[Epimedium-derived flavonoids prevent ovariectomy-induced osteoporosis in rats independent of its enhancement in intestinal calcium absorption].
OBJECTIVE
To test our hypothesis whether a group of flavonoids (FE) derived from herbal Epimedium exerted its prevention of estrogen-deficiency-induced osteoporosis mainly through an enhancement in intestinal calcium absorption.


METHODS
Forty-five 12-month-old female Wistar rats were randomly assigned into one sham-operated group and four ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX group), OVX with FE (FE group), OVX with calcium supplement (CS group), and OVX with FE and CS. Daily oral administration of FE (10 mg x kg(-1) x (d(-1)) and/or CS (56 mg x kg(-1) x d(-1)) started on day 4 after OVX for 12 weeks. Before sacrificing the animals, urine and serum samples were collected for assaying indicators for intestinal calcium absorption, regulator of calcium homeostasis and markers for bone turnover. Then, the left proximal femur was dissected for the primary-end-point index (failure force), and the second-end-point indexes (pQCT-calculated densitometry, geometry and micro-CT-quantified 3-D trabecula microarchitecture), as well as pQCT-defined cross-sectional envelope.


RESULTS
FE prevented OVX-induced deterioration in failure force as well as the second-end-point indexes with no increase in uterus weight. CS had no prevention effect on OVX-induced reduction in failure force. Two-way factorial interaction analysis between FE and CS showed that the un-enhanced suppression of parathyroid hormone for calcium homeostasis provided no link between the enhanced intestinal calcium absorption and the enhanced inhibition of bone resorption in the present study. Furthermore, discrepancy between the enhanced intestinal calcium absorption and the un-enhanced primary / second-end-point indexes as well as anabolic effect was also found by the interaction analysis.


CONCLUSIONS
Independent of intestinal calcium absorption, FE inhibited bone resorption, stimulated bone formation and accordingly prevented osteoporosis without hyperplastic effect on uterus in the OVX rat model.
Qin
Ling
L
Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong, Hong Kong SAR, China. Lingqin@cuhk.edu.hk
Zhang
Ge
G
Wang
Xin-Luan
XL
Shi
Yin-Yu
YY
Kong
Ying-Yan
YY
Yang
Xiao-En
XE
Sheng
Hui
H
Liang
Bing-Zhong
BZ
Liang
Guo-Sui
GS
Yao
Xin-Sheng
XS
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D034181:Epimedium / Q000737:chemistry*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control*; D010052:Ovariectomy / Q000009:adverse effects; D008517:Phytotherapy; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D005419:Flavonoids; D002118:Calcium