The effect of precision study sample size is not considered in current recommendations for assessing bone mineral density (BMD) change. Intuitively, a larger sample size should provide greater confidence in the derived least significant change (LSC), which should translate into a more confident determination of change. We evaluated an empirical Monte Carlo simulation method for estimating the significance of an observed change in BMD that simultaneously considers the magnitude of the change, the LSC point estimate, and the precision study sample size. This method showed a progressive increase in the ability to identify BMD change using larger precision study sample sizes. Approaches that consider the error in the LSC estimate may provide more robust determinations of BMD change even when the precision study sample size is limited.