Minimum sample size requirements for bone density precision assessment produce inconsistency in clinical monitoring
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/cm2) 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/cm2, 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.
KeywordsBone densitometry Dual-energy X-ray absorptiometry Osteoporosis Precision Sample size
- 3.Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere S, Thamsborg G, Liberman UA, Delmas PD, Malice MP, Czachur M, Daifotis AG (1998) Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med 339:292–299PubMedCrossRefGoogle Scholar
- 6.Miller PD, Bonnick SL, Rosen CJ, Altman RD, Avioli LV, Dequeker J, Felsenberg D, Genant HK, Gennari C, Harper KD, Hodsman AB, Kleerekoper M, Mautalen CA, McClung MR, Meunier PJ, Nelson DA, Peel NF, Raisz LG, Recker RR, Utian WH, Wasnich RD, Watts NB (1996) Clinical utility of bone mass measurements in adults: consensus of an international panel. The Society for Clinical Densitometry. Semin Arthritis Rheum 25:361–372PubMedCrossRefGoogle Scholar
- 15.Altman DG (1991) Practical statistics for medical research. Chapman and Hall, LondonGoogle Scholar
- 16.Gordis L (2000) Epidemiology. W.B. Saunders, PhiladelphiaGoogle Scholar
- 18.Crilly RG, Sebaldt RJ, Hodsman AB, Adachi JD, Brown JP, Goldsmith CH, Hanley DA, Olszynski WO, Ste-Marie LG, Stephenson GF (2000) Predicting subsequent bone density response to intermittent cyclical therapy with etidronate from initial density response in patients with osteoporosis. Osteoporos Int 11:607–614PubMedCrossRefGoogle Scholar
- 19.Leslie WD (2006) The importance of spectrum bias on bone density monitoring in clinical practice. Bone (in press)Google Scholar
- 22.Khan AA, Brown J, Faulkner K, Kendler D, Lentle B, Leslie W, Miller PD, Nicholson L, Olszynski WP, Watts NB (2002) Standards and guidelines for performing central dual X-ray densitometry from the Canadian panel of International Society for Clinical Densitometry. J Clin Densitom 5:435–445PubMedCrossRefGoogle Scholar