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Impact of Femoral Neck and Lumbar Spine BMD Discordances on FRAX Probabilities in Women: A Meta-analysis of International Cohorts

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Abstract

There are occasional marked discordances in BMD T-scores at the lumbar spine (LS) and femoral neck (FN). We investigated whether such discordances could contribute independently to fracture prediction using FRAX. We studied 21,158 women, average age 63 years, from 10 prospective cohorts with baseline FRAX variables as well as FN and LS BMD. Incident fractures were collected by self-report and/or radiographic reports. Extended Poisson regression examined the relationship between differences in LS and FN T-scores (ΔLS–FN) and fracture risk, adjusted for age, time since baseline and other factors including FRAX 10-year probability for major osteoporotic fracture calculated using FN BMD. To examine the effect of an adjustment for ΔLS–FN on reclassification, women were separated into risk categories by their FRAX major fracture probability. High risk was classified using two approaches: being above the National Osteoporosis Guideline Group intervention threshold or, separately, being in the highest third of each cohort. The absolute ΔLS–FN was greater than 2 SD for 2.5 % of women and between 1 and 2 SD for 21 %. ΔLS–FN was associated with a significant risk of fracture adjusted for baseline FRAX (HR per SD change = 1.09; 95 % CI = 1.04–1.15). In reclassification analyses, only 2.3–3.2 % of the women moved to a higher or lower risk category when using FRAX with ΔLS–FN compared with FN-derived FRAX alone. Adjustment of estimated fracture risk for a large LS/FN discrepancy (>2SD) impacts to a large extent on only a relatively small number of individuals. More moderate (1–2SD) discordances in FN and LS T-scores have a small impact on FRAX probabilities. This might still improve clinical decision-making, particularly in women with probabilities close to an intervention threshold.

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Acknowledgments

The Rochester study was supported by the National Institute of Musculoskeletal and Skin Diseases (R01 AR27065), U.S. Public Health Service. The AHS has been conducting at the Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan, which is a private, non-profit foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the U.S. Department of Energy (DOE), the latter in part through DOE Award DE-HS0000031 to the National Academy of Sciences. CaMos is currently funded by the Canadian Institutes for Health Research (CIHR), with additional support from Amgen, Merck Frosst Canada Ltd, and Eli Lilly and Company. The OSTPRE study was supported by the Academy of Finland. The Women’s Health Initiative programme is funded by the National Heart, Lung, and Blood Institute, the National Institutes of Health, and the US Department of Health and Human Services. Mr OS (Hong Kong) is also supported by National Institutes of Health funding. The Dubbo Osteoporosis Epidemiology study has been supported by the National Health and Medical Research Council of Australia and by untied educational grants from Amgen, GE-LUNAR, Lilly, Merck Sharp and Dohme, Novartis, Sanofi-Aventis and Servier.

Conflict of Interest

There are no conflicts of interest to declare.

Human and Animal Rights and Informed Consent

Participants in the cohorts included in this analysis provided informed consent at enrolment to the individual cohort studies.

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Authors and Affiliations

  1. Academic Unit of Bone Metabolism and Mellanby Centre for Bone Research, University of Sheffield, Metabolic Bone Centre, Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK

    E. McCloskey

  2. WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK

    H. Johansson & J. A. Kanis

  3. Consulting Statistician, Gothenburg, Sweden

    A. Odén

  4. Department of Medicine, University of Manitoba, Winnipeg, MB, Canada

    W. D. Leslie

  5. Health Management & Promotion Center, Hiroshima Atomic Bomb Casualty Council, Hiroshima, Japan

    S. Fujiwara

  6. Sektion Biomedizinische Bildgebung, Klinik für Diagnostische Radiologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany

    C. C. Glüer

  7. Department of Orthopaedics, Kuopio University Hospital, Kuopio, Finland

    H. Kroger

  8. BCRU, University of Eastern Finland, Joensuu, Finland

    H. Kroger

  9. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    A. Z. LaCroix

  10. Center for Clinical and Basic Research (CCBR), Hong Kong, Hong Kong

    E. Lau

  11. Division of Epidemiology College of Medicine, Mayo Clinic, Rochester, MN, USA

    L. J. Melton III

  12. Garvan Institute of Medical Research, St. Vincent’s Hospital, University of Notre Dame Australia, UNSW Australia, Sydney, NSW, Australia

    J. A. Eisman

  13. Arthritis Research UK Epidemiology Unit, School of Translational Medicine Musculoskeletal Research Group, University of Manchester, Manchester, UK

    T. W. O’Neill

  14. Department of Medicine, McGill University, Montreal, Canada

    D. Goltzman

  15. School of Medicine & Dentistry, Medical School, Foresterhill, Aberdeen, Scotland

    D. M. Reid

Authors
  1. H. Johansson
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  2. J. A. Kanis
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  3. A. Odén
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  4. W. D. Leslie
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  5. S. Fujiwara
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  6. C. C. Glüer
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  7. H. Kroger
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  9. E. Lau
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  10. L. J. Melton III
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  11. J. A. Eisman
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  12. T. W. O’Neill
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  14. D. M. Reid
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  15. E. McCloskey
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Correspondence to E. McCloskey.

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Johansson, H., Kanis, J.A., Odén, A. et al. Impact of Femoral Neck and Lumbar Spine BMD Discordances on FRAX Probabilities in Women: A Meta-analysis of International Cohorts. Calcif Tissue Int 95, 428–435 (2014). https://doi.org/10.1007/s00223-014-9911-2

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