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Isoflavones are water-soluble chemicals found in many plants. Ipriflavone is a semisynthetic version of an isoflavone found in soy .
Soy isoflavones have effects in the body somewhat similar to those of estrogen. This should be beneficial, but it is possible that soy could present some of the risks of estrogen, as well. In 1969, a research project was initiated to manufacture a type of isoflavone that would possess the bone-stimulating effects of estrogen without any estrogen-like activity elsewhere in the body. Such a product would help prevent osteoporosis, but cause no other health risks.
Ipriflavone was the result. After 7 successful years of experiments with animals, human research was started in 1981. Today, ipriflavone is available in over 22 countries and in most drugstores in the United States as a nonprescription dietary supplement. It is an accepted treatment for osteoporosis in Italy, Turkey, and Japan.
According to all but one study, ipriflavone combined with calcium can slow and perhaps slightly reverse bone breakdown. It also seems to help reduce the pain of fractures caused by osteoporosis. However, since it does not appear to have any estrogenic effects anywhere else in the body, it shouldn't increase the risk of breast or uterine cancer. On the other hand, it won't reduce the hot flashes, night sweats, mood changes, or vaginal dryness of menopause, nor prevent heart disease.
Note:A recent, large study found that ipriflavone might reduce white blood cell count in some individuals. See Safety Issues for more information.
Sources
Ipriflavone is not an essential nutrient and is not found in food. It must be taken as a supplement.
Therapeutic Dosages
The proper dosage of ipriflavone is 200 mg 3 times daily, or 300 mg twice daily. A calcium supplement providing 1,000 mg of calcium daily should be taken as well.
What Is the Scientific Evidence for Ipriflavone?
Numerous double-blind, placebo-controlled studies involving a total of over 1,700 participants have examined the effects of ipriflavone on various forms of osteoporosis. 1 2 3 4 5 6 7 8 9 10 11 Overall, it appears that ipriflavone can slow the progression of osteoporosis and perhaps reverse it to some extent. For example, a 2-year, double-blind study followed 198 postmenopausal women who showed evidence of bone loss. 12 At the end of the study, there was a gain in bone density of 1% in the ipriflavone group and a loss of 0.7% in the placebo group. These numbers may sound small, but they can add up to a lot of bone over time.
However, the largest and longest study of ipriflavone found no benefit. 13 In this 3-year trial of 474 postmenopausal women, no differences in the extent of osteoporosis were seen between the ipriflavone and placebo groups. How can this failure be accounted for in view of all the successful trials that came before? Perhaps because the researchers in this study gave women only 500 mg of calcium daily. All other major studies of ipriflavone gave participants 1,000 mg of calcium daily. It's possible that ipriflavone requires the higher dose of calcium in order to work properly.
Ipriflavone, like estrogen, probably works by fighting bone breakdown. 14 15 16 However, there is some evidence that it may also increase new bone formation, too. 17 Combining ipriflavone with estrogen may enhance anti-osteoporosis benefits. 18 However, we do not know for sure whether such combinations increase or reduce the other risks (or benefits) of estrogen.
Ipriflavone may also be helpful for preventing osteoporosis in women who are taking Lupron or corticosteroids , medications that accelerate bone loss. 19 (However, the combined use of ipriflavone and drugs that suppress the immune system, such as corticosteroids, presents potential risks. See Safety Issues.)
Finally, for reasons that are not at all clear, ipriflavone appears to be able to reduce pain in osteoporosis-related fractures that have already occurred. 20
References
- 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. Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass. Calcif Tissue Int. 61 Suppl 1():S19-22.
- Valente M, Bufalino L, Castiglione GN, D'Angelo R, Mancuso A, Galoppi P, Zichella L. Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass. Calcif Tissue Int. 54(5):377-80.
- Kovács AB. Efficacy of ipriflavone in the prevention and treatment of postmenopausal osteoporosis. Agents Actions. 41(1-2):86-7.
- Adami S, Bufalino L, Cervetti R, Di Marco C, Di Munno O, Fantasia L, Isaia GC, Serni U, Vecchiet L, Passeri M. Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years. Osteoporos Int. 7(2):119-25.
- Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int. 61 Suppl 1():S23-7.
- Agnusdei D, Zacchei F, Bigazzi S, Cepollaro C, Nardi P, Montagnani M, Gennari C. Metabolic and clinical effects of ipriflavone in established post-menopausal osteoporosis. Drugs Exp Clin Res. 15(2):97-104.
- Agnusdei D, Crepaldi G, Isaia G, Mazzuoli G, Ortolani S, Passeri M, Bufalino L, Gennari C. A double blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss. Calcif Tissue Int. 61(2):142-7.
- Maugeri D, Panebianco P, Russo MS, Motta M, Tropea S, Motta L, Garozzo C, Lomeo E, Barbagallo Sangiorgi G, Scuderi G, Carozzo M, Cantatore FP, Perpignano G, Ferraraccio A, Ennas F. Ipriflavone-treatment of senile osteoporosis: results of a multicenter, double-blind clinical trial of 2 years. Arch Gerontol Geriatr. 19(3):253-63.
- Passeri M, Biondi M, Costi D, et al. Effects of 2-year therapy with ipriflavone in elderly women with established osteoporosis. Ital J Mineral Electrolyte Metab. 1995;9:137-144.
- Agnusdei D, Adami S, Cervetti R, Crepaldi G, Di Munno O, Fantasia L, Isaia GC, Letizia G, Ortolani S, Passeri M. Effects of ipriflavone on bone mass and calcium metabolism in postmenopausal osteoporosis. Bone Miner. 19 Suppl 1():S43-8.
- Alexandersen P, Toussaint A, Christiansen C, Devogelaer JP, Roux C, Fechtenbaum J, Gennari C, Reginster JY, Ipriflavone Multicenter European Fracture Study. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA. 285(11):1482-8.
- Agnusdei D, Crepaldi G, Isaia G, Mazzuoli G, Ortolani S, Passeri M, Bufalino L, Gennari C. A double blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss. Calcif Tissue Int. 61(2):142-7.
- Alexandersen P, Toussaint A, Christiansen C, Devogelaer JP, Roux C, Fechtenbaum J, Gennari C, Reginster JY, Ipriflavone Multicenter European Fracture Study. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA. 285(11):1482-8.
- Agnusdei D, Crepaldi G, Isaia G, Mazzuoli G, Ortolani S, Passeri M, Bufalino L, Gennari C. A double blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss. Calcif Tissue Int. 61(2):142-7.
- Benvenuti S, Petilli M, Frediani U, Tanini A, Fiorelli G, Bianchi S, Bernabei PA, Albanese C, Brandi ML. Binding and bioeffects of Ipriflavone on a human preosteoclastic cell line. Biochem Biophys Res Commun. 201(3):1084-9.
- Bonucci E, Silvestrini G, Ballanti P, Masi L, Franchi A, Bufalino L, Brandi ML. Cytological and ultrastructural investigation on osteoblastic and preosteoclastic cells grown in vitro in the presence of ipriflavone: preliminary results. Bone Miner. 19 Suppl 1():S15-25.
- Cheng SL, Zhang SF, Nelson TL, Warlow PM, Civitelli R. Stimulation of human osteoblast differentiation and function by ipriflavone and its metabolites. Calcif Tissue Int. 55(5):356-62.
- Melis GB, Paoletti AM, Bartolini R, Tosti Balducci M, Massi GB, Bruni V, Becorpi A, Ottanelli S, Fioretti P, Gambacciani M. Ipriflavone and low doses of estrogens in the prevention of bone mineral loss in climacterium. Bone Miner. 19 Suppl 1():S49-56.
- Gambacciani M, Cappagli B, Piaggesi M, et al. Ipriflavone prevents the loss of bone mass in pharmacological menopause induced by GnRH-agonists. Calcif Tissue Int. 1997;61(suppl 1):S15-S18.
- Maugeri D, Panebianco P, Russo MS, Motta M, Tropea S, Motta L, Garozzo C, Lomeo E, Barbagallo Sangiorgi G, Scuderi G, Carozzo M, Cantatore FP, Perpignano G, Ferraraccio A, Ennas F. Ipriflavone-treatment of senile osteoporosis: results of a multicenter, double-blind clinical trial of 2 years. Arch Gerontol Geriatr. 19(3):253-63.