ECTS Abstracts (2015) 1 P369

The epigenetically active small chemical N-methyl pyrrolidone (NMP) prevents ovariectomy-induced osteoporosis in rats

Bebeka Gjoksi, Chafik Ghayor & Franz E Weber

University Hospital Zurich, Zurich, Switzerland.

Osteoporosis is a chronic skeletal disorder, prevalent in post-menopausal women influenced by hormonal factors causing a huge economic burden on our ageing society. Currently, there are several treatments for osteoporosis however; they all display some sort of limitation and/or side effects making the need for new treatments imperative. We have previously demonstrated that NMP is a bioactive drug which enhances bone regeneration in vivo and acts as an enhancer of bone morphogenetic protein (BMP) in vitro. NMP also inhibits osteoclast differentiation and attenuates bone resorption. In the present study, we tested NMP as a bromodomain inhibitor and for osteoporosis prevention on ovariectomised (OVX) induced rats while treated systemically with NMP. Female Sprague- Dawley rats were ovariectomised and weekly NMP treatment was administrated 1 week after surgery for 15 weeks. Bone parameters and related serum biomarkers were analysed. Fifteen weeks of NMP treatment slowed down body weight gain and prevented bone loss of the treated group compared with the control. In the same time both deterioration of overall bone loss and trabecular microstructure were preserved. Moreover, mineral apposition rate and bone biomarkers of bone turnover in the treatment group were at similar levels with those of the Sham group. Due to the function of NMP as a low affinity bromodomain inhibitor and its mechanism of action involving osteoblasts/osteoclasts balance and inhibitory effect on inflammatory cytokines, NMP is a promising therapeutic compound for the prevention of osteoporosis.

Disclosure: The authors declared no competing interests. This research work was supported by grants from the Swiss National Science Foundation (31003A 140868) and (CR32I3_152809).

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