The Influence of Smoking on Bone Loss and Response to Nasal Estradiol

Objective: To investigate the influence of smoking on bone during therapy with nasally administrated estradiol in sequential combination with oral progesterone in early postmenopausal women. In addition, to observe the consequences of smoking on bone in untreated women.

Methods: Post-hoc exploratory analyses of data from 270 postmenopausal women randomized to 2 years' therapy with daily nasal administration of 17beta-estradiol or placebo sequentially combined with oral micronized progesterone in the active groups or placebo in the placebo group.

Results: During treatment with nasal estradiol, the bone mineral density (BMD) of the lumbar spine had increased less at 2 years in smokers as compared to non-smokers (2.6% vs. 3.9%, p = 0.03). Parallel changes were seen in the placebo group (-3.6% vs. -2.4%, p = 0.08). In the total hip BMD, there was no difference in the response to estradiol in smokers vs. non-smokers (1.4% vs. 1.4%, p = 0.89), whereas the change in the hip on the placebo was similar to that seen in the spine (-3.7% vs. -2.6%, p = 0.08). Supportive changes were seen in urinary CTX and in serum osteocalcin.

Conclusions: These results indicate that cigarette smoking may reduce the efficacy of nasal estradiol to increase bone mass in early postmenopausal women. In addition, smoking may increase spontaneous bone loss in untreated women.