant acid phosphatase, a bone resorption marker. Taken together, our findings suggest that bone homeostasis is perturbed but can be rescued by smoking cessation.
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