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Bone selective protective effect of a novel bone-seeking estrogen on trabecular bone in ovariectomized rats.

Abstract：

:The drawbacks of estrogen restrict the clinical use of hormone replacement therapy, and it would be most helpful to explore new estrogenic substances that could prevent bone loss and be free from any adverse effects. We synthesized a new compound named bone-seeking estrogen (SE2) by combining 17β-estradiol (E2) with iminodiacetic acid through the Mannich reaction. E2 and SE2 were labeled with isotope (3)H, and the tissue distribution tests of E2-(3)H and SE2-(3)H were analyzed by the radioactivity. The specific nuclear binding of E2 and SE2 in osteoblasts was measured. SE2 exhibited significantly greater affinity for bone but lower affinity for ovary and uterus than did E2, and SE2 maintained a high affinity for the estrogen receptor alpha similar to that of E2. SE2 administration did not induce uterine hypertrophy. Body weight increase was significantly suppressed by treatment with E2 but not by SE2 after ovariectomy (OVX). SE2 decreased bone turnover as E2 after OVX detected by serum biochemical markers. Bone histology and micro-CT analysis revealed that SE2 administration, similar to E2, could improve bone mass and trabecular architecture after OVX. Biomechanical analyses showed that SE2 treatment effectively increased mechanical properties after OVX. The results suggested that SE2 was effective in preventing OVX-induced bone loss and exhibited few side effects on body weight and uterine hypertrophy, which was beneficial in reducing the adverse effects caused by E2. SE2 may be a better choice than E2 for the prevention of postmenopausal osteoporosis.

journal_name

Calcif Tissue Int

journal_title

Calcified tissue international

authors

Zhao Q,Liu X,Zhang L,Shen X,Qi J,Wang J,Qian N,Deng L

doi

10.1007/s00223-013-9739-1

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

172-83

issue

2

eissn

0171-967X

issn

1432-0827

journal_volume

93

pub_type

杂志文章

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