Skip to main content

Mild morphometric vertebral fractures predict vertebral fractures but not non-vertebral fractures

Osteoporosis International volume 25, pages 235–241 (2014)Cite this article

Abstract

Summary

In this meta-analysis of the control arms of four phase 3 trials, mild vertebral fractures were a significant risk factor for future vertebral fractures but not for non-vertebral fracture.

Introduction

A prior vertebral fracture is a risk factor for future fracture that is commonly used as an eligibility criterion for treatment and in the assessment of fracture probability. The aim of this study was to determine the prognostic significance of a morphometric fracture according to the severity of fracture.

Methods

We examined the control (placebo) treated arms of four phase 3 trials. Vertebral fracture status was graded at baseline in 7,623 women, and fracture outcomes were documented over the subsequent 20,000 patient-years. Fracture outcomes were characterised as a further vertebral fracture, a non-vertebral fracture or a clinical fracture (non-vertebral plus clinical vertebral fracture). The relative risk of fracture was computed from the merged β coefficients of each trial weighted according to the variance.

Results

Mild vertebral fractures were a significant risk factor for vertebral fractures [risk ratio (RR) = 2.17; 95 % CI = 1.70–2.76] but were not associated with an increased risk of non-vertebral fractures (RR = 1.08; 95 % CI = 0.86–1.36). Moderate/severe vertebral fractures were associated with a high risk of vertebral fractures (RR = 4.23; 95 % CI = 3.58–5.00) and a moderate though significant increase in non-vertebral fracture risk (RR = 1.64; 95 % CI = 1.38–1.94).

Conclusions

Prior moderate/severe morphometric vertebral fractures are a strong and significant risk factor for future fracture. The presence of a mild vertebral fracture is of no significant prognostic value for non-vertebral fractures. These findings should temper the use of morphometric fractures in the assessment of risk and the design of phase 3 studies.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1

References

  1. Delmas PD, Marin F, Marcus R, Misurski DA, Mitlak BH (2007) Beyond hip: importance of other nonspinal fractures. Am J Med 120:381–7

    CAS  PubMed  Article  Google Scholar 

  2. Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. Br Med J 312:1254–9

    CAS  Article  Google Scholar 

  3. Dawson-Hughes B; National Osteoporosis Foundation Guide Committee (2008) A revised clinician's guide to the prevention and treatment of osteoporosis. J Clin Endocrinol Metab 93:2463–5

    Article  Google Scholar 

  4. Compston J, Cooper A, Cooper C, on behalf of the National Osteoporosis Guideline Group (NOGG) et al (2009) Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK. Maturitas 62:105–108

    CAS  PubMed  Article  Google Scholar 

  5. Papaioannou A, Morin S, Cheung AM et al (2010) 2010 Clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 182:1864–73

    PubMed Central  PubMed  Article  Google Scholar 

  6. Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster J-Y on behalf of the Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF) (2013) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 24:23–57

    Article  Google Scholar 

  7. McCloskey EV, Kanis JA (1996) The assessment of vertebral deformity. In: Genant H, Jergas M, van Kuijk C (eds) Vertebral fracture in osteoporosis. University of California, San Francisco, pp 215–233

    Google Scholar 

  8. Jiang G, Eastell R, Barrington NA, Ferrar L (2004) Comparison of methods for the visual identification of prevalent vertebral fracture in osteoporosis. Osteoporos Int 15:887–96

    CAS  PubMed  Article  Google Scholar 

  9. Black DM, Palermo L, Nevitt MC, Genant HK, Christensen L, Cummings SR (1999) Defining incident vertebral deformity: a prospective comparison of several approaches. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 14:90–101

    CAS  PubMed  Article  Google Scholar 

  10. Eastell R, Cedel SL, Wahner HW, Riggs BL, Melton LJ (1991) Classification of vertebral fractures. J Bone Miner Res 6:207–15

    CAS  PubMed  Article  Google Scholar 

  11. Genant HK, Jergas M, Palermo L et al (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. The study of Osteoporotic Fractures Research Group. J Bone Miner Res 11:984–96

    CAS  PubMed  Article  Google Scholar 

  12. Cooper C, Atkinson EJ, O'Fallon WM, Melton LJ 3rd (1992) Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985–1989. J Bone Miner Res 7:221–7

    CAS  PubMed  Article  Google Scholar 

  13. Ettinger B, Black DM, Nevitt MC et al (1992) Contribution of vertebral deformities to chronic back pain and disability. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 7:449–56

    CAS  PubMed  Article  Google Scholar 

  14. Johnell O, Gullberg B, Kanis JA (1997) The hospital burden of vertebral fracture in Europe: a study of national register sources. Osteoporos Int 7:138–44

    CAS  PubMed  Article  Google Scholar 

  15. Van Staa TP, Dennison EM, Leufkens HG, Cooper C (2001) Epidemiology of fractures in England and Wales. Bone 29:517–22

    PubMed  Article  Google Scholar 

  16. Kanis JA, Johnell O, Oden A et al (2004) The risk and burden of vertebral fractures in Sweden. Osteoporos Int 15:20–6

    CAS  PubMed  Article  Google Scholar 

  17. Lindsay R, Silverman SL, Cooper C et al (2001) Risk of new vertebral fracture in the year following a fracture. JAMA 285:320–3

    CAS  PubMed  Article  Google Scholar 

  18. Klotzbuecher CM, Ross PD, Landsman PB, Abbot TA, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15:721–39

    CAS  PubMed  Article  Google Scholar 

  19. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD et al (2004) (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459–68

    CAS  PubMed  Article  Google Scholar 

  20. Reginster J-Y, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C et al (2005) Strontium ranelate reduces the risk of nonvertebral fracture in postmenopausal women with osteoporosis: TROPOS study. J Clinl Endocrinol Metab 90:2816–22

    CAS  Article  Google Scholar 

  21. Silverman SL, Christiansen C, Genant HK, Vukicevic S, Zanchetta JR, de Villiers TJ et al (2008) Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo- and active controlled clinical trial. J Bone Miner Res 23:1923–34

    CAS  PubMed  Article  Google Scholar 

  22. Ettinger B, Black DM, Mitlak BH et al. (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282: 637–45. Erratum in: JAMA 1999; 282 :2124.

    Google Scholar 

  23. Kanis JA, Johansson H, Oden A, McCloskey EV (2009) Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX®. Bone 44:49–54

    Google Scholar 

  24. Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–48

    CAS  PubMed  Article  Google Scholar 

  25. Wu CY, Li J, Jergas M, Genant HK (1995) Comparison of semiquantitative and quantitative techniques for the assessment of prevalent and incident vertebral fractures. Osteoporos Int 5:354–70

    CAS  PubMed  Article  Google Scholar 

  26. Stone KL, Seeley DG, Lui LY et al (2003) BMD at multiple sites and risk of fracture of multiple types: Long-term results from the study of osteoporotic fractures. J Bone Miner Res 18:1947–54

    PubMed  Article  Google Scholar 

  27. Kanis JA, Oden A, Johnell O, Jonsson B, de Laet C, Dawson A (2001) The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporos Int 12:417–427

    CAS  PubMed  Article  Google Scholar 

  28. Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP (1998) Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int 8:468–486

    CAS  PubMed  Article  Google Scholar 

  29. Lu Y, Fuerst T, Hui S, Genant HK (2001) Standardization of bone mineral density at femoral neck, trochanter and Ward’s triangle. Osteoporos Int 12:438–444

    CAS  PubMed  Article  Google Scholar 

  30. Kanis JA, Jönsson B, Odén A, McCloskey EV (2011) A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX®. Osteoporos Int 22:2347–2355, Erratum Osteoporos Int 222357 2358

    CAS  PubMed  Article  Google Scholar 

  31. Kanis JA on behalf of the World Health Organization Scientific Group (2008) Assessment of osteoporosis at the primary health-care level. Technical Report. WHO Collaborating Centre, University of Sheffield, UK. Accessible at http://www.shef.ac.uk/FRAX. Accessed 1 May 2013

  32. Kanis JA, Johnell O, De Laet C et al (2004) A meta-analysis of previous fracture and subsequent fracture risk. Bone 35:375–82

    CAS  PubMed  Article  Google Scholar 

  33. Roux C, Fechtenbaum J, Kolta S, Briot K, Girard M (2007) Mild prevalent and incident vertebral fractures are risk factors for new fractures. Osteoporos Int 18:1617–24

    CAS  PubMed  Article  Google Scholar 

  34. Gunnes M, Mellstrom D, Johnell O (1998) How well can a previous fracture indicate a new fracture? A questionnaire study of 29,802 postmenopausal women. Acta Orthop Scand 69:508–512

    CAS  PubMed  Article  Google Scholar 

  35. Ross PD, Genant HK, Davis JW, Miller PD, Wasnich RD (1993) Predicting vertebral fracture incidence from prevalent fractures and bone density among non-black, osteoporotic women. Osteoporos Int 3:120–126

    CAS  PubMed  Article  Google Scholar 

  36. Davis JW, Grove JS, Wasnich RD, Ross PD (1999) Spatial relationships between prevalent and incident spine fractures. Bone 24:261–264

    CAS  PubMed  Article  Google Scholar 

  37. Wasnich RD, Davis JW, Ross PD (1994) Spine fracture risk is predicted by non-spine fractures. Osteoporos Int 4:1–5

    CAS  PubMed  Article  Google Scholar 

  38. Delmas PD, Genant HK, Crans GG et al (2003) Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 33:522–532

    CAS  PubMed  Article  Google Scholar 

  39. Siris ES, Genant HK, Laster AJ, Chen P, Misurski DA, Krege JH (2007) Enhanced prediction of fracture risk combining vertebral fracture status and BMD. Osteoporos Int 18:761–70

    CAS  PubMed  Article  Google Scholar 

  40. Black DM, Arden NK, Palermo L, Pearson J, Cummings SR (1999) Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. Study of Osteoporotic Fractures Research Group. J Bone Miner Res 14:821–828

    CAS  PubMed  Article  Google Scholar 

  41. Puisto V, Heliovaara M, Impivaara O et al (2010) Severity of vertebral fracture and risk of hip fracture: a nested case–control study. Osteoporos Int 22:63–68

    PubMed  Article  Google Scholar 

  42. Spector TD, McCloskey EV, Doyle DV, Kanis JA (1993) Prevalence of vertebral fracture in women and the relationship with bone density and symptoms: the Chingford Study. J Bone Miner Res 8:817–22

    CAS  PubMed  Article  Google Scholar 

  43. Pongchaiyakul C, Nguyen ND, Jones G, Center JR, Eisman JA, Nguyen TV (2005) Asymptomatic vertebral deformity as a major risk factor for subsequent fractures and mortality: a long-term prospective study. J Bone Miner Res 20:1349–55

    PubMed  Article  Google Scholar 

  44. Haentjens P, Johnell O, Kanis JA, Network on Male Osteoporosis in Europe (NEMO) et al (2004) Evidence from data searches and life-table analyses for gender-related differences in absolute risk of hip fracture after Colles' or spine fracture: Colles' fracture as an early and sensitive marker of skeletal fragility in white men. J Bone Miner Res 19:1933–44

    PubMed  Article  Google Scholar 

Download references

Acknowledgments

We are grateful to Dr Arkadi Chines (Pfizer now at Amgen), Patricia Belissa-Mathiot (Servier) and Bruce Mitlak and Russel Burge (Lilly) for their cooperation.

Conflicts of interest

Analyses of these data were made possible by support from Lilly, Pfizer and Servier. The companies had no part in the analysis of data or in writing this report though were circulated this report for comment before publication.

Author information

Affiliations

  1. WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK

    H. Johansson, A. Odén, E. V. McCloskey & J. A. Kanis

Authors
  1. H. Johansson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Odén
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. V. McCloskey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. A. Kanis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. A. Kanis.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Johansson, H., Odén, A., McCloskey, E.V. et al. Mild morphometric vertebral fractures predict vertebral fractures but not non-vertebral fractures. Osteoporos Int 25, 235–241 (2014). https://doi.org/10.1007/s00198-013-2460-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-013-2460-0

Keywords

  • Fracture risk
  • Meta-analysis
  • Vertebral morphometry