Skip to main content
SpringerLink
Log in

Which is the preferred site for bone mineral density monitoring as an indicator of treatment-related anti-fracture effect in routine clinical practice? A registry-based cohort study

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Change in total hip bone mineral density (BMD) provides a robust indication of anti-fracture effect during treatment monitoring in routine clinical practice, whereas spine BMD change is not independently associated with fracture risk.

Purpose

The role of monitoring bone mineral density (BMD) as an indicator of an anti-fracture effect is controversial. Discordance between the spine and hip BMD is common and creates uncertainty in clinical practice.

Methods

Using a population-based BMD Registry for the Province of Manitoba, Canada, we compared change in the spine and hip BMD as an indicator of treatment-related fracture risk reduction. The study cohort included 6093 women age > 40 years initiating osteoporosis treatment with two consecutive dual-energy X-ray absorptiometry (DXA) scans (mean interval 4.7 years). We computed change in the spine, total hip, and femur neck BMD between the first and second DXA scans as categorical (categorized as stable, detectable decrease, or detectable increase) and continuous measures. We modeled time to first incident fracture, ascertained from health services data, using Cox regression adjusted for baseline fracture probability.

Results

During a mean follow-up of 12.1 years, 995 women developed incident major osteoporotic fractures (MOF) including 246 with hip fractures and 301 with clinical vertebral fractures. Women with a detectable decrease in total hip BMD compared with stable BMD experienced an increase in MOF (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.25–1.70) while those with a detectable increase in total hip BMD experienced a decrease in MOF (aHR 0.71, 95% CI 0.61–0.83), and these results were not attenuated when adjusted for change in spine BMD. Similar results were seen for hip and clinical vertebral fracture outcomes, when BMD change was assessed as a continuous measure, and when femur neck BMD monitoring was used instead of total hip BMD monitoring.

Conclusions

Treatment-related increases in total hip BMD are associated with lower MOF, hip, and clinical vertebral fracture risk compared with stable BMD, while BMD decreases are associated with higher fracture risk. In contrast, spine BMD change is not independently associated with fracture risk.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Compston JE, McClung MR, Leslie WD (2019) Osteoporosis. Lancet 393(10169):364–376

    Article  CAS  PubMed  Google Scholar 

  2. Cummings SR, Bates D, Black DM (2002) Clinical use of bone densitometry: scientific review. JAMA. 288(15):1889–1897

    Article  PubMed  Google Scholar 

  3. Force USPST (2011) Screening for osteoporosis: U.S. preventive services task force recommendation statement. Ann Intern Med 154(5):356–364

    Article  Google Scholar 

  4. Compston J, Cooper A, Cooper C, Gittoes N, Gregson C, Harvey N et al (2017) UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 12(1):43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R, National Osteoporosis Foundation (2014) Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 25(10):2359–2381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kanis JA, Harvey NC, Cooper C, Johansson H, Oden A, McCloskey EV et al (2016) A systematic review of intervention thresholds based on FRAX: a report prepared for the National Osteoporosis Guideline Group and the International Osteoporosis Foundation. Arch Osteoporos 11(1):25

    Article  PubMed  PubMed Central  Google Scholar 

  7. MacLean C, Newberry S, Maglione M, McMahon M, Ranganath V, Suttorp M, Mojica W, Timmer M, Alexander A, McNamara M, Desai SB, Zhou A, Chen S, Carter J, Tringale C, Valentine D, Johnsen B, Grossman J (2008) Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med 148(3):197–213

    Article  PubMed  Google Scholar 

  8. Murad MH, Drake MT, Mullan RJ, Mauck KF, Stuart LM, Lane MA, Abu Elnour NO, Erwin PJ, Hazem A, Puhan MA, Li T, Montori VM (2012) Clinical review. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. J Clin Endocrinol Metab 97(6):1871–1880

    Article  CAS  PubMed  Google Scholar 

  9. Saito T, Sterbenz JM, Malay S, Zhong L, MacEachern MP, Chung KC (2017) Effectiveness of anti-osteoporotic drugs to prevent secondary fragility fractures: systematic review and meta-analysis. Osteoporos Int 28(12):3289–3300

    Article  CAS  PubMed  Google Scholar 

  10. Papaioannou A, Morin S, Cheung AM, Atkinson S, Brown JP, Feldman S, Hanley DA, Hodsman A, Jamal SA, Kaiser SM, Kvern B, Siminoski K, Leslie WD, for the Scientific Advisory Council of Osteoporosis Canada (2010) 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ. 182(17):1864–1873

    Article  PubMed  PubMed Central  Google Scholar 

  11. Compston J (2009) Monitoring osteoporosis treatment. Best Pract Res Clin Rheumatol 23(6):781–788

    Article  PubMed  Google Scholar 

  12. Bruyere O, Reginster JY (2014) Monitoring of osteoporosis therapy. Best Pract Res Clin Endocrinol Metab 28(6):835–841

    Article  PubMed  Google Scholar 

  13. Bell KJ, Hayen A, Macaskill P, Irwig L, Craig JC, Ensrud K et al (2009) Value of routine monitoring of bone mineral density after starting bisphosphonate treatment: secondary analysis of trial data. BMJ. 338:b2266

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hochberg MC, Greenspan S, Wasnich RD, Miller P, Thompson DE, Ross PD (2002) Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab 87(4):1586–1592

    Article  CAS  PubMed  Google Scholar 

  15. Wasnich RD, Miller PD (2000) Antifracture efficacy of antiresorptive agents are related to changes in bone density. J Clin Endocrinol Metab 85(1):231–236

    Article  CAS  PubMed  Google Scholar 

  16. Bouxsein ML, Eastell R, Lui LY, Wu LA, de Papp AE, Grauer A, Marin F, Cauley JA, Bauer DC, Black DM, for the FNIH Bone Quality Project (2019) Change in bone density and reduction in fracture risk: a meta-regression of published trials. J Bone Miner Res. https://doi.org/10.1002/jbmr.3641

  17. Leslie WD, Majumdar SR, Morin SN, Lix LM (2016) Change in bone mineral density is an indicator of treatment-related antifracture effect in routine clinical practice: a registry-based cohort study. Ann Intern Med 165(7):465–472

    Article  PubMed  Google Scholar 

  18. Shepherd JA, Lu Y, Wilson K, Fuerst T, Genant H, Hangartner TN, Wilson C, Hans D, Leib ES (2006) Cross-calibration and minimum precision standards for dual-energy X-ray absorptiometry: the 2005 ISCD Official Positions. J Clin Densitom 9(1):31–36

    Article  PubMed  Google Scholar 

  19. Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA (2011) Spine-hip discordance and fracture risk assessment: a physician-friendly FRAX enhancement. Osteoporos Int 22(3):839–847

    Article  CAS  PubMed  Google Scholar 

  20. Johansson H, Kanis JA, Oden A, Leslie WD, Fujiwara S, Gluer CC et al (2014) Impact of femoral neck and lumbar spine BMD discordances on FRAX probabilities in women: a meta-analysis of international cohorts. Calcif Tissue Int 95(5):428–435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Abrahamsen B, Stilgren LS, Hermann AP, Tofteng CL, Barenholdt O, Vestergaard P et al (2001) Discordance between changes in bone mineral density measured at different skeletal sites in perimenopausal women--implications for assessment of bone loss and response to therapy: the Danish osteoporosis prevention study. J Bone Miner Res 16(7):1212–1219

    Article  CAS  PubMed  Google Scholar 

  22. Kozyrskyj AL, Mustard CA (1998) Validation of an electronic, population-based prescription database. Ann Pharmacother 32(11):1152–1157

    Article  CAS  PubMed  Google Scholar 

  23. Leslie WD, Metge C (2003) Establishing a regional bone density program: lessons from the Manitoba experience. J Clin Densitom 6(3):275–282

    Article  PubMed  Google Scholar 

  24. Leslie WD, Caetano PA, Macwilliam LR, Finlayson GS (2005) Construction and validation of a population-based bone densitometry database. J Clin Densitom 8(1):25–30

    Article  PubMed  Google Scholar 

  25. Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Johnston Jr CC, Lindsay R (1998) Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int 8(5):468–489

    Article  CAS  PubMed  Google Scholar 

  26. 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(4):262–270

    Article  CAS  PubMed  Google Scholar 

  27. Gluer CC (1999) Monitoring skeletal changes by radiological techniques. J Bone Miner Res 14(11):1952–1962

    Article  CAS  PubMed  Google Scholar 

  28. Leslie WD (2008) Factors affecting short-term bone density precision assessment and the effect on patient monitoring. J Bone Miner Res 23(2):199–204

    Article  PubMed  Google Scholar 

  29. Kanis JA, Oden A, Johansson H, Borgstrom F, Strom O, McCloskey E (2009) FRAX and its applications to clinical practice. Bone. 44(5):734–743

    Article  PubMed  Google Scholar 

  30. Leslie WD, Lix LM, Langsetmo L, Berger C, Goltzman D, Hanley DA, Adachi JD, Johansson H, Oden A, McCloskey E, Kanis JA (2011) Construction of a FRAX(R) model for the assessment of fracture probability in Canada and implications for treatment. Osteoporos Int 22(3):817–827

    Article  CAS  PubMed  Google Scholar 

  31. Bisson EJ, Finlayson ML, Ekuma O, Marrie RA, Leslie WD (2019) Accuracy of FRAX(R) in people with multiple sclerosis. J Bone Miner Res. https://doi.org/10.1002/jbmr.3682

  32. Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA et al (2010) Independent clinical validation of a Canadian FRAX tool: fracture prediction and model calibration. J Bone Miner Res 25(11):2350–2358

    Article  PubMed  Google Scholar 

  33. Fraser LA, Langsetmo L, Berger C, Ioannidis G, Goltzman D, Adachi JD et al (2011) Fracture prediction and calibration of a Canadian FRAX(R) tool: a population-based report from CaMos. Osteoporos Int 22(3):829–837

    Article  PubMed  Google Scholar 

  34. Lix LM, Azimaee M, Osman BA, Caetano P, Morin S, Metge C, Goltzman D, Kreiger N, Prior J, Leslie WD (2012) Osteoporosis-related fracture case definitions for population-based administrative data. BMC Public Health 12:301

    Article  PubMed  PubMed Central  Google Scholar 

  35. Epp R, Alhrbi M, Ward L, Leslie WD (2018) Radiological validation of fracture definitions from administrative data. J Bone Miner Res 33(Supp 1):S275

    Google Scholar 

  36. Tsang JF, Leslie WD (2007) Exclusion of focal vertebral artifacts from spine bone densitometry and fracture prediction: a comparison of expert physicians, three computer algorithms, and the minimum vertebra. J Bone Miner Res 22(6):789–798

    Article  PubMed  Google Scholar 

  37. Jones G, Nguyen T, Sambrook PN, Kelly PJ, Eisman JA (1995) A longitudinal study of the effect of spinal degenerative disease on bone density in the elderly. J Rheumatol 22(5):932–936

    CAS  PubMed  Google Scholar 

  38. Gourlay ML, Fine JP, Preisser JS, May RC, Li C, Lui LY, Ransohoff DF, Cauley JA, Ensrud KE (2012) Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med 366(3):225–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the Manitoba Centre for Health Policy (MCHP) for use of data contained in the Population Health Research Data Repository (HIPC Project Number 2016/2017-29). The results and conclusions are those of the authors, and no official endorsement by the MCHP, Manitoba Health, or other data providers is intended or should be inferred. This article has been reviewed and approved by the members of the Manitoba Bone Density Program Committee.

Grant support

Dr. Lix is supported by a Tier 1 Canada Research Chair.

Author information

Authors and Affiliations

  1. Department of Medicine (C5121), University of Manitoba, 409 Tache Avenue, Winnipeg, Manitoba, R2H 2A6, Canada

    W. D. Leslie, P. Martineau, M. Bryanton & L. M. Lix

  2. Harvard University, Boston, USA

    P. Martineau

Authors
  1. W. D. Leslie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Martineau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Bryanton
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. M. Lix
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to W. D. Leslie.

Ethics declarations

The study was approved by the Health Research Ethics Board for the University of Manitoba.

Conflict of interest

None.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOC 209 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leslie, W.D., Martineau, P., Bryanton, M. et al. Which is the preferred site for bone mineral density monitoring as an indicator of treatment-related anti-fracture effect in routine clinical practice? A registry-based cohort study. Osteoporos Int 30, 1445–1453 (2019). https://doi.org/10.1007/s00198-019-04975-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-019-04975-y

Keywords

Search

Navigation