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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

English

Unique Identifier

97309224

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MeSH Heading (Major)

Bone Density|*DE; Isoflavones|AE/*TU; Osteoporosis, Postmenopausal|ME/*PC/PP; Radius|*PP

MeSH Heading

Aged; Bone and Bones|ME; Female; Human; Hydroxyproline|UR; Middle Age

Publication Type

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

ISSN

0937-941X

Country of Publication

ENGLAND

Record 32 from database: MEDLINE
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Title

Effects of combined low dose of the isoflavone derivative ipriflavone and estrogen replacement on bone mineral density and metabolism in postmenopausal women.

Author

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

Address

Department of Obstetrics and Gynecology, University of Pisa, Italy. marco.gambacciani@ntt.it

Source

Maturitas, 1997 Sep, 28:1, 75-81

Abstract

OBJECTIVES: To assess the pattern of biochemical markers of bone metabolism and vertebral bone mineral density in early postmenopausal women treated with combined ipriflavone and low dose conjugated estrogens. METHODS: Bone biochemical markers and vertebral bone density were evaluated in a longitudinal, comparative, 2 year study conducted in postmenopausal women treated with sole calcium supplementation (500 mg/day), or with either ipriflavone (IP) at the standard dose (600 mg/day) plus the same calcium dose, low dose conjugated estrogens (CE) (0.3 mg/day) plus calcium, or low dose IP (400 mg/day) plus low dose CE (0.3 mg/day) plus calcium. The results were analyzed by repeated measures analysis of variance, as appropriate. RESULTS: No modifications of both urinary excretion of hydroxyproline and plasma osteocalcin levels were observed in calcium and in CE-treated women, while vertebral bone density significantly decreased (P < 0.0001) in both groups. In IP or IP + CE-treated women, plasma osteocalcin did not show any modification, while urinary hydroxyproline showed a significant (P < 0.05) decrease, that paralleled a significant (P < 0.05) increase in vertebral bone density. CONCLUSION: Postmenopausal IP administration, at the standard dose of 600 mg/day, can prevent the increase in bone turnover and the decrease in bone density that follow ovarian failure. The same effect can be obtained with the combined administration of low dose (400 mg/day) IP with low dose (0.3 mg/day) CE.

Language of Publication

English

Unique Identifier

98053486

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MeSH Heading (Major)

Bone Density|*DE; Estrogen Replacement Therapy|*MT; Estrogens, Non-Steroidal|*PD/TU; Isoflavones|*PD/TU; Osteoporosis, Postmenopausal|*PC; Postmenopause|*DE

MeSH Heading

Administration, Oral; Adult; Comparative Study; Female; Human; Longitudinal Studies; Middle Age; Time Factors

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0378-5122

Country of Publication

IRELAND

Record 33 from database: MEDLINE
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Title

Efficacy of ipriflavone in established osteoporosis and long-term safety.

Author

Agnusdei D; Bufalino L

Address

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

Source

Calcif Tissue Int, 1997, 61 Suppl 1:, S23-7

Abstract

Ipriflavone (i.p.), an isoflavone derivative, is currently used in several countries for prevention and treatment of osteoporosis. Recently, 149 elderly, osteoporotic women (65-79 years) with prevalent vertebral fractures were enrolled in two Italian, multicenter, double-blind, 2-year studies. Women were randomly allocated to receive either oral i.p. (200 mg T.I.D. at meals) or matching placebo, plus 1 g oral calcium daily. One hundred eleven subjects completed the 2-year treatment period. A significant increase in forearm bone mineral density (BMD), measured by dual photon absorptiometry (DPA), was obtained after i.p. treatment. Women receiving the placebo showed only a limited bone loss during the treatment period, probably due to calcium supplement; however, a significant between-treatment difference was obtained in both studies. Urinary hydroxyproline was significantly decreased in i.p.-treated patients, suggesting a reduction in bone turnover rate. A reduction of incident vertebral fractures was observed in i.p.-treated women compared with control subjects. A significant improvement of bone pain and mobility has also been pointed out in one of the studies. To date, 2769 patients have been treated with i.p., for a total of 3132 patient/years, in 60 clinical studies performed in Italy, Japan, and Hungary and reviewed for long-term safety assessment. The incidence of adverse reactions in ipriflavone-treated patients (14.5%) was similar to that observed in subjects receiving the placebo (16.1%). Side effects were mainly gastrointestinal. Few patients presented reversible modifications of laboratory parameters. The data from the above studies show that long-term treatment with i.p. may be considered safe, and may increase bone density and possibly prevent fractures in elderly patients with established osteoporosis.

Language of Publication

English

Unique Identifier

97409224

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MeSH Heading (Major)

Bone Density|*DE; Bone Remodeling|*DE; Isoflavones|AD/AE/PD/*TU; Osteoporosis, Postmenopausal|CO/*DT; Spinal Fractures|EP/*PC/PP

MeSH Heading

Absorptiometry, Photon; Administration, Oral; Aged; Analysis of Variance; Calcitriol|BL; Calcium, Dietary|AD/TU; Double-Blind Method; Female; Human; Hydroxyproline|UR; Incidence; Italy|EP; Prevalence

Publication Type

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

ISSN

0171-967X

Country of Publication

UNITED STATES

Record 34 from database: MEDLINE
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Title

Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta.

Author

Kuiper GG; Lemmen JG; Carlsson B; Corton JC; Safe SH; van der Saag PT; van der Burg B; Gustafsson JA

Address

Center for Biotechnology and Department of Medical Nutrition, Karolinska Institute, Huddinge, Sweden. george.kuiper@csb.ki.se

Source

Endocrinology, 1998 Oct, 139:10, 4252-63

Abstract

The rat, mouse and human estrogen receptor (ER) exists as two subtypes, ER alpha and ER beta, which differ in the C-terminal ligand-binding domain and in the N-terminal transactivation domain. In this study, we investigated the estrogenic activity of environmental chemicals and phytoestrogens in competition binding assays with ER alpha or ER beta protein, and in a transient gene expression assay using cells in which an acute estrogenic response is created by cotransfecting cultures with recombinant human ER alpha or ER beta complementary DNA (cDNA) in the presence of an estrogen-dependent reporter plasmid. Saturation ligand-binding analysis of human ER alpha and ER beta protein revealed a single binding component for [3H]-17beta-estradiol (E2) with high affinity [dissociation constant (Kd) = 0.05 - 0.1 nM]. All environmental estrogenic chemicals [polychlorinated hydroxybiphenyls, dichlorodiphenyltrichloroethane (DDT) and derivatives, alkylphenols, bisphenol A, methoxychlor and chlordecone] compete with E2 for binding to both ER subtypes with a similar preference and degree. In most instances the relative binding affinities (RBA) are at least 1000-fold lower than that of E2. Some phytoestrogens such as coumestrol, genistein, apigenin, naringenin, and kaempferol compete stronger with E2 for binding to ER beta than to ER alpha. Estrogenic chemicals, as for instance nonylphenol, bisphenol A, o, p'-DDT and 2',4',6'-trichloro-4-biphenylol stimulate the transcriptional activity of ER alpha and ER beta at concentrations of 100-1000 nM. Phytoestrogens, including genistein, coumestrol and zearalenone stimulate the transcriptional activity of both ER subtypes at concentrations of 1-10 nM. The ranking of the estrogenic potency of phytoestrogens for both ER subtypes in the transactivation assay is different; that is, E2 >> zearalenone = coumestrol > genistein > daidzein > apigenin = phloretin > biochanin A = kaempferol = naringenin > formononetin = ipriflavone = quercetin = chrysin for ER alpha and E2 >> genistein = coumestrol > zearalenone > daidzein > biochanin A = apigenin = kaempferol = naringenin > phloretin = quercetin = ipriflavone = formononetin = chrysin for ER beta. Antiestrogenic activity of the phytoestrogens could not be detected, except for zearalenone which is a full agonist for ER alpha and a mixed agonist-antagonist for ER beta. In summary, while the estrogenic potency of industrial-derived estrogenic chemicals is very limited, the estrogenic potency of phytoestrogens is significant, especially for ER beta, and they may trigger many of the biological responses that are evoked by the physiological estrogens.

Language of Publication

English

Unique Identifier

98422127

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MeSH Heading (Major)

Environmental Pollutants|*ME; Estrogens, Non-Steroidal|*ME; Receptors, Estrogen|*ME

MeSH Heading

Binding, Competitive; Coumestrol|PD; DDT|PD; Estradiol|ME; Estrogens; Flavones|PD; Human; Polychlorinated Biphenyls|PD; Structure-Activity Relationship; Support, Non-U.S. Gov't; Transcription, Genetic|DE; Zearalenone|PD

Publication Type

JOURNAL ARTICLE

ISSN

0013-7227

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (phytoestrogens); 0 (Environmental Pollutants); 0 (Estrogens); 0 (Estrogens, Non-Steroidal); 0 (Flavones); 0 (Polychlorinated Biphenyls); 0 (Receptors, Estrogen); 17924-92-4 (Zearalenone); 479-13-0 (Coumestrol); 50-28-2 (Estradiol); 50-29-3 (DDT)

Record 35 from database: MEDLINE
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Title

Evaluation of the drug therapy for established osteoporosis by dual-energy x-ray absorptiometry.

Author

Shiota E

Address

Department of Orthopaedic Surgery, Saiseikai Yahata Hospital, Kitakyushu, Japan.

Source

Fukuoka Igaku Zasshi, 1998 Jun, 89:6, 172-8

Abstract

The effects of the drug therapies for the osteoporosis were evaluated by DXA of lumbar vertebrae and the frequency of vertebral fractures. Females above the age of 50 suffering from senile or postmenopausal osteoporosis were randomly divided into four treatment groups. In the single drug therapy groups, patients received either ipriflavone 600 mg/day (OSTEN), or elcatonin 20 IU/week (CT). In the multiple drug treatment groups, patients received either daily oral administration of 2 g calcium lactate and 0.5 microgram alphacalcidol (Ca.D), or a repeated 14-week cycle of daily oral administration of 2 micrograms alphacalcidol for 2 weeks, 600 mg of ipriflavone for 4 weeks, and 2 g calcium lactate together with 0.5 microgram alphacalcidol for 8 weeks (ADFR). The BMD was maintained in each treatment group regardless of age and BMI. Fracture incidence could not be suppressed in the OSTEN and Ca.D groups. A tendency of improvement was observed in subjects without spinal fracture. DXA can accurately judge the drug efficacy at 12 months after treatment. Early evaluation and treatment are advisable in postmenopausal or senile osteoporosis.

Language of Publication

English

Unique Identifier

98360427

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MeSH Heading (Major)

Osteoporosis|*DT

MeSH Heading

Bone Density; Calcitonin|AA/TU; Calcium Compounds|TU; Densitometry, X-Ray; Female; Human; Hydroxycholecalciferols|TU; Isoflavones|TU; Lactates|TU; Middle Age; Osteoporosis, Postmenopausal|DT

Publication Type

JOURNAL ARTICLE

ISSN

0016-254X

Country of Publication

JAPAN

CAS Registry/EC Number

0 (calcium lactate); 0 (Calcium Compounds); 0 (Hydroxycholecalciferols); 0 (Isoflavones); 0 (Lactates); 35212-22-7 (Yambolap); 41294-56-8 (1-hydroxycholecalciferol); 60731-46-6 (elcatonin); 9007-12-9 (Calcitonin)

Record 36 from database: MEDLINE
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Title

Culture of stromal cells derived from medullary cavity of human long bone in the presence of 1,25-dihydroxyvitamin D3, recombinant human bone morphogenetic protein-2, or ipriflavone.

Author

Shibano K; Watanabe J; Iwamoto M; Ogawa R; Kanamura S

Address

Department of Orthopedics, Kansai Medical University, Moriguchi, Osaka, Japan.

Source

Bone, 1998 Mar, 22:3, 251-8

Abstract

We previously showed that stromal cells derived from bone marrow specimens formed at the fracture site of human long bone differentiated during culture to polygonal cells and spindle cells, and polygonal cells, but not spindle cells, produced calcified matrix. To clarify the origin of polygonal and/or spindle cells, and factors necessary for differentiation of marrow stromal cells to osteogenic cells, we cultured stromal cells derived from the normal (unfractured) medullary cavity (SCN) as well as stromal cells from the medullary cavity distant from the fracture site (SCF). After 3 weeks of primary culture and 2 days of secondary culture, the cells were cultured in medium containing 1,25-dihydroxyvitamin D3 (VD), recombinant human bone morphogenetic protein-2 (BMP), or ipriflavone (IF) for 3 weeks. For biochemical analysis, cells reaching confluence after 3 weeks of secondary culture were cultured with one of the factors for 3 days. Some of SCF cultured with VD or IF were transformed to polygonal cells, and showed high alkaline phosphatase (ALPase) activity and high osteocalcin and insoluble calcium production. Cloned polygonal cells from the SCF formed nodules and aggregates consisting of calcium. Other SCF cultured with VD or IF and SCF cultured with BMP were spindle shaped. Some spindle-shaped cells from SCF cultured with BMP or IF revealed high ALPase activity and high osteocalcin production, comparable with the spindle cells from the fracture site. However, spindle-shaped cells from SCF cultured with VD and other spindle-shaped cells from SCF cultured with BMP or IF showed low ALPase activity and low osteocalcin production. The results show that SCF probably contain at least three subpopulations: (a) cells that differentiate to polygonal cells by the influence of VD or IF; (b) cells that differentiate to the spindle cells by the influence of BMP or IF; and (c) cells that are not transformed by the influence of VD, BMP, or IF.

Language of Publication

English

Unique Identifier

98173152

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MeSH Heading (Major)

Bone Marrow Cells|CY/*DE/ME; Bone Morphogenetic Proteins|*PD; Calcitriol|*PD; Isoflavones|*PD; Osteogenesis|*DE

MeSH Heading

Adolescence; Adult; Alkaline Phosphatase|ME; Calcium|ME; Cell Count|DE; Cell Culture; Cells, Cultured; Human; Middle Age; Osteoblasts|CY; Osteocalcin|ME; Recombinant Proteins; Stromal Cells|DE/ME

Publication Type

JOURNAL ARTICLE

ISSN

8756-3282

Country of Publication

UNITED STATES

Record 37 from database: MEDLINE
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Title

Stimulation of human osteoblast differentiation and function by ipriflavone and its metabolites.

Author

Cheng SL; Zhang SF; Nelson TL; Warlow PM; Civitelli R

Address

Division of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, Missouri.

Source

Calcif Tissue Int, 1994 Nov, 55:5, 356-62

Abstract

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.

Language of Publication

English

Unique Identifier

95171296

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MeSH Heading (Major)

Isoflavones|ME/*PD; Osteoblasts|CY/*DE/PH; Stem Cells|CY/*DE/PH

MeSH Heading

Alkaline Phosphatase|ME; Analysis of Variance; Blotting, Northern; Bone Marrow|CY/DE; Calcification, Physiologic|DE; Calcium|ME; Cell Differentiation|DE; Cells, Cultured; Collagen|DE/GE; Cytokines|DE/GE; Dexamethasone|PD; Gene Expression Regulation, Developmental|DE/GE; Human; Nucleic Acid Hybridization; Proteoglycans|DE/GE; RNA, Messenger|BI; Sialoglycoproteins|DE/GE; Stromal Cells|CY/DE; Structure-Activity Relationship; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0171-967X

Country of Publication

UNITED STATES

Record 38 from database: MEDLINE

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Title

Miscellaneous and experimental agents.

Author

Reginster JY

Address

UnitÆe d'Exploration du MÆetabolisme Osseux et du Cartilage ArticulaireUniversitÆe de LiÆege, Belgium.

Source

Am J Med Sci, 1997 Jan, 313:1, 33-40

Abstract

Current therapeutic approaches to postmenopausal bone loss or established osteoporosis vary widely among the different regions of the world. Because no treatment of osteoporosis has unequivocally demonstrated full prevention of the appearance or the recurrence of axial or peripheral fractures so far, many investigational compounds are being developed. Anabolic steroids act mainly as inhibitors of bone resorption with very few, if any, effects on bone formation. Because of the high occurrence of signs of virilization and the weak effects on bone structure, the risk/benefit ratio in osteoporosis should be considered at least problematic. If ongoing large-scale trials confirm the expected benefits of estrogen antagonist/agonists on the skeleton and confirm no cardiovascular risk to postmenopausal women with optimal uterine safety, these substances are likely to become the most prominent alternative to hormonal replacement therapy after the menopause. Additional studies are requested to evaluate the potential benefit of growth hormone or insulin-like growth factors in treatment of osteoporosis. Ipriflavone acts predominantly as an inhibitor of bone resorption. To confirm the efficacy of ipriflavone on the prevention of vertebral fractures and its effects on bone mineral density in women with postmenopausal established osteoporosis, a large multicentric European study is being conducted. Treatment with parathyroid peptides induces a significant gain in bone mass, mainly in the axial skeleton. Long-term studies that compare peptides, doses, and regimes are needed to better understand the exact position of parathyroid peptides as treatment of osteoporosis. Prolonged administration of strontium to postmenopausal osteoporotic women resulted in a decoupling between bone resorption and formation that yielded a significant increase in the lumbar spine bone mineral density of treated subjects. In the view of these promising results and of the excellent tolerance of strontium during preliminary trials, additional investigations of this compound in prevention and treatment of osteoporosis should be promptly initiated. Several other compounds have been punctually suggested for treatment of osteoporosis or are at very early stages of development. Finally, besides pharmacologic approaches to the treatment of osteoporosis, hip fractures may also be reduced by the use of hip protectors.

Language of Publication

English

Unique Identifier

97154446

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MeSH Heading (Major)

Osteoporosis, Postmenopausal|*DT/*PC

MeSH Heading

Anabolic Steroids|AE/TU; Animal; Bone Density|DE; Bone Remodeling; Bone Resorption; Estrogen Antagonists|AE/TU; Estrogens|AE/TU; Female; Hip Fractures|PC; Human; Insulin|PD/TU; Insulin-Like Growth Factor I|PD/TU; Isoflavones|TU; Parathyroid Hormones|TU; Strontium|TU; Tamoxifen|AE/TU; Trace Elements|TU

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0002-9629

Country of Publication

UNITED STATES

Record 39 from database: MEDLINE

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Title

Design for an ipriflavone multicenter European fracture study.

Author

Reginster JY; Bufalino L; Christiansen C; Devogelaer JP; Gennari C; Riis BJ; Roux C

Address

Bone and Cartilage Metabolism Unit, University of LiÄege, Belgium.

Source

Calcif Tissue Int, 1997, 61 Suppl 1:, S28-32

Abstract

In order to investigate the efficacy of ipriflavone (i.p.) on the prevention of vertebral fractures and the effect on bone mineral density (BMD) in women with postmenopausal osteoporosis, a large multicentric European study was designed and is presently ongoing. Included in the study were 460 Caucasian, nonobese postmenopausal women aged > 45 and < 75 years, menopaused for at least 12 months. Inclusion was on the basis of a lumbar bone mineral density (BMD) lower than 2 SD compared with healthy women aged 50 years, corresponding to values below 0.860 g/cm2 (antero-posterior measurement) by Hologic QDR 1000. Women with prevalent vertebral fractures were excluded as well as those presenting secondary osteoporosis or having been treated with medications that could affect bone metabolism. This study was designed as a 3-year, double-blind, placebo-controlled, parallel group study that randomized the women to the oral administration of either 3 x 200 mg/day of i.p. or placebo. All patients received a daily supplement of 500 mg calcium. The primary purpose of the study was to evaluate the efficacy of i.p. in preventing vertebral nontraumatic fractures. Fracture is defined here as a > or = 20% decrease in any anterior, central, or posterior T4-L4 vertebral height. Blinded vertebral X-ray readings and vertebral morphometry have been centralized in an independent Center, with standardized evaluation of two experts. Power calculations have been based on the hypothesis that 21% of placebo-treated patients would fracture within 3 years and that treatment with i.p. would lead to a 50% reduction in the incidence of fracture. Statistical tests have been designed to have a power of 80%, with a type I error equal to 5%. Secondary endpoints were changes in vertebral, radial, and femoral BMD. Centralized controls on 100% BMD scans would ensure the good quality of BMD readings. This study should verify the hypothesis that i.p. significantly decreases the risk of vertebral fracture in postmenopausal, osteoporotic women.

Language of Publication

English

Unique Identifier

97409225

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MeSH Heading (Major)

Bone Density|*DE; Isoflavones|AD/PD/*TU; Osteoporosis, Postmenopausal|*DT/PP; Research Design|*ST; Spinal Fractures|*PC

MeSH Heading

Aged; Biological Markers|BL/UR; Bone Remodeling|DE; Calcium|AD/TU; Caucasoid Race; Densitometry, X-Ray; Double-Blind Method; Europe; Female; Follow-Up Studies; Human; Middle Age; Quality Control; Radioimmunoassay; Statistics; Support, Non-U.S. Gov't; Treatment Outcome

Publication Type

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

ISSN

0171-967X

Country of Publication

UNITED STATES

Record 40 from database: MEDLINE

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Title

In vitro and in vivo effects of ipriflavone on bone formation and bone biomechanics.

Author

Civitelli R

Address

Division of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, Missouri, USA.

Source

Calcif Tissue Int, 1997, 61 Suppl 1:, S12-4

Abstract

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.

Language of Publication

English

Unique Identifier

97409221

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MeSH Heading (Major)

Bone and Bones|*DE/PH; Bone Density|*DE; Bone Development|*DE; Bone Remodeling|*DE; Isoflavones|*PD/TU

MeSH Heading

Animal; Biomechanics; Human; Male; Osteoblasts|CY/DE; Osteoporosis|DT/PC/PP; Rats; Rats, Sprague-Dawley

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0171-967X

Country of Publication

UNITED STATES

Record 41 from database: MEDLINE

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Title

Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass.

Author

Valente M; Bufalino L; Castiglione GN; DAngelo R; Mancuso A; Galoppi P; Zichella L

Address

1st Obstetrics and Gynecological Department, La Sapienza University, Rome, Italy.

Source

Calcif Tissue Int, 1994 May, 54:5, 377-80

Abstract

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.

Language of Publication

English

Unique Identifier

94340462

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MeSH Heading (Major)

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

MeSH Heading

Absorptiometry, Photon; Aged; Biological Markers|BL/UR; Bone Resorption|DT; Comparative Study; Densitometry, X-Ray; Female; Human; Lumbar Vertebrae; Middle Age; Radius

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0171-967X

Country of Publication

UNITED STATES

Record 42 from database: MEDLINE

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Title

Interactions between ipriflavone and the estrogen receptor.

Author

Petilli M; Fiorelli G; Benvenuti S; Frediani U; Gori F; Brandi ML

Address

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

Source

Calcif Tissue Int, 1995 Feb, 56:2, 160-5

Abstract

Estrogen replacement therapy is effective in the prevention of postmenopausal osteoporosis, and a direct action of 17-beta-estradiol (17 beta E2) on osteoblastic and osteoclastic cells has been demonstrated. The inhibition of bone resorption by ipriflavone (IP), an isoflavone derivative devoid of estrogenic properties but active in potentiating the effects of estrogen on bone tissue, has been shown in in vitro and in vivo studies and confirmed by clinical data. To investigate the molecular mechanisms that underlie IP effect, we studied the possible interactions of IP and its four main in vivo metabolites (I, II, III, and V) with the estrogen receptor (ER) in the human preosteoclastic cell line FLG 29.1, whose growth and function are modulated by the compound. In parallel experiments, the human breast cancer cell line MCF7 was also analyzed. IP binding sites were demonstrated in the nuclear fraction of FLG 29.1 cells. 17 beta E2 and other steroid compounds failed to displace IP binding to intact FLG 29.1 cells. Similarly, IP and metabolites I, III, and V were not able to displace 17 beta E2 binding to intact MCF7 cells, whereas metabolite II showed an IC50 of 61 nM. 17 beta E2 binding to FLG 29.1 cells was increased after preincubation with metabolites I, III, and V. IP and its metabolites did not induce ER-dependent gene expression in FLG 29.1 and MCF7 cells transfected with a reporter gene and an estrogen response element (ERE).(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

95254365

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MeSH Heading (Major)

Isoflavones|ME/*PD; Receptors, Estrogen|*DE/GE/ME

MeSH Heading

Binding, Competitive; Cell Line; Chloramphenicol O-Acetyltransferase|GE; Female; Genes, Reporter; Human; Osteoclasts|DE/ME; Support, Non-U.S. Gov't; Transfection; Tumor Cells, Cultured|DE/ME

Publication Type

JOURNAL ARTICLE

ISSN

0171-967X

Country of Publication

UNITED STATES

Record 43 from database: MEDLINE
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Title

Metabolic and bone effects after administration of ipriflavone and salmon calcitonin in postmenopausal osteoporosis.

Author

Cecchettin M; Bellometti S; Cremonesi G; Solimeno LP; Torri G

Address

Clinical Pathology Laboratory, Institute of Orthopedics, G Pini, Milan, Italy.

Source

Biomed Pharmacother, 1995, 49:10, 465-8

Abstract

Forty postmenopausal women with bone mineral density (BMD) > 2 standard deviations below the mean value for healthy age matched controls were enrolled into an open controlled study to evaluate the metabolic and bone effects of ipriflavone (IP) versus salmon calcitonin (sCT) over a 12 month period. Both treatments significantly increased BMD after 6 and 12 months. A 4.3% increase of BMD was obtained in the IP treated group and a 1.9% in the sCT treated group after 12 months (p < 0.001 between treatments). Bone metabolism markers (serum osteocalcin, alkaline phosphatase, urinary calcium and hydroxyproline/creatinine ratio) were significantly reduced in both groups (p < 0.001). The reduction of urinary hydroxyproline/creatinine ratio was significantly greater (p < 0.05) in the IP group after 12 months. Both treatments were well tolerated. Four patients in the IP group reported gastralgia while two patients in the sCT group reported pruritus and one patient epistaxis.

Language of Publication

English

Unique Identifier

96306481

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MeSH Heading (Major)

Bone and Bones|*ME; Bone Density|*DE; Calcitonin|*PD; Isoflavones|*PD; Neurotransmitters|*PD; Osteoporosis, Postmenopausal|*ME/*PP

MeSH Heading

Aged; Aged, 80 and over; Animal; Biological Markers|AN; Female; Human; Middle Age; Salmon

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0753-3322

Country of Publication

FRANCE

Record 44 from database: MEDLINE
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Title

Effects of ipriflavone and its metabolites on human articular chondrocytes cultivated in clusters.

Author

Bassleer CT; Franchimont PP; Henrotin YE; Franchimont NM; Geenen VG; Reginster JY

Address

Department of Endocrinology, B23, University Hospital-Sart-Tilman, LiÄege, Belgium.

Source

Osteoarthritis Cartilage, 1996 Mar, 4:1, 1-8

Abstract

Ipriflavone (IP) is an isoflavone derivative that was suggested to have bone-sparing effects in post-menopausal and senile osteoporosis. A moderate stimulatory effect of IP and its metabolites on proliferation of osteoblastic cells was reported in rat osteoblastic osteosarcoma cell line. We investigated the effects of different concentrations (0, 1, 10 and 100 micrograms/ml) of IP and its metabolites (MET I, II, III and V) on the incorporation of [3H] thymidine and production of proteoglycans (PG) and type II collagen (COL II) by human articular chondrocytes during a 12-day period, in a three-dimensional chondrocyte culture model. [3H]thymidine uptake was measured in chondrocyte clusters, and specific PG and COL II radioimmunoassays were performed every 4 days on the culture medium and cell clusters. Incubation with IP or its metabolites did not affect [3H]thymidine uptake regardless of the dose. PG released into the culture medium and PG cluster content rose significantly (P < 0.025) in presence of IP (1, 10 and 100 micrograms/ml). MET I increased PG release in culture medium (10 and 100 micrograms/ml) and PG cluster content (100 micrograms/ml). MET II has no effect on PG production. MET III increased PG in culture medium (100 microgram/ml) but did not influence PG cluster content while MET V (100 micrograms/ml) increased both PG release in culture medium and PG cluster content. COL II release in culture medium and COL II cluster content were significantly (P < 0.025) increased in presence of IP (10 and 100 micrograms/ml), MET III (1, 10 and 100 micrograms/ml) or MET V (100 micrograms/ml). MET I and II did not significantly affect COL II production.

Language of Publication

English

Unique Identifier

96298710

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MeSH Heading (Major)

Analgesics|*PD; Cartilage, Articular|CY/*DE/ME; Isoflavones|*PD

MeSH Heading

Cell Division|DE; Cells, Cultured; Collagen|BI/DE; DNA|BI; DNA Replication|DE; Human; Proteoglycans|BI/DE; Radioimmunoassay; Thymidine|ME

Publication Type

JOURNAL ARTICLE

ISSN

1063-4584

Country of Publication

ENGLAND

Record 45 from database: MEDLINE
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Title

Therapy for osteoporosis. Miscellaneous and experimental agents.

Author

Reginster JY; Taquet AN; Gosset C

Address

Bone and Articular Cartilage Research Unit, University of Liège, Belgium.

Source

Endocrinol Metab Clin North Am, 1998 Jun, 27:2, 453-63

Abstract

None of the currently available medications for osteoporosis have demonstrated an ability to fully prevent the occurrence of new vertebral or peripheral osteoporotic fractures once the disease is established. Several new therapies, therefore, are currently being developed to optimize the risk/benefit ratio of osteoporosis treatment. This article discusses a number of treatments currently being considered, including anabolic steroids, growth hormone or insulin-like growth factors, ipriflavone, parathyroid peptides, and strontium. Several other compounds have been suggested recently for treatment of osteoporosis and other are at very early stages of their development. In addition to pharmacologic approaches to the treatment of osteoporosis, hip protectors also may reduce hip fractures.

Language of Publication

English

Unique Identifier

98333756

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MeSH Heading (Major)

Osteoporosis|*DT

MeSH Heading

Anabolic Steroids|TU; Human; Insulin-Like Growth Factor I|TU; Isoflavones|TU; Parathyroid Hormones|TU; Strontium|TU

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0889-8529

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Anabolic Steroids); 0 (Isoflavones); 0 (Parathyroid Hormones); 35212-22-7 (Yambolap); 67763-96-6 (Insulin-Like Growth Factor I); 7440-24-6 (Strontium)

Record 46 from database: MEDLINE
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Title

Growth-inhibitory effect of tamoxifen and quercetin and presence of type II estrogen binding sites in human laryngeal cancer cell lines and primary laryngeal tumors.

Author

Ferrandina G; Almadori G; Maggiano N; Lanza P; Ferlini C; Cattani P; Piantelli M; Scambia G; Ranelletti FO

Address

Institute of Gynecology, UniversitÄa Cattolica del Sacro Cuore, Rome, Italy.

Source

Int J Cancer, 1998 Aug, 77:5, 747-54

Abstract

Quercetin and tamoxifen, in a range of concentrations between 0.01 and 5 microM, exert a dose-dependent inhibition on the anchorage-dependent and anchorage-independent cell growth of Hep2 and CO-K3 laryngeal cancer cell lines. Cell cycle analysis revealed that the growth-inhibitory effect was associated with a block of the cells at the G2/M checkpoint of the cell cycle followed by DNA fragmentation. This suggests that the failure of cells to proceed through the G2/M checkpoint can be a trigger for apoptosis. The induction of apoptosis by quercetin and tamoxifen was confirmed immunocytochemically by the in situ nick end labeling (TUNEL) reaction. These compounds also exerted a dose-dependent growth-inhibitory effect on primary tumor cells, as assessed by colony-forming assay and bromodeoxyuridine labeling. Laryngeal cancer cell lines and primary tumor cells expressed Type II estrogen binding sites (Type II EBS) with binding characteristics similar to those of Type II EBS in other tumor cells. Since the affinities of quercetin and tamoxifen for Type II EBS were correlated with their growth-inhibitory potential while ipriflavone neither interacted with these sites nor inhibited cell growth, the possibility exists that the action of these compounds is mediated, at least in part, by the interaction with Type II EBS. In conclusion, our data indicate that quercetin and tamoxifen could be potentially useful in laryngeal cancer treatment.

Language of Publication

English

Unique Identifier

98351595

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MeSH Heading (Major)

Cell Cycle|*DE; Cell Division|*DE; Laryngeal Neoplasms|*PA/SU; Quercetin|*TO; Receptors, Estrogen|AN/*ME; Tamoxifen|*TO

MeSH Heading

Apoptosis|DE; Cell Line; Dose-Response Relationship, Drug; Estradiol|ME; Human; Isoflavones|TO; Kinetics; Support, Non-U.S. Gov't; Time Factors; Tumor Cells, Cultured; Tumor Stem Cell Assay

Publication Type

JOURNAL ARTICLE

ISSN

0020-7136

Country of Publication

UNITED STATES

Record 47 from database: MEDLINE
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Title

Gastrojejunal fistula caused by gastric ulcer.

Author

Matsuoka M; Yoshida Y; Hayakawa K; Fukuchi S

Address

Department of Gastroenterology, Mishuku Hospital, Tokyo, Japan.

Source

J Gastroenterol, 1998 Apr, 33:2, 267-71

Abstract

We report a case of gastrojejunal fistula caused by benign gastric ulcer, a very rare condition. The patient was an 81-year-old-woman who had had multiple recurrences of gastric ulcer. She also had diabetes mellitus. She was admitted to our hospital because of a left femoral head fracture, necessitating a mechanical bone head exchange operation. She had severe abdominal pain and anemia on the 48th postoperative day. Gastroendoscopic examination revealed a giant ulcer with a long-axis diameter of more than 5cm on the lesser curvature of the gastric body. She was treated with intravenous famotidine and all oral intake was restricted; her symptoms were alleviated. Two weeks later, a fistula had formed between the stomach and the jejunum just anal to the duodeno-jejunal flexure. She was placed on an ulcer diet, and was discharged with no symptoms on the 151st postoperative day. She has remained asymptomatic for 1 1/2, years to date. Lack of H2-antagonist administration, operative stress, and administration of ipriflavone appeared to have induced gastric ulcer recurrence, and formation of the fistula between the stomach and the jejunum seemed to have been facilitated by the patient being very lean and having minimal mesenteric adipose tissue.

Language of Publication

English

Unique Identifier

98266997

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MeSH Heading (Major)

Gastric Fistula|*ET; Intestinal Fistula|*ET; Jejunal Diseases|*ET; Stomach Ulcer|*CO/ET

MeSH Heading

Aged; Aged, 80 and over; Case Report; Female; Femoral Fractures|SU; Human; Recurrence; Stress|CO

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES

ISSN

0944-1174

Country of Publication

JAPAN

Record 48 from database: MEDLINE
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Title

Management of osteoporosis and Paget's disease. An appraisal of the risks and benefits of drug treatment.

Author

Gennari C; Nuti R; Agnusdei D; Camporeale A; Martini G

Address

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

Source

Drug Saf, 1994 Sep, 11:3, 179-95

Abstract

Osteoporosis is a major public health problem occurring primarily among the postmenopausal population. Osteoporosis is a preventable disease, but despite several advances in its prevention, treatment of the established disease to date remains a major challenge to be managed by primary care physicians. Stabilisation of bone mass and prevention of falls are of paramount importance in any therapeutic programme for osteoporotic patients with established vertebral fractures. Drug therapy for osteoporosis can be divided operationally into 2 main categories: those that inhibit bone resorption, and thus reduce bone turnover, and those that stimulate bone formation, exerting an anabolic effect. Therapeutic agents that inhibit bone remodeling would appear to be best suited to those patients with high turnover osteoporosis (about 30%). Included in this category are calcium, vitamin D and its metabolites, gonadal steroids, calcitonin, ipriflavone and bisphosphonates. Although estrogen replacement therapy has been proven to be effective in older females, calcitonin appears to be the treatment of choice for this population since it stabilises or increases bone mass and also has reported analgesic properties. Drugs that stimulate bone remodeling or bone formation would be best suited to patients with low turnover osteoporosis (about 70%). The agent in this class that is widely used is sodium fluoride. New therapies include intermittent injections of synthetic parathyroid hormone, and cyclic bisphosphonates to activate then depress resorption and formation. Any attempts to stabilise the skeleton with any drug regimen must be accompanied by an adequate calcium supply, i.e. 1200 to 1500 mg/day). The theoretical basis of tailoring treatment for osteoporosis to the underlying histology has not yet been fully proven, but there is increasing experimental support to this approach. Drugs that inhibit bone turnover, such as calcitonin, appear to be effective in increasing bone mass for 1.5 to 2 years, about the time it would take to replenish the remodeling space in a patient with high turnover osteoporosis. In contrast, although bone mass appears to increase for as long as 5 years in patients treated with sodium fluoride, there has been no consistent reduction in occurrence of vertebral or hip fractures. Paget' disease of bone is a focal disorder of the skeleton characterised by excessive resorption and subsequently disorganised formation of bone. The aetiology of the disease is unknown. Paget's disease may be mono-ostotic or polyostotic; pain and bone deformities due to enlargement of skeletal segments represent the main clinical aspects. However, in many patients the disease may be asymptomatic.(ABSTRACT TRUNCATED AT 400 WORDS)

Language of Publication

English

Unique Identifier

95110457

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MeSH Heading (Major)

Bone Remodeling|*DE; Fractures|*PC; Osteitis Deformans|*DT; Osteoporosis, Postmenopausal|*DT

MeSH Heading

Bone Development|DE; Calcitonin|AD/AE/TU; Calcium|AD/AE/TU; Diphosphonates|AD/AE/TU; Drug Therapy, Combination; Estrogen Replacement Therapy|AE; Female; Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0114-5916

Country of Publication

NEW ZEALAND

Record 49 from database: MEDLINE
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Title

Management of postmenopausal osteoporosis.

Author

Di Renzo GC; Coata G; Cosmi EV; Melis GB; Maietta L; Volpe A

Address

Institute of Obstetrics and Gynecology, University of Perugia, Italy.

Source

Eur J Obstet Gynecol Reprod Biol, 1994 Jul, 56:1, 47-53

Abstract

More than 25% of postmenopausal women are at risk of osteoporosis. In order to avoid its consequences, it is necessary to find an appropriate prevention and/or treatment. We studied: (1) 15 postmenopausal women treated with percutaneous estradiol (50 micrograms/24 h) plus MPA (10 mg/10 days/month); (2) 15 postmenopausal women treated with synthetic calcitonin nasal spray at the daily dose of 100 IU; (3) 10 postmenopausal women treated with nandrolone decanoate (50 mg every 3 weeks); (4) 10 postmenopausal women treated with ipriflavone (600 mg/day); and (5) 10 postmenopausal women treated with sodium fluoride (20 mg) plus calcium (600 mg). Clinical examination, bone mass measurement (total BMD), hematochemical and urinary parameters of bone metabolism (calcium, urinary hydroxyproline, PTH) and growth factors (as IGF-I and TNF-beta) were evaluated. After 6 months of therapy, a complete prevention of bone resorption was achieved. In agreement with current literature, we observed that the various therapeutic approaches have all some positive effect on BMD, with different results on pain, blood biochemical parameters and growth factors' concentrations.

Language of Publication

English

Unique Identifier

95073549

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MeSH Heading (Major)

Osteoporosis, Postmenopausal|*DT/*PC/PP

MeSH Heading

Aged; Bone Density; Bone Remodeling; Calcitonin|TU; Estrogen Replacement Therapy; Female; Human; Middle Age; Risk Factors; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0301-2115

Country of Publication

IRELAND

Record 50 from database: MEDLINE
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Title

Natural and synthetic isoflavones in the prevention and treatment of chronic diseases.

Author

Brandi ML

Address

Department of Clinical Physiopathology, University of Florence, Italy.

Source

Calcif Tissue Int, 1997, 61 Suppl 1:, S5-8

Abstract

The evidence that natural isoflavones protect against several chronic diseases is both observational and experimental. In humans, epidemiologic findings clearly show a higher incidence of some common types of cancer (i.e., breast, prostate, and colon) and of coronary heart diseases in Western populations exposed to limited amounts of soybean isoflavones (i.e., genistein, daidzein) in the diet. Further evidence for cancer and cardiac protection and antiatherogenic effects resulting from soybean isoflavones administration has been noted in various experimental animal models. Isoflavones may also prevent postmenopausal bone loss and osteoporosis. In fact, genistein has been reported to be as active as estrogens in maintaining bone mass in ovariectomized rats. Moreover, the synthetic isoflavone derivative ipriflavone is able to reduce bone loss in various types of animal models of experimental osteoporosis providing a rationale on its use in the prevention and treatment of postmenopausal and senile osteoporosis in humans. The mechanism through which isoflavones may exert the above-mentioned effects seems to depend, at least in part, on their mixed estrogen agonist-antagonist properties. An alternative hypothetical mechanism could derive from other biochemical actions of isoflavones such as inhibition of enzymatic activity, in particular protein kinases, or activation of an "orphan" receptor distinct from the estrogen type I receptor.

Language of Publication

English

Unique Identifier

97409219

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MeSH Heading (Major)

Coronary Disease|DT/EP/*PC; Estrogens, Non-Steroidal|PD/*TU; Isoflavones|PD/*TU; Neoplasms|DT/EP/*PC

MeSH Heading

Animal; Diet; Disease Models, Animal; Female; Human; Osteoporosis, Postmenopausal|DT/EP/PC; Plants; Receptors, Estrogen|DE; Soybeans|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0171-967X

Country of Publication

UNITED STATES

Record 51 from database: MEDLINE
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Title

Synthesis and bone resorption effect of alkoxy-substituted xanthones.

Author

Pifferi G; Da Re P; Valenti P; Bisi A; Malandrino S

Address

Institute of Pharmaceutical Chemistry, University of Milan, Italy.

Source

Arch Pharm (Weinheim), 1997 Jul, 330:7, 233-4

Abstract

A topological modification of ipriflavone 1, a recent antiosteoporotic drug, is described. The flavone moiety of 1 has been replaced by a xanthone one. Among the new derivatives, the 3,6-diisopropoxyxanthone (2a) has shown significant bone resorption inhibition in in vitro and in vivo tests.

Language of Publication

English

Unique Identifier

97457494

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MeSH Heading (Major)

Bone Resorption|*DT; Xanthenes|*CS/*PD

MeSH Heading

Animal; Human; Rats

Publication Type

JOURNAL ARTICLE

ISSN

0365-6233

Country of Publication

GERMANY

Record 52 from database: MEDLINE
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Title

Interaction with type II estrogen binding sites and antiproliferative activity of tamoxifen and quercetin in human non-small-cell lung cancer.

Author

Caltagirone S; Ranelletti FO; Rinelli A; Maggiano N; Colasante A; Musiani P; Aiello FB; Piantelli M

Address

Department of Pathology, Gabriele D'Annunzio University, Chieti, Italy.

Source

Am J Respir Cell Mol Biol, 1997 Jul, 17:1, 51-9

Abstract

The antiestrogen tamoxifen is thought to antagonize the effects of estrogens by competing with them for estrogen receptor (ER) binding. However, tarnoxifen can also reverse multidrug resistance, synergize with cisplatin cytotoxicity, and inhibit growth in ER-negative lung cancer cells. In addition to ERs, rat and human target tissues contain a second binding macromolecule termed the type II estrogen binding site (type II EBS). It has been shown that tamoxifen and flavonoids, a widely distributed class of natural substances with a variety of biologic actions, bind to type II EBS and inhibit the growth of several tumor cell types. At present, conflicting data about ERs and an absence of data about type II EBSs exist for lung tumors. We have tested non-small-cell lung carcinoma cell lines and primary tumor cells for the presence of ERs and type II EBSs and have evaluated the effects of tamoxifen and quercetin (pentahydroxyflavone) on the growth of these cells. Using a whole-cell assay and nuclear and cytosolic radiobinding experiments with [3H]estradiol as tracer, we have found that SK-LU1, SW900, ChaGo-K-1, H441, H661, and A549 cells, as well as primary tumors, bind estrogen specifically. This binding results mainly from the presence of a large number of type II EBSs, whereas ERs are absent or present at low concentrations. Type II EBSs bound tamoxifen and quercetin with similar affinity. Cell counts and a thymidine incorporation assay showed that both compounds inhibit cell growth in a concentration-dependent manner at concentrations ranging from 10 nM to 1 microM. Neither ipriflavone, an isoflavone, nor rutin, the 3-rhamnosylglucoside of quercetin, bound type II EBSs or inhibited cell growth. These findings suggest that tamoxifen and quercetin could regulate lung cancer cell growth through a binding interaction with type II EBSs. This mechanism could also be active in vivo, in that we have observed that nuclear and cytosolic type II EBSs were present in all primary lung cancers tested (n = 12), and that tamoxifen and quercetin were effective in inhibiting in vitro bromodeoxyuridine (BrdU) incorporation and proliferation-cell nuclear antigen expression by neoplastic cells in these cancers.

Language of Publication

English

Unique Identifier

97367506

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MeSH Heading (Major)

Carcinoma, Non-Small-Cell Lung|ME/*PA; Lung Neoplasms|ME/*PA; Quercetin|*TO; Receptors, Estrogen|*ME; Tamoxifen|*TO

MeSH Heading

Aged; Analgesics|PD; Animal; Binding, Competitive; Cell Division|DE; Cell Line; Cell Nucleus|ME; Cytosol|ME; DNA, Neoplasm|AI/BI; Estradiol|ME; Female; Human; Isoflavones|ME/PD; Kinetics; Male; Middle Age; Rats; Rutin|ME/PD; Support, Non-U.S. Gov't; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

1044-1549

Country of Publication

UNITED STATES

Record 53 from database: MEDLINE
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Title

Advanced glycation end products enhance osteoclast-induced bone resorption in cultured mouse unfractionated bone cells and in rats implanted subcutaneously with devitalized bone particles.

Author

Miyata T; Notoya K; Yoshida K; Horie K; Maeda K; Kurokawa K; Taketomi S

Address

Institute of Medical Sciences, Tokai University School of Medicine, Isehara, Japan.

Source

J Am Soc Nephrol, 1997 Feb, 8:2, 260-70

Abstract

Advanced glycation end products (AGE) are formed in long-lived matrix proteins by a nonenzymatic reaction with sugar. The presence of AGE in beta 2-microglobulin-amyloid fibrils of dialysis-related amyloidosis, one of the characteristic features of which is an accelerated bone resorption around amyloid deposits, was recently demonstrated. This suggested a potential link of AGE in bone resorption and initiated this investigation of whether AGE enhance bone resorption. When mouse unfractionated bone cells containing osteoclasts were cultured on dentin slices, both AGE-modified beta 2-microglobulin and BSA increased the number of resorption pits formed by osteoclasts, whereas their normal counterparts of those modified with the early glycation products did not. AGE proteins, however, did not increase the number of newly formed osteoclasts, even in the coculture of mouse bone marrow cells with osteoblastic cells isolated from mouse calvaria. Enhanced bone resorption was also observed when unfractionated bone cells were cultured on AGE-modified dentin slices. AGE-enhanced bone resorption was effectively inhibited by calcitonin and ipriflavone, both of which are inhibitors of bone resorption. AGE-enhanced bone resorption was further supported by in vivo evidence that rat bone particles-upon incubation with glucose for 60 days (AGE-bone particles)-when implanted subcutaneously in rats, were resorbed to a much greater extent than control bone particles upon parallel incubation without glucose. These findings suggest that AGE enhance osteoclast-induced bone resorption. Although the mechanism remains unknown, AGE are unlikely to promote differentiation of osteoclast progenitors into osteoclasts, suggesting that AGE activate osteoclasts or alter microenvironments favorable for bone resorption by osteoclasts. The modification of bone matrices with AGE might play a role in the remodeling of senescent bone matrix tissues, further implicating a pathological significance of AGE in dialysis-related amyloidosis or osteoporosis associated with diabetes and aging.

Language of Publication

English

Unique Identifier

97200410

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MeSH Heading (Major)

Bone Resorption|*ET/PC/*PP; Glycosylation End Products, Advanced|*PD/*PH/UR; Osteoclasts|*DE/*PH

MeSH Heading

beta 2-Microglobulin|PD/PH/UR; Amyloidosis|ET/PP; Animal; Bone Transplantation|PH; Calcitonin|PD; Cells, Cultured; Hemodialysis|AE; Human; In Vitro; Isoflavones|PD; Male; Mice; Rats; Rats, Sprague-Dawley; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

1046-6673

Country of Publication

UNITED STATES

Record 54 from database: MEDLINE
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Title

Clinical guidelines for the treatment of osteoporosis in Japan.

Author

Fujita T

Address

Kobe University, Calcium Research Institute, Kishiwada, Osaka, Japan.

Source

Calcif Tissue Int, 1996, 59 Suppl 1:, 34-7

Abstract

In Japan, unlike in the United States and Europe, where osteoporosis is synonymous with postmenopausal osteoporosis, the need for treatment of osteoporosis has been emphasized only for elderly women with established disease. This may be because women in the immediate postmenopausal period in Japan are virtually free of symptoms such as lumbago and signs such as spinal compression fracture. Osteoporosis typically does not manifest itself until about age 65; therefore, postmenopausal osteoporosis with vertebral fracture below the age of 60 is quite rare in Japan. Unique features of treatment for osteoporosis in Japan include rare use of estrogen replacement therapy, common use of vitamin D derivatives (especially 1alpha(OH) vitamin D) without notable side effects, and use of calcitonin almost exclusively in a low-dose intermittent regimen (20 U/week). Similarly, the use of ipriflavone is common, and calcium supplementation, especially with an active absorbable algae calcium with high bioavailability (AAACa), is effective and popular. The emphasis on the use of calcium, vitamin D, and calcitonin in the treatment of osteoporosis may be explained by an extremely low dietary calcium intake in Japan. Other factors that favor reliance on the calcium-focused approach and avoidance of estrogen include a fatalistic and naturalistic view toward menopause; an uneasiness with hormone replacement therapy; an older female population who seek osteoporosis treatment because of uneventful immediate postmenopausal periods; and the efficient absorption of calcium from the intestine with favorable response to exogenous vitamin D due to a long-standing calcium deficiency and possibly a low incidence of vitamin D-receptor abnormalities.

Language of Publication

English

Unique Identifier

97020107

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MeSH Heading (Major)

Alkaline Phosphatase|*UR; Bone Density|*; Calcium|*UR; Fractures|*DI/ET; Hydroxyproline|*UR; Osteoporosis|*CO/PP/UR

MeSH Heading

Aged; Aged, 80 and over; Biological Markers; Female; Human; Risk Factors

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0171-967X

Country of Publication

UNITED STATES

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