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Research Reports On

ipriflavone

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Record 1 from database: MEDLINE
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Title

Effects of ipriflavone administration on bone mass and metabolism in ovariectomized women.

Author

Gambacciani M; Spinetti A; Cappagli B; Taponeco F; Felipetto R; Parrini D; Cappelli N; Fioretti P

Address

Istituto di Clinica Ostetrica e Ginecologica, Università di Pisa, Italy.

Source

J Endocrinol Invest, 1993 May, 16:5, 333-7

Abstract

The aim of the present study was to assess the effects of ipriflavone administration in the prevention of the rapid bone loss that follows ovariectomy in women. After 10-30 days from bilateral ovariectomy, patients received either the sole calcium supplementation (500 mg/day, n = 16) or ipriflavone (600 mg/day, n = 16) in addition to the same daily calcium supplement for 12 months. In calcium-treated subjects urinary hydroxyproline excretion, serum alkaline phosphatase and plasma bone Gla protein levels showed a substantial (p < 0.01) increase, while radial bone density significantly (p < 0.01) decreased 6 months after surgery. In ipriflavone treated group the patterns of biochemical markers indicated that ipriflavone can restrain the bone remodeling processes and radial bone density showed no significant modification during the 12 month study period. These results demonstrate that ipriflavone administration prevents the rapid bone loss that follows ovariectomy. Thus, ipriflavone can represent an attractive alternative for the prevention of osteoporosis in postmenopausal women who present contraindications to the estrogen replacement therapy.

Language of Publication

English

Unique Identifier

93308352

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MeSH Heading (Major)

Bone and Bones|*DE/ME; Bone Density|*DE; Isoflavones|PD/*TU; Osteoporosis, Postmenopausal|*PC; Ovary|*PH

MeSH Heading

Double-Blind Method; Female; Human; Middle Age; Ovariectomy|AE

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0391-4097

Country of Publication

ITALY

CAS Registry/EC Number

0 (Isoflavones); 35212-22-7 (Yambolap)

Record 2 from database: MEDLINE
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Title

Lack of any estrogenic effect of ipriflavone in postmenopausal women.

Author

Melis GB; Paoletti AM; Cagnacci A; Bufalino L; Spinetti A; Gambacciani M; Fioretti P

Address

Istituto di Ginecologia Ostetricia e Fisiopatologia della Riproduzione Umana, University of Cagliari, Italy.

Source

J Endocrinol Invest, 1992 Nov, 15:10, 755-61

Abstract

Estrogen replacement therapy (ERT) has been demonstrated to prevent osteoporosis in postmenopausal women (PMW). However, several contraindications exist for ERT and many PMW cannot be treated. It has also been shown that too low doses of ERT are able to exert therapeutical effects on some climacteric symptoms but not on bone and compounds exerting synergic actions with ERT on bone without effects on other organs could be useful. The isoflavone derivative, ipriflavone, seems to have this effect but data are lacking on its endocrine effect in humans; thus, this study was undertaken to clarify in PMW whether ipriflavone exerts estrogenic activity. Evaluation of LH and FSH secretion during a 24-h period was performed in a group of 15 PMW after a single oral dose of 600 or 1,000 mg of ipriflavone or placebo, and after 7, 14 and 21 days of oral treatment with ipriflavone 600 mg and 1,000 mg/daily, administered in three divided doses. LH secretion was also evaluated during naloxone infusion before and after 21 days of ipriflavone, placebo or conjugated estrogen treatment (0.625 mg/day; CE). LH response to NAL treatment was absent during ipriflavone and placebo such as it was observed before treatments. By contrast, a significant increase of LH plasma levels was measured during naloxone infusion in CE-treated women. This result demonstrates that ipriflavone is unable to exert the same effects that estrogens do in PMW. In addition, no changes like in placebo group were seen on vaginal cytology in this group of subjects after 21 days, whereas a significant increase of superficial vaginal cells was observed after 21 days of CE treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

93147470

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MeSH Heading (Major)

Estrogen Replacement Therapy|*; Estrogens|*BL; Isoflavones|*TU

MeSH Heading

Estradiol|BL; Female; FSH|BL; Human; LH|BL; Middle Age; Naloxone|PD; Prolactin|BL; Radioimmunoassay

Publication Type

CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; JOURNAL ARTICLE

ISSN

0391-4097

Country of Publication

ITALY

CAS Registry/EC Number

0 (Estrogens); 0 (Isoflavones); 35212-22-7 (Yambolap); 465-65-6 (Naloxone); 50-28-2 (Estradiol); 9002-62-4 (Prolactin); 9002-67-9 (LH); 9002-68-0 (FSH)

Record 3 from database: MEDLINE
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Title

Ipriflavone and low doses of estrogens in the prevention of bone mineral loss in climacterium.

Author

Melis GB; Paoletti AM; Bartolini R; Tosti Balducci M; Massi GB; Bruni V; Becorpi A; Ottanelli S; Fioretti P; Gambacciani; M; et al

Address

Department of Gynecology Obstetrics and Pathophysiology of Human Reproduction, University of Cagliari, Italy.

Source

Bone Miner, 1992 Oct, 19 Suppl 1:, S49-56

Abstract

Estrogen replacement therapy can counteract all postmenopausal symptoms. While low estrogen doses (0.15-0.30 mg of conjugated estrogens/day) can counteract neurovegetative and psychological symptoms, higher estrogen doses (at least 0.625 mg of conjugated estrogens/day) are required to prevent bone mineral loss in postmenopausal women. However, if contra-indications to high estrogen doses exist, drugs other than estrogens can represent a suitable treatment for postmenopausal osteoporosis both alone or in combination with low estrogen doses. Experimental and clinical data have shown that ipriflavone is effective in the treatment of established postmenopausal osteoporosis. With the purpose of evaluating whether ipriflavone is able to enhance estrogen activity on bone metabolism, 133 postmenopausal women were randomly submitted to the treatment with: (1) placebo; (2) 0.15 mg/day of conjugated estrogens; (3) 0.30 mg/day of conjugated estrogens; (4) 0.15 mg/day of conjugated estrogens plus 600 mg/day of ipriflavone; (5) 0.30 mg/day of conjugated estrogens plus 600 mg/day of ipriflavone. One g/day of calcium supplementation was given to all women. In all subjects bone mineral density was measured before and after 6 and 12 months of treatment at the distal radius by dual-photon absorptiometry. A moderate decrease of bone mineral density was evidenced in women submitted to placebo or to estrogen therapy alone. By contrast, an increase of BMD was measured after 12 months of treatment in the women treated with 0.15 (not significant) or 0.30 mg/day (P < 0.01) of conjugated estrogens associated with ipriflavone. Both dosages of conjugated estrogens were able to induce a significant reduction of neurovegetative symptoms. The increase of bone density obtained with the combination of conjugated estrogens with ipriflavone demonstrates that this combination improves the effects of low estrogen doses on bone mass representing a satisfactory approach in the prevention and treatment of all symptoms related to the climacteric syndrome.

Language of Publication

English

Unique Identifier

93044804

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MeSH Heading (Major)

Bone Density|*DE; Estrogen Replacement Therapy|*; Isoflavones|PD/*TU; Osteoporosis, Postmenopausal|*DT/PP

MeSH Heading

Densitometry, X-Ray; Double-Blind Method; Drug Therapy, Combination; Female; Human; Middle Age

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL

ISSN

0169-6009

Country of Publication

NETHERLANDS

CAS Registry/EC Number

0 (Isoflavones); 35212-22-7 (Yambolap)

Record 4 from database: MEDLINE
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Title

Metabolic and clinical effects of ipriflavone in established post-menopausal osteoporosis.

Author

Agnusdei D; Zacchei F; Bigazzi S; Cepollaro C; Nardi P; Montagnani M; Gennari C

Address

Institute of Medical Semeiotics, University of Siena, Italy.

Source

Drugs Exp Clin Res, 1989, 15:2, 97-104

Abstract

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.

Language of Publication

English

Unique Identifier

89289413

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MeSH Heading (Major)

Bone and Bones|*ME; Flavones|*TU; Isoflavones|AE/*TU; Osteoporosis|*DT/ME

MeSH Heading

Clinical Trials; Double-Blind Method; Female; Human; Middle Age; Pain|ET; Random Allocation

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0378-6501

Country of Publication

SWITZERLAND

CAS Registry/EC Number

0 (Flavones); 0 (Isoflavones); 35212-22-7 (Yambolap)

Record 5 from database: MEDLINE
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Title

Effects of ipriflavone on bone remodeling in primary hyperparathyroidism.

Author

Mazzuoli G; Romagnoli E; Carnevale V; Scarda A; Scarnecchia L; Pacitti MT; Rosso R; Minisola S

Address

Cattedra di Medicina Interna, University of Rome, La Sapienza, Italy.

Source

Bone Miner, 1992 Oct, 19 Suppl 1:, S27-33

Abstract

The aim of this study was to evaluate the effects of ipriflavone treatment on bone remodeling in primary hyperparathyroidism. Nine patients, 6 females and 3 males (mean +/- SD age 56 +/- 12.5 years) were treated with 1200 mg/day of ipriflavone by oral administration divided in 3 daily doses. All patients were treated for 21 days; in 5 patients treatment was prolonged to 42 days. In all patients the main serum and urinary parameters of bone remodeling were evaluated. The results suggest that ipriflavone affects bone remodeling by inhibiting bone resorption without affecting bone formation. Ipriflavone is, therefore, indicated in the treatment of metabolic bone diseases characterized by a high bone turnover.

Language of Publication

English

Unique Identifier

93044800

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MeSH Heading (Major)

Bone Remodeling|*DE; Hyperparathyroidism|*DT/PP; Isoflavones|*PD/TU

MeSH Heading

Adult; Aged; Calcium|BL/UR; Creatinine|BL/UR; Female; Human; Hydroxyproline|BL; Male; Middle Age; Osteocalcin|BL; Phosphorus|BL

Publication Type

JOURNAL ARTICLE

ISSN

0169-6009

Country of Publication

NETHERLANDS

CAS Registry/EC Number

0 (Isoflavones); 104982-03-8 (Osteocalcin); 35212-22-7 (Yambolap); 51-35-4 (Hydroxyproline); 60-27-5 (Creatinine); 7440-70-2 (Calcium); 7723-14-0 (Phosphorus)

Record 6 from database: MEDLINE
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Title

Cytological and ultrastructural investigation on osteoblastic and preosteoclastic cells grown in vitro in the presence of ipriflavone: preliminary results.

Author

Bonucci E; Silvestrini G; Ballanti P; Masi L; Franchi A; Bufalino L; Brandi ML

Address

Department of Human Biopathology, University La Sapienza, Rome, Italy.

Source

Bone Miner, 1992 Oct, 19 Suppl 1:, S15-25

Abstract

The effects of ipriflavone on bone cells were studied in vitro on pre-osteoclastic (FLG 29.1) and osteoblast-like (Saos-2) cells grown for 48 h either separately or in co-cultures, with or without the addition of PTH. Histological, ultrastructural and histochemical (TRAP-activity demonstration) methods were used. The main results show that ipriflavone reduces replication of FLG 29.1 cells and inhibits TRAP production by these cells both in controls and in co-cultures treated with PTH. Moreover, it has a moderate stimulatory effect on proliferation of osteoblast-like cells and reduces the PTH-induced degenerative changes of Saos-2 cells. These results suggest that the inhibitory effect of ipriflavone on FLG 29.1 cells might be indirect and might be mediated by the osteoblast-like cells.

Language of Publication

English

Unique Identifier

93044799

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MeSH Heading (Major)

Isoflavones|*PD; Osteoblasts|*DE/UL; Osteoclasts|*DE/UL

MeSH Heading

Acid Phosphatase|ME; Cell Adhesion|DE; Cell Division|DE; Human; Microscopy, Electron; Parathyroid Hormones|PD; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0169-6009

Country of Publication

NETHERLANDS

CAS Registry/EC Number

EC 3.1.3.2 (Acid Phosphatase); 0 (Isoflavones); 0 (Parathyroid Hormones); 35212-22-7 (Yambolap)

Record 7 from database: MEDLINE
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Title

Double-blind study on the effectiveness of a bioflavonoid in the control of tinnitus in otosclerosis.

Author

Sziklai I; Komora V; Ribári O

Address

Department of Otorhinolaryngology, Semmelweis University Medical School, Budapest, Hungary.

Source

Acta Chir Hung, 1992-93, 33:1-2, 101-7

Abstract

Ipriflavone (7-isopropoxy-isoflavone) was attempted to relieve tinnitus of otosclerotic patients prior to stapedectomy and continuing the treatment postoperatively in a 6 months regimen. As a whole the double-blind study revealed effectiveness of Ipriflavone in the control of tinnitus when preoperatively administered as well as in combination with stapedectomy. The small number of cases (9 patients treated with Ipriflavone and 7 patients with placebo) needs further confirmation of the present data. Predominantly low-tone tinnitus rises the possibility of its cochlear origin in otosclerosis, as a consequence of mechanical or hydrodynamic causes or hydrostatic pressure elevation due to spread of the otosclerotic focus onto the cochlear duct.

Language of Publication

English

Unique Identifier

94136042

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MeSH Heading (Major)

Isoflavones|*TU; Otosclerosis|CO/PP/*SU; Tinnitus|*DT/ET

MeSH Heading

Adult; Audiometry, Pure-Tone; Combined Modality Therapy; Double-Blind Method; Human; Middle Age; Premedication; Stapes Surgery

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE

ISSN

0231-4614

Country of Publication

HUNGARY

CAS Registry/EC Number

0 (Isoflavones); 35212-22-7 (Yambolap)

Record 8 from database: MEDLINE
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Title

Effect of ipriflavone on bone mineral density and calcium-related factors in elderly females.

Author

Nakamura S; Morimoto S; Takamoto S; Onishi T; Fukuo K; Koh E; Kitano S; Miyashita Y; Yasuda O; Tamatani M; et al

Address

Department of Medicine, Hanwa-senboku Hospital, Osaka, Japan.

Source

Calcif Tissue Int, 1992, 51 Suppl 1:, S30-4

Abstract

The effects of ipriflavone (7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one) on bone mineral density (BMD) of the 3rd lumbar vertebra and on calcium (Ca)-related factors, including serum calcitonin (CT) levels before and after rapid calcium infusion (4 mg/kg for 5 minutes), were studied in 11 elderly female subjects (80 +/- 2 years of age, mean +/- SE). Ipriflavone (IP) administration (600 mg/day, 7 months) resulted in inhibition of BMD loss in 7 patients (responders, mean change of BMD value 2.2 +/- 2.3%), whereas 4 patients showed a loss of BMD (nonresponders, mean change of BMD value -13.1 +/- 2.6%) compared with pretreatment values. The responder group showed a significant increase in mean pretreatment serum CT levels (from 20 +/- 2 pg/ml to 42 +/- 7 pg/ml, P < 0.05) after treatment with IP, and a significant decrease in the mean basal serum level of corrected Ca (from 9.6 +/- 0.2 mg/dl to 8.7 +/- 0.1 mg/dl, P < 0.01) after treatment with IP; nonresponders did not show these changes. For responders, both the percentage of change and the maximal value of serum CT in response to Ca infusion were maintained at rather high levels, both before and after IP treatment; nonresponders showed almost no response to a stimulation test for CT. These findings suggest that IP inhibits bone loss in elderly female subjects possibly through the mechanism of increasing CT secretion.

Language of Publication

English

Unique Identifier

93045731

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MeSH Heading (Major)

Bone Density|*DE; Calcitonin|*BL; Isoflavones|*PD/TU; Osteoporosis|*DT/PP

MeSH Heading

Aged; Aged, 80 and over; Alkaline Phosphatase|BL; Calcitriol|BL; Calcium|ME/PD; Female; Human; Lumbar Vertebrae; Parathyroid Hormones|BL; Phosphates|UR

Publication Type

JOURNAL ARTICLE

ISSN

0171-967X

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 3.1.3.1 (Alkaline Phosphatase); 0 (Isoflavones); 0 (Parathyroid Hormones); 0 (Phosphates); 32222-06-3 (Calcitriol); 35212-22-7 (Yambolap); 7440-70-2 (Calcium); 9007-12-9 (Calcitonin)

Record 9 from database: MEDLINE
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Title

Ipriflavone: pharmacological properties and usefulness in postmenopausal osteoporosis.

Author

Reginster JY

Address

Centre Universitaire d'Investigation du Métabolisme Osseux et du Cartilage Articulaire (CIMOCA), University of Liège, Belgium.

Source

Bone Miner, 1993 Dec, 23:3, 223-32

Abstract

Ipriflavone (IP) is an isoflavone derivative available in several countries for investigational and/or therapeutic use. Inhibition of bone resorption was demonstrated in several models, both in vitro and in vivo for IP and its metabolites. Their mechanisms of action on bone are not yet fully elucidated but some of them are widely accepted. IP does not possess, per se, any estrogenic activity. It appears that IP-related inhibition of bone resorption might be mediated by an indirect effect on osteoclast and related to an inhibition of recruitment and/or differentiation of pre-osteoclast, maybe through a modulation of osteoblast response to PTH. Clinical studies in Paget's disease of bone or primary hyperparathyroidism have confirmed preferential inhibition of bone resorption suggesting a clinical interest in postmenopausal osteoporosis. Preliminary (1 year) results of double blind placebo controlled studies designed in postmenopausal and senile osteoporosis confirm a reduction in bone turnover rate in patients treated with 600 mg/day of IP, resulting in a significant bone-sparing effect both at lumbar and radial levels. All clinical and pharmacological trials confirm a very good tolerance of IP with a frequency of adverse reactions equal to that observed during administration of a placebo. Providing ongoing studies will confirm the actual promising preliminary results, IP seems a very interesting new non hormonal approach for prevention and treatment of postmenopausal and senile osteoporosis.

Language of Publication

English

Unique Identifier

94198651

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MeSH Heading (Major)

Bone Resorption|*DT; Isoflavones|PD/PK/*TU; Osteoporosis, Postmenopausal|*DT

MeSH Heading

Animal; Clinical Trials; Disease Models, Animal; Female; Human; Hyperparathyroidism|DT; Osteitis Deformans|DT; Rats

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0169-6009

Country of Publication

IRELAND

CAS Registry/EC Number

0 (Isoflavones); 35212-22-7 (Yambolap)

Record 10 from database: MEDLINE
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Title

Effect of ipriflavone and estrogen on the differentiation and proliferation of osteogenic cells.

Author

Kakai Y; Kawase T; Nakano T; Mikuni-Takagaki Y; Saito S

Address

Department of Oral Biochemistry, Kanagawa Dental College, Japan.

Source

Calcif Tissue Int, 1992, 51 Suppl 1:, S11-5

Abstract

The effect of ipriflavone (IP) on the proliferation and differentiation of rat osteoblast-like (ROB) cells and human periodontal ligament fibroblasts (HPLF) was studied in the presence and absence of estrogen. ROB cells were isolated from newborn rat calvaria by sequential collagenase digestion and HPLF from the outgrowth of human periodontal ligament in culture. The alkaline phosphatase (ALP) activity, employed as a marker of bone cell differentiation, was significantly enhanced by IP in both cell types; however, the concentration at which IP had a maximal effect was lower in ROB cells than in HPLF (10(-10) versus 10(-7) M, respectively). Cell proliferation judged by DNA content was either constant (ROB cells) or slightly increased (HPLF) by IP up to 10(-10) M, and decreased significantly above that concentration. In addition, the dose-dependent effect of estrogen on the growth and differentiation of each cell type in the presence and absence of IP was also tested. At the concentrations of IP which showed maximum effects in the induction of ALP, 10(-10) M for ROB cells and 10(-7) M for HPLF, IP inhibited DNA increase in an estrogen-independent manner. Estradiol (10(-11)-10(-9) M) itself increased the growth rate of both cell types significantly in a dose-dependent manner. Regardless of the concentrations of estradiol tested, ALP activities of both ROB cells and HPLF were elevated by the addition of IP. The ratio of ALP in the presence and absence of IP was similar over the range of estradiol concentrations tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

93045726

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MeSH Heading (Major)

Estradiol|*PD; Fibroblasts|CY/*DE; Isoflavones|*PD; Osteoblasts|CY/*DE/EN

MeSH Heading

Alkaline Phosphatase|ME; Animal; Cell Differentiation|DE; Cell Division|DE; Dose-Response Relationship, Drug; Female; Human; Rats; Rats, Sprague-Dawley

Publication Type

JOURNAL ARTICLE

ISSN

0171-967X

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 3.1.3.1 (Alkaline Phosphatase); 0 (Isoflavones); 35212-22-7 (Yambolap); 50-28-2 (Estradiol)

Record 11 from database: MEDLINE
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Title

Effect of ipriflavone on bone mass in elderly osteoporotic women.

Author

Passeri M; Biondi M; Costi D; Bufalino L; Castiglione GN; Di Peppe C; Abate G

Address

Internal Medicine Institute, University of Parma, Italy.

Source

Bone Miner, 1992 Oct, 19 Suppl 1:, S57-62

Abstract

A study in elderly osteoporotic women was performed to assess the effect of one year treatment with ipriflavone (IP) on bone mass and bone biomarkers. Twenty-eight women aged over 65, with diagnosis of osteoporosis and X-ray evidence of at least one vertebral fracture, were treated with IP tablets (600 mg/day) or placebo (PL), according to a randomized, double-blind, parallel-group design. One g/day calcium supplementation was given to all patients. After 12 months a significant increase (+6%, P < 0.05) of bone mineral density (BMD) at the distal radius (DPA) was obtained in the IP-group. Serum osteocalcin (BGP) and urinary HO-proline/creatinine (HOP/Cr) values were reduced in the same group. BMD values did not change (-0.3%) in the placebo group. One woman of the PL-group was withdrawn from treatment because of worsening of pain, due to new vertebral crushes. Side effects (mainly gastrointestinal) arose in 8 IP- and in 5 PL-treated women. The compliance to the oral administration was good.

Language of Publication

English

Unique Identifier

93044805

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MeSH Heading (Major)

Bone Density|*DE; Isoflavones|PD/*TU; Osteoporosis|*DT/PP

MeSH Heading

Aged; Aged, 80 and over; Creatinine|UR; Double-Blind Method; Female; Human; Hydroxyproline|UR; Osteocalcin|BL; Spinal Fractures|ET

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0169-6009

Country of Publication

NETHERLANDS

CAS Registry/EC Number

0 (Isoflavones); 104982-03-8 (Osteocalcin); 35212-22-7 (Yambolap); 51-35-4 (Hydroxyproline); 60-27-5 (Creatinine)

Record 12 from database: MEDLINE
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Title

Effects of ipriflavone on bone mass and calcium metabolism in postmenopausal osteoporosis.

Author

Agnusdei D; Adami S; Cervetti R; Crepaldi G; Di Munno O; Fantasia L; Isaia GC; Letizia G; Ortolani S; Passeri M; et al

Address

Institute of Internal Medicine, University of Siena, Italy.

Source

Bone Miner, 1992 Oct, 19 Suppl 1:, S43-8

Abstract

Recently it has been demonstrated that ipriflavone (IP), an isoflavone derivative, is able to increase bone mass in patients with established postmenopausal osteoporosis (PMO). Here we present a preliminary report of a 2-year multicenter, double-blind, placebo-controlled clinical study performed in order to evaluate the efficacy and tolerability of IP in PMO. A large number of patients with PMO, referred to 12 Italian centers, was randomly divided into 2 groups and treated with oral IP (600 mg/day) or placebo (Pl). All patients received an oral Ca supplement (1 g/day). One hundred and twenty six patients completed 1 year of the study. Bone mineral density (BMD) of the distal radius, measured by DPA, serum osteocalcin (BGP), and urinary hydroxyproline excretion (HOP/Cr), were measured before and after 12 months. After 12 months, a significant increase in BMD was observed in the IP-treated group (P < 0.05). IP determined a reduction of HOP/Cr, while in Pl-treated patients a significant increase of this index, as well as of BGP, was observed. After 12 months the difference between the two groups resulted significant (P < 0.05) for BGP. The drug was well tolerated and the patients' compliance to the oral treatment resulted excellent. The results of this study indicate that IP is able to increase bone mass in patients with PMO.

Language of Publication

English

Unique Identifier

93044803

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MeSH Heading (Major)

Bone Density|*DE; Calcium|*ME; Isoflavones|AD/PD/*TU; Osteoporosis, Postmenopausal|*DT/PP

MeSH Heading

Aged; Double-Blind Method; Female; Human; Italy; Middle Age

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL

ISSN

0169-6009

Country of Publication

IRELAND

CAS Registry/EC Number

0 (Isoflavones); 35212-22-7 (Yambolap); 7440-70-2 (Calcium)

Record 13 from database: MEDLINE
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Title

Short-term treatment of Paget's disease of bone with ipriflavone.

Author

Agnusdei D; Camporeale A; Gonnelli S; Gennari C; Baroni MC; Passeri M

Address

Institute of Internal Medicine, University of Siena, Italy.

Source

Bone Miner, 1992 Oct, 19 Suppl 1:, S35-42

Abstract

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.

Language of Publication

English

Unique Identifier

93044802

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MeSH Heading (Major)

Bone and Bones|DE/*ME; Isoflavones|AD/*TU; Osteitis Deformans|*DT/ME

MeSH Heading

Administration, Oral; Aged; Alkaline Phosphatase|BL; Creatinine|UR; Double-Blind Method; Female; Human; Hydroxyproline|UR; Male; Middle Age; Pain|DT

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0169-6009

Country of Publication

NETHERLANDS

CAS Registry/EC Number

EC 3.1.3.1 (Alkaline Phosphatase); 0 (Isoflavones); 35212-22-7 (Yambolap); 51-35-4 (Hydroxyproline); 60-27-5 (Creatinine)

Record 14 from database: MEDLINE
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Title

Steady-state pharmacokinetics of ipriflavone and its metabolites in patients with renal failure.

Author

Rondelli I; Acerbi D; Ventura P

Address

Chemical and Biopharmaceutical Research Department, Chiesi Farmaceutici S.p.A., Parma, Italy.

Source

Int J Clin Pharmacol Res, 1991, 11:4, 183-92

Abstract

Ipriflavone is a recently introduced anti-osteoporotic agent extensively metabolized to four major metabolites (M1, M2, M3, M5). Its pharmacokinetics, after repeated doses of the drug, was investigated in patients with renal failure and compared with those of healthy volunteers. Plasma levels at steady-state of the unchanged drug, and its metabolites M1, M2 and M5 were higher in the patient group, with the presence of secondary peaks, which could be explained by the biliary excretion of the substances. Evaluation of renal elimination in patients in respect to healthy volunteers was performed by a "relative renal elimination index". The index decreased with the increase of renal disease mainly when the renal failure was moderate to severe.

Language of Publication

English

Unique Identifier

92258999

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MeSH Heading (Major)

Isoflavones|*PK; Kidney Failure, Chronic|CO/*ME

MeSH Heading

Adult; Aged; Female; Human; Male; Middle Age; Osteoporosis|DT

Publication Type

JOURNAL ARTICLE

ISSN

0251-1649

Country of Publication

SWITZERLAND

CAS Registry/EC Number

0 (Isoflavones); 35212-22-7 (Yambolap)

Record 15 from database: MEDLINE
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Title

Effect of ipriflavone--a synthetic derivative of natural isoflavones--on bone mass loss in the early years after menopause.

Author

Gennari C; Agnusdei D; Crepaldi G; Isaia G; Mazzuoli G; Ortolani S; Bufalino L; Passeri M

Address

Internal Medicine and Medical Pathology Institute, University of Siena, Italy.

Source

Menopause, 1998 Spring, 5:1, 9-15

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.

Language of Publication

English

Unique Identifier

98353614

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MeSH Heading (Major)

Bone Density|*DE; Isoflavones|AD/PD/*TU; Osteoporosis, Postmenopausal|*PC

MeSH Heading

Administration, Oral; Alkaline Phosphatase|BL; Biological Markers|BL/UR; Calcium|AD/TU/UR; Cohort Studies; Creatinine|UR; Female; Human; Hydroxyproline|UR; Middle Age; Osteocalcin|BL; Spine|DE/PH; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

1072-3714

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 3.1.3.1 (Alkaline Phosphatase); 0 (Biological Markers); 0 (Isoflavones); 104982-03-8 (Osteocalcin); 35212-22-7 (Yambolap); 51-35-4 (Hydroxyproline); 60-27-5 (Creatinine); 7440-70-2 (Calcium)

Record 16 from database: MEDLINE
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Title

Ipriflavone as an inhibitor of human cytochrome P450 enzymes.

Author

Monostory K; Vereczkey L; Lévai F; Szatmári I

Address

Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.

Source

Br J Pharmacol, 1998 Feb, 123:4, 605-10

Abstract

1. Reduction of theophylline metabolism and elimination were observed in a theophylline-treated patient during ipriflavone administration. After withdrawal of ipriflavone, the serum theophylline level decreased to an extent similar to that found before administration of ipriflavone. The effects of ipriflavone and its major metabolites 7-hydroxy-isoflavone and 7-(1-carboxy-ethoxy)-isoflavone on cytochrome P450 activities were studied in vitro in human liver microsomes from three donors. 2. Ipriflavone and 7-hydroxy-isoflavone competitively inhibited phenacetin O-deethylase and tolbutamide hydroxylase activity. The parent compound and its dealkylated metabolite were strong inhibitors exhibiting Ki values around 10-20 microM, while 7-(1-carboxy-ethoxy)-isoflavone had no effect on the cytochrome P450 activities investigated. 7-Hydroxy-isoflavone is the only one that influenced nifedipine oxidase activity. It competitively inhibited this activity with a Ki value of 129.5 microM. 3. The steady state concentrations of ipriflavone and 7-hydroxy-isoflavone in plasma of patients receiving 3 x 200 mg daily doses of ipriflavone for 48 weeks were found to be 0.33 +/- 0.32 microM and 1.44 +/- 0.77 microM, respectively. 4. The results indicate that the decrease in theophylline metabolism observed in a patient treated with ipriflavone may be due to a competitive interaction of ipriflavone or its metabolite, 7-hydroxy-isoflavone with CYP1A2. On the other hand, our in vitro findings predict some more interaction with CYP2C9.

Language of Publication

English

Unique Identifier

98176554

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MeSH Heading (Major)

Cytochrome P-450|*AI; Enzyme Inhibitors|BL/*PD; Isoenzymes|*AI; Isoflavones|BL/*PD

MeSH Heading

Human; Kinetics; Microsomes, Liver|DE/EN

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE

ISSN

0007-1188

Country of Publication

ENGLAND

Record 17 from database: MEDLINE
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Title

Binding and bioeffects of Ipriflavone on a human preosteoclastic cell line.

Author

Benvenuti S; Petilli M; Frediani U; Tanini A; Fiorelli G; Bianchi S; Bernabei PA; Albanese C; Brandi ML

Address

Department of Clinical Physiopathology, University of Florence, School of Medicine, Italy.

Source

Biochem Biophys Res Commun, 1994 Jun, 201:3, 1084-9

Abstract

Ipriflavone, a synthetic isoflavone derivative, reduces bone resorption by inhibiting osteoclasts activity. In order to evaluate the role of Ipriflavone on osteoclast growth and differentiation, we tested Ipriflavone and its four "in vivo" main metabolites (Metabolites I, II, III, and V) on a clonal population of human osteoclast precursor cells (FLG 29.1). Pharmacological doses of Ipriflavone and Metabolite III were able to inhibit cell proliferation and interleukin 6 release. In co-cultures of FLG 29.1 cells and osteoblastic (Saos-2) cells Ipriflavone at 1 microM dose inhibited the adhesion of FLG 29.1 cells to the osteoblastic monolayer and reduced the immunocytochemical reaction of the vitronectin receptor. Binding studies with tritiated Ipriflavone showed the presence of a single specific binding site, wtih a Kd of about 70 nM and a binding capacity of 8 fmol/10(6) cells. These results demonstrate a direct effect of Ipriflavone and of Metabolite III on the human osteoclast precursor cell line FLG 29.1.

Language of Publication

English

Unique Identifier

94296373

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MeSH Heading (Major)

Isoflavones|*PD; Osteoclasts|CY/*DE

MeSH Heading

Cell Adhesion|DE; Cell Differentiation|DE; Cell Division|DE; Cell Line; Female; Human; In Vitro; Integrins|ME; Interleukin-6|ME; Receptors, Cytoadhesin|ME; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0006-291X

Country of Publication

UNITED STATES

Record 18 from database: MEDLINE
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Title

Ipriflavone prevents the bone mass reduction in premenopausal women treated with gonadotropin hormone-releasing hormone agonists.

Author

Gambacciani M; Spinetti A; Piaggesi L; Cappagli B; Taponeco F; Manetti P; Weiss C; Teti GC; La Commare P; Facchini V

Address

Department of Obstetrics and Gynecology University of Pisa, Italy.

Source

Bone Miner, 1994 Jul, 26:1, 19-26

Abstract

In the present study we assessed the effects of ipriflavone in the prevention of increased bone turnover and the rapid bone loss that follows medical induced hypogonadism caused by the administration of a gonadotropin hormone-releasing hormone agonist (GnRH-A). In a double blind, placebo-controlled study, ipriflavone (600 mg/day, tdd (three divided doses)) or identical placebo tablets were given with 500 mg/day of calcium to patients treated with 3.75 mg leuproreline acetate every 30 days, for 6 months. In placebo-treated subjects (n = 39), urinary hydroxyproline excretion and plasma bone GLA protein levels showed a substantial (P < 0.01) increase, while spine bone density and total body bone density significantly (P < 0.01) decreased after 3 and 6 months of GnRH-A administration. Conversely, in ipriflavone treated group (n = 39), no significant difference in bone markers and bone density was evidenced. These data indicate that ipriflavone can restrain the bone remodeling processes and prevent the rapid bone loss that follows medical induced hypogonadism. Thus, ipriflavone administration can be of value in the prevention of osteopenia in women treated with GnRH-A.

Language of Publication

English

Unique Identifier

95037886

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MeSH Heading (Major)

Bone Diseases, Metabolic|ME/PA/*PC; Gonadorelin|*AG/PH; Isoflavones|*TU; Premenopause|*ME/PH

MeSH Heading

Adult; Bone and Bones|DE/ME/PA; Bone Density|DE/PH; Comparative Study; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Female; Human; Hydroxyproline|UR; Middle Age; Osteocalcin|BL; Time Factors

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0169-6009

Country of Publication

IRELAND

Record 19 from database: MEDLINE
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Title

Ipriflavone inhibits bone resorption in intact and ovariectomized rats.

Author

Cecchini MG; Fleisch H; Mühibauer RC

Address

Department of Pathophysiology, University of Berne, Switzerland.

Source

Calcif Tissue Int, 1997, 61 Suppl 1:, S9-11

Abstract

The aim of this study was to investigate the possible inhibitory effect of ipriflavone on bone resorption in rats. For this purpose, 10-week-old, intact and ovariectomized (OVX) rats, prelabeled from birth with [3H]-tetracycline, were used. Bone resorption was monitored by measuring the urinary excretion of [3H]. The animals were fed a purified diet devoid of naturally occurring flavonoids. In the intact rats, the daily meal was given either as a single portion or divided into four portions, a procedure known to lead by itself to a decrease in bone resorption. Ipriflavone, given 7 days after OVX at the dose of 400 mg/kg B.W. daily mixed with the food, led within 2-3 days to a significant decrease in bone resorption equivalent to that of 27.2 micrograms/kg s.c. of 17 beta-estradiol. The inhibition was sustained for the length of the experiment, up to 21 days. Ipriflavone given 7 days before OVX prevented the increase in bone resorption induced by castration, the effect being dose-dependent between 50 and 400 mg/kg B.W. In contrast to 17 beta-estradiol, a 5-week treatment with ipriflavone failed to prevent the OVX-induced uterine atrophy. Significant inhibition of bone resorption was also seen in intact animals, provided they rapidly ingested the daily meal. Actually, the decrease in bone resorption induced by portioning the daily food masked the inhibitory effect of ipriflavone in intact animals. In conclusion, ipriflavone can decrease bone resorption in both intact and OVX animals given a purified diet as a single daily meal. In the OVX model, ipriflavone mimics the osteoprotective effect of estrogen. However, the lack of a uterotropic effect suggests that the compound can discriminate between bone and reproductive tissues.

Language of Publication

English

Unique Identifier

97409220

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MeSH Heading (Major)

Bone Resorption|*PC; Isoflavones|AD/PD/*TU

MeSH Heading

Administration, Oral; Analysis of Variance; Animal; Bone Remodeling|DE; Comparative Study; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Estradiol|AD/PD/TU; Female; Human; Isotope Labeling; Osteoporosis, Postmenopausal|DT/PC; Ovariectomy; Rats; Support, Non-U.S. Gov't; Urine|CH; Uterus|DE/PA

Publication Type

JOURNAL ARTICLE

ISSN

0171-967X

Country of Publication

UNITED STATES

Record 20 from database: MEDLINE
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Title

Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass.

Author

Gennari C; Adami S; Agnusdei D; Bufalíno L; Cervetti R; Crepaldi G; Di Marco C; Di Munno O; Fantasia L; Isaia GC; Mazzuoli GF; Ortolani S; Passeri M; Serni U; Vecchiet L

Address

Internal Medicine and Medical Pathology Institute, University of Siena, Policlinico Le Scotte, Italy.

Source

Calcif Tissue Int, 1997, 61 Suppl 1:, S19-22

Abstract

We present the results of two multicenter, double-blind, placebo-controlled, 2-year studies to evaluate the efficacy and tolerability of ipriflavone in postmenopausal women (PMW) with low bone mass. 453 PMW (aged 50-65 years) with a vertebral (VMD) or radial (RMD) mineral density value 1 SD lower compared with age-matched controls, were randomly selected to receive oral ipriflavone (200 mg T.I.D. at meals) or matching placebo, plus 1 g oral calcium daily. Vertebral (study A, by dual X-ray absorptiometry-DXA) and radial (study B, by dual photon absorptiometry-DPA) bone density, serum bone Gla-protein (BGP), and urinary hydroxyproline/creatinine (HOP/Cr) were measured every 6 months. In both studies, the Valid Completers (VC) analysis showed a maintenance of bone mass in ipriflavone-treated women, whereas in the placebo group, bone mineral density (BMD) was significantly decreased. The final outcome was a bone-sparing effect of 1.6% in study A, and of 3.5% in study B after 2 years. The Intention to Treat (ITT) analysis confirmed the decrease in the placebo group, with no changes in ipriflavone-treated women. A significant (P < 0.05) between-treatment difference was found in both studies. Biochemical markers of bone turnover decreased in patients treated with ipriflavone, thus suggesting a reduction of bone turnover rate. Twenty-six women treated with ipriflavone and 28 receiving the placebo dropped out because of side effects, mainly gastrointestinal. The compliance to the oral long-term treatment was good. The results of these studies show that ipriflavone is able to prevent both axial and peripheral bone loss in PMW with low bone mass, and is well tolerated.

Language of Publication

English

Unique Identifier

97409223

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MeSH Heading (Major)

Bone Density|*DE; Bone Remodeling|*DE; Isoflavones|AD/AE/PD/*TU; Osteoporosis, Postmenopausal|*DT

MeSH Heading

Administration, Oral; Aged; Analysis of Variance; Biological Markers|BL/UR; Cohort Studies; Creatinine|UR; Densitometry, X-Ray; Double-Blind Method; Female; Human; Hydroxyproline|UR; Lumbar Vertebrae|PH; Middle Age; Osteocalcin|BL; Radius|PH

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL

ISSN

0171-967X

Country of Publication

UNITED STATES

Record 21 from database: MEDLINE
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Title

Efficacy of ipriflavone in the prevention and treatment of postmenopausal osteoporosis.

Author

Kovács AB

Address

CHINOIN Pharmaceutical and Chemical Works Co. Ltd., Clinical Development Group, Budapest, Hungary.

Source

Agents Actions, 1994 Mar, 41:1-2, 86-7

Abstract

The efficacy of ipriflavone was investigated in a 1-year double-blind, placebo-controlled, parallel group clinical trial. Ninety-one postmenopausal women completed the study, 41 received ipriflavone and 50 placebo treatment. After six months the bone mineral density of the L2-L4 vertebral region increased in the ipriflavone-treated group (0.015 g/cm2), whereas it decreased in the placebo-treated group. The differences between the treatment groups were statistically significant. Our results support the efficacy of ipriflavone in the treatment of postmenopausal osteoporosis. Since the positive effect was more pronounced after 6 months, the possibility of an intermittent ipriflavone treatment might be taken into consideration in the future.

Language of Publication

English

Unique Identifier

94360966

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MeSH Heading (Major)

Bone Density|*DE; Isoflavones|AD/PD/*TU; Osteoporosis, Postmenopausal|*DT/PC

MeSH Heading

Aged; Comparative Study; Densitometry, X-Ray; Double-Blind Method; Female; Human; Lumbar Vertebrae; Middle Age

Publication Type

CLINICAL TRIAL; CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE

ISSN

0065-4299

Country of Publication

SWITZERLAND

Record 22 from database: MEDLINE
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Title

Bone density changes in postmenopausal women with the administration of ipriflavone alone or in association with low-dose ERT.

Author

de Aloysio D; Gambacciani M; Altieri P; Ciaponi M; Ventura V; Mura M; Genazzani AR; Bottiglioni F

Address

Department of Obstetrics and Gynecology, University of Bologna, Italy.

Source

Gynecol Endocrinol, 1997 Aug, 11:4, 289-93

Abstract

Ipriflavone is a synthetic flavonoid that has been shown to exert a direct inhibitory effect on osteoclastic activity and possibly stimulate the osteoblast activity in different experimental models. The aim of the present study was to evaluate the effects of either ipriflavone alone or ipriflavone plus low dose hormone replacement therapy (HRT) in the prevention of postmenopausal bone loss. Patients were randomly allocated to different treatment groups receiving calcium (500 mg/day, control group), continuous HRT (25 or 50 micrograms/day of transdermal 17 beta-estradiol) plus medrogestone 5 mg/day for 12 days/month, ipriflavone at the standard dose of 600 mg/day, or finally ipriflavone 600 mg/day plus 17 beta-estradiol 25 micrograms/day plus medrogestone 5 mg/day for 12 days/month. No significant differences in basal levels of biochemical markers of bone turnover or in basal bone mineral density (BMD) values were evident in the different groups. In the control group after 12 months, spine BMD showed a significant (p < 0.05) 3.41% decrease. The pattern of BMD modification was significantly different from controls in the high dose HRT group (+1.84%), the ipriflavone group (+0.11%), and the combined ipriflavone/HRT group (-0.22%). Conversely, the BMD pattern in the low dose HRT group (-0.55%) was similar to that observed in controls. Thus, present results confirm that ipriflavone and 50 micrograms/day of transdermal 17 beta-estradiol are effective measures in the prevention of postmenopausal osteopenia. A lower transdermal estrogen dose is unable to increase the antiresorptive effect of ipriflavone and did not exert any further action in the prevention of postmenopausal osteopenia.

Language of Publication

English

Unique Identifier

97418453

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MeSH Heading (Major)

Bone Density|*; Estrogen Replacement Therapy|*; Isoflavones|*TU; Postmenopause|*

MeSH Heading

Administration, Cutaneous; Alkaline Phosphatase|BL; Body Mass Index; Bone Remodeling; Creatinine|UR; Estradiol|AD/TU; Female; Human; Hydroxyproline|UR

Publication Type

JOURNAL ARTICLE

ISSN

0951-3590

Country of Publication

ENGLAND

Record 23 from database: MEDLINE
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Title

A double blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss.

Author

Agnusdei D; Crepaldi G; Isaia G; Mazzuoli G; Ortolani S; Passeri M; Bufalino L; Gennari C

Address

Institute of Internal Medicine and Medical Pathology, University of Siena, Nuovo Policlinico, Viale Bracci I-53100-Siena, Italy.

Source

Calcif Tissue Int, 1997 Aug, 61:2, 142-7

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.

Language of Publication

English

Unique Identifier

97383376

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MeSH Heading (Major)

Isoflavones|AE/*TU; Osteoporosis, Postmenopausal|*PC; Spinal Diseases|*PC

MeSH Heading

Aged; Bone Remodeling; Double-Blind Method; Female; Human; Middle Age; Patient Compliance

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0171-967X

Country of Publication

UNITED STATES

Record 24 from database: MEDLINE
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Title

The effect of ipriflavone and its main metabolites on theophylline biotransformation.

Author

Monostory K; Vereczkey L

Address

Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest, Hungary.

Source

Eur J Drug Metab Pharmacokinet, 1996 Jan, 21:1, 61-6

Abstract

The effect of ipriflavone and its major metabolites, 7-hydroxy-isoflavone and 7-(1-carboxy-ethoxy)-isoflavone on theophylline metabolism was examined in vitro in human liver microsomes. The compounds inhibited the N-demethylation to 1- or 3-methylxanthine, the major pathway of theophylline metabolism. The effect showed concentration dependence. The oxidation of theophylline to 1,3-dimethyluric acid was slightly affected by ipriflavone and its metabolites and the effect was non-specific. Results indicate that the reduction of theophylline clearance by concomitant ipriflavone administration observed by Takahashi et al. [Takahashi J., Kawakatsu K., Wakayama T., Sawaoka H. (1992): Elevation of serum theophylline levels by ipriflavone in a patient with chronic obstructive pulmonary disease. Eur. J. Clin. Pharmacol., 43, 207-208] is primarily due to an interaction of the inhibitory ipriflavone and/or its metabolites with cytochrome P450 enzyme(s) that mediate N-demethylation of theophylline.

Language of Publication

English

Unique Identifier

96436863

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MeSH Heading (Major)

Analgesics|ME/*PD; Bronchodilator Agents|BL/ME/*PK; Isoflavones|ME/*PD; Microsomes, Liver|*ME; Theophylline|BL/ME/*PK

MeSH Heading

Biotransformation; Bone Remodeling; Human; Male

Publication Type

JOURNAL ARTICLE

ISSN

0398-7639

Country of Publication

SWITZERLAND

Record 25 from database: MEDLINE
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Title

Prevention of early postmenopausal bone loss using low doses of conjugated estrogens and the non-hormonal, bone-active drug ipriflavone.

Author

Agnusdei D; Gennari C; Bufalino L

Address

Institute of Internal Medicine and Medical Pathology, University of Siena, Italy.

Source

Osteoporos Int, 1995, 5:6, 462-6

Abstract

Hormone replacement therapy is the optimal therapeutic choice for postmenopausal syndrome. While low doses of estrogens (0.3 mg/day of conjugated estrogens) can counteract neurovegetative menopausal symptoms, higher doses (0.625 mg/day of conjugated estrogens) are required to prevent bone loss in postmenopausal women. Experimental and clinical studies have shown that ipriflavone, a non-hormonal isoflavone derivative, is effective in the prevention and treatment of postmenopausal osteoporosis. The aim of the present investigation was to evaluate the efficacy and tolerability of ipriflavone and very low doses of equine conjugated estrogens on bone loss in early postmenopausal women. Eighty-three healthy postmenopausal women (50.3 +/- 0.7 years) were enrolled for this 1-year multicenter study. All subjects were randomly allocated to receive: double placebo (n = 24; group A), placebo plus conjugated equine estrogens 0.30 mg/day (n = 31; group B) or conjugated equine estrogens 0.30 mg/day plus oral ipriflavone 200 mg tris in die at meals (n = 28; group C), according to a double-masked design. Among women who completed the treatment period (valid completers), those of group A showed a progressive decrease in forearm bone density (FBD; measured by dual photon absorptiometry) that reached 1.7% after 12 months. The women in group B maintained their FBD in the first 6 months of treatment but, at the end of the study, showed a bone loss of 1.4% compared with basal values. By contrast, women in group C showed a significant increase in FBD after 1 year of treatment (+5.6%; p < 0.01). Both valid completers and intention to treat analyses revealed a significant difference (p < 0.05) between group A and group C over the study period. None of the treatments produced significant changes of biochemical markers of bone turnover, while hot flushes and other climacteric symptoms were significantly reduced after the sixth month of treatment in women receiving estrogens. Adverse events were generally mild, and did not differ among the groups. The results of this study suggest that low doses of estrogens combined with ipriflavone could represent a new therapeutic approach to the treatment of the postmenopausal syndrome.

Language of Publication

English

Unique Identifier

96241283

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MeSH Heading (Major)

Estrogens, Conjugated|*AD/AE; Isoflavones|*AD/AE; Osteoporosis, Postmenopausal|*PC/PP

MeSH Heading

Bone Density|PH; Bone Remodeling; Climacteric|PH; Drug Therapy, Combination; Female; Forearm|PP; Human; Middle Age; Time Factors; Treatment Outcome

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL

ISSN

0937-941X

Country of Publication

ENGLAND

Record 26 from database: MEDLINE
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Title

Efficacy of ipriflavone and 1 alpha vitamin D therapy for the cessation of vertebral bone loss.

Author

Ushiroyama T; Okamura S; Ikeda A; Ueki M

Address

Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Japan.

Source

Int J Gynaecol Obstet, 1995 Mar, 48:3, 283-8

Abstract

OBJECTIVE: This study investigated whether a combined regimen of ipriflavone and 1 alpha vitamin D is effective in stopping postmenopausal bone loss. METHODS: Ninety-eight postmenopausal women were recruited and randomly assigned to one of four groups: group 1, ipriflavone alone; group 2, 1 alpha vitamin D alone; group 3, combined regimen of ipriflavone and 1 alpha vitamin D; group 4, no treatment. Vertebral bone mineral density, measured by dual energy X-ray absorptiometry, serum alkaline phosphatase, calcitonin, parathyroid hormone, osteocalcin, urinary calcium and hydroxyproline were measured before and at the 6th, 12th and 18th month of the study. All comparisons were made using Student's t-test of means. RESULT: There was a significant reduction in vertebral bone loss in the patients receiving the combined therapy (mean loss after 18 months 0.33% in the combination group vs. 2.37%, 1.15% and 3.70% in the ipriflavone alone, 1 alpha vitamin D alone, and control groups, respectively; P < 0.001). CONCLUSION: These findings suggest that the combined regimen could prevent postmenopausal bone loss.

Language of Publication

English

Unique Identifier

95301069

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MeSH Heading (Major)

Isoflavones|*TU; Osteoporosis, Postmenopausal|*DT/PC; Vitamin D|*TU

MeSH Heading

Drug Therapy, Combination; Female; Human; Middle Age

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0020-7292

Country of Publication

IRELAND

Record 27 from database: MEDLINE
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Title

New treatment strategies: ipriflavone, strontium, vitamin D metabolites and analogs.

Author

Brandi ML

Address

Department of Clinical Physiopathology, University of Florence, Medical School, Italy.

Source

Am J Med, 1993 Nov 30, 95:5A, 69S-74S

Abstract

Drugs used to treat osteoporosis can be grouped in two main categories: those that decrease bone resorption and those that increase bone formation. Antiresorptive drugs are active in preventing bone fractures in patients characterized by a negative calcium balance. However, because antiresorptive agents are often coupled to inhibition of bone formation, inhibitors of bone resorption may not be candidates as potential curative drugs in osteoporosis. Conversely, drugs that act by increasing bone formation produce an increase in bone mass above the fracture threshold; therefore, these agents are good candidates for the treatment of osteoporosis. The ideal curative drug in osteoporosis should have the ability both to decrease bone resorption and to maintain a relatively high rate of bone formation, thus inducing a favorable uncoupling of bone remodeling.

Language of Publication

English

Unique Identifier

94078980

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MeSH Heading (Major)

Bone Resorption|*DT/ME; Isoflavones|CH/PD/*TU; Osteogenesis|*DE; Osteoporosis, Postmenopausal|*DT/ME; Strontium|CH/PD/*TU; Vitamin D|AA/PD/*TU

MeSH Heading

Aged; Animal; Bone Remodeling|DE; Female; Human; Rats

Publication Type

CONSENSUS DEVELOPMENT CONFERENCE; JOURNAL ARTICLE; REVIEW

ISSN

0002-9343

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Isoflavones); 1406-16-2 (Vitamin D); 35212-22-7 (Yambolap); 7440-24-6 (Strontium)

Record 28 from database: MEDLINE
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Title

Radioimmunoassay of circulating alpha-interferon with reference to aging and osteoporosis.

Author

Shiozawa S; Tanaka Y; Morimoto I; Miyauchi A; Yamatani T; Fujita T

Address

Department of Medicine, Kobe University School of Medicine, Japan.

Source

Gerontology, 1989, 35:5-6, 305-10

Abstract

Circulating immunoreactive alpha-interferon in elderly individuals was 0.139 +/- 0.042 ng/ml in males and 0.111 +/- 0.033 ng/ml in females at ages 70-79, and 0.120 +/- 0.045 ng/ml in males and 0.105 +/- 0.039 ng/ml in females at ages 80-89. These values were significantly lower than those in young adults (p less than 0.01), but higher compared with the values found in disease states including rheumatoid arthritis (p less than 0.0025). There was no correlation between circulating alpha-interferon and bone mass indices, such as bone mineral content or quantitative computed tomography values, in these elderly individuals. Circulating alpha-interferon was, however, significantly increased in senile osteoporotic patients after 2 months of treatment with 1 alpha-hydroxyvitamin D3 or calcitonin, whereas it was unaltered in patients receiving ipriflavone or in nonosteoporotic individuals without medication. These findings indicate that circulating alpha-interferon, which is highest in young adults, declines with aging. It appears that circulating alpha-interferon is maintained at a certain steady-state level in healthy elderly individuals. Although there was no apparent relationship between bone mass indices and circulating alpha-interferon, it is possible that bone and cellular metabolism related to vitamin D3 may be contributing factors for the maintenance of circulating alpha-interferon.

Language of Publication

English

Unique Identifier

90201717

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MeSH Heading (Major)

Aging|*IM; Interferon Type I|*BL; Osteoporosis|*IM

MeSH Heading

Aged; Aged, 80 and over; Female; Human; Male; Middle Age; Radioimmunoassay; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0304-324X

Country of Publication

SWITZERLAND

CAS Registry/EC Number

0 (Interferon Type I)

Record 29 from database: MEDLINE
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Title

New perspectives in the treatment of postmenopausal osteoporosis: ipriflavone.

Author

Moscarini M; Patacchiola F; Spacca G; Palermo P; Caserta D; Valenti M

Address

Department of Surgery, University of Aquila, Italy.

Source

Gynecol Endocrinol, 1994 Sep, 8:3, 203-7

Abstract

The efficacy and safety of ipriflavone, a new anti-osteoporotic agent, has been evaluated in an open study in 100 agent, has been evaluated in an open study in 100 osteoporotic women. Ipriflavone was administered as oral capsules dosed at 200 mg, 3 times a day for 12 months. Ninety women completed the study, and the results indicate that the bone mineral density was increased by 2% and 5.8% after 6 and 12 months, respectively. Pain and rachis mobility seemed to be positively influenced by ipriflavone. Only three women complained of side-effects (gastralgia and nausea) and asked to stop the therapy.

Language of Publication

English

Unique Identifier

95149725

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MeSH Heading (Major)

Isoflavones|AD/AE/*TU; Osteoporosis, Postmenopausal|*DT/PP

MeSH Heading

Administration, Oral; Aged; Bone Density|DE/PH; Female; Human; Middle Age; Pain|DT; Spine|PH

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE

ISSN

0951-3590

Country of Publication

ENGLAND

Record 30 from database: MEDLINE
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Title

Ipriflavone prevents the loss of bone mass in pharmacological menopause induced by GnRH-agonists.

Author

Gambacciani M; Cappagli B; Piaggesi L; Ciaponi M; Genazzani AR

Address

Department of Obstetrics and Gynecology Piero Fioretti, S. Chiara Hospital, Pisa, Italy.

Source

Calcif Tissue Int, 1997, 61 Suppl 1:, S15-8

Abstract

In a double-blind, placebo controlled study, ipriflavone (600 mg/day, T.D.D.) or identical placebo tablets were given with 500 mg/day of calcium to patients treated with the gonadotropin hormone-releasing hormone agonist (Gn-RH-A) leuproreline acetate, 3.75 mg every 30 days for 6 months. In placebo-treated subjects (n = 39), urinary hydroxyproline excretion and plasma osteocalcin levels showed a significant (P < 0.01 and P < 0.05, respectively) increase, whereas spine bone density and total body bone density significantly (P < 0.001 and P < 0.05, respectively) decreased after 3 and 6 months of GnRH-A administration. Conversely, in the ipriflavone-treated group (n = 39), no significant difference in bone markers and bone density was evidenced. These data indicate that ipriflavone can restrain the bone remodeling processes and prevent the rapid bone loss that follows medically induced hypogonadism.

Language of Publication

English

Unique Identifier

97409222

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MeSH Heading (Major)

Antineoplastic Agents, Hormonal|*AE/TU; Bone Density|*DE; Bone Remodeling|*DE; Gonadorelin|*AG; Isoflavones|AD/PD/*TU; Leuprolide|*AE/TU; Osteoporosis, Postmenopausal|CI/*PC

MeSH Heading

Analysis of Variance; Comparative Study; Densitometry, X-Ray; Female; Follow-Up Studies; Human; Hypogonadism|CI/CO; Leiomyoma|DT; Lumbar Vertebrae|PH; Menopause|PH; Metrorrhagia|DT; Treatment Outcome; Uterine Neoplasms|DT; Uterus|DE/PA

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0171-967X

Country of Publication

UNITED STATES

Record 31 from database: MEDLINE
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Title

Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years.

Author

Adami S; Bufalino L; Cervetti R; Di Marco C; Di Munno O; Fantasia L; Isaia GC; Serni U; Vecchiet L; Passeri M

Address

Internal Medicine Institute, University of Verona, Parma, Italy.

Source

Osteoporos Int, 1997, 7:2, 119-25

Abstract

Two hundred and fifty-five postmenopausal women with distal forearm bone mineral density (BMD) 1 SD below the mean value for normal age-matched postmenopausal subjects were randomly allocated to a 2-year treatment with oral ipriflavone (200 mg t.i.d) or a matched placebo, according to a double-masked, parallel group design. All patients also received a 1 g/day calcium supplement. Distal radius BMD and bone metabolism markers were measured at baseline, and every 6 months. Blood haematology and chemistry and physical parameters were monitored at the same time. One hundred and ninety-six patients completed 2 years of treatment. BMD changes from baseline were analysed according to valid completers (VC) and intention to treat (ITT) analyses. In both cases radial BMD was maintained in patients treated with ipriflavone while in decrease in those receiving the placebo, the between-treatment difference being significant at year 1 and year 2. Urinary hydroxyproline/creatinine levels were decreased in the ipriflavone-treated group and increased in the placebo group, with a significant between-treatment difference. Adverse reactions, mainly gastrointestinal, occurred to a similar extent in the two treatment groups.

Language of Publication

Englis