• Journal of Pharmaceutical Investigation
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• v.40 no.2
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• pp.79-84
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• 2010

Osteoporosis was traditionally defined by the occurrence of nontraumatic fractures, especially of the spine, in the setting of low bone mass. Bisphosphonates are an important group of therapeutic agents for the management of osteoporosis, as they inhibit bone resorption and increase bone density, thereby potentially decreasing fracture risk. Risedronate sodium is a bisphosphonate class used by oral formulation. In this study, risedronate was transdermally delivered by iontophoresis. Effects of polarity, pH, current density, and drug concentration were studied using a side-by-side diffusion cell including the hairless mice skin. In addition we studied effect of enhancers. The flux was evaluated by HPLC/UV system. The amount of transported drug under iontophoretic delivery was approximately 186 fold higher than that under passive delivery. Flux was proportional to the increase of drug concentration and current density. The flux was observed about 0.68mg/$cm^2$ when the amout of Propyleneglycol monolaurate (PGML) used 1% as enhancer. Results indicated that iontophoresis is an effective method for transdermal administration of risedronate sodium

• Journal of the korean academy of Pediatric Dentistry
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• v.27 no.2
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• pp.309-317
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• 2000

Bisphosphonates inhibit bone resorption in vivo and in vitro. Currently proposed mechanism of action of bisphosphonates involves both direct effect on osteoclasts and indirect effect through the mediation of osteoblasts. Recent understanding of molecular mechanism of osteoclastogenesis indicates that osteoclast differentiation is quite tightly regulated by signaling molecules from differentiating osteoblasts. Therefore this investigation was designed to elucidate the effect of bisphosphonate on osteoblast differentation. For this purpose, in vitro effects of etidronate and alendronate on the expression of Cbfa1 a master control gene of osteoblast differentiation, several bone marker genes, and formation of calcified nodules were evaluated. To evaluate the effect of bisphosphonate on calcified nodule formation, osteoblasts isolated from rat calvaria were cultured in a-MEM containing $10^{-4},\;10^{-5},\;10^{-6}M$ of etidronate or $10^{-6},\;10^{-7},\;10^{-8}M$ of alendronate for 15 days, and then stained by alizarin red to determine mineralization. To evaluate the effect of bisphosphonate on osteoblast differentiation, osteoblast cells were cultured in a-MEM containing $10^{-4},\;10^{-5},\;10^{-6}M$ of etidronate or $10^{-6}$ M of alendronate for 8 days. And then total RNA was extracted and northern blot analysis was done to examine the expression of Cbfa1, type I collagen, alkaline phosphatase, osteopontin and osteocalcin. The results were as follows: 1. Etidronate suppressed the calcification of bone nodule in dose dependent manner, while alendronate didn't. 2. The expression of Cbfa1 was decreased dose dependently by etidronate, but increased by alendronate. 3. Etidronate suppressed the expression of type I collagen, osteopontin and osteocalcin in dose dependent manner however alendronate promote the expression of osteoblast marker gene. 4. The expression of alkaline phosphatase was not affected either etidronate nor alendronate. These results suggest that etidronate suppressed the expression of Cbfa1 in dose dependent manner, and consequently the expression of osteoblast marker genes, such as type I collagen, osteopontin and osteocalcin were also suppressed in similar manner. And finally this decreased expression of osteoblastic marker gene prevent calcined bone nodule formation.