Sample size requirements for bone density precision assessments and effect on patient categorization: A Monte Carlo simulation study

A sample size of 30 degrees of freedom (df) for bone mineral density (BMD) precision studies may be insufficient for reliably categorizing change. Monte Carlo simulation was used to evaluate the effect of precision study sample size on identifying change in clinical patients. Least significant change (LSC) from 198 spine and 193 total hip scan-pairs was used to categorize change for 1420 patients undergoing BMD monitoring. Relative to this reference change fraction (RCF), LSC limits were identified that gave specified deviations from the RCF (− 25% to + 25%). Confidence limits (95% and 80%) for these LSC values (5 to 500 df) were estimated using ‘bootstrap’ samplings. A sample size providing 140 df is needed to avoid overdetecting spine change by 5% and 150 df to avoid underdetecting spine change by 5% with 95% confidence limits. A sample size of 30 df resulted in up to a 12.5% overdetection and 10.0% underdetection of spine or hip change based upon 95% confidence limits. In conclusion, assessing the effect of precision study sample size on classifying change in monitored patients is an important element of the precision assessment that is neglected in current recommendations. Sample sizes larger than 30 df are required if low levels of categorization error are to be achieved.