Comparative effects of 17beta-estradiol, raloxifene and genistein on bone 3D microarchitecture and volumetric bone mineral density in the ovariectomized mice.
This study assessed the effect of estradiol, raloxifene and genistein on the preservation of bone 3D-microarchitecture and volumetric bone mineral density (vBMD) in the ovariectomized mouse model. Our results indicated that raloxifene was more effective in preserving bone ovariectomized-induced changes, the advantage being concentrated in both bone microarchitecture and vBMD.


BACKGROUND
This study assessed the effect of different estrogen receptor (ER) agonists on the preservation of bone 3D-microarchitecture and volumetric bone mineral density (vBMD) in the ovariectomized (OVX) mouse model.


METHODS
Twelve-week-old female C57BL/6 mice were randomly assigned to one of five groups: (1) SHAM-operated + vehicle; (2) OVX + vehicle; (3) OVX + 17beta-estradiol (5 microg/kg); (4) OVX + raloxifene (1 mg/kg); (5) OVX + genistein (25 mg/kg), during 4-weeks. Bone microarchitecture and trabecular, cortical and total vBMD of distal femur were imaged by ex vivo microcomputed tomography (micro-CT).


RESULTS
Ovariectomy produced a global deterioration involving both trabecular and cortical 3D-microarchitecture and vBMD. Raloxifene maintained both microarchitecture and vBMD, whereas estradiol prevented deterioration of some microstructural parameters, such as trabecular thickness (Tb.Th), trabecular bone pattern factor (Tb.Pf), and cortical periosteal perimeter (Ct.Pe.Pm), but did not completely block the loss in vBMD. Mice treated with genistein exhibited the less favourable profile in both vBMD and microstructural parameters preserving only cross-sectional bone area (B.Ar) and Ct.Pe.Pm in cortical bone.


CONCLUSIONS
Our data indicate that, at the selected doses, raloxifene was more effective in preserving bone OVX-induced changes than either estradiol or genistein, the advantage being concentrated in both bone microarchitecture and vBMD.
Cano
A
A
Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Valencia, Spain.
Dapía
S
S
Noguera
I
I
Pineda
B
B
Hermenegildo
C
C
del Val
R
R
Caeiro
J R
JR
García-Pérez
M A
MA
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D010052:Ovariectomy; D020849:Raloxifene Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000819:agonists; D055114:X-Ray Microtomography / Q000379:methods
D050071:Bone Density Conservation Agents; D011960:Receptors, Estrogen; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D019833:Genistein