Ipriflavone

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K. Yoshida - One of the best experts on this subject based on the ideXlab platform.

  • Effect of Ipriflavone on expression of markers characteristic of the osteoblast phenotype in rat bone marrow stromal cell culture.
    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2009
    Co-Authors: Kohei Notoya, K. Yoshida, Ryoichi Tsukuda, Shigehisa Taketomi
    Abstract:

    The effects of Ipriflavone on cellular proliferation and differentiation of osteoblasts were investigated using stromal cells isolated from the femoral bone marrow of young rats. To induce the formation of mineralized bone-like tissue in vitro, the cells were cultured in the presence of beta-glycerophosphate and dexamethasone. Ipriflavone was added when subculturing was started. After 14 days of culturing with Ipriflavone (10(-7)-10(-5) M), increases in both the alkaline phosphatase activity and the hydroxyproline content per culture dish and a slight decrease in the saturated cell density were observed. Furthermore, continuous treatment with Ipriflavone for 14-33 days resulted in an increase in the area of bone-like mineralized tissue accompanied by an increase in the secretion of osteocalcin. When culture medium lacking dexamethasone was used, rat bone marrow stromal cells neither differentiated into osteoblasts nor formed bone-like tissue, and under these conditions, Ipriflavone had no effect on the proliferation or the phenotypic expression of the cells. These results suggest that Ipriflavone directly stimulates markers of the osteoblast phenotype at a certain stage in bone formation without affecting undifferentiated cells that have not been committed to the osteogenic lineage.

  • Increase in femoral bone mass by Ipriflavone alone and in combination with 1α-hydroxyvitamin D_3 in growing rats with skeletal unloading
    Calcified Tissue International, 1996
    Co-Authors: K Notoya, S Taketomi, K. Yoshida, R. Rsukuda, M. Tsuda
    Abstract:

    We assessed the possibility that Ipriflavone treatment might result in bone restoration in immobilized rats. We also investigated the effect of combined treatment with Ipriflavone and vitamin D_3 on the bone. Male Sprague-Dawley rats, 6 weeks of age, were subjected to unilateral sciatic neurectomy. Three weeks after the operation, Ipriflavone (100 mg/kg), 1α-hydroxyvitamin D_3 [1α(OH)D_3, 25 ng/kg], or both Ipriflavone and 1α(OH)D_3 were orally administered every day for 12 or 24 weeks. After 12 weeks of treatment, only the group receiving combined treatment with Ipriflavone and 1α(OH)D_3 showed increases in total femur calcium content (+16.4%, compared with the control). After 24 weeks, both animals treated with Ipriflavone alone and those that had received the combination of Ipriflavone and 1α(OH)D_3 showed significant increases in femur calcium content (+18.0% and +23.8%, respectively). In these treatment groups, X-ray analysis revealed an increase in bone mineral density over the entire length of the femur, and an increase in cortical diameter at the midshaft without affecting medullary width. Administration of 1α(OH)D_3 (25 ng/kg) alone had no effect. Body weight, femur length, and serum markers of calcium and bone metabolism were not affected in any group. We evaluated the relationship between Ipriflavone and vitamin D_3 in bone cells in a culture system using rat bone marrow stromal cells in which the cells subsequently form mineralized bone-like tissue. Continuous treatment with Ipriflavone (10^−5 M) for 21 days resulted in an increase in osteocalcin secretion, and enhanced its response to 1α,25-dihydroxyvitamin D_3 (10^−11 M-10^−8 M). These findings indicate that Ipriflavone treatment increases the femoral bone mass in immobilized rats. In addition, a low dose of 1α(OH)D_3, which did not induce hypercalcemia, in combination with Ipriflavone, augmented the stimulatory effect of Ipriflavone alone on the bone mass, possibly due to a direct effect of each agent on osteoblastic cells.

  • Increase in femoral bone mass by Ipriflavone alone and in combination with 1α-hydroxyvitamin D3 in growing rats with skeletal unloading
    Calcified tissue international, 1996
    Co-Authors: Kohei Notoya, K. Yoshida, Ryoichi Tsukuda, Shigehisa Taketomi, M. Tsuda
    Abstract:

    We assessed the possibility that Ipriflavone treatment might result in bone restoration in immobilized rats. We also investigated the effect of combined treatment with Ipriflavone and vitamin D3 on the bone. Male Sprague-Dawley rats, 6 weeks of age, were subjected to unilateral sciatic neurectomy. Three weeks after the operation, Ipriflavone (100 mg/kg), 1α-hydroxyvitamin D3 [1α(OH)D3, 25 ng/kg], or both Ipriflavone and 1α(OH)D3 were orally administered every day for 12 or 24 weeks. After 12 weeks of treatment, only the group receiving combined treatment with Ipriflavone and 1α(OH)D3 showed increases in total femur calcium content (+16.4%, compared with the control). After 24 weeks, both animals treated with Ipriflavone alone and those that had received the combination of Ipriflavone and 1α(OH)D3 showed significant increases in femur calcium content (+18.0% and +23.8%, respectively). In these treatment groups, X-ray analysis revealed an increase in bone mineral density over the entire length of the femur, and an increase in cortical diameter at the midshaft without affecting medullary width. Administration of 1α(OH)D3 (25 ng/kg) alone had no effect. Body weight, femur length, and serum markers of calcium and bone metabolism were not affected in any group. We evaluated the relationship between Ipriflavone and vitamin D3 in bone cells in a culture system using rat bone marrow stromal cells in which the cells subsequently form mineralized bone-like tissue. Continuous treatment with Ipriflavone (10−5 M) for 21 days resulted in an increase in osteocalcin secretion, and enhanced its response to 1α,25-dihydroxyvitamin D3 (10−11 M-10−8 M). These findings indicate that Ipriflavone treatment increases the femoral bone mass in immobilized rats. In addition, a low dose of 1α(OH)D3, which did not induce hypercalcemia, in combination with Ipriflavone, augmented the stimulatory effect of Ipriflavone alone on the bone mass, possibly due to a direct effect of each agent on osteoblastic cells.

  • Similarities and differences between the effects of Ipriflavone and vitamin K on bone resorption and formation in vitro
    Bone, 1995
    Co-Authors: K Notoya, K. Yoshida, Shigehisa Taketomi, Y. Shirakawa, M. Tsuda
    Abstract:

    The effects of Ipriflavone and vitamin K on bone metabolism were examined using a culture system. Vitamin K 1 and vitamin K 2 (10 −7 M-10 −5 M) inhibited both the activation of mature osteoclasts and the formation of new osteoclasts without affecting the growth of progenitor cells in cultures of mouse unfractionated bone cells. The inhibitory effects of vitamin K on bone resorption were similar to those of Ipriflavone and were not affected by the vitamin K antagonist warfarin. When Ipriflavone was added to the culture medium in combination with vitamin K 2 , an additive inhibitory effect on bone resorption was observed. An additive effect was also observed in organ cultures of mouse calvaria. On the other hand, Ipriflavone, but neither vitamin K 1 nor vitamin K 2 , stimulated cellular alkaline phosphatase (ALP) activity on rat bone marrow stromal cells under culture conditions in which cells subsequently form mineralized bone-like tissue. Vitamin K 1 and vitamin K 2 also did not modulate the stimulatory effect of Ipriflavone on the ALP activity of the cells. These results suggest that the inhibitory effects of vitamin K on bone resorption are similar to those of Ipriflavone through mechanisms that may be independent of the γ-carboxylation system, while the effects of vitamin K on osteoblast phenotype expression are different from those of Ipriflavone.

  • inhibitory effect of Ipriflavone on osteoclast mediated bone resorption and new osteoclast formation in long term cultures of mouse unfractionated bone cells
    Calcified Tissue International, 1993
    Co-Authors: Kohei Notoya, K. Yoshida, Shigehisa Taketomi, Iwao Yamazaki, Masayoshi Kumegawa
    Abstract:

    To study the effect of Ipriflavone on osteoclast-mediated bone resorption and new osteoclast formation, we used an unfractionated bone cell culture system containing mature osteoclasts from femur and tibia of newborn mice. Ipriflavone (10−5 M) inhibited pit formation on dentin slices and caused a decrease in the number of tartrate-resistant acid phosphatase (TRAP)-positive (+) multinucleate cells (MNCs) in a 4-day culture period in which no increase in the number of TRAP(+)-MNCs was observed in the presence of 5% fetal bovine serum (FBS) and 10−8 M 1α,25-dihydroxy-vitamin D3 (1α,25(OH)2D3). During the following 12 days, both the total area of the pits and the number of TRAP(+)-MNCs increased in the control. Continuous treatment with Ipriflavone also inhibited the increase in pit area during this period. These effects of Ipriflavone were reversible. Furthermore, the differentiation of osteoclasts was examined when preexisting TRAP(+)-MNCs were removed by incubation in the absence of 1α,25(OH)2D3 for the initial 4 days in culture dishes without dentin slices. When 1α,25(OH)2D3 and Ipriflavone were added to the medium on the 4th day, Ipriflavone inhibited new TRAP(+)-MNC formation stimulated by 1α,25(OH)2D3 in a dose-dependent manner. However, pretreatment of the cells with Ipriflavone before the addition of 1α,25(OH)2D3 did not inhibit TRAP(+)-MNC formation. These results indicate that Ipriflavone inhibits both the activation of mature osteoclasts and the formation of new osteoclasts without affecting growth of TRAP-negative progenitor cells.

Carlo Gennari - One of the best experts on this subject based on the ideXlab platform.

  • Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial.
    JAMA, 2001
    Co-Authors: Peter Alexandersen, Carlo Gennari, Anne Toussaint, Claus Christiansen, Jean-pierre Devogelaer, Christian Roux, Jacques Fechtenbaum, Jean-yves Reginster
    Abstract:

    Data on the efficacy and safety of Ipriflavone for prevention of postmenopausal bone loss are conflicting. To investigate the effect of oral Ipriflavone on prevention of postmenopausal bone loss and to assess the safety profile of long-term treatment with Ipriflavone in postmenopausal osteoporotic women. Prospective, randomized, double-blind, placebo-controlled, 4-year study conducted in 4 centers in Belgium, Denmark, and Italy from August 1994 to July 1998. Four hundred seventy-four postmenopausal white women, aged 45 to 75 years, with bone mineral densities (BMDs) of less than 0.86 g/cm(2). Patients were randomly assigned to receive Ipriflavone, 200 mg 3 times per day (n = 234), or placebo (n = 240); all received 500 mg/d of calcium. Efficacy measures included spine, hip, and forearm BMD and biochemical markers of bone resorption (urinary hydroxyproline corrected for creatinine and urinary CrossLaps [Osteometer Biotech, Herlev, Denmark] corrected for creatinine), assessed every 6 months. Laboratory safety measures and adverse events were recorded every 3 months. Based on intent-to-treat analysis, after 36 months of treatment, the annual percentage change from baseline in BMD of the lumbar spine for Ipriflavone vs placebo (0.1% [95% confidence interval (CI), -7.9% to 8.1%] vs 0.8% [95% CI, -9.1% to 10.7%]; P =.14), or in any of the other sites measured, did not differ significantly between groups. The response in biochemical markers was also similar between groups (eg, for hydroxyproline corrected for creatinine, 20.13 mg/g [95% CI, 18.85-21.41 mg/g] vs 20.67 mg/g [95% CI, 19.41-21.92 mg/g]; P =.96); urinary CrossLaps corrected for creatinine, 268 mg/mol (95% CI, 249-288 mg/mol) vs 268 mg/mol (95% CI, 254-282 mg/mol); P =.81. The number of women with new vertebral fracture was identical or nearly so in the 2 groups at all time points. Lymphocyte concentrations decreased significantly (500/microL (0.5 x 10(9)/L]) in women treated with Ipriflavone. Thirty-one women (13.2%) in the Ipriflavone group developed subclinical lymphocytopenia, of whom 29 developed it during Ipriflavone treatment. Of these, 15 (52%) of 29 had recovered spontaneously by 1 year and 22 (81%) of 29 by 2 years. Our data indicate that Ipriflavone does not prevent bone loss or affect biochemical markers of bone metabolism. Additionally, Ipriflavone induces lymphocytopenia in a significant number of women.

  • Effect of Ipriflavone--a synthetic derivative of natural isoflavones--on bone mass loss in the early years after menopause.
    Menopause (New York N.Y.), 1998
    Co-Authors: Carlo Gennari, Donato Agnusdei, Gaetano Crepaldi, Giancarlo Isaia, Gianfranco Mazzuoli, Sergio Ortolani, Lidia Bufalino, Mario Passeri
    Abstract:

    We studied whether oral administration of Ipriflavone, a synthetic derivative of naturally occurring isoflavones, could prevent bone loss occurring shortly after menopause. Fifty-six women with low vertebral bone density and with postmenopausal age less than five years were randomly allocated to receive either Ipriflavone, 200 mg three times daily, or placebo. All subjects also received 1,000 mg elemental calcium daily. Vertebral bone density declined after two years in women taking only calcium (4.9 +/- 1.1%, SEM, p = 0.001), but it did not change in those receiving Ipriflavone (-0.4 +/- 1.1%, n.s.). A significant (p = 0.010) between-treatment difference was evidenced at both year 1 and year 2. At the end of the study, urine hydroxyproline/creatinine excretion was higher in the control group than in the Ipriflavone group, as compared to no difference at baseline. Five patients taking Ipriflavone and five taking placebo experienced gastrointestinal discomfort or other adverse reactions, but only one and four subjects, respectively, had to discontinue the study. Ipriflavone prevents the rapid bone loss following early menopause. This effect is associated with a reduction of bone turnover rate.

  • effect of Ipriflavone a synthetic derivative of natural isoflavones on bone mass loss in the early years after menopause
    Menopause, 1998
    Co-Authors: Carlo Gennari, Donato Agnusdei, Gaetano Crepaldi, Giancarlo Isaia, Gianfranco Mazzuoli, Sergio Ortolani, Lidia Bufalino, Mario Passeri
    Abstract:

    Objective We studied whether oral administration of Ipriflavone, a synthetic derivative of naturally occurring isoflavones, could prevent bone loss occurring shortly after menopause. Design Fifty-six women with low vertebral bone density and with postmenopausal age less than five years were randomly allocated to receive either Ipriflavone, 200 mg three times daily, or placebo. All subjects also received 1,000 mg elemental calcium daily. Results Vertebral bone density declined after two years in women taking only calcium (4.9 +/- 1.1%, SEM, p = 0.001), but it did not change in those receiving Ipriflavone (-0.4 +/- 1.1%, n.s.). A significant (p = 0.010) between-treatment difference was evidenced at both year 1 and year 2. At the end of the study, urine hydroxyproline/creatinine excretion was higher in the control group than in the Ipriflavone group, as compared to no difference at baseline. Five patients taking Ipriflavone and five taking placebo experienced gastrointestinal discomfort or other adverse reactions, but only one and four subjects, respectively, had to discontinue the study. Conclusions Ipriflavone prevents the rapid bone loss following early menopause. This effect is associated with a reduction of bone turnover rate.

  • A double blind, placebo-controlled trial of Ipriflavone for prevention of postmenopausal spinal bone loss.
    Calcified tissue international, 1997
    Co-Authors: Donato Agnusdei, L. Bufalino, Gaetano Crepaldi, Gianfranco Mazzuoli, Sergio Ortolani, Mario Passeri, G.c. Isaia, Carlo Gennari
    Abstract:

    One hundred ninety-eight postmenopausal women (aged 50-65 years) with vertebral bone density (VBD) 1 SD below the mean value for normal, age-matched, postmenopausal subjects were enrolled in six Italian centers and 134 completed 2 years of treatment. All subjects were randomly allocated to a 2-year treatment with oral Ipriflavone (200 mg t.i.d.) or a matching placebo, according to a double-blind, parallel group design. All patients also received an oral daily calcium supplement of 1 g as calcium carbonate. VBD and markers of bone turnover were measured at baseline, and every 6 months. A complete routine analysis of liver and kidney functions along with hematological parameters were measured before and at the end of treatment period. The valid completers analysis showed a significant increase of VBD in Ipriflavone-treated women with average percent changes of +1.4 after 1 year, and +1% at the end of treatment period (P < 0.05). The placebo group presented a significant decrease of VBD after 2 years of treatment (P < 0.05). The difference between treatments was significant (P < 0.01). The intention to treat analysis confirmed the significant decrease of VBD in the placebo group, with no changes in Ipriflavone-treated women. Skeletal ALP significantly decreased in Ipriflavone-treated women (P < 0.05). Serum BGP and urine HOP/Cr showed a significant decrease only in Ipriflavone-treated women, suggesting an inhibitory effect on bone turnover rate. Adverse reactions, mainly gastrointestinal, occurred to a similar extent in the two treatment groups. The evaluation of patients' compliance, assessed by residual tablets count, revealed a drug intake of more than 80% after 2 years in 92.5% and 92.8% of patients treated with Ipriflavone or placebo, respectively. This study demonstrates that Ipriflavone can prevent bone loss in postmenopausal women with low bone mass.

Mario Passeri - One of the best experts on this subject based on the ideXlab platform.

  • Effect of Ipriflavone--a synthetic derivative of natural isoflavones--on bone mass loss in the early years after menopause.
    Menopause (New York N.Y.), 1998
    Co-Authors: Carlo Gennari, Donato Agnusdei, Gaetano Crepaldi, Giancarlo Isaia, Gianfranco Mazzuoli, Sergio Ortolani, Lidia Bufalino, Mario Passeri
    Abstract:

    We studied whether oral administration of Ipriflavone, a synthetic derivative of naturally occurring isoflavones, could prevent bone loss occurring shortly after menopause. Fifty-six women with low vertebral bone density and with postmenopausal age less than five years were randomly allocated to receive either Ipriflavone, 200 mg three times daily, or placebo. All subjects also received 1,000 mg elemental calcium daily. Vertebral bone density declined after two years in women taking only calcium (4.9 +/- 1.1%, SEM, p = 0.001), but it did not change in those receiving Ipriflavone (-0.4 +/- 1.1%, n.s.). A significant (p = 0.010) between-treatment difference was evidenced at both year 1 and year 2. At the end of the study, urine hydroxyproline/creatinine excretion was higher in the control group than in the Ipriflavone group, as compared to no difference at baseline. Five patients taking Ipriflavone and five taking placebo experienced gastrointestinal discomfort or other adverse reactions, but only one and four subjects, respectively, had to discontinue the study. Ipriflavone prevents the rapid bone loss following early menopause. This effect is associated with a reduction of bone turnover rate.

  • effect of Ipriflavone a synthetic derivative of natural isoflavones on bone mass loss in the early years after menopause
    Menopause, 1998
    Co-Authors: Carlo Gennari, Donato Agnusdei, Gaetano Crepaldi, Giancarlo Isaia, Gianfranco Mazzuoli, Sergio Ortolani, Lidia Bufalino, Mario Passeri
    Abstract:

    Objective We studied whether oral administration of Ipriflavone, a synthetic derivative of naturally occurring isoflavones, could prevent bone loss occurring shortly after menopause. Design Fifty-six women with low vertebral bone density and with postmenopausal age less than five years were randomly allocated to receive either Ipriflavone, 200 mg three times daily, or placebo. All subjects also received 1,000 mg elemental calcium daily. Results Vertebral bone density declined after two years in women taking only calcium (4.9 +/- 1.1%, SEM, p = 0.001), but it did not change in those receiving Ipriflavone (-0.4 +/- 1.1%, n.s.). A significant (p = 0.010) between-treatment difference was evidenced at both year 1 and year 2. At the end of the study, urine hydroxyproline/creatinine excretion was higher in the control group than in the Ipriflavone group, as compared to no difference at baseline. Five patients taking Ipriflavone and five taking placebo experienced gastrointestinal discomfort or other adverse reactions, but only one and four subjects, respectively, had to discontinue the study. Conclusions Ipriflavone prevents the rapid bone loss following early menopause. This effect is associated with a reduction of bone turnover rate.

  • A double blind, placebo-controlled trial of Ipriflavone for prevention of postmenopausal spinal bone loss.
    Calcified tissue international, 1997
    Co-Authors: Donato Agnusdei, L. Bufalino, Gaetano Crepaldi, Gianfranco Mazzuoli, Sergio Ortolani, Mario Passeri, G.c. Isaia, Carlo Gennari
    Abstract:

    One hundred ninety-eight postmenopausal women (aged 50-65 years) with vertebral bone density (VBD) 1 SD below the mean value for normal, age-matched, postmenopausal subjects were enrolled in six Italian centers and 134 completed 2 years of treatment. All subjects were randomly allocated to a 2-year treatment with oral Ipriflavone (200 mg t.i.d.) or a matching placebo, according to a double-blind, parallel group design. All patients also received an oral daily calcium supplement of 1 g as calcium carbonate. VBD and markers of bone turnover were measured at baseline, and every 6 months. A complete routine analysis of liver and kidney functions along with hematological parameters were measured before and at the end of treatment period. The valid completers analysis showed a significant increase of VBD in Ipriflavone-treated women with average percent changes of +1.4 after 1 year, and +1% at the end of treatment period (P < 0.05). The placebo group presented a significant decrease of VBD after 2 years of treatment (P < 0.05). The difference between treatments was significant (P < 0.01). The intention to treat analysis confirmed the significant decrease of VBD in the placebo group, with no changes in Ipriflavone-treated women. Skeletal ALP significantly decreased in Ipriflavone-treated women (P < 0.05). Serum BGP and urine HOP/Cr showed a significant decrease only in Ipriflavone-treated women, suggesting an inhibitory effect on bone turnover rate. Adverse reactions, mainly gastrointestinal, occurred to a similar extent in the two treatment groups. The evaluation of patients' compliance, assessed by residual tablets count, revealed a drug intake of more than 80% after 2 years in 92.5% and 92.8% of patients treated with Ipriflavone or placebo, respectively. This study demonstrates that Ipriflavone can prevent bone loss in postmenopausal women with low bone mass.

Kohei Notoya - One of the best experts on this subject based on the ideXlab platform.

  • Effect of Ipriflavone on expression of markers characteristic of the osteoblast phenotype in rat bone marrow stromal cell culture.
    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2009
    Co-Authors: Kohei Notoya, K. Yoshida, Ryoichi Tsukuda, Shigehisa Taketomi
    Abstract:

    The effects of Ipriflavone on cellular proliferation and differentiation of osteoblasts were investigated using stromal cells isolated from the femoral bone marrow of young rats. To induce the formation of mineralized bone-like tissue in vitro, the cells were cultured in the presence of beta-glycerophosphate and dexamethasone. Ipriflavone was added when subculturing was started. After 14 days of culturing with Ipriflavone (10(-7)-10(-5) M), increases in both the alkaline phosphatase activity and the hydroxyproline content per culture dish and a slight decrease in the saturated cell density were observed. Furthermore, continuous treatment with Ipriflavone for 14-33 days resulted in an increase in the area of bone-like mineralized tissue accompanied by an increase in the secretion of osteocalcin. When culture medium lacking dexamethasone was used, rat bone marrow stromal cells neither differentiated into osteoblasts nor formed bone-like tissue, and under these conditions, Ipriflavone had no effect on the proliferation or the phenotypic expression of the cells. These results suggest that Ipriflavone directly stimulates markers of the osteoblast phenotype at a certain stage in bone formation without affecting undifferentiated cells that have not been committed to the osteogenic lineage.

  • Increase in femoral bone mass by Ipriflavone alone and in combination with 1α-hydroxyvitamin D3 in growing rats with skeletal unloading
    Calcified tissue international, 1996
    Co-Authors: Kohei Notoya, K. Yoshida, Ryoichi Tsukuda, Shigehisa Taketomi, M. Tsuda
    Abstract:

    We assessed the possibility that Ipriflavone treatment might result in bone restoration in immobilized rats. We also investigated the effect of combined treatment with Ipriflavone and vitamin D3 on the bone. Male Sprague-Dawley rats, 6 weeks of age, were subjected to unilateral sciatic neurectomy. Three weeks after the operation, Ipriflavone (100 mg/kg), 1α-hydroxyvitamin D3 [1α(OH)D3, 25 ng/kg], or both Ipriflavone and 1α(OH)D3 were orally administered every day for 12 or 24 weeks. After 12 weeks of treatment, only the group receiving combined treatment with Ipriflavone and 1α(OH)D3 showed increases in total femur calcium content (+16.4%, compared with the control). After 24 weeks, both animals treated with Ipriflavone alone and those that had received the combination of Ipriflavone and 1α(OH)D3 showed significant increases in femur calcium content (+18.0% and +23.8%, respectively). In these treatment groups, X-ray analysis revealed an increase in bone mineral density over the entire length of the femur, and an increase in cortical diameter at the midshaft without affecting medullary width. Administration of 1α(OH)D3 (25 ng/kg) alone had no effect. Body weight, femur length, and serum markers of calcium and bone metabolism were not affected in any group. We evaluated the relationship between Ipriflavone and vitamin D3 in bone cells in a culture system using rat bone marrow stromal cells in which the cells subsequently form mineralized bone-like tissue. Continuous treatment with Ipriflavone (10−5 M) for 21 days resulted in an increase in osteocalcin secretion, and enhanced its response to 1α,25-dihydroxyvitamin D3 (10−11 M-10−8 M). These findings indicate that Ipriflavone treatment increases the femoral bone mass in immobilized rats. In addition, a low dose of 1α(OH)D3, which did not induce hypercalcemia, in combination with Ipriflavone, augmented the stimulatory effect of Ipriflavone alone on the bone mass, possibly due to a direct effect of each agent on osteoblastic cells.

  • inhibitory effect of Ipriflavone on osteoclast mediated bone resorption and new osteoclast formation in long term cultures of mouse unfractionated bone cells
    Calcified Tissue International, 1993
    Co-Authors: Kohei Notoya, K. Yoshida, Shigehisa Taketomi, Iwao Yamazaki, Masayoshi Kumegawa
    Abstract:

    To study the effect of Ipriflavone on osteoclast-mediated bone resorption and new osteoclast formation, we used an unfractionated bone cell culture system containing mature osteoclasts from femur and tibia of newborn mice. Ipriflavone (10−5 M) inhibited pit formation on dentin slices and caused a decrease in the number of tartrate-resistant acid phosphatase (TRAP)-positive (+) multinucleate cells (MNCs) in a 4-day culture period in which no increase in the number of TRAP(+)-MNCs was observed in the presence of 5% fetal bovine serum (FBS) and 10−8 M 1α,25-dihydroxy-vitamin D3 (1α,25(OH)2D3). During the following 12 days, both the total area of the pits and the number of TRAP(+)-MNCs increased in the control. Continuous treatment with Ipriflavone also inhibited the increase in pit area during this period. These effects of Ipriflavone were reversible. Furthermore, the differentiation of osteoclasts was examined when preexisting TRAP(+)-MNCs were removed by incubation in the absence of 1α,25(OH)2D3 for the initial 4 days in culture dishes without dentin slices. When 1α,25(OH)2D3 and Ipriflavone were added to the medium on the 4th day, Ipriflavone inhibited new TRAP(+)-MNC formation stimulated by 1α,25(OH)2D3 in a dose-dependent manner. However, pretreatment of the cells with Ipriflavone before the addition of 1α,25(OH)2D3 did not inhibit TRAP(+)-MNC formation. These results indicate that Ipriflavone inhibits both the activation of mature osteoclasts and the formation of new osteoclasts without affecting growth of TRAP-negative progenitor cells.

  • Inhibitory effect of Ipriflavone on pit formation in mouse unfractionated bone cells
    Calcified Tissue International, 1992
    Co-Authors: Kohei Notoya, K. Yoshida, Shigehisa Taketomi, Iwao Yamazaki, Masayoshi Kumegawa
    Abstract:

    Effects of Ipriflavone (7-isopropoxyisoflavone) on osteoclast-induced bone resorption were evaluated using an unfractionated bone cell culture system containing mature osteoclasts from the femur and tibia of newborn mice. When cells were cultured for 4 days on dentin slices in the presence of 5% fetal bovine serum and 10^−8 M 1α,25(OH)_2D_3, Ipriflavone (3 x 10^−7-3 x 10^−5 M) inhibited pit formation and caused a decrease in the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs). The lowest significant effect was observed at a concentration of 10^−6 M. Unlike Ipriflavone, calcitonin inhibited pit formation 4 days after the culture was started without affecting the number of TRAP-positive MNCs. Ipriflavone still inhibited pit formation when the culture period was 13 days, when new osteoclasts were expected to be formed. These findings suggest that Ipriflavone inhibits new osteoclast formation and bone resorption at the cellular level.

K Notoya - One of the best experts on this subject based on the ideXlab platform.

  • Novel Ipriflavone receptors coupled to calcium influx regulate osteoclast differentiation and function.
    Endocrinology, 1996
    Co-Authors: A Miyauchi, K Notoya, S Taketomi, Y Takagi, Y Fujii, K Jinnai, K Takahashi, Kazuo Chihara, Takuo Fujita
    Abstract:

    Ipriflavone (7-isopropoxyisoflavone) is an effective antiresorptive agent used to treat osteoporosis. However, the mechanism of its action on osteoclasts and their precursor cells is not well understood. To determine whether the mechanism involves direct effects on osteoclasts or their precursors, we examined the effects of Ipriflavone on cytosolic free calcium ([Ca2+]i) in osteoclasts and their precursors and measured specific binding of 3H-labeled Ipriflavone. Highly purified chicken osteoclast precursors, which spontaneously differentiate into multinucleated osteoclasts in 3-6 days, were loaded with fura-2, and the subcellular [Ca2+]i distribution was monitored by videoimaging. Ipriflavone induced a rapid increase in [Ca2+]i followed by a sustained elevation [EC50 = 5 x 10(-7) M, 263 +/- 74 nM (SE) (n = 8) above basal levels, by 10(-6) M Ipriflavone, sustained phase]. The responses were the same in differentiated chicken osteoclasts and isolated rabbit osteoclasts. An influx of extracellular Ca2+ is likely to be responsible for the Ipriflavone-induced change in [Ca2+]i because the response was abolished by 0.5 mM LaCl3, or by Ca-free medium containing EGTA. Moreover, high [Ca2+]i levels were detected adjacent to the cell membrane after Ipriflavone addition. Ipriflavone induced Ca influx mainly through dihydropyridine-insensitive Ca2+ channels, because nicardipine (10(-7)M) and verapamil (10(-7)M) had no effects on Ipriflavone-induced [Ca2+]i responses. [3H]Ipriflavone binding studies indicated the presence of specific Ipriflavone binding sites (two classes), both in precursor cells [dissociation constant (Kd), 7.60 x 10(-8)M, 2.67 x 10(-6)M] and in mature osteoclasts (Kd, 4.98 x 10(-8)M, 3.70 x 10(-6)M). Specific Ipriflavone binding was not displaced by various modulators of avian osteoclast function, such as estradiol (10(-8)M) or retinoic acid (10(-6)M), indicating that Ipriflavone receptors differ from the receptors for these Ca-regulating hormones. The fusion of osteoclast precursor cells was significantly inhibited by Ipriflavone, which led to dose-dependent inhibition of bone resorption and tartrate-resistant acid phosphatase activity. Novel specific Ipriflavone receptors that are coupled to Ca2+ influx were demonstrated in osteoclasts and their precursor cells. These Ipriflavone receptors may provide a mechanism to regulate osteoclast differentiation and function.

  • Increase in femoral bone mass by Ipriflavone alone and in combination with 1α-hydroxyvitamin D_3 in growing rats with skeletal unloading
    Calcified Tissue International, 1996
    Co-Authors: K Notoya, S Taketomi, K. Yoshida, R. Rsukuda, M. Tsuda
    Abstract:

    We assessed the possibility that Ipriflavone treatment might result in bone restoration in immobilized rats. We also investigated the effect of combined treatment with Ipriflavone and vitamin D_3 on the bone. Male Sprague-Dawley rats, 6 weeks of age, were subjected to unilateral sciatic neurectomy. Three weeks after the operation, Ipriflavone (100 mg/kg), 1α-hydroxyvitamin D_3 [1α(OH)D_3, 25 ng/kg], or both Ipriflavone and 1α(OH)D_3 were orally administered every day for 12 or 24 weeks. After 12 weeks of treatment, only the group receiving combined treatment with Ipriflavone and 1α(OH)D_3 showed increases in total femur calcium content (+16.4%, compared with the control). After 24 weeks, both animals treated with Ipriflavone alone and those that had received the combination of Ipriflavone and 1α(OH)D_3 showed significant increases in femur calcium content (+18.0% and +23.8%, respectively). In these treatment groups, X-ray analysis revealed an increase in bone mineral density over the entire length of the femur, and an increase in cortical diameter at the midshaft without affecting medullary width. Administration of 1α(OH)D_3 (25 ng/kg) alone had no effect. Body weight, femur length, and serum markers of calcium and bone metabolism were not affected in any group. We evaluated the relationship between Ipriflavone and vitamin D_3 in bone cells in a culture system using rat bone marrow stromal cells in which the cells subsequently form mineralized bone-like tissue. Continuous treatment with Ipriflavone (10^−5 M) for 21 days resulted in an increase in osteocalcin secretion, and enhanced its response to 1α,25-dihydroxyvitamin D_3 (10^−11 M-10^−8 M). These findings indicate that Ipriflavone treatment increases the femoral bone mass in immobilized rats. In addition, a low dose of 1α(OH)D_3, which did not induce hypercalcemia, in combination with Ipriflavone, augmented the stimulatory effect of Ipriflavone alone on the bone mass, possibly due to a direct effect of each agent on osteoblastic cells.

  • Similarities and differences between the effects of Ipriflavone and vitamin K on bone resorption and formation in vitro
    Bone, 1995
    Co-Authors: K Notoya, K. Yoshida, Shigehisa Taketomi, Y. Shirakawa, M. Tsuda
    Abstract:

    The effects of Ipriflavone and vitamin K on bone metabolism were examined using a culture system. Vitamin K 1 and vitamin K 2 (10 −7 M-10 −5 M) inhibited both the activation of mature osteoclasts and the formation of new osteoclasts without affecting the growth of progenitor cells in cultures of mouse unfractionated bone cells. The inhibitory effects of vitamin K on bone resorption were similar to those of Ipriflavone and were not affected by the vitamin K antagonist warfarin. When Ipriflavone was added to the culture medium in combination with vitamin K 2 , an additive inhibitory effect on bone resorption was observed. An additive effect was also observed in organ cultures of mouse calvaria. On the other hand, Ipriflavone, but neither vitamin K 1 nor vitamin K 2 , stimulated cellular alkaline phosphatase (ALP) activity on rat bone marrow stromal cells under culture conditions in which cells subsequently form mineralized bone-like tissue. Vitamin K 1 and vitamin K 2 also did not modulate the stimulatory effect of Ipriflavone on the ALP activity of the cells. These results suggest that the inhibitory effects of vitamin K on bone resorption are similar to those of Ipriflavone through mechanisms that may be independent of the γ-carboxylation system, while the effects of vitamin K on osteoblast phenotype expression are different from those of Ipriflavone.