A flavonoid called icariin may join calcium and vitamin D
as key weapons in the fight against osteoporosis.
In addition to exercise, the best results have occurred from the use of supplements using various forms of calcium (e.g., carbonate, citrate, citrate-malate) and vitamin D, as well as supplementation with ipriflavone. Most recently, we have seen that the unique flavonoid icariin, derived from the horny goat weed plant, has an ability to increase bone density at the hip and lumbar spine in postmenopausal women. Health practitioners should be aware that horny goat weed with standardized icariin will likely soon replace ipriflavone in most bone supplements due to new legislation making ipriflavone available only by prescription in many countries.
Searching for a Natural Way to Increase Bone Density
Many studies have suggested that calcium and/or vitamin D supplementation slows down bone loss after age 50 and decreases osteoporotic fractures. The search remained to identify ideal amounts of calcium and vitamin D that could increase bone density. One study demonstrated that supplementation with calcium carbonate (1,550 mg/day) and vitamin D (1,400 IU/day) increased bone density in postmenopausal women and men over age 50 who had previously sustained bone fractures. This was the first study to demonstrate that the combination of calcium with vitamin D (in the absence of exercise) could increase bone density in individuals who were at high risk for osteoporotic fractures. Note that those who exercised showed the greatest increase in bone density. Thus, it appears prudent for individuals 50 and older (and possibly starting at a younger age) to supplement with calcium and vitamin D, along with participating in regular exercise, as a natural means to prevent and reverse bone loss.
Ipriflavone: Two Sides to the Story
Prior to this, the only other natural agent shown to improve bone density was a supplement known as ipriflavone. This is a semi-synthetic agent produced chemically from either genistein or diadzein (the common flavonoids found in soybeans). There is little naturally occurring ipriflavone in plants and food. It is primarily a man-made agent that has been shown to improve bone density in postmenopausal women. There is considerable evidence to show that it inhibits osteoclasts and appears to stimulate osteoblasts to build more bone. The liver metabolizes ipriflavone into 7-hydroxy-ipriflavone and 7-(1-carboxy-ethoxy)-isoflavone. Ipriflavone and its derivatives are then bound to albumin and distributed to tissues throughout the body.
The downside to ipriflavone is that it can produce lymphocytopeina (which is reversible prior to discontinuation) and it acts in a similar manner as the flavonoid in grapefruit juice (naringin), inhibiting certain detoxification enzymes in the liver and thus potentiating the effects of caffeine and drugs such as celecoxib (Celebrex), cyclobenzaprine (Flexeril), NSAIDs, and warfarin (Coumadin). It may also potentiate the effects of bisphosphonates for the treatment of osteoporosis, calcitonin, estrogen and selective estrogen receptor modulators (SERMs).
Ipriflavone is a classified as a drug in Japan, Argentina and many parts of Europe, where it is available by prescription only and used for the prevention and treatment of osteoporosis and osteopenia. The Canadian government has also changed the status of ipriflavone from a supplement to a drug. This means that ipriflavone must be removed from all supplements sold in Canada. The U.S. government is closely monitoring the results of ipriflavone research studies and may classify it as a drug in the near future, in which case it will not be available without a prescription from a medical doctor.
Icariin As an All-Natural Alternative: Research Findings Are Promising
Icariin is a flavonoid glycoside compound derived from several species of plants in the epimedium family, which are commonly known as horny goat weed or yin yang huo. A number of experimental and human studies have shown that icariin can inhibit osteoclastic activity of bone as well as stimulate osteoblast activity, which has been linked to a possible therapeutic role in the treatment of osteoporosis.
One study showed that icariin could increase bone density in postmenopausal women. Researchers in China recruited 85 healthy, late postmenopausal women, and randomly assigned them to receive either a daily dose of epimedium (60 mg icariin, 15 mg daidzein, and 3 mg genistein) or placebo. All women received a daily calcium supplement (300 mg). After two years of supplementation, bone mineral density at the hip (femoral neck) and lower spine (lumbar) had increased by 1.6 and 1.3 percent, respectively, in the epimedium group, and decreased by 1.8 percent and 2.4 percent, respectively, in the placebo group. The researchers stated, "The difference in lumbar spine between the two groups was significant at both 12 and 24 months, whereas the difference in the femoral neck was marginal at 12 months and significant at 24 months."
The women supplemented with epimedium showed a 39 percent decrease in levels of deoxypyrdinoline (a urinary marker of bone resorption) after two years, whereas urinary levels of deoxypyrdinoline were unchanged in women in the placebo group. In addition, no increase in endometrial (lining of the uterus) thickness was observed in either group, nor were there any other changes consistent with risk of endometrial cancer. By comparison, there are concerns that ipriflavone may increase risk of uterine cancer by acting as a selective estrogen receptor modulator on uterine tissue. This was the first human study to show that supplementation with epimedium can increase bone density in the hip and lumbar spine in postmenopausal women. It is important to note that the dosage of icariin was 60 mg/day. This appears to be the critical daily dosage at which increase in bone density is likely to occur.
A Comprehensive Approach
At present, the pharmaceutical approach to the prevention and treatment of osteoporosis remains problematic. Many women report untoward side effects from the use of biphosphonate drugs, and compliance is often very poor. The same is true for other osteoporosis drugs with respect to adverse side effects, complications, contraindications and drug-drug interactions.
Complementary health care practitioners are in a position to counsel patients on preserving and improving their bone density, and the critical importance of doing so, with respect to morbidity mortality and quality of life. In addition to regular weight-bearing exercise, supplementation with calcium and vitamin D, as well as ipriflavone and icariin flavonoid, are the only evidence-based natural agents shown to increase bone density in postmenopausal women and other high-risk individuals.
Of course, bones also require other nutrients. Vitamin C, zinc, copper, manganese and B vitamins can easily be provided by a high-potency multivitamin and mineral supplement, and adequate vitamin K is provided by gut bacteria and green leafy vegetables. In addition, the newest generation of bone-support supplements provide additional amounts of calcium, vitamin D, magnesium, boron, silica and icariin at levels that enable individuals to achieve intake levels consistent with the those reported in this research review.
Resources
- Hitz MF, Jenson JB, Eskildsen PC. Bone mineral density and bone markers in patients with recent low-energy fracture: effect of 1-year treatment with calcium and vitamin D. Am J Clin Nutr, 2007;86:251-9.
- Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int, 1999:61:S23-7.
- Head KA. Ipriflavone: an important bone-building isoflavone. Altern Med Rev, 1999;4:10-22.
- Avioli LV. The future of ipriflavone in the management of osteoporotic syndromes. Calcif Tissue Int, 1997;61(Suppl 1):S33-5 [review].
- Adami S, Bufalino L, Cervetti R, et al. Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years. Osteoporos Int, 1997;7:119-25.
- Nozaki M, Hashimoto K, Inoue Y, et al. Treatment of bone loss in oophorectomized women with a combination of ipriflavone and conjugated equine estrogen. Int J Gynaecol Obstet, 1998;62:69-75.
- Gennari C, Adami S, Agnusdei D, et al. Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass. Calcif Tissue Int 1997;61:S19-22.
- Gennari C, Agnusdei D, Crepaldi G, et al. Effect of ipriflavone, a synthetic derivative of natural isoflavones, on bone mass loss in the early years after menopause. Menopause, 1998;5:9-15.
- 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 Metabol, 1995;9:137-44.
- Kovacs AB. Efficacy of ipriflavone in the prevention and treatment of postmenopausal osteoporosis. Agents Actions, 1994;41(1-2):86-7.
- Alexandersen P, Toussaint A, Christiansen C, et al. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA, 2001;285:1482-8.
- Acerbi D, Poli G, Ventura P. Comparative bioavailability of two oral formulations of ipriflavone in healthy volunteers at steady-state. Evaluation of two different dosage schemes. Eur J Drug Metabol Pharmacokinet, 1998;23:172-7.
- Rondelli I, Acerbi D, Ventura P. Steady-state pharmacokinetics of ipriflavone and its metabolites in patients with renal failure. Int J Clin Pharm Res, 1991;11:183-92.
- Liu JJ, Li SP, Wang YT. Optimization for quantitative determination of four flavonoids in Epimedium by capillary zone electrophoresis coupled with diode array detection using central composite design. J Chromatogr A, 2005;1103(2):344-9.
- Yin XX, Chen ZQ, Liu ZJ, et al. Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2. Chin Med J;120(3):204-10.
- Zhang G, Qin L, Shi Y. Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial. J Bone Miner Res, 2007;22(7):1072-9.
- Chen KM, Ge BF, Liu XY, et al. Icariin inhibits the osteoclast formation induced by RANKL and macrophage-colony stimulating factor in mouse bone marrow culture. Pharmazie, 2007;62(5):388-91.
- Huang J, Yuan L, Wang X, et al. Icaritin and its glycosides enhance osteoblastic, but suppress osteoclastic, differentiation and activity in vitro. Life Sci, 2007;81(10):832-40.
- Zhang DW, Cheng Y, Wang NL, et al. Effects of total flavonoids and flavonol glycosides from Epimedium koreanum nakai on the proliferation and differentiation of primary osteoblasts. Phytomedicine, 200815(1-2):55-61.
- Qin L, Han T, Zhang Q, et al. Antiosteoporotic chemical constituents from Er-Xian Decoction, a traditional Chinese herbal formula. J Ethnopharmacol, 2008;118 (2):271-9.
Click here for more information about James P. Meschino, DC, MS.