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Perspectives on the non-invasive evaluation of femoral strength in the assessment of hip fracture risk

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Abstract

Summary

We reviewed the experimental and clinical evidence that hip bone strength estimated by BMD and/or finite element analysis (FEA) reflects the actual strength of the proximal femur and is associated with hip fracture risk and its changes upon treatment.

Introduction

The risk of hip fractures increases exponentially with age due to a progressive loss of bone mass, deterioration of bone structure, and increased incidence of falls. Areal bone mineral density (aBMD), measured by dual-energy X-ray absorptiometry (DXA), is the most used surrogate marker of bone strength. However, age-related declines in bone strength exceed those of aBMD, and the majority of fractures occur in those who are not identified as osteoporotic by BMD testing. With hip fracture incidence increasing worldwide, the development of accurate methods to estimate bone strength in vivo would be very useful to predict the risk of hip fracture and to monitor the effects of osteoporosis therapies.

Methods

We reviewed experimental and clinical evidence regarding the association between aBMD and/orCT-finite element analysis (FEA) estimated femoral strength and hip fracture risk as well as their changes with treatment.

Results

Femoral aBMD and bone strength estimates by CT-FEA explain a large proportion of femoral strength ex vivo and predict hip fracture risk in vivo. Changes in femoral aBMD are strongly associated with anti-fracture efficacy of osteoporosis treatments, though comparable data for FEA are currently not available.

Conclusions

Hip aBMD and estimated femoral strength are good predictors of fracture risk and could potentially be used as surrogate endpoints for fracture in clinical trials. Further improvements of FEA may be achieved by incorporating trabecular orientations, enhanced cortical modeling, effects of aging on bone tissue ductility, and multiple sideway fall loading conditions.

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Acknowledgments

We are grateful to the Committee of Scientific Advisors of the International Osteoporosis Foundation for their review and endorsement of this paper.

Preparation of this manuscript was supported by an unrestricted grant from AgNovos to the International Osteoporosis Foundation. The sponsor did not have any role in preparation, review, or approval of the manuscript.

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Authors and Affiliations

  1. Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, and Department of Orthopedic Surgery, Harvard Medical School, Boston, MA, USA

    M. L. Bouxsein

  2. ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland

    P. Zysset

  3. Section of Biomedical Imaging, Department of Radiology and Neuroradiology, University Medical Center of Schleswig-Holstein, Campus Kiel, Kiel, Germany

    C. C. Glüer

  4. Oregon Osteoporosis Center, Portland, OR, USA

    M. McClung

  5. Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC, Australia

    M. McClung

  6. Division of Bone Disease, Department of Internal Medicine Specialties, Faculty of Medicine, Geneva University Hospital, Geneva, Switzerland

    E. Biver & S. L. Ferrari

  7. International Osteoporosis Foundation (IOF), Nyon, Switzerland

    D.D. Pierroz

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  1. M. L. Bouxsein
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  4. M. McClung
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  7. S. L. Ferrari
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on behalf of the IOF Working Group on Hip Bone Strength as a Therapeutic Target

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Correspondence to S. L. Ferrari.

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Conflict of interest

MLB reports consulting fees from AgNovos Healthcare and Keros Therapeutics and research funding from Amgen and Radius and from the Foundation for NIH (FNIH) Bone Quality Project. CCG reports consulting fees from AgNovos Healthcare and Mindways Software, Inc. and research funding from AgNovos. SLF reports consulting and/or speaker honoraria from Amgen, UCB, Lilly, Labatec, Agnovos, Pfizer. MRM reports consulting fees from Amgen and Myovant and honorarium from Amgen. PhZ reports research funding from Mereo BioPharma and Nobel Biocare. EB and DP have nothing to declare.

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Bouxsein, M.L., Zysset, P., Glüer, C.C. et al. Perspectives on the non-invasive evaluation of femoral strength in the assessment of hip fracture risk. Osteoporos Int 31, 393–408 (2020). https://doi.org/10.1007/s00198-019-05195-0

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