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An NMR metabolomic study on the effect of alendronate in ovariectomized mice
Shin-Yu Chen1, Hui-Tzu Yu2, Ju-Po Kao3
1Department of Food Science and Biotechnology, National Chung Hsing University (NCHU), Taiwan, R.O.C.; NCHU-UCD Plant and Food Biotechnology Center, NCHU, Taiwan, R.O.C.; Agricultural Biotechnology Center, NCHU, Taiwan, R.O.C.
Abstract:
Alendronate sodium (Fosamax) is most widely used for the prevention and treatment of osteoporosis. It is a type of anti-resorptive agent that reduces the risk of fractures by changing bone turnover and bone mineral density. We investigated the effect of Fosamax on a mouse model of osteoporosis. Twenty-seven female C57BL/6JNarl mice were divided into three groups: sham, ovariectomized (OVX) and OVX + Fosamax (Fosamax). After 23 weeks, bone density of femurs was analyzed using microcomputed tomography (micro-CT), and serum was analyzed for osteoblast and osteoclast activity, as well as metabolites using nuclear magnetic resonance (NMR) spectroscopy. Fosamax increased bone mineral density and cortical bone thickness, and decreased osteoblast activity slightly. Fosamax did not significantly change osteoclast activity. Serum metabolomics revealed that Fosamax had profound effects on overall metabolism, as significantly higher concentrations of metabolites associated with energy metabolism (including TCA-cycle intermediates and glucose), 3-hydroxybutyrate, taurine, allantoin, acetate, and ethanol, as well as lower concentrations of aspartate were observed in the Fosamax-treated mice compared with the OVX mice. These results suggest that alendronate may work by increasing bone density through altered metabolic activity.
Insights
Alendronate sodium (Fosamax) treatment in an osteoporosis mouse model increased bone density and cortical thickness. This bone density increase was linked to significant alterations in energy metabolism and other metabolites.
Area of Science:
- Biomedical Sciences
- Metabolomics
- Bone Biology
Background:
- Osteoporosis is a prevalent condition characterized by reduced bone mineral density and increased fracture risk.
- Alendronate sodium (Fosamax) is a widely prescribed bisphosphonate for osteoporosis management, acting as an anti-resorptive agent.
- The precise mechanisms by which alendronate influences bone turnover and overall metabolism are not fully elucidated.
Purpose of the Study:
- To investigate the effects of alendronate sodium on bone density and metabolic profiles in a mouse model of osteoporosis.
- To analyze changes in osteoblast and osteoclast activity following alendronate treatment.
- To explore the impact of alendronate on serum metabolite concentrations using nuclear magnetic resonance (NMR) spectroscopy.
Main Methods:
- Ovariectomized (OVX) mice were treated with alendronate sodium (Fosamax) and compared to sham-operated and OVX control groups.
- Bone mineral density and cortical bone thickness were assessed using microcomputed tomography (micro-CT).
- Serum samples were analyzed for osteoblast/osteoclast activity markers and comprehensive metabolomic profiling via NMR spectroscopy.
Main Results:
- Alendronate treatment significantly increased bone mineral density and cortical bone thickness in OVX mice.
- A slight decrease in osteoblast activity was observed, with no significant change in osteoclast activity.
- Serum metabolomics revealed significant alterations in energy metabolism, including elevated TCA-cycle intermediates, glucose, 3-hydroxybutyrate, taurine, allantoin, acetate, and ethanol, with decreased aspartate.
Conclusions:
- Alendronate sodium effectively enhances bone density and cortical thickness in an osteoporosis model.
- The therapeutic effects of alendronate may be associated with profound alterations in host metabolism, particularly energy metabolism.
- These findings suggest a potential link between alendronate's mechanism of action and its impact on metabolic pathways, warranting further investigation.
