Minimum sample size requirements for bone density precision assessment produce inconsistency in clinical monitoring

Abstract

Detection of change during bone mineral density (BMD) monitoring is affected by test precision. The International Society of Clinical Densitometry (ISCD) recommends that each center determine precision error using repeat measurements in 30 subjects (or an equivalent method providing 30 degrees of freedom). We hypothesized that this sample size may be too small for a robust precision estimate, which could affect the performance of BMD monitoring in clinical practice. Replicate measurements of the spine and total hip (198 spine and 193 hip scan pairs) were obtained (interval 6+/-5 days). The sample was randomly divided into six groups of 30 patients each. Root mean square standard deviation (RMS-SD in g/cm(2)) and coefficient of variation (RMS-CV in %) precision errors and corresponding 95% least significant change (LSC) were calculated for each group and the pooled sample. LSC cutoffs were applied to 1,420 individuals from the Manitoba Bone Density Program who had follow-up measurements on the same instrument (interval 21+/-9 months). While the pooled spine RMS-SD was 0.017 and pooled hip RMS-SD was 0.009 g/cm(2), sample sizes of 30 gave a range of RMS-SD point estimates from 0.012 to 0.021 for the spine and from 0.008 to 0.012 for the hip. When the respective LSC cutoffs were applied to the 1,420 follow-up scan pairs, the fraction of patients categorized with significant change in the spine varied from 20.7% to 46.0%; four of the six LSCs based upon 30 subjects gave fractions significantly different from the pooled LSC of 30.7%. Significant change fractions for the hip varied from 31.1% to 51.1%; two of the six LSCs based upon 30 subjects gave fractions significantly different from the pooled LSC of 40.1%. Similar results were obtained using relative precision errors. BMD precision studies using a sample size of 30 are insufficient to reliably characterize precision error or change during clinical monitoring.