Your browser does not support JavaScript!
http://iet.metastore.ingenta.com
1887

access icon free Evaluating treatment of osteoporosis using particle swarm on a bone remodelling mathematical model

Bone loss in osteoporosis, commonly observed in postmenopausal women and the elderly, is caused by an imbalance in activities of bone-forming osteoblasts and bone-resorbing osteoclasts. To treat osteoporosis and increase bone mineral density (BMD), physical activities and drugs are often recommended. Complex systems dynamics prevent an intuitive prediction of treatment strategies, and little is known about an optimal sequence for the combinatorial use of available treatments. In this study, the authors built a mathematical model of bone remodelling and developed a treatment strategy for mechanical loading and salubrinal, a synthetic chemical agent that enhances bone formation and prevents bone resorption. The model formulated a temporal BMD change of a mouse's whole skeleton in response to ovariectomy, mechanical loading and administration of salubrinal. Particle swarm optimisation was employed to maximise a performance index (a function of BMD and treatment cost) to find an ideal sequence of treatment. The best treatment was found to start with mechanical loading followed by salubrinal. As treatment costs increased, the sequence started with no treatment and usage of salubrinal became scarce. The treatment strategy will depend on individual needs and costs, and the proposed model is expected to contribute to the development of personalised treatment strategies.

References

    1. 1)
      • 27. Erlebacher, A., Filvaroff, E.H., Ye, J.-Q., Derynck, R.: ‘Osteoblastic responses to TGF-beta during bone remodeling’, Mol. Biol. Cell, 1998, 9, (7), pp. 19031918 (doi: 10.1091/mbc.9.7.1903).
    2. 2)
      • 13. Lemaire, V., Tobin, F.L., Greller, L.D., Cho, C.R., Suva, L.J.: ‘Modeling the interactions between osteoblast and osteoclast activities in bone remodeling’, J. Theor. Biol., 2004, 229, (3), pp. 293309 (doi: 10.1016/j.jtbi.2004.03.023).
    3. 3)
      • 4. Simkin, A., Ayalon, J., Leichter, I.: ‘Increased trabecular bone density due to bone-loading exercises in postmenopausal osteoporotic women’, Calcif. Tissue Int., 1987, 40, (2), pp. 5963 (doi: 10.1007/BF02555706).
    4. 4)
      • 17. Pivonka, P., Zimak, J., Smith, D.W., et al: ‘Model structure and control of bone remodeling: a theoretical study’, Bone, 2008, 43, (2), pp. 249263 (doi: 10.1016/j.bone.2008.03.025).
    5. 5)
      • 7. Zanchetta, J., Bogado, C., Ferretti, J., et al: ‘Effects of teriparatide [recombinant human parathyroid hormone (1-34)] on cortical bone in postmenopausal women with osteoporosis’, J. Bone Miner. Res., 2003, 18, (3), pp. 539543 (doi: 10.1359/jbmr.2003.18.3.539).
    6. 6)
      • 25. Hamamura, K., Yokota, H.: ‘Stress to endoplasmic reticulum of mouse osteoblasts induces apoptosis and transcriptional activation for bone remodeling’, FEBS Lett., 2007, 581, (9), pp. 17691774 (doi: 10.1016/j.febslet.2007.03.063).
    7. 7)
      • 24. Takayanagi, H., Kim, S., Koga, T., et al: ‘Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts’, Dev. Cell, 2002, 3, (6), pp. 889901 (doi: 10.1016/S1534-5807(02)00369-6).
    8. 8)
      • 20. Traina, T.A., Dugan, U., Higgins, B., et al: ‘Optimizing chemotherapy dose and schedule by Norton-Simon mathematical modeling’, Breast Dis., 2010, 31, (1), pp. 718.
    9. 9)
      • 10. Hamamura, K., Tanjung, N., Yokota, H.: ‘Suppression of osteoclastogenesis through phosphorylation of eukaryotic translation initiation factor 2 alpha’, J. Bone Miner. Metab., 2013, pp. 111.
    10. 10)
      • 14. Chen, A., Hamamura, K., Zhang, P., Chen, Y., Yokota, H.: ‘Systems analysis of bone remodelling as a homeostatic regulator’, IET Syst. Biol., 2010, 4, (1), pp. 5263 (doi: 10.1049/iet-syb.2008.0151).
    11. 11)
      • 30. Koizumi, M., Tanjung, N.G., Chen, A., et al: ‘Administration of salubrinal enhances radiation-induced cell death of SW1353 chondrosarcoma cells’, Anticancer Res., 2012, 32, (9), pp. 36673673.
    12. 12)
      • 15. Kennedy, J., Eberhart, R.C.: ‘A discrete binary version of the particle swarm algorithm’. Proc. IEEE Int. Conf. Systems, Man and Cybernetics, 1997, 5, pp. 41044108.
    13. 13)
      • 8. Edwards, M., Bain, S., Bailey, M., Lantry, M., Howard, G.: ‘17-Beta estradiol stimulation of endosteal bone formation in the ovariectomized mouse: an animal model for the evaluation of bone-targeted estrogens’, Bone, 1992, 13, (1), pp. 2934 (doi: 10.1016/8756-3282(92)90358-4).
    14. 14)
      • 26. Yang, X., Matsuda, K., Bialek, P., et al: ‘ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology: implication for Coffin-Lowry syndrome’, Cell, 2004, 117, (3), pp. 387398 (doi: 10.1016/S0092-8674(04)00344-7).
    15. 15)
      • 12. Komarova, S.V., Smith, R.J., Dixon, S.J., Sims, S.M., Wahl, L.M.: ‘Mathematical model predicts a critical role for osteoclast autocrine regulation in the control of bone remodeling’, Bone, 2003, 33, (2), pp. 206215 (doi: 10.1016/S8756-3282(03)00157-1).
    16. 16)
      • 9. Boyce, M., Bryant, K.F., Jousse, C., et al: ‘A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress’, Science, 2005, 307, (5711), pp. 935939 (doi: 10.1126/science.1101902).
    17. 17)
      • 11. He, L., Lee, J., Jang, J.H., et al: ‘Osteoporosis regulation by salubrinal through eIF2α mediated differentiation of osteoclast and osteoblast’, Cell. Signal., 2013, 25, (2), pp. 552560 (doi: 10.1016/j.cellsig.2012.11.015).
    18. 18)
      • 16. Warden, S.J., Fuchs, R.K., Castillo, A.B., Nelson, I.R., Turner, C.H.: ‘Exercise when young provides lifelong benefits to bone structure and strength’, J. Bone Miner. Res., 2007, 22, (2), pp. 251259 (doi: 10.1359/jbmr.061107).
    19. 19)
      • 1. Robling, A.G., Turner, C.H.: ‘Mechanical signaling for bone modeling and remodeling’, Crit. Rev. Eukaryot. Gene. Expr., 2009, 19, (4), pp. 319338 (doi: 10.1615/CritRevEukarGeneExpr.v19.i4.50).
    20. 20)
      • 28. Zhang, P., Tanaka, S.M., Jiang, H., Su, M., Yokota, H.: ‘Diaphyseal bone formation in murine tibiae in response to knee loading’, J. Appl. Physiol., 2006, 100, (5), pp. 14521459 (doi: 10.1152/japplphysiol.00997.2005).
    21. 21)
      • 3. Dalsky, G.P., Stocke, K.S., Ehsani, A.A., Slatopolsky, E., Lee, W.C., Lee, S.C.: ‘Weight-bearing training and lumbar bone mineral content in postmenopausal women’, Ann. Intern. Med., 1988, 108, (6), pp. 824828 (doi: 10.7326/0003-4819-108-6-824).
    22. 22)
      • 23. Zhang, P., Jiang, C., Ledet, E., Yokota, H.: ‘Loading- and unloading-driven regulation of phosphorylation of eIF2α’, Biol. Sci. Space, 2011, 25, (1), pp. 36 (doi: 10.2187/bss.25.3).
    23. 23)
      • 18. Noble, S.L., Sherer, E., Hannemann, R.E., Ramkrishna, D., Vik, T., Rundell, A.E.: ‘Using adaptive model predictive control to customize maintenance therapy chemotherapeutic dosing for childhood acute lymphoblastic leukemia’, J. Theor. Biol., 2010, 264, (3), pp. 9901002 (doi: 10.1016/j.jtbi.2010.01.031).
    24. 24)
      • 21. Bord, S., Ireland, D., Beavan, S., Compston, J.: ‘The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts’, Bone, 2003, 32, (2), pp. 136141 (doi: 10.1016/S8756-3282(02)00953-5).
    25. 25)
      • 6. Cummings, S.R., Martin, J.S., McClung, M.R., et al: ‘Denosumab for prevention of fractures in postmenopausal women with osteoporosis’, N. Engl. J. Med., 2009, 361, (8), pp. 756765 (doi: 10.1056/NEJMoa0809493).
    26. 26)
      • 5. Favus, M.J.: ‘Bisphosphonates for osteoporosis’, N. Engl. J. Med., 2010, 363, (21), pp. 20272035 (doi: 10.1056/NEJMct1004903).
    27. 27)
      • 29. Liu, Y., Yokota, H.: ‘Modeling transcriptional regulation in chondrogenesis using particle swarm optimization’. Proc. IEEE Symp. Computational Intelligence in Bioinformatics and Computational Biology, 2005, pp. 17.
    28. 28)
      • 2. Christiansen, C., Riis, B., Rodbro, P.: ‘Prediction of rapid bone loss in postmenopausal women’, Lancet, 1987, 329, (8542), pp. 11051108 (doi: 10.1016/S0140-6736(87)91671-0).
    29. 29)
      • 31. Vahle, J.L., Long, G.G., Sandusky, G., Westmore, M., Ma, Y.L., Sato, M.: ‘Bone neoplasms in F344 rats given teriparatide [rhpth(1-34)] are dependent on duration of treatment and dose’, Toxicol. Pathol., 2004, 32, (4), pp. 426438 (doi: 10.1080/01926230490462138).
    30. 30)
      • 22. Robling, A.G., Niziolek, P.J., Baldridge, L.A., et al: ‘Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin’, J. Biol. Chem., 2008, 283, (9), pp. 58665875 (doi: 10.1074/jbc.M705092200).
    31. 31)
      • 19. Zurakowski, R., Teel, A.R.: ‘A model predictive control based scheduling method for HIV therapy’, J. Theor. Biol., 2006, 238, (2), pp. 368382 (doi: 10.1016/j.jtbi.2005.05.004).
http://iet.metastore.ingenta.com/content/journals/10.1049/iet-syb.2013.0009
Loading

Related content

content/journals/10.1049/iet-syb.2013.0009
pub_keyword,iet_inspecKeyword,pub_concept
6
6
Loading
This is a required field
Please enter a valid email address