Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ipriflavone (IP), an isoflavone derivative, seems to prevent the loss of bone mass through the inhibition of bone resorption, mainly inhibiting the recruitment of osteoclasts. We investigated whether a brief course of treatment with IP can reduce biochemical parameters of accelerated bone turnover and bone pain in patients with active Paget's disease of bone. Sixteen patients (9 males and 7 females) with active Paget's disease were randomly allocated to two different crossed-over dose regimens of treatment with IP (600 mg/day vs. 1200 mg/day). Each treatment course lasted 30 days and the wash-out period between the two sequences was 15 days. Serum alkaline phosphatase (Al.Ph.) and urinary hydroxyproline/creatinine excretion (HOP/Cr) were reduced after each sequence. At the end of the 600/1200 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 32% and 25.6% respectively. At the end of the 1200/600 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 33% (P < 0.01) and 24.1% (P < 0.05) respectively. Furthermore, a significant decrease in bone pain was observed during the 1200/600 mg/day sequence (P < 0.01). Both treatment schedules were well tolerated and the patients' compliance resulted excellent. Our results indicate that short-term treatment with IP can reduce biochemical parameters of disease activity and bone pain in patients with active Paget's disease of bone.
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PMID:Short-term treatment of Paget's disease of bone with ipriflavone. 142 19

Protective effects of ipriflavone, an isoflavone derivative, in osteoporosis are believed to be caused by the inhibitory action on bone resorption. A direct effect of ipriflavone on bone formation is as yet unknown. Ipriflavone and four of its metabolites (I, II, III, and V) were examined for their effects on parathyroid hormone response, collagen synthesis, alkaline phosphatase activity, and cell proliferation in a clonal cell population of rat osteoblastic cells. Pretreatment of osteoblasts with high concentrations of ipriflavone for 48 h significantly inhibited the cAMP response to parathyroid hormone, producing a shift in the dose-response curve; at lower concentrations metabolites II and III potentiated the cAMP accumulation induced by low doses of parathyroid hormone. The 48 h treatment with metabolite V at the 1 nM dose significantly stimulated collagen synthesis in osteoblastic cells. Ipriflavone and metabolite I showed a biphasic stimulatory action on the alkaline phosphatase activity of osteoblasts, with a maximal effect at the 0.1 and 1 nM doses, respectively. A similar biphasic response was observed with ipriflavone and metabolite I on osteoblastic cell growth, with a maximal effect at the 0.1 nM concentration. These results suggest a direct role of ipriflavone in modulating the synthetic and growth properties of osteoblast-like cells.
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PMID:Effects of ipriflavone and its metabolites on a clonal osteoblastic cell line. 166 5

Twenty patients with post-menopausal osteoporosis were randomly divided into two groups of ten patients and treated under double-blind conditions with ipriflavone (Osteofix) or placebo. The dosage was 600 mg/day given in three doses and treatment lasted 6 months. All the patients received an oral calcium supply (1 g per day). At baseline and then after 3 and 6 months, the following parameters were controlled: bone mineral content at the lumbar spine, distal radius and femoral shaft; parameters of bone metabolism (alkaline phosphatase, PTH, osteocalcin, calcitonin, calciuria and hydroxyprolinuria); clinical conditions (pain at rest and on movement, motility). Ipriflavone facilitated the conservation of bone mass, that increased in one of the tested areas (distal radius). On the contrary, a bone mineral loss was found in the group treated with placebo, which was significant in the spine. Pain and motility significantly improved in the group treated with ipriflavone; there was an initial improvement in the control group, followed by a sharp worsening. The parameters investigated showed a significant reduction of osteocalcin in the ipriflavone group that indicates a modulation on bone turnover. The drug was well tolerated and compliance to oral treatment was excellent.
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PMID:Metabolic and clinical effects of ipriflavone in established post-menopausal osteoporosis. 266 Nov 84

To assess the potential impact of ipriflavone on the biomechanical properties and mineral composition of bone, we administered two doses (200 or 400 mg/kg bw) of the drug orally to adult male rats for 1 month. Bone biomechanics were evaluated by vibration damping, an index of strain energy loss, and impact strength (the amount of energy required to fracture after a single impact). At the higher dose, ipriflavone significantly decreased vibration damping of rat femurs by 23.0 +/- 9.8% compared with control, vehicle-treated animals, suggesting a higher capacity to withstand dynamic stress. This result was confirmed by the impact strength studies showing that a higher energy (49.6 +/- 21.3% above control) was required to fracture femurs of rat treated with 400 mg/kg bw ipriflavone. The high dose of ipriflavone increased bone mineral density, assessed by both volume displacement and ash analysis (4.2% and 2.5% above controls, respectively). The relative content of calcium, phosphorus, and magnesium in the ashes was not different among the treated and untreated groups, indicating that no gross abnormalities in mineral composition of bone occurred after ipriflavone administration. Similarly, there were no differences in serum calcium and magnesium levels between treated and control animals at the end of the study, whereas lower circulating phosphorus levels were detected in the latter. Ipriflavone treatment was not associated with significant changes in serum alkaline phosphatase nor type I collagen telopeptide levels, two markers of bone turnover. In summary, 1-month treatment with ipriflavone increased bone density and improved the biomechanical properties of adult rat male bones without altering mineral composition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ipriflavone improves bone density and biomechanical properties of adult male rat bones. 775 27

Ipriflavone (IP), an isoflavone derivative, has been shown to interfere with bone remodeling by inhibiting bone resorption and perhaps stimulating bone formation. In this study, we have analyzed the effect of IP and its metabolites on the differentiation and function of human osteoblastic cells. Bone marrow stromal osteoprogenitor cells (BMC) and trabecular bone osteoblasts (HOB) were isolated from human donors. The former can be induced to differentiate by treatment with dexamethasone, whereas the latter represent a more differentiated osteoblast. Incubation of BMC with metabolite III (10(-5) M) for 1 week induced modest but significant changes of alkaline phosphatase activity. Though both IP and metabolite III stimulated the expression of bone sialoprotein mRNA, a protein involved in cell attachment to the matrix, only metabolite III increased the steady-state level of decorin mRNA, a collagen fibrillogenesis-regulating proteoglycan. Metabolites III and V, but not the other isoflavones, increased the expression of type I collagen mRNA in HOB, whereas no detectable changes were observed in BMC cells with any of the experimental compounds. In HOB, an increased abundance of osteopontin and bone sialoprotein mRNA were also obtained after 1-week treatment with IP or metabolite V. No appreciable effects of IP or its metabolites were seen on osteocalcin expression and synthesis by either cell type. Finally, IP consistently increased the amount of 45Ca incorporated into the cell layer by BMC, and stimulated mineralization of both BMC and HOB, assessed by von Kossa staining. Thus, IP and its metabolites regulate the differentiation and biosynthetic properties of human bone-forming cells by enhancing the expression of some important matrix proteins and facilitating the mineralization process.
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PMID:Stimulation of human osteoblast differentiation and function by ipriflavone and its metabolites. 786 17

Ipriflavone (IP) (7-isopropoxyisoflavone), a synthetic isoflavone derivative, is active in both inhibiting bone resorption and enhancing osteoblast function. This property suggested its clinical use in the treatment of involutional osteoporosis, and in the prevention of postmenopausal bone mass loss. Forty postmenopausal women with low bone mineral content were enrolled and randomly treated for 12 months with IP 600 mg/day or placebo (PL), according to a double-blind, parallel group design. All patients wee also given an oral calcium supplementation (1 g/day). Bone mineral density (BMD) was measured at the spine (L2-L4) by dual-energy X-ray absorptiometry and at the distal radius by single-photon absorptiometry. Bone metabolism markers (serum calcium, phosphate, osteocalcin, and alkaline phosphatase, and urinary calcium, phosphate, and hydroxyproline) were assessed at the same times. After 12 months, a reduction of BMD was evidenced in the PL-treated group, at both the spine (-2.2%, P < 0.01 vs baseline) and the forearm (-1.2%). In the IP-treated group, an increase of BMD was obtained (+1.2%, P < 0.01 vs placebo, at the spine; +3%, not significant, at the forearm). Bone markers were in the normal range for postmenopausal women; no statistically significant modifications were observed during the treatment period. Three patients were withdrawn from the treatment in the IP-treated group, and two in the PL-treated group for gastrointestinal disturbances. In the other women, the tolerance of the drug was good and the compliance with the oral treatment was excellent.
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PMID:Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass. 806 53

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.
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PMID:Effect of ipriflavone on expression of markers characteristic of the osteoblast phenotype in rat bone marrow stromal cell culture. 819 34

The aim of this study is to evaluate the association between GnRH analogues and ipriflavone, drug modulating the bone turnover limiting the negative bone effects of analogue. Thirty patients (33 +/- 5.4 years, mean +/- SD) affect by benign gynecological conditions in which there was an indication to use GnRH analogs have been treated with leuprolide acetate at the monthly intramuscular dose of 3.75 mg, for six months. Fifteen of these patients also received 600 mg/day per os of ipriflavone (group A), while the other 15 patients have been treated exclusively with leuprolide acetate (group B). Before and after treatment, radial bone mineral density (BMD) and main markers of bone turnover were measured in all patients. Before treatment no difference in the considered parameters could be detected between the two groups. In group A, after 6 months of treatment no significant decrease in BMD and no variations in the bone turnover parameters. On the contrary, in group B, after six months of treatment, a significant decrease (p < 0.05) in BMD was observed in comparison to basal and group A values. In the same group alkaline phosphatase, osteocalcin and urinary calcium/creatinine and hydroxyproline/creatinine ratio proved significantly increased in comparison to basal and group A values (both with p < 0.05). Ipriflavone, therefore, seems to be effective in counteracting the negative effects of GnRH-a induced on bone.
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PMID:[Effects of ipriflavone on bone loss induced by GnRH analog]. 900 68

Ipriflavone (i.p.) positively affects bone density in postmenopausal osteoporosis, primarily by inhibiting bone resorption. Using in vitro models of human osteoblast differentiation, we have observed that i.p. 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 i.p. 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 i.p. for 1 month. i.p. significantly decreased vibration damping, an index of strain energy loss. Because vibration damping increases as bone porosity increases, the results indicate that i.p.-treated bones acquired a higher capacity to withstand dynamic stress. In fact, 1.5-fold higher energy was required to fracture femurs of i.p.-treated rats after a single supramaximal impact. i.p. 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 i.p. administration. As a measure of bone crystallinity, X-ray diffraction analysis was performed. The broadening parameter beta 1/2 for the (310) and (002) reflections was not significantly different between i.p.-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 i.p. increased bone density and improved the biomechanical properties of adult male rat bones without altering mineral composition or bone crystallinity.
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PMID:In vitro and in vivo effects of ipriflavone on bone formation and bone biomechanics. 926 10

Ipriflavone (7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one) is a synthetic flavonoid that has been shown to stimulate the activity of osteoblasts. We show here that ipriflavone also promotes the deposition of calcium and the formation of mineralized nodules by newborn rat calvarial osteoblast-like (ROB) cells as well as the activity of alkaline phosphatase. We reported previously that endothelin-1 inhibits the differentiation of ROB cells [Y. Hiruma et al. (1998) J. Cardiovasc. Pharmacol. 31, S521-S523]. Therefore, we examined the effects of ipriflavone on the expression of endothelin receptors in ROB cells by polymerase chain reaction-Southern blot analysis and in binding assays with 125I-labeled endothelin-1. Ipriflavone reduced levels of endothelin ETA receptors (to 48% of the control level) in ROB cells around day 7 in our standard cultures, while it had no apparent effect on the expression of the mRNA for the endothelin ETA receptor. By contrast, treatment with 10(-7) M endothelin-1 on days 6 through 9 alone suppressed mineralization by ROB cells. Ipriflavone also reduced the ability of endothelin-1 to inhibit mineralization by ROB cells. These results suggest that the acceleration of osteoblastic differentiation by ipriflavone might be due, at least in part, to a time-specific down-regulation of endothelin receptors.
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PMID:Ipriflavone down-regulates endothelin receptor levels during differentiation of rat calvarial osteoblast-like cells. 1039 35


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