title: An NMR metabolomic study on the effect of alendronate in ovariectomized mice.
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.
authors.affiliation: Department 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.
authors.forename: Shin-Yu
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University (NCHU), Taiwan, R.O.C.
authors.forename: Hui-Tzu
authors.initials: HT
authors.lastname: Yu
authors.affiliation: Veterinary Medical Teaching Hospital, College of Veterinary Medicine, NCHU, Taiwan, R.O.C.
authors.forename: Ju-Po
authors.initials: JP
authors.lastname: Kao
authors.affiliation: Veterinary Medical Teaching Hospital, College of Veterinary Medicine, NCHU, Taiwan, R.O.C.
authors.forename: Chung-Chun
authors.initials: CC
authors.lastname: Yang
authors.affiliation: Department 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.
authors.forename: Shen-Shih
authors.initials: SS
authors.lastname: Chiang
authors.affiliation: Department of Food Science and Technology, University of California Davis, Davis, California, United States of America.
authors.forename: Darya O
authors.initials: DO
authors.lastname: Mishchuk
authors.affiliation: Department 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.
authors.forename: Jeng-Leun
authors.initials: JL
authors.lastname: Mau
authors.affiliation: Department of Food Science and Technology, University of California Davis, Davis, California, United States of America; Department of Nutrition, University of California Davis, Davis, California, United States of America.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Slupsky
mesh_terms: D019386:Alendronate / Q000008:administration & dosage*; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D055432:Metabolomics; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology; D010052:Ovariectomy
chemical_list: D005947:Glucose; D019386:Alendronate