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A Simulation Model at Trabecular Level to Predict Effects of Antiresorptive Treatment after Menopause

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Abstract

Antiresorptive drugs are widely used to prevent osteoporotic fractures in men and women. Large clinical trials have shown vertebral fracture risk reductions up to 50%, resulting from relatively small increases of 3–8% in bone mineral density (BMD). We developed a computer model that mimics bone turnover in human vertebral cancellous bone during menopause and antiresorptive treatment. This model links cell activity in trabeculae to changes in bone volume and mechanical properties. We asked whether treatment started shortly after menopause is better than treatment started late after menopause. In order to answer this question we used the model to simulate menopause and 5 years of anti-resorptive treatment with two different agents: one incorporated in the tissue, one not incorporated. We found that late treatment can result in almost the same bone mass as early treatment, but early treatment is much better in conserving the strength and stiffness of the cancellous bone. The effect of the incorporation of drugs in the tissue (giving the drugs a long half-life) was small. After discontinuation of treatment, bone was lost slower, but after 20 years the difference between the incorporated and the not incorporated drug in stiffness and bone volume was below 3%. This kind of simulation model may be used to preclinically test new pharmaceuticals and treatment protocols and to predict long-term effects of treatment before patient data become available.

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Acknowledgements

J.C. van der Linden was supported by the Dutch Foundation for Research (NWO/MW), the National Computing Facilities Foundation (NCF) provided computing time. The authors thank Prof. Ruegsegger for providing the CT-scan data from the European Union project “Assessment of bone quality in osteoporosis.”

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Authors and Affiliations

  1. Erasmus MC, Department of Orthopaedics, Ee1614, P.O.Box 1738, 3000 DR Rotterdam, The Netherlands

    J. C. van der Linden

  2. Erasmus MC, Department of Orthopaedics, H 974, P.O.Box 2040, 3000 CA Rotterdam, The Netherlands

    J. A. N. Verhaar

  3. Erasmus MC, Department of Internal Medicine, D433, P.O.Box 2040, 3000 CA Rotterdam, The Netherlands

    H. A. P. Pols

  4. Erasmus MC, Department of Orthopaedics, Ee1614, P.O.Box 1738, 3000 DR Rotterdam, The Netherlands

    H. Weinans

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  1. J. C. van der Linden
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van der Linden, J., Verhaar, J., Pols, H. et al. A Simulation Model at Trabecular Level to Predict Effects of Antiresorptive Treatment after Menopause . Calcif Tissue Int 73, 537–544 (2003). https://doi.org/10.1007/s00223-002-2151-x

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