ESPE Abstracts (2015) 84 P-2-232

Bone

Regulation of Bone Growth Via Ligand-Specific Activation of Oestrogen Receptor α

Maryam Iravania, Marie Lagerquistb, Claes Ohlssonb & Lars Savendahla

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aKarolinska Institute, Stockholm, Sweden; bInstitute of Medicine, Gothenburg University, Gothenburg, Sweden


Background: Oestrogens are well known for their capacity to promote bone maturation and at high doses to induce growth plate closure and thereby stop further growth. High-dose oestrogen treatment has therefore been used to limit growth in extremely tall girls. However, recent data suggest that this treatment may have severe side effects, including increased risk of cancer and reduced fertility.

Objective and hypotheses: We hypothesised that oestrogenic effects in bone are mediated via ERα signalling which could open up for more selective treatment of extreme tall stature using selective oestrogen receptor modulators.

Method: 12-weeks-old ovariectomised female C57BL/6 mice were subcutaneously injected for 4 weeks with E2 or a selective ERα (PPT), ERβ (DPN) or GPER1 (G1) agonist. Tibiae and femur lengths were measured and growth plate morphology was analysed.

Results: E2 and PPT treated mice had shorter tibiae and femur bones when compared to vehicle treated controls while those animals treated with DPN or G1 had similar bone lengths as controls. Growth plate height and hypertrophic zone height were reduced in animals treated with E2 or PPT but not in those treated with DPN or GI further supporting that the effect was mediated via ERα.

Conclusion: Our data show that the oestrogenic effects on bone growth and growth plate maturation are mainly mediated via ERα. Our findings may have direct implications for the development of new more selective treatment modalities of extreme tall stature using selective oestrogen receptor modulators that may have less side effects than high-dose E2 treatment.

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