Osteoporosis International

, Volume 17, Issue 11, pp 1673–1680 | Cite as

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

  • W. D. Leslie
  • A. Moayyeri
  • For the Manitoba Bone Density Program
Original Article



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.


Bone densitometry Dual-energy X-ray absorptiometry Osteoporosis Precision Sample size 



This article has been reviewed and approved by the members of the Manitoba Bone Density Program Committee. The author and Committee would like to express their gratitude to Manitoba Health, the Winnipeg Regional Health Authority, and the Brandon Regional Health Authority for their vision, trust, and support in the establishment of this program.


  1. 1.
    Arlot ME, Sornay-Rendu E, Garnero P, Vey-Marty B, Delmas PD (1997) Apparent pre- and postmenopausal bone loss evaluated by DXA at different skeletal sites in women: the OFELY cohort. J Bone Miner Res 12:683–690PubMedCrossRefGoogle Scholar
  2. 2.
    Pouilles JM, Tremollieres F, Ribot C (1993) The effects of menopause on longitudinal bone loss from the spine. Calcif Tissue Int 52:340–343PubMedCrossRefGoogle Scholar
  3. 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
  4. 4.
    Silverberg SJ, Gartenberg F, Jacobs TP, Shane E, Siris E, Staron RB, Bilezikian JP (1995) Longitudinal measurements of bone density and biochemical indices in untreated primary hyperparathyroidism. J Clin Endocrinol Metab 80:723–728PubMedCrossRefGoogle Scholar
  5. 5.
    Bland JM, Altman DG (1996) Measurement error. BMJ 312:1654PubMedGoogle Scholar
  6. 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
  7. 7.
    Lenchik L, Kiebzak GM, Blunt BA (2002) What is the role of serial bone mineral density measurements in patient management? J Clin Densitom 5(Suppl):S29–38:S29–S38PubMedCrossRefGoogle Scholar
  8. 8.
    Bonnick SL, Johnston CC Jr, Kleerekoper M, Lindsay R, Miller P, Sherwood L, Siris E (2001) Importance of precision in bone density measurements. J Clin Densitom 4:105–110PubMedCrossRefGoogle Scholar
  9. 9.
    Leslie WD, Metge C (2003) Establishing a regional bone density program: lessons from the Manitoba experience. J Clin Densitom 6:275–282PubMedCrossRefGoogle Scholar
  10. 10.
    Leslie WD, Caetano PA, Macwilliam LR, Finlayson GS (2005) Construction and validation of a population-based bone densitometry database. J Clin Densitom 8:25–30PubMedCrossRefGoogle Scholar
  11. 11.
    Faulkner KG, McClung MR (1995) Quality control of DXA instruments in multicenter trials. Osteoporos Int 5:218–227PubMedCrossRefGoogle Scholar
  12. 12.
    Orwoll ES, Oviatt SK, Biddle JA (1993) Precision of dual-energy x-ray absorptiometry: development of quality control rules and their application in longitudinal studies. J Bone Miner Res 8:693–699PubMedGoogle Scholar
  13. 13.
    Wahner HW, Looker A, Dunn WL, Walters LC, Hauser MF, Novak C (1994) Quality control of bone densitometry in a national health survey (NHANES III) using three mobile examination centers. J Bone Miner Res 9:951–960PubMedCrossRefGoogle Scholar
  14. 14.
    Gluer CC, Blake G, Lu Y, Blunt BA, Jergas M, Genant HK (1995) Accurate assessment of precision errors: how to measure the reproducibility of bone densitometry techniques. Osteoporos Int 5:262–270PubMedCrossRefGoogle Scholar
  15. 15.
    Altman DG (1991) Practical statistics for medical research. Chapman and Hall, LondonGoogle Scholar
  16. 16.
    Gordis L (2000) Epidemiology. W.B. Saunders, PhiladelphiaGoogle Scholar
  17. 17.
    Bolotin HH, Sievanen H, Grashuis JL (2003) Patient-specific DXA bone mineral density inaccuracies: quantitative effects of nonuniform extraosseous fat distributions. J Bone Miner Res 18:1020–1027PubMedCrossRefGoogle Scholar
  18. 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. 19.
    Leslie WD (2006) The importance of spectrum bias on bone density monitoring in clinical practice. Bone (in press)Google Scholar
  20. 20.
    Siminoski K, Leslie WD, Frame H, Hodsman A, Josse RG, Khan A, Lentle BC, Levesque J, Lyons DJ, Tarulli G, Brown JP (2005) Recommendations for bone mineral density reporting in Canada. Can Assoc Radiol J 56:178–188PubMedGoogle Scholar
  21. 21.
    Leslie WD, Ward LM (2004) Bone density monitoring with the total hip site: time for a re-evaluation? J Clin Densitom 7:269–274PubMedCrossRefGoogle Scholar
  22. 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
  23. 23.
    Haddaway MJ, Davie MW, McCall IW (1992) Bone mineral density in healthy normal women and reproducibility of measurements in spine and hip using dual-energy X-ray absorptiometry. Br J Radiol 65:213–217PubMedCrossRefGoogle Scholar
  24. 24.
    Reginster JY, Deroisy R, Zegels B, Jupsin I, Albert A, Franchimont P (1995) Long-term performance in vitro and in vivo of dual-energy X-ray absorptiometry. Clin Rheumatol 14:180–186PubMedCrossRefGoogle Scholar
  25. 25.
    Henzell S, Dhaliwal S, Pontifex R, Gill F, Price R, Retallack R, Prince R (2000) Precision error of fan-beam dual X-ray absorptiometry scans at the spine, hip, and forearm. J Clin Densitom 3:359–364PubMedCrossRefGoogle Scholar
  26. 26.
    Phillipov G, Seaborn CJ, Phillips PJ (2001) Reproducibility of DXA: potential impact on serial measurements and misclassification of osteoporosis. Osteoporos Int 12:49–54PubMedCrossRefGoogle Scholar
  27. 27.
    Ravaud P, Reny JL, Giraudeau B, Porcher R, Dougados M, Roux C (1999) Individual smallest detectable difference in bone mineral density measurements. J Bone Miner Res 14:1449–1456PubMedCrossRefGoogle Scholar
  28. 28.
    Faulkner KG (1998) Bone densitometry: choosing the porper skeletal site to measure. J Clin Densitom 1:279–285PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2006

Authors and Affiliations

  • W. D. Leslie
    • 1
  • A. Moayyeri
    • 2
  • For the Manitoba Bone Density Program
  1. 1.Department of MedicineUniversity of ManitobaWinnipegCanada
  2. 2.Endocrinology & Metabolism Research Center, Shariati HospitalTehran University of Medical SciencesTehranIran

Personalised recommendations