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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

Published on Apr 9, 2007in Journal of Bone and Mineral Research5.71
· DOI :10.1359/jbmr.070405
Ge Zhang31
Estimated H-index: 31
(SHU: Shanghai University),
Ling Qin52
Estimated H-index: 52
(CUHK: The Chinese University of Hong Kong),
Yinyu Shi4
Estimated H-index: 4
(SHU: Shanghai University)
Cite
Abstract
Epimedium brevicornum maxim, a nonleguminous medicinal plant, has been found to be rich in phytoestrogen flavonoids. Results from a 24-month randomized double-blind placebo-controlled clinical trial showed that Epimedium-derived phytoestrogen flavonoids were able to exert beneficial effects on preventing bone loss in late postmenopausal women, without resulting in a detectable hyperplasia effect on the endometrium. Introduction: We performed a 24-mo randomized double-blind placebo-controlled clinical trial for evaluating the effect of the Epimedium-derived phytoestrogen flavonoids (EPFs) on BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness in postmenopausal women. Materials and Methods: One hundred healthy late postmenopausal women, with a natural menopausal history within 10 ∼18 yr and with a BMD T-score at the lumbar spine between −2 and −2.5 SD, were randomized into EPF treatment group (n = 50; a daily dose of 60 mg Icariin, 15 mg Daidzein, and 3 mg Genistein) or placebo control group (n = 50). All participants received 300 mg element calcium daily. BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness were measured at baseline and 12 and 24 mo after intervention. Results: Eighty-five participants completed the trial. The patterns of BMD changes were significantly different between the EPF treatment group and placebo control group by repeated-measures ANOVA (p = 0.045 for interaction between time and group at femoral neck; p = 0.006 for interaction between time and group at lumbar spine). BMD was found with a decreased tendency in the placebo control group at 12 (femoral neck: −1.4%, p = 0.104; lumbar spine: −1.7%, p = 0.019) and 24 mo (femoral neck: −1.8%, p = 0.048; lumbar spine: −2.4%, p = 0.002), whereas EPF treatment maintained BMD at 12 (femoral neck: 1.1%, p = 0.285; lumbar spine:1.0%, p = 0.158) and 24 mo (femoral neck: 1.6%, p = 0.148; lumbar spine: 1.3%, p = 0.091). The difference in lumbar spine between the two groups was significant at both 12 (p = 0.044) and 24 mo (p = 0.006), whereas the difference in the femoral neck was marginal at 12 mo (p = 0.061) and significant at 24 mo (p = 0.008). Levels of bone biochemical markers did not change in the placebo control group. In contrast, EPF intervention significantly decreased levels of deoxypyrdinoline at 12 (−43%, p = 0.000) and 24 mo (−39%, p = 0.000), except for osteocalcin at 12 (5.6%, p = 0.530) and 24 mo (10.7%, p = 0.267). A significant difference in deoxypyrdinoline between the two groups was found at both 12 (p = 0.000) and 24 mo (p = 0.001). Furthermore, neither serum estradiol nor endometrial thickness was found to be changed in either groups during the clinical trial. Conclusions: EPFs exert a beneficial effect on preventing bone loss in late postmenopausal women without resulting in a detectable hyperplasia effect on the endometrium.
  • References (60)
  • Citations (143)
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References60
Newest
Published on Aug 1, 2006in Journal of Nutritional Biochemistry4.49
Hui-Ying Huang1
Estimated H-index: 1
(TMU: Taipei Medical University),
Hsiao-Ping Yang1
Estimated H-index: 1
(TMUH: Taipei Medical University Hospital)
+ 3 AuthorsShih Yi Huang22
Estimated H-index: 22
(TMU: Taipei Medical University)
Abstract It is believed that soy isoflavone has much potential effectiveness on the postmenopausal status; however, the optimal dose for preventing postmenopausal bone loss still remains unclear. This open-labeled, self-controlled pilot study was undertaken to determine the effect of 1-year supplementation of different high dosages of soy isoflavone in postmenopausal Taiwanese women. Forty-three women aged 45–67 years were enrolled and randomly assigned into a control (C), 100 mg/day isoflavone ...
Published on Jun 1, 2006in Bone4.36
Ge Zhang31
Estimated H-index: 31
(CUHK: The Chinese University of Hong Kong),
Ling Qin52
Estimated H-index: 52
(CUHK: The Chinese University of Hong Kong)
+ 4 AuthorsKwong-Sak Leung38
Estimated H-index: 38
(CUHK: The Chinese University of Hong Kong)
Aim: Factorial design was used to test our hypothesis whether a group of flavonoids (FE) derived from herbal Epimedium Brevicornum Maxim exerted its preventive effects on estrogen-deficiency-induced osteoporosis mainly through an enhancement in intestinal calcium absorption. Materials and methods: Forty-five 12-month-old female Wistar rats were used and randomly assigned into sham-operated group and four ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX group), OVX with FE (FE group), OVX ...
Published on May 1, 2006in Phytochemistry2.90
Zuzana Mackova4
Estimated H-index: 4
(Institute of Chemical Technology in Prague),
R. Koblovská6
Estimated H-index: 6
(Institute of Chemical Technology in Prague),
Oldrich Lapcik5
Estimated H-index: 5
(Institute of Chemical Technology in Prague)
Abstract Common emphasis of the fact that isoflavonoids are characteristic metabolites of leguminous plants sometimes leads to overlooking that the presence of isoflavonoids has been reported in several dozen other families. The spectrum of isoflavonoid producing taxa includes the representatives of four classes of multicellular plants, namely the Bryopsida, the Pinopsida, the Magnoliopsida and the Liliopsida. A review, recently published by Reynaud et al. [Reynaud, J., Guilet D., Terreux R., Lu...
Published on May 1, 2006in International Journal of Oncology3.57
Vera Cappelletti18
Estimated H-index: 18
,
Patrizia Miodini17
Estimated H-index: 17
+ 1 AuthorsMaria Grazia Daidone52
Estimated H-index: 52
High consumption of phytoestrogen-rich food correlates with reduced incidence of breast cancer. However, the effect of phytoestrogens on growth of pre-existing breast tumors presents concerns when planning the use of phytoestrogens as chemoprevention strategy. Genistein, the active phytoestrogen in soy, displays weak estrogenic activity mediated by estrogen receptor (ER) with a preferential binding for the ER-B species. However, no information is at present available on the interaction between p...
Published on Feb 20, 2006in Journal of Bone and Mineral Research5.71
Jian Wu39
Estimated H-index: 39
,
Jun Oka19
Estimated H-index: 19
+ 8 AuthorsKazuhiko Yamada17
Estimated H-index: 17
The combined intervention of isoflavone intake and walking exercise over 1 year in postmenopausal Japanese women exhibited a trend for a greater effect on prevention of bone loss at the total hip and Ward's triangle regions. Introduction: The additive effects of isoflavones and exercise on bone and lipid metabolism have been shown in estrogen-deficient animals. In this study, we determined the effects of isoflavone intake, walking exercise, and their interaction on bone, fat mass, and lipid meta...
Published on Jan 1, 2006in Endocrine Journal1.94
Takeshi Usui25
Estimated H-index: 25
Interest in the physiologic and pharmacologic role of bioactive compounds present in plants has increased dramatically over the last decade. Of particular interest in relation to human health are the classes of compounds known as the phytoestrogens, which embody several groups of non-steroidal estrogens, including isoflavones and lignans that are widely distributed within nature. The impact of dietary phytoestrogens on normal biologic processes was first recognized in sheep. Observations of shee...
Published on Dec 1, 2005in Die Pharmazie
Chen Km3
Estimated H-index: 3
,
Ge Bf3
Estimated H-index: 3
+ 3 AuthorsWang Y3
Estimated H-index: 3
The herb Epimedium has long been used in Traditional Chinese Medicine to treat bone fracture and prevent osteoporosis. Researchers believe that the flavonoids contained in the herb are the effective component for this activity. However, no single flavonoid has been studied for its effect on bone-related cells. In the present study, icariin, one of the major flavonoids of the herb, supplemented the primary culture medium of rat bone marrow stromal cells (rMSCs) at 0.1 μM, 1 μM and 10 μM respectiv...
Xiao Qiangbing1
Estimated H-index: 1
(HUST: Huazhong University of Science and Technology),
Chen Anmin4
Estimated H-index: 4
(HUST: Huazhong University of Science and Technology),
Guo Fengjin1
Estimated H-index: 1
(HUST: Huazhong University of Science and Technology)
To study the effects of Icariin on expression of osteopontin (OPN) mRNA and type I collagen in rat osteoblastsin vitro and to explore its possible mechanisms in preventing osteoporosis. OB was isolated from calvaria of new-born new-born fetal Sprague-Dawley (SD) rats by means of modified sequential collagenase digestion and incubated in MEM medium and the cell morphology was observed under inverted phase contrast microscope, OB was identified by alkaline phosphatase (ALP) staining. Different con...
Published on Nov 1, 2005in Journal of Nutrition4.42
Pierangela Totta11
Estimated H-index: 11
,
Filippo Acconcia29
Estimated H-index: 29
+ 4 AuthorsMaria Marino38
Estimated H-index: 38
Daidzein (D), a soy isoflavone, is almost completely metabolized in the gut and liver. This biotransformation converts D to more water-soluble products and may affect its biological activity. The ability of daidzein metabolites to modulate 17/3-estradiol (E2)-sensitive gene transcription, cell growth, and a proapoptotic cascade was determined in human cancer cells devoid of any estrogen receptor (ER) and rendered E2 sensitive after transfection with ER/3. The data show that D and some but not al...
Published on Sep 1, 2005in Osteoporosis International3.82
Warren T. K. Lee19
Estimated H-index: 19
(CUHK: The Chinese University of Hong Kong),
Catherine S. K. Cheung9
Estimated H-index: 9
+ 5 AuthorsJack C. Y. Cheng50
Estimated H-index: 50
(CUHK: The Chinese University of Hong Kong)
Generalized low bone mass has been well documented in patients with adolescent idiopathic scoliosis (AIS). However, studies linking calcium-intake (CA), weight-bearing physical-activity (PA) and bone mass of AIS are lacking. We aimed to study the relationship between CA, PA and bone mass in AIS girls and compared to those of healthy non-AIS controls during the peripubertal period. Newly diagnosed AIS girls (n=596) aged 11–16 years with Cobb angle ≥10° were recruited to compare with age-matched h...
Cited By143
Newest
Published on Feb 14, 2019in Scientific Reports4.01
Yuxin Zheng6
Estimated H-index: 6
(SHU: Shanghai University),
Xuezong Wang5
Estimated H-index: 5
(SHU: Shanghai University)
+ 24 AuthorsYongfang Zhao5
Estimated H-index: 5
Falls in late postmenopausal women with osteopenia usually cause fractures with severe consequences. This 36-month randomized, double-blind and placebo-controlled trial with a 10-year observational follow-up study aimed to investigate the long-term effect of herbal formula Bushen Yijing Fang (BSYJF) on fall risk in the late postmenopausal women with osteopenia. 140 late postmenopausal women (Femoral neck T-score, −2.5~−2 SD) were recruited and randomized to orally receive calcium carbonate 300 m...
Published on Jun 20, 2019in Expert Opinion on Drug Delivery5.40
Ana Cláudia Fernandes Lima1
Estimated H-index: 1
(University of Minho),
Helena Ferreira8
Estimated H-index: 8
(University of Minho)
+ 1 AuthorsNuno M. Neves41
Estimated H-index: 41
(University of Minho)
AbstractIntroduction: The unique structure of bone and cartilage makes the systemic delivery of free drugs to those connective tissues very challenging. Consequently, effective and targeted delivery for bone and cartilage is of utmost importance. Engineered biodegradable polymers enable designing carriers for a targeted and temporal controlled release of one or more drugs in concentrations within the therapeutic range. Also tissue engineering strategies can allow drug delivery to advantageously ...
Published on Jan 1, 2019in Frontiers in Endocrinology3.63
Vanessa Nicolin14
Estimated H-index: 14
(UniTS: University of Trieste),
Nunziatina De Tommasi32
Estimated H-index: 32
(UNISA: University of Salerno)
+ 3 AuthorsRoberto Di Lenarda30
Estimated H-index: 30
(UniTS: University of Trieste)
During the past, a more comprehensive knowledge of mechanisms implicated in bone resorption processes has driven researchers to develop a compound library of many small molecules that specifically interfere with the genesis of osteoclast precursors cells. Natural compounds that suppress osteoclast commitment may have therapeutic value in treating pathologies associated with bone resorption like osteoporosis, rheumatoid arthritis, bone metastasis and periodontal disease. The present review is foc...
John F. Rebhun3
Estimated H-index: 3
,
Qin Du + 8 AuthorsMinjie Li
Abstract Objective To investigate the development of a minimal traditional Chinese medicine (TCM) formula using selected TCM ingredients and evaluating their biological activity with bone-specific in vitro tests. Finally, determining if the minimal formula can maintain bone mineral density (BMD) in a low bone mass (LBM)/osteoporosis (OP) model system. Methods and results Sixteen different TCM plant extracts were tested for estrogenic, osteogenic and osteoclastic activities. Despite robust activa...
Published on May 31, 2019in American Journal of Sports Medicine6.09
Cheng Zheng1
Estimated H-index: 1
(Wuhan Sports University),
LuHongbin16
Estimated H-index: 16
(CSU: Central South University)
+ 6 AuthorsCan Chen4
Estimated H-index: 4
(CSU: Central South University)
Background:Tendon-bone interface (TBI) injuries are common in sports activities. Owing to the limited regenerative ability of the TBI, its functional healing remains a difficulty in clinical practice. Icariin (ICA) provides strong stimulation for osteogenesis. Platelet-rich plasma (PRP) can be used as a carrier for bioactive molecules, although its ability to provide sustained release for such molecules needs improvement.Hypothesis:Freeze-dried PRP (FD-PRP) as a carrier for ICA can provide susta...
Published on Jul 1, 2019in Journal of Ethnopharmacology3.41
Wenxiao Wu (Peking Union Medical College), Ting Wang + 6 AuthorsBo Li1
Estimated H-index: 1
(Peking Union Medical College)
Abstract Ethnopharmacological relevance Xian-Ling-Gu-Bao (XLGB) Fufang is an herbal formula that has been used in clinical settings to treat osteoporosis, osteoarthritis, aseptic bone necrosis, and climacteric syndrome. Despite its uses, XLGB treatment has been linked to potential liver injury. To date, there is a lack of clear demonstration of such toxicity in animal models. Aim of the study As animal models fail to reproduce the XLGB hepatotoxicity reported in humans, because human hepatocytes...
Published on Jul 1, 2019in Fish & Shellfish Immunology3.30
Xiao‐Chuan Zheng1
Estimated H-index: 1
(NAU: Nanjing Agricultural University),
Xiaochuan Zheng + 8 AuthorsChang He
Abstract We investigated the effects of icariin (ICA) on growth performance, antioxidant capacity and non-specific immunity in Chinese mitten crab ( Eriocheir sinensis ). A total of 200 healthy crabs (average weight: 33.58 ± 0.05 g) were randomly assigned to four treatments with five replicates, each with ten individuals per pool. There were four dietary treatments: the control group (fed with the basal diet), the ICA 50 group, the ICA100 group, and the ICA 200 group (fed with the basal diet sup...
Published on Jun 1, 2019in Maturitas3.65
Evangelia Mareti1
Estimated H-index: 1
,
Christina Abatzi + 2 AuthorsDimitrios G. Goulis30
Estimated H-index: 30
Abstract Background Phytoestrogens constitute an alternative, non-pharmacologic approach for the management of menopausal symptoms. However, few studies have focused on their safety, specifically in relation to endometrial thickness and breast density. Aim To systematically search for and quantitatively synthesize the evidence regarding the effect of phytoestrogens on endometrial thickness and breast density in perimenopausal and postmenopausal women. Methods Randomized controlled trials (RCTs) ...
Published on Jun 1, 2019in Natural Product Communications0.55
E. Sherwood Brown36
Estimated H-index: 36
(UTSW: University of Texas Southwestern Medical Center),
Collette Bice1
Estimated H-index: 1
(UTSW: University of Texas Southwestern Medical Center)
+ 7 AuthorsNyokabi Miingi (TTUHSC: Texas Tech University Health Sciences Center)