Mild morphometric vertebral fractures predict vertebral fractures but not non-vertebral fractures
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.
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.
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.
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).
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.
KeywordsFracture risk Meta-analysis Vertebral morphometry
- 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 24:23–57CrossRefGoogle 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 215–233Google 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 23:1923–34PubMedCrossRefGoogle 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 44:49–54Google 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 2358PubMedCrossRefGoogle 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
- 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 19:1933–44PubMedCrossRefGoogle Scholar