Unlabelled: In this meta-analysis of international cohorts, current smoking is confirmed as a significant BMD-independent predictor of future fracture with a stronger relationship in men than in women. A causative and reversible effect of smoking on fracture risk is suggested by past smoking having a significantly lower risk than current smoking.

Purpose: In this meta-analysis of international cohorts, the aim was to examine the relationship of current and past smoking with fracture risk to provide an update for future iterations of the FRAX tool.

Methods: The risk of fracture associated with current and past smoking was estimated using an extended Poisson model applied separately to each of 58 prospective international cohort studies. Covariates included current time since start of follow up, current age, and in an additional model, BMD at the femoral neck. The results of the different studies were merged by using inverse-variance weighted β-coefficients.

Results: This analysis included a total of 1,691,024 participants (61.2% women, overall mean age 58.8 years). Current smoking, documented in 12.1% of all participants (15.2% and 10.1% respectively in men and women), was associated with a significantly increased risk of any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and particularly hip fracture in both sexes. The hazard ratio (HR) for fracture was greater in men than in women for all fracture categories [e.g. hip fracture HR (95% confidence interval): 1.78 (1.58-2.00) vs. 1.64 (1.50-1.78)]. Low BMD explained about 19-54% of the increase in risk. When compared with never smoking, past smoking was associated with a significantly lower risk than current smoking [e.g. hip fractures for men, HR in past smokers: 1.08 (1.05-1.12) vs. 1.73, 95%CI (1.46-2.05) in current smokers].

Conclusions: Our results confirm the association between current smoking and increased fracture risk that is partly independent of BMD; these data will be used to inform future iterations of FRAX.