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.

Potential for estimation of Young's modulus based on computed tomography numbers in bone: A validation study using a nano-indentation test on murine maxilla

“…The BMD values obtained from the μCT images of the mouse maxilla ranged from 0.83 g/cm 3 to 1.55 g/cm 3 , which were considerably larger than values of the previous data, which ranged from 0.12 g/ cm 3 to 1.00 g/cm 3 for the same strain of mice, C57BL/6J mice [27][28][29][30]. This might be partly attributed to the difference in the targeted bones, which could be a key factor determining the BMD values in mice [31].…”

“…This might be partly attributed to the difference in the targeted bones, which could be a key factor determining the BMD values in mice [31]. Spinal [29], tibia [28], and femoral bones [27,29,30] have been used in previous studies, while the maxillary bone was used in the present study. Technical factors, including the scanner type, voltage, and kernel [32], can also affect the magnitude of the CT numbers in μCT and quantitative computed tomography (QCT) images; thus, this could cause the large discrepancy in BMD values between the previous and present studies [8].…”

Metabolomics and Its Application in the Development of Discovering Biomarkers for Osteoporosis Research

“…Alendronate sodium, a nitrogen-containing bisphosphonate, is widely used for the prevention and treatment of osteoporosis. Chen and coworkers revealed that alendronate had profound effects on the serum metabolites in the OVX mice with significantly higher concentrations of 3-hydroxybutyrate, taurine, allantoin, acetate, and ethanol, as well as lower concentration of aspartate, associated with energy metabolism [37]. Evidence for the protective role of strontium fructose 1,6-diphosphate (FDP-Sr) against bone loss is by stimulating bone formation and suppressing bone absorption [50].…”

Consumption of vitamin D2 enhanced mushrooms is associated with improved bone health

“…Taurine supplementation has been shown to increase bone mineral density in rats [50,51]. Furthermore, the pulsed P. ferulae treated mice had higher serum taurine concentrations than mice treated with alendronate [52], suggesting the pulsed P. ferulae may induce higher concentrations of metabolites related to bone health [52]. Arginine is involved in the synthesis of substrates (polyamines and proline) that are implicated in collagen synthesis [50,53,54].…”