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Antibodies for the Treatment of Bone Diseases: Preclinical Data

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Principles of Osteoimmunology

Abstract

Osteoporosis is a complex systemic disease. Therefore, researchers have to rely on rodent and large animal models for the development of new antiosteoporotic therapeutics. Rodent models are well established and have been widely used in osteoporosis research. However, the US Food and Drug Administration (FDA), besides rats, also demands the use of large animal models in preclinical testing of antiosteoporotic substances with an experimental time frame of 12 months when using rats and 16 months when using larger species. According to FDA regulations, valid animal models have to develop an osteoporotic phenotype either spontaneously or after ovariectomy (OVX). There exist several ways of inducing osteopenia or osteoporotic phenotypes in mammals, such as OPG gene knockout, systemic RANKL administration, prolonged glucocorticoid administration, age-related osteoporosis, dietary calcium shortage, OVX, and combinations. All these manipulations have specific advantages and disadvantages, and the physiological relevance has to be proven for each model. Although calcium shortage itself may induce osteopenia to some extent, it is usually combined with OVX, which may be considered the main model of postmenopausal and thus estrogen deficiency-induced osteoporosis. In preclinical studies, all novel antibodies for the treatment of bone diseases have been tested at least in the ovariectomized rat model.

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Authors and Affiliations

  1. Clinical Department for Farm Animals, University of Veterinary Medicine Vienna, Vienna, 1210, Austria

    Wolfgang Sipos DVM

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  1. Wolfgang Sipos DVM
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Correspondence to Wolfgang Sipos DVM .

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  1. Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria

    Peter Pietschmann

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Sipos, W. (2016). Antibodies for the Treatment of Bone Diseases: Preclinical Data. In: Pietschmann, P. (eds) Principles of Osteoimmunology. Springer, Cham. https://doi.org/10.1007/978-3-319-34238-2_9

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