Planta Med 2014; 80 - WS25
DOI: 10.1055/s-0034-1394566

The rat as model for research on prevention and treatment of postmenopausal osteoporosis

A Keiler 1, O Zierau 1, R Bernhardt 2, G Vollmer 1
  • 1Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, 01062 Dresden, Germany
  • 2Max Bergmann Center of Biomaterials and Institute of Materials Science, Technische Universität Dresden, Budapester Str. 27, 01069 Dresden, Germany

Animal species used in osteoporosis research comprise rabbits, dogs, primates and rodents with rats being the preferred small animal model. Depending on the research question, different experimental protocols can be applied in order to induce osteoporosis, e.g. immobilization, inflammation, dietary or hormonal intervention. In addition, the choice of the age is crucial. Skeletally immature rats (till 2.5 months of age) for example are appropriate when factors influencing peak bone mass are in focus. In contrast the ovariectomized skeletally mature rat (> 10 months of age) is the experimental model for postmenopausal osteoporosis. Regarding the evaluation of agents for the treatment or prevention of this type of osteoporosis, regulatory bodies published guidelines recommending the usage of two animal species, one being the ovariectomized rat and additionally a non-rodent animal species [1 – 3]. Another critical point is the usage of adequate controls, especially if tested compounds or extracts possess solely weak activities. The overall hormonal milieu of an ageing organism depends on life style experiences, like pregnancies for females. In this context we recently showed that the bone-sparing effects of E2 substitution depend on the parity status of the rats which in turn correlates with differences in the achieved E2 serum levels [4]. Significant differences could also be observed with regard to the uterotrophic response, suggesting that the parity-dependent hormonal milieu might account for possible discrepancies of results within published studies. Moreover, these observations indicate that the parity status might impact on the potency of natural compounds tested for their estrogenic potency.

References:

[1] FDA Division of Metabolic and Endocrine Drug Products. Guidelines for preclinical and clinical evaluation of agents used in the prevention or treatment of postmenopausal osteoporosis. 1994.

[2] WHO. Guidelines for preclinical evaluation and clinical trials in osteoporosis. 1998.

[3] Committee for medicinal products for human use, (CHMP). Guideline on the evaluation of new medicinal products in the treatment of primary osteoporosis. EMEA 2005.

[4] Keiler AM, Bernhardt R, Scharnweber D, Jarry H, Vollmer G, Zierau O. Comparison of estrogenic responses in bone and uterus depending on the parity status in Lewis rats. J Steroid Biochem Mol Biol 2013; 133: 101 – 109.