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Osteoporosis International
Published in: Osteoporosis International 2/2008

01-02-2008 | Original Article

Estradiol rapidly inhibits osteoclastogenesis and RANKL expression in bone marrow cultures in postmenopausal women: a pilot study

Published in: Osteoporosis International | Issue 2/2008

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Abstract

Summary

We examined RANKL expression and OCL formation in cultured bone marrow cells from eight postmenopausal women in response to E2. E2 treatment inhibited the ability of hematopoietic cells to form OCLs in response to RANKL, and decreased RANKL production. These changes are likely involved in the ability of E2 to influence the development of osteoporosis.

Introduction

Estrogen (E2) deficiency at menopause increases osteoclast (OCL) formation and bone resorption, predisposing women to osteoporosis. We examined receptor activator of NF-kappa B-ligand (RANKL) expression and in vitro OCL formation in cultured bone marrow cells from eight postmenopausal women before and after 3 weeks of E2 therapy and three untreated premenopausal women.

Methods

TRAP staining and resorption pit assay determined OCL number and function. Flow cytometry measured the distribution of marrow cell types and expression of RANKL in the macrophage-enriched fraction (R1) and a lymphocyte-enriched fraction (R2).

Results

RANKL (3–100 ng/ml) produced a dose-dependent increase in in vitro OC formation and E2 therapy significantly (p < 0.01) inhibited OCL formation by 33 to 50%. A small proportion of marrow cells bound anti- RANKL Ab (0.2–4.3%). There was no effect of E2 on the percentage of cells binding the anti-RANKL Ab in the R1 fraction. In the R2 fraction E2 treatment decreased the percentage of cells binding anti-RANKL Ab by 68 ± 9% (p < 0.01).

Conclusion

Three weeks of E2 treatment had a dual action. It inhibited the ability of hematopoietic cells to form OCLs in response to RANKL, and decreased the production of RANKL in cells of the bone marrow. The observed changes in the osteoclastic potential of bone marrow cells are likely involved in the ability of E2 to regulate bone mass and influence the development of osteoporosis.
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Metadata
Title
Estradiol rapidly inhibits osteoclastogenesis and RANKL expression in bone marrow cultures in postmenopausal women: a pilot study
Publication date
01-02-2008
Published in
Osteoporosis International / Issue 2/2008
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-007-0452-7

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