Female estrogen receptor β-/- mice are partially protected against age-related trabecular bone loss

S. H. Windahl, K. Hollberg, O. Vidal, J. Å Gustafsson, C. Ohlsson, G. Andersson

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119 Scopus citations


Recently, it has been shown that inactivation of estrogen receptor β (ER-β) by gene targeting results in increased cortical bone formation in adolescent female mice. To study the possible involvement of ER-β in the regulation of the mature skeleton, we have extended the analyses to include 1-year-old ER-β knockout mice (ER-β-/-). Male ER-β-/- mice did not express any significant bone phenotypic alterations at this developmental stage. However, the increase in cortical bone parameters seen already in the adolescent female ER-β-/- mice was maintained in the older females. The aged female ER-β-/- mice further exhibited a significantly higher trabecular bone mineral density (BMD) as well as increased bone volume/total volume (BV/TV) compared with wild-type (wt) mice. This was caused by a less pronounced loss of trabecular bone during adulthood in female ER-β-/- mice. The growth plate width was unaltered in the female ER-β-/mice. Judged by the expression of the osteoclast marker tartrate-resistant acid phosphatase (TRAP) and cathepsin K (cat K; reverse-transcription-polymerase chain reaction [RT-PCR]) as well as the serum levels of C-terminal type I collagen cross-linked peptide, bone resorption appeared unaffected. However, an increase in the messenger RNA (mRNA) expression levels of the osteoblast marker core-binding factor α1 (Cbfa1) suggested an anabolic effect in bones of old female ER-β-/- mice. In addition, the mRNA expression of ER-α was augmented, indicating a role for ER-α in the development of this phenotype. Taken together, the results show that ER-α is involved in the regulation of trabecular bone during adulthood in female mice and suggest that ER-β acts in a repressive manner, possibly by counteracting the stimulatory action of ER-α on bone formation.

Original languageEnglish (US)
Pages (from-to)1388-1398
Number of pages11
JournalJournal of Bone and Mineral Research
Issue number8
StatePublished - 2001


  • Bone
  • Estrogen receptor β
  • Osteoblasts
  • Osteoclasts
  • Transgenic

ASJC Scopus subject areas

  • Surgery


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