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Updated: Oct 2, 2026
Trabecular Bone Microarchitecture Evaluation in an Osteoporosis Mouse Model
Published on: September 8, 2023
Two different pathways for the maintenance of trabecular bone in adult male mice
Marie K Lindberg1, Sofia Movérare, Stanko Skrtic
1Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
Abstract:
Androgens may regulate the male skeleton either directly via activation of the androgen receptor (AR) or indirectly via aromatization of androgens into estrogen and, thereafter, via activation of estrogen receptors (ERs). There are two known estrogen receptors, ER-alpha and ER-beta. The aim of this study was to investigate the relative roles of ER-alpha, ER-beta, and AR in the maintenance of trabecular bone in male mice. Seven-month-old male mice, lacking ER-alpha (ERKO), ER-beta (BERKO), or both receptors (DERKO), were orchidectomized (orx) and treated for 3 weeks with 0.7 microg/mouse per day of 17beta-estradiol or vehicle. No reduction in trabecular bone mineral density (BMD) was seen in ERKO, BERKO, or DERKO mice before orx, showing that neither ER-a nor ER-beta is required for the maintenance of a normal trabecular BMD in male mice. After orx, there was a pronounced decrease in trabecular BMD, similar for all groups, resulting in equal levels of trabecular BMD in all genotypes. This reduction was reversed completely in wild-type (WT) and BERKO mice treated with estrogen, and no significant effect of estrogen was found in ERKO or DERKO mice. In summary, the trabecular bone is preserved both by a testicular factor, presumably testosterone acting via AR and by an estrogen-induced activation of ER-alpha. These results indicate that AR and ER-alpha are redundant in the maintenance of the trabecular bone in male mice. In contrast, ER-beta is of no importance for the regulation of trabecular bone in male mice.
Insights
Androgen receptor (AR) and estrogen receptor-alpha (ER-alpha) maintain male trabecular bone, with ER-beta playing no significant role. These receptors are redundant for bone maintenance in male mice.
Area of Science:
- Endocrinology
- Bone Biology
- Andrology
Background:
- Androgens influence male bone health directly via androgen receptors (AR) and indirectly through estrogen receptors (ERs).
- Two main estrogen receptors, ER-alpha and ER-beta, are known.
- The specific roles of AR, ER-alpha, and ER-beta in male trabecular bone maintenance require clarification.
Purpose of the Study:
- To investigate the distinct and overlapping roles of ER-alpha, ER-beta, and AR in maintaining trabecular bone in male mice.
- To determine the necessity of each receptor for normal bone mineral density (BMD) in adult male mice.
Main Methods:
- Utilized male mice genetically deficient in ER-alpha (ERKO), ER-beta (BERKO), or both (DERKO).
- Orchidectomy (orx) was performed on seven-month-old mice to simulate androgen deprivation.
- Mice received either 17beta-estradiol or vehicle treatment for three weeks post-orx to assess receptor-mediated effects on trabecular BMD.
Main Results:
- Trabecular BMD was maintained normally in ERKO, BERKO, and DERKO mice prior to orchidectomy, indicating no baseline requirement for ER-alpha or ER-beta.
- Orchidectomy caused a similar significant decrease in trabecular BMD across all genotypes.
- Estrogen treatment fully restored BMD in wild-type and BERKO mice but had no effect in ERKO or DERKO mice, highlighting ER-alpha's crucial role in estrogen's bone-protective effect.
Conclusions:
- Testicular factors, likely testosterone acting via AR, and estrogen acting via ER-alpha, both preserve male trabecular bone.
- AR and ER-alpha demonstrate redundancy in maintaining trabecular bone in male mice.
- ER-beta is not essential for the regulation of trabecular bone in male mice.
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