Flavonoids derived from herbal Epimedium Brevicornum Maxim prevent OVX-induced osteoporosis in rats independent of its enhancement in intestinal calcium absorption.
OBJECTIVE
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.


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 with calcium supplement (CS group), and OVX with FE and CS (FE + CS group). Daily oral administration of FE (10 mg/kg/day) and/or CS (56 mg/kg/day) started on day 4 after OVX for 12 weeks. Before sacrificing the animals, urine and serum samples were collected for assaying indicators related to intestinal calcium absorption, regulator for calcium homeostasis, and markers of bone turnover. The left proximal femur was dissected for evaluation of the primary end-point (failure force), the second end-points (pQCT-quantified densitometry, geometry, and micro-CT-quantified 3-D trabecula micro-architecture), and pQCT-defined cross-sectional envelope.


RESULTS
FE was found to be able to prevent OVX-induced reduction in failure force as well as the above second end-points, without resulting in an increased uterus weight. CS had no preventive 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 did not provide link between the enhanced intestinal calcium absorption and the enhanced inhibition of bone resorption in the present study. Furthermore, the discrepancies between the enhanced intestinal calcium absorption and the un-enhanced end-point measures as well as anabolic effect were also revealed by the interaction analysis.


CONCLUSIONS
The present study suggested that FE inhibited bone resorption, stimulated bone formation, and accordingly prevented osteoporosis without hyperplastic effect on uterus in the OVX rat model, which was however independent of an enhancement in intestinal calcium absorption.
Zhang
G
G
Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, N.T. Hong Kong SAR, PR China.
Qin
L
L
Hung
W Y
WY
Shi
Y Y
YY
Leung
P C
PC
Yeung
H Y
HY
Leung
K S
KS
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D034181:Epimedium / Q000737:chemistry*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006706:Homeostasis; D021621:Imaging, Three-Dimensional; D007408:Intestinal Absorption / Q000187:drug effects*; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D010024:Osteoporosis / Q000517:prevention & control*; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical
D005419:Flavonoids; D002118:Calcium