Ipriflavone Bone Support Complex


Research-Proven Bone Builder

By Jim English

Osteoporosis is a systemic skeletal disease characterized by low bone mass and accelerated deterioration of bone tissue. Affecting more than 28 million Americans and an even greater number of Europeans, the condition manifests itself primarily in the elderly and is more likely to occur in women than in men. In fact, on average about one elderly caucasian woman in two will suffer a bone fracture in contrast to only one man in forty for the same age group. Caucasian and Asian women are particularly affected, and up to 80 percent of all women of Northern European descent are prone to developing the disease.

Halting Bone Loss

Conventional drug therapies treat osteoporosis by decreasing bone resorption. At any given time, 5 to 10 percent of bone mass has been resorbed but not replaced. By decreasing resorption of bone, a gain in bone density of 5 to 10 percent is possible over a period of about 2 to 3 years. Post-menopausal women with osteoporosis may benefit from hormonal therapy using estrogen with progesterone. The estrogen retards bone resorption and thus diminishes bone loss. This effect is most prominent in the first years after menopause.

Other common drugs used to treat osteoporosis include:

  • Alendronate, a biphosphonate, inhibits osteoclastic (bone absorbing) activity. Alendronate can be effective in inhibiting bone loss after menopause, particularly in women who cannot tolerate estrogen therapy.
  • Raloxifene, a selective estrogen receptor modulator that may also replace estrogen therapy. Raloxifene can act in concert with estrogen in bone to inhibit resorption and decrease the risk for fractures.
  • Calcitonin, a hormone that decreases bone resorption. Calcitonin is expensive and must be taken by injection.
  • Sodium fluoride, increases measured bone density in vertebra, but seems to have no overall effectiveness in reducing vertebral fracture.

Ipriflavone, The Natural Alternative

Ipriflavone (7-isopropoxy iso-flavone) is a synthetic isoflavone derivative that acts primarily to suppress bone resorption. Other in vitro studies have shown that ipriflavone can stimulate osteoblasts to form new bone. Unlike the bone-building drug treatments that can produce serious side effects, the only reported side effect from ingesting ipriflavone is an upset stomach in a small percentage of the users. (1,2) This makes ipriflavone a powerful and safe agent for preventing and treating osteoporosis.

Ipriflavone is a registered treatment for osteoporosis in many European countries and Japan. It is used as an alternative to hormone treatments for increasing bone mass and relieving the pain of osteoporosis. It’s often used in conjunction with low dosages of estrogen to increase their anti-osteoporotic effects. (3,4) The research has also demonstrated that ipriflavone appears to produce its strongest bone-building actions when given in conjunction with other bone-supporting supplements.

Prevents Bone Loss and Fractures 

Even though the discovery of ipriflavone dates back to the 1930s, it was not produced in the laboratory until the 1970s. Animal studies, which began in 1974, led to human studies being conducted in 1981. During the 1980s and 1990s a number of randomized, double-blind, placebo controlled studies demonstrated ipriflavone could prevent or decrease the loss of bone mass in postmenopausal women. (5,7)

Other research studies have shown that taking a daily dose of 600 mg of ipriflavone could increase bone density by as much as 9 percent in three to nine months and cause a significant reduction of fractures after two years of treatment. Since then, close to 500 patients treated with ipriflavone in double-blind, placebo controlled studies have noted significant gains of between.5 to 7.1 percent in total body, forearm and vertebral bone mineral density. Ipriflavone has also resulted in the relief of pain and an increase in mobility. (8,9)

Structure and Function Similar With Estrogen 

Researchers have shown that chemical structure of ipriflavone is similar to the structure of estrogen. That explains why it mimics the action of estrogen on preventing bone loss. Estrogens inhibit bone-degrading osteoclast activity that causes bone resorption and ipriflavone protects bone in a similar manner. (10,13)

Despite the ability of ipriflavone to augment the activity of naturally occurring or administered estrogens, ipriflavone does not have any estrogenic effects on the hypothalamus and pituitary gland. It does not have the estrogenic actions of stimulating breast and uterine tissue either. (14,15) These estrogenic actions may be dangerous for postmenopausal women who are genetically prone to female cancers. Ipriflavone simply improves the structure of bone and prevents the loss of bone without any harmful side effects.

Stronger Actions Than Calcitonin

Researchers have compared the bone restoring effects of ipriflavone with the FDA-approved osteoporosis treatment hormone Calcitonin. The study found that ipriflavone had a greater ability to inhibit the formation of osteoclasts and bone resorption, while simultaneously stimulating the formation of osteoblasts to form new bone cells. (16,17) Unlike calcitonin, ipriflavone was found to be free of serious side effects.

Builds New Bone 

Research shows that ipriflavone activates osteoblasts. When osteoblasts are exposed to ipriflavone and its metabolites, the cellular process of manufacturing bone-matrix proteins and bone-mineral deposition is stimulated.

Clinical human trials have demonstrated significant increase of bone density from ipriflavone treatment. (18,19) Furthermore, the research indicates that the bone-building actions of ipriflavone are more pronounced when ipriflavone is administered in conjunction with several other bone-support nutrients: 1) calcium, 2) vitamin D, and 3) vitamin K.

Ipriflavone and Calcium 

Ipriflavone has been shown to work with calcium supplements to help maintain stronger bones. Ipriflavone improves calcium metabolism in bone by fusing itself to specific binding sites in precursor cells and mature osteoclasts, the cells that digest bone. As a result, ipriflavone alters bone calcium flux and inhibits bone resorption. (24)

One two-year study evaluated ipriflavone’s spinal bone-building effects in postmenopausal women with low vertebral bone density. These women took either 200 mg of ipriflavone, three times daily along with 1 gram of calcium, or only calcium and a placebo. Following six months of ipriflavone-calcium supplementation, spinal bone density increased 1.4 percent, a clinically significant amount, In the control group taking the placebo, bone density decreased overall by 1.2 percent after two years. Additionally, twenty women enrolled in the placebo group who had recently become menopausal experienced a 4.9 percent decrease in bone density after the second year. This is most likely explained by the fact that the most rapid loss of bone occurs within the first five years of menopause. (20)

Another group of scientists examined the ability of ipriflavone to prevent bone loss occurring shortly after menopause. Fifty-six postmenopausal women with low vertebral bone density received either 200 mg of ipriflavone three times daily or a placebo. All subjects also received 1,000 mg of elemental calcium daily. After two years researchers noted that there was no loss in vertebral bone density in the women receiving both ipriflavone and calcium, while women taking only calcium experienced a 4.9 percent loss in bone density. (21,23)

Calcium Hydroxyapatite 

The most effective form of calcium to use with ipriflavone appears to be Microcrystalline Hydroxyapatite (MCHC). MCHC is an extract of whole bone that contains calcium, magnesium, zinc, silica, manganese, and many other trace minerals in their natural ratios, as well as residues of matrix, proteins, and glycosaminoglycans.

Reconstructs Bone 

MCHC is the only form of calcium that has been shown to reconstruct bone and restore bone loss when taken as a supplement. This makes MCHC the ideal companion supplement to ipriflavone. In a study of osteoporotic postmenopausal women with the complication of primary biliary cirrhosis, MCHC not only reduced bone loss but it actually increased cortical bone thickness. Those taking MCHC showed a 6.1 percent increase in bone thickness. Conversely, calcium gluconate halted the bone loss but did not restore it, and the group receiving no supplementation continued to show accelerated loss of bone. Other studies show that MCHC has a higher level of absorption and greater bioavailability than either calcium gluconate or calcium carbonate. (25,28)

MCHC has other proven benefits on bone formation. Elderly subjects taking MCHC experienced more rapid healing of fractures when compared to the rate of healing in subjects who did not take MCHC. MCHC has also been shown to dramatically reduce bone loss in surgically induced postmenopausal women, and MCHC has been called a valuable therapy in preventing osteoporosis in individuals with rheumatoid arthritis. (29,30)

Vitamin D and Ipriflavone 

Vitamin D and its metabolites stimulate the absorption of calcium from the gut and the resorption of calcium in bone. In fact, a deficiency of vitamin D and a failure to metabolize vitamin D in the liver are known factors in the development of osteoporosis. Ipriflavone and vitamin D have been found to work synergistically to increase bone mineral density. In research studies, a combination of vitamin D3 and ipriflavone have shown superior bone building actions when compared to taking ipriflavone alone. The combination regimen increased bone mineral density over the entire length of the femur while the administration of Vitamin D3 alone had no effect.

An 18-month study found that the combined regimen of ipriflavone and vitamin D3 was effective in stopping postmenopausal bone loss. The mean bone loss of the combined regimen group was.33 percent versus 2.37 percent for the ipriflavone alone group, 1.15 percent for the vitamin D3 alone group and and 3.70 percent for the control group. The synergistic actions of ipriflavone and vitamin D regimen may be the result of a direct effect of each agent on osteoblastic (bone forming) cells. (31,32)

Vitamin K and Ipriflavone 

Ipriflavone and vitamin K’s actions on bone metabolism are complementary. Vitamin K is needed to convert the inactive portion of the bone protein osteocalcin to the active form that anchors calcium in bone. Vitamin K also inhibits the resorptive actions of mature osteoclasts while halting the formation of new osteoclasts.

Researchers have demonstrated that the inhibitory effects of vitamin K on bone resorption are similar to those of ipriflavone but operate through different mechanisms. As a result the combination of vitamin K and ipriflavone has additive actions in preventing bone resorption. (33)

Maximum Bone Building Support with Ipriflavone Complex 

For maximum benefits on rebuilding strong bones and in preventing osteoporosis, a combination regimen of ipriflavone with vitamin D, calcium MCHP, vitamin K and other bone-support agents that includes magnesium is recommended. The same processes that result in osteoporosis also lead to a loss of jaw bone in periodontal diseases. Therefore it seems resaonable to speculate that ipriflavone would be of benefit to those with periodontal disease just as it is for those suffering from osteoporosis.


1. Miyauchi, A., et al. Novel ipriflavone receptors coupled to calcium influx regulate osteoclast differentiation and function. Endocrinology, 13: 3544-50, 1996.
2. Kitatani K; Morii H Ipriflavone Nippon Rinsho, 62(1):1537-43 1998 Jun.
3. Sz´ant´o F [Experience with ipriflavone therapy in postmenopausal osteoporosis Orv Hetil, 61 Suppl 1(1):2801-3 1997 Nov 2.
4. Affinito P; Palomba S; et al. Postmenopausal osteoporosis: therapeutic approaches Minerva Ginecol, 49(3):109-20 1997 Mar.
5. Agnusdei D; Zacchei F; et al. Metabolic and clinical effects of ipriflavone in established post-menopausal osteoporosis Drugs Exp Clin Res, 61 Suppl 1(1):97-104 1989.
6. Attila BK Overview of clinical studies with ipriflavone Acta Pharm Hung, 61 Suppl 1(2):223-8 1995 Nov
7. Bossanyi A; Bucsi L. A new treatment possibility for osteoporosis with osteochin (ipriflavone) tablets Magy Traumatol Orthop Helyreallito Seb, 61 Suppl 1(2):109-15 1989.
8. Gennari C; Adami S; et al. Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass. Calcif Tissue Int, 61 Suppl 1(Adami S):S19-22 1997.
9. Agnusdei D; Bufalino L Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int, 61 Suppl 1:S23-7 1997.
10. Kuiper GG; Lemmen et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology, 139(10):4252-63 1998 Oct.
11. Brandi ML Natural and synthetic isoflavones in the prevention and treatment of chronic diseases. Calcif Tissue Int, 313(1):S5-8 1997.
12. Kakai, Yoshio, et al, Effect of Ipriflavone and Estrogen on the Differentiation and Proliferation of Osteoclast Cells, Calcified Tissue International, 1992 Springer-Verlag, New York.
13. Notoya K; et al. Stimulatory effect of ipriflavone on formation of bone-like tissue in rat bone marrow stromal cell culture. Calcif Tissue Int, 51 Suppl 1(-AD-):S16-20 1992.
14. Melis, G.B., et al. Lack of any estrogenic effect of ipriflavone in postmenopausal women. J Endocrinol Invest, 15: 755-61, 1992.
15. Petilli, M., et al. Interactions between ipriflavone and the estrogen receptor. Calcif Tissue Int, 56: 160-65,1995.
16. Lobianco R; Merola B; et al Randomized comparative study using carbocalcitonin i.m. vs carbocalcitonin nasal spray vs ipriflavone x os in the treatment of post-menopausal osteoporosis] Minerva Endocrinol, 61 Suppl 1(2):79-84 1992 Apr-Jun.
17. Cecchettin M; et al. Metabolic and bone effects after administration of ipriflavone and salmon calcitonin in postmenopausal osteoporosis. Biomed Pharmacother, 61 Suppl 1(10):465-8 1995.
18. Fiore CE; et al. Modification of cortical and trabecular mineral density of the femur, induced by ipriflavone therapy, Clinical results after 12 months Clin Ter, 61 Suppl 1(1):13-9 1995 Jan.
19. Notoya K; et al. Increase in femoral bone mass by ipriflavone alone and in combination with 1 alpha-hydroxyvitamin D3 in growing rats with skeletal unloading. Calcif Tissue Int, 58(2):88-94 1996 Feb.
20. Gennari C; Agnusdei D; et al Effect of ipriflavone – a synthetic derivative of natural isoflavones – on bone mass loss in the early years after menopause. Menopause, 5(1):9-15 1998 Spring.
21 Agnusdei D; Zacchei F; et al. Metabolic and clinical effects of ipriflavone in established post-menopausal osteoporosis. Drugs Exp Clin Res, 15(2):97-104 1989.
22. Agnusdei, D., et al.. A double blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss. Calcif Tissue Int, 61: 142-47, 1997.
23. Gennari C; Agnusdei D; et al Effect of ipriflavone – a synthetic derivative of natural isoflavones – on bone mass loss in the early years after menopause. Menopause, 61 Suppl 1(1):9-15 1998 Spring.
24. Miyauchi A; et al. Novel ipriflavone receptors coupled to calcium influx regulate osteoclast differentiation and function. Endocrinology, 137(8):3544-50 1996 Aug.
25. Nilsen KH; Jayson Ml: Dixon AS “Microcrystalline calcium hydroxyapatite compound in corticosteroid-treated rheumatoid patients: a controlled study.” Br Med J 1978 Oct 21;2(6145):1124.
26. Ruegsegger P; Keller A; Dambacher MA “Comparison of the treatment effects of ossein-hydroxyapatite compound and calcium carbonate in osteoporotic females. Osteoporosis Int 1995 Jan;5(1):30-4.
27. Dent, C.E., Davies. l.J.T., “Calcium metabolism in bone disease; effects of treatment with microcrystalline calcium hydroxyapatite compound with dihydrotachysterol Journal of the Royal Society of Medicine, (1980) 13:780-787.
28. Epstein O; et al. “Vitamin D, hydroxyapatite, and calcium gluconate in treatment of cortical bone thinning in post -menopausal women with primary biliary cirrhosis.” Am J Clin Nutr 1982 Sep;36(3):426-30.
29. Mills, TJ, Davis, H. Broadhorst, BW. True Use of Whole Bone in the Treatment of Fracture’s Manitoba Medical Review 1965;45:92-96.
30. Stephan,J. J. Pospichal J. et al “Prospective T tal of Ossein-Hydroxyapatite compound in surgically induced postmenopausal women. ” Bone (1989) 10, 179-185.
31. Ushiroyama T; et al. Efficacy of ipriflavone and 1 alpha vitamin D therapy for the cessation of vertebral bone loss. Int J Gynaecol Obstet, 61 Suppl 1(1):283-8 1995 Mar.
32. Notoya K; et al. Increase in femoral bone mass by ipriflavone alone and in combination with 1 alpha-hydroxyvitamin D3 in growing rats with skeletal unloading. Author Calcif Tissue Int, 58(2):88-94 1996 Feb.
33. Notoya K; et al. Similarities and differences between the effects of ipriflavone and vitamin K on bone resorption and formation in vitro. Bone, 16(4 Suppl):349S-353S 1995 Apr.


Submit a comment or feedback:

Please enter your comment!
Please enter your name here