To investigate whether angiogenesis changes in early menopausal
osteoporosis treated with
estrogen replacement therapy, 120 rats were randomly divided into five groups:
sham operation group (
SHAM),
ovariectomy group (OVX), and
ovariectomy plus three different
estrogen doses replacement
therapy groups (OVX + E2). We detected the bone microarchitecture and measured the expression levels of
estrogen receptor beta (ERβ),
vascular endothelial growth factor (
VEGF),
osteoprotegerin (OPG), and receptor activator of NF-κB
ligand (RANKL). CD31 immunofluorescence and
silica gel perfusion imaging were used to analyze the vascular distribution. We confirmed that the femur BMD of ovariectomized rats was significantly lower than
SHAM group and OVX+E2 groups. After
estrogen therapy, the local microvascular formation increased after
estrogen treatment in a dose dependent manner. ERβ was downregulated and
VEGF was upregulated, positively correlated with
estrogen dosage. We successfully constructed an
osteoporosis model of ovariectomized rats with
estrogen replacement therapy. We also found angiogenesis changed in early menopausal
osteoporosis treated with
estrogen replacement therapy. We indicated that
estrogen replacement therapy increased angiogenesis through
VEGF upregulation. However, we observed that, at the highest doses of
estrogen studied, increased angiogenesis was associated with a decrease in BMD, the underlying mechanisms of which remain unclear.