According to the U.S. National Osteoporosis Foundation, 10 million people over the age of 50 have the disease and about 80 percent are women.1 A further 34 million are at risk due to low bone mass (osteopenia).
The vast majority of epidemiological and clinical research on the role of plants in osteoporosis treatment and prevention has focused on phytoestrogenic plant compounds. Data strongly suggest that ingesting phytoestrogenic compounds produces a lower incidence of osteoporosis and bone fractures, as well as menopausal symptoms such as hot flashes.2 Most of this research has been on soy isoflavones. However, other plants may also be important, including those that can act as alternative sources of isoflavones.
Red Clover
In a randomized, double-blind clinical trial, women ages 49 to 65 received isoflavones from red clover extract (43.5 mg/day) or placebo for 12 months.3 The daily dose of isoflavones consisted of 26 mg biochanin A, 16 mg formononetin, 1 mg genistein and 0.5 mg daidzein. Loss of lumbar spine bone-mineral content and bone mineral density (BMD) was significantly lower in the women taking the isoflavones than in those taking the placebo. There were no significant differences between groups with respect to changes in dietary intakes of calcium and vitamin D over the 12-month period.
This preparation (at a similar dosage) was evaluated in a trial of the same design in women ages 35 to 70 with a family history of breast cancer. Treatment was administered for three years. Bone mineral densities of the lumbar spine and femur were not significantly affected. However, more than 80 percent of the women in the study were premenopausal, and the potential bone loss could be expected to be less than in postmenopausal patients. The effect on BMD was, in fact, a secondary objective of this study.4
An earlier clinical study investigated the effect of several doses of isoflavones from red clover extract taken daily for six months. Compared to baseline, doses of 57 mg/day and 85.5 mg/day increased BMD of the proximal radius and ulna in postmenopausal women. Participants received calcium (1,000-1,200 mg/day) in a supplement throughout the study. Due to the short trial duration, and therefore the potentially small changes in BMD, the forearm was assessed, as it provides higher precision in these circumstances.5
Kudzu
Puearia lobata (known as kudzu or kuzu) is a prolific vine that covers much of the southeastern United States and is one of the richest sources of isoflavones. Animal studies support the use of kuzu for the prevention and treatment of poor bone density.6-7
Black Cohosh
Black cohosh has been shown to have favorable effects on bone metabolism. An experimental model was designed to understand the mechanism behind this activity and to compare its effects with estrogen and testosterone.8 This study suggests that the bone-sparing effect of black cohosh is mediated by inhibition of osteoclast activity. RANK (receptor activator of nuclear factor kappa B) and its ligand RANKL largely regulate osteoclast activity and bone breakdown. Crosslaps (or Ratlaps in rats), the cross-linked collagens (telopeptides) are markers of bone degradation. Black cohosh, estradiol (E2) and testosterone (T) were given to castrated rats of both sexes. Both E2 and black cohosh reduced levels of Ratlaps, but only in the females. The authors suggested that the bone-sparing effect of black cohosh is therefore partly mediated by inhibition of osteoclast activity.
In contrast, the metabolic marker for bone formation, bone-specific alkaline phosphatase, was significantly increased by black cohosh in a clinical study.9 Therapeutic effects of a black cohosh extract were compared to conjugated estrogens and placebo in postmenopausal women. The trial involved 62 patients and was a double-blind, randomized, placebo-controlled study, with around 20 subjects in each group. This finding indicates an increased activity of the osteoblast cells, which are responsible for bone formation. Bone-specific alkaline phosphatase remained unchanged in the placebo and estrogen groups.
Epidemium
The aerial parts of several species of Epimedium, including Epimedium sagittatum and E. brevicornum (also known as Epimedium brevicornu), are used in traditional Chinese medicine.10-11 In the West it is often known as horny goat weed. Epimedium is said to strengthen bones.12 It is used for a large number of applications, including weakness of the limbs and lower back, rheumatic pain and hypertension of menopause.10,11 Flavonoids, in particular icariin (a flavonol glycoside), are major constituents of medicinal Epimedium.13
One clinical trial evaluated a daily dose of icariin (60 mg, extracted from Epimedium), daidzein (15 mg) and genistein (3 mg) in late postmenopausal women. Bone mineral density was maintained in the femoral neck and lumbar spine at both 12 months and 24 months. In contrast, the placebo group experienced a significant decrease. Nonskeletal factors (muscle force coefficient of the lower limb and the dynamic balance coefficient) related to the femoral neck were also significantly increased from baseline at 24 months for the treatment group. These factors did not change in the placebo group. Both the placebo and treatment groups received supplemental calcium (300 mg/day).14-15
Herbs and Exercise
Isoflavone phytoestrogens appear to combine synergistically with exercise, which is often recommended for increasing BMD, possibly by stimulating estrogen receptors. However, the increases in BMD are often small with exercise alone. Isoflavone intake and walking exercise over one year in postmenopausal Japanese women exhibited a trend for a greater effect on prevention of bone loss at the total hip and the neck of the femur.16 The trial involved 136 postmenopausal women and was randomized and placebo-controlled. BMD, fat mass, serum lipid, and serum and urinary isoflavone concentrations were assessed. Patients were divided into four groups: placebo, walking (45 minutes/day, three days/week) with placebo, isoflavone intake (75 mg of isoflavone conjugates/day) or combination of isoflavone plus walking.
The combined intervention showed a trend for a greater effect on BMD at the hip and neck of femur than either intervention by itself. Serum HDL concentration significantly increased at 12 months after the combined intervention. Significant reduction in fat mass in the whole body and the trunk were observed at three, six and 12 months, and in the legs and arms at six and 12 months.
Author's Acknowledgment: Thanks to Rob Santich and Michelle Morgan for their assistance in the preparation of this article.
References
- See www.nof.org/osteoporosis/diseasefacts.html.
- Dixon RA. Phytoestrogens. Ann Rev Plant Biol, 2004;55(1):225-61.
- Atkinson C, Compston JE, Day NE, et al. The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr, 2004;79(2):326-33.
- Powles TJ, Howell A, Evans DG, et al. Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer. Menopause Int, 2008;14(1):6-12.
- Clifton-Bligh PB, Baber RJ, Fulcher GR, et al. The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism. Menopause, 2001;8(4):259-65.
- Wang X, Wu J, Chiba H, et al. Puerariae radix prevents bone loss in ovariectomized mice. J Bone Miner Metab, 2003;21(5):268-75.
- Zheng G, Zhang X, Meng Q et al. Protective effect of total isoflavones from Pueraria lobata on secondary osteoporosis induced by dexamethasone in rats. Zhong Yao Cai, 2002;25(9):643-46.
- Seidlova-Wuttke D, Jarry H, Wuttke W. Mechanisms of action of antiosteoporotic effects of a special Cimicifuga racemosa (CR) extract: inhibition of the RANK-RANKL-osteoprotegerin triad. Planta Med, 2007;73:995.
- Wuttke W, Seidlova-Wuttke D, Gorkow C. The Cimicifuga preparation BNO 1055 vs. Conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. Maruritas, 2003;44(Suppl 1):S67-77.
- Pharmacopoeia Commission of the People's Republic of China. Pharmacopoeia of the People's Republic of China (English Ed.) Beijing: Chemical Industry Press, 1997.
- Chang HM, But PP, eds. Pharmacology and Applications of Chinese Materia Medica, Volume 2. Singapore: World Scientific, 1987.
- Bensky D, Clavey S, Stoger E. Chinese Herbal Medicine: Materia Medica, 3rd Edition Seattle: Eastland Press, 2004.
- Tang W, Eisenbrand G. Chinese Drugs of Plant Origin. Berlin: Springer-Verlag, 1992.
- 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.
- Zhang G, Qin L, Shi Y. Bone, 2008;43(Suppl 1):S64-5.
- Wu J, Oka J, Tabata I, et al. Effects of isoflavone and exercise on BMD and fat mass in postmenopausal Japanese women: a 1-year randomized placebo-controlled trial. J Bone Miner Res, 2006;21(5):780-9.
Kerry Bone is a practicing herbalist; co-founder and head of research and development at MediHerb; and principal of the Australian College of Phytotherapy. He also is the author of several books on herbs and herbal therapy, including Principles and Practice of Phytotherapy and The Essential Guide to Herbal Safety.