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Abstract
Osteoporosis is a chronic progressive disorder and is regarded as an important worldwide health issue. The development of novel treatments and the comparison of the effects of novel and existing treatments in osteoporosis are complicated by the difficulties of establishing drug effects on disease progression, as reflected in the slowly changing primary biomarker, bone mineral density. In recent years, research has considerably improved our understanding of the pathophysiology of osteoporosis. Specifically, various biomarkers have been identified that reflect bone physiology at the cellular level. These biomarkers mirror the dynamics of bone formation and degradation on a shorter timescale than bone mineral density as a composite measure. These markers can therefore, in principle, be used to characterize the underlying regulatory system and to quantify drug effects in osteoporosis.
Recently, the concept of disease system analysis has been proposed as a novel approach to characterize, in a strictly quantitative manner, drug effects on disease progression. This approach integrates physiology, disease progression and drug treatment in a comprehensive mechanism-based model, using dynamic information on a network of biomarkers. This review focuses on the use of disease system analysis for the characterization of drug effects on osteoporosis. It is concluded that, although the development of fully mechanistic disease system models may be practically impossible, parsimonious — but mechanism-based — disease system models may ultimately be used to adequately predict the long-term effects of drug treatment on clinical outcomes.
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Acknowledgements
This research was performed within the framework of project no. D2-104 of the Dutch Top Institute Pharma (Leiden, the Netherlands;www.tipharma.com). The authors have no conflicts of interest that are directly relevant to the contents of this review.
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Pharmacokinetics, Pharmacodynamics, Pharmacometrics (P3), Schering-Plough, Oss, The Netherlands
Teun M. Post & Thomas Kerbusch
Department of Medicine, Division of Endocrinology, Columbia University, New York, New York, USA
Serge C. L. M. Cremers
Division of Pharmacology, Leiden-Amsterdam Center for Drug Research, Gorleaus Laboratories, PO Box 9502, 2300 RA, Leiden, The Netherlands
Meindert Danhof
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- Serge C. L. M. Cremers
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Post, T.M., Cremers, S.C.L.M., Kerbusch, T.et al. Bone Physiology, Disease and Treatment.Clin Pharmacokinet49, 89–118 (2010). https://doi.org/10.2165/11318150-000000000-00000
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