In Vitro and In Vivo effects of ipriflavone on bone formation and bone biomechanics

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Abstract
Ipriflavone (IP) positively affects bone density in postmenopausal osteoporosis, primarily by inhibiting bone resorption. Using in vitro models of human osteoblast differentiation, we have observed that IP and some of its metabolites stimulate the expression of bone sialoprotein, decorin, and type I collagen, and facilitate the deposition of mineralized matrix. This suggests that IP may stimulate bone formation in addition to its antiresorptive activity. To assess whether these effects translate into an improved bone “quality” in vivo, we measured biomechanical properties, mineral composition, and crystallinity of femurs of 12-week-old, male, Sprague-Dawley rats treated with IP for 1 month. IP significantly decreased vibration damping, an index of strain energy loss. Because vibration damping increases as bone porosity increases, the results indicate that IP-treated bones acquired a higher capacity to withstand dynamic stress. In fact, 1.5-fold higher energy was required to fracture femurs of IP-treated rats after a single supramaximal impact. IP also increased BMD, assessed by both volume displacement and ash analysis, whereas the relative contents of Ca, P, and Mg in the ashes were not affected. Thus, no gross abnormalities in mineral composition of bone occurred after IP administration. As a measure of bone crystallinity, X-ray diffraction analysis was performed. The broadening parameter β1/2 for the (310) and (002) reflections was not significantly different between IP-treated and control animals. Similarly, there were no differences in serum levels of Ca, Mg, alkaline phosphatase, and type I collagen telopeptides between treated and control animals at the end of the study. Therefore, 1-month treatment with IP increased bone density and improved the biomechanical properties of adult male rat bones without altering mineral composition or bone crystallinity.