Androgens inhibit the osteogenic response to mechanical loading in adult male mice

Mieke Sinnesael, Michaël R Laurent, Ferran Jardi, Vanessa Dubois, Ludo Deboel, Peter Delisser, Geert J Behets, Patrick C D'Haese, Geert Carmeliet, Frank Claessens, Dirk Vanderschueren

Research output: Contribution to journalArticle (Academic Journal)peer-review

23 Citations (Scopus)

Abstract

Androgens are well known to enhance exercise-induced muscle hypertrophy, however whether androgens also influence bone's adapative response to mechanical loading remains unclear. We studied the adaptive osteogenic response to unilateral in vivo mechanical loading of tibia in adult male mice in both a long and a short term experimental set-up. Mice were divided in 4 groups: sham-operated, orchidectomized (ORX), testosterone (ORX+T) or non-aromatizable dihydrotestosterone (ORX+DHT) replacement. Significant interactions between androgen status and osteogenic response to mechanical loading were observed. Cortical thickness increased by T (0.14 vs. 0.11 mm sham, p<0.05) and DHT (0.17 vs. 0.11 mm sham, p<0.05). However, T partially (+36%) and DHT completely (+10%) failed to exhibit the loading-related increase observed in sham (+107%) and ORX (+131%, all p<0.05) mice. ORX decreased periosteal bone formation (PsBFR), which was restored to sham levels by T and DHT. However, both androgens completely suppressed the loading-related increase in PsBFR. Short term loading decreased the number of sclerostin positive osteocytes in sham, whereas in control fibulas, ORX decreased and T increased the number of sclerostin positive osteocytes. Loading no longer downregulated sclerostin in ORX or T groups. In conclusion, both T and DHT suppress the osteogenic response to mechanical loading.

Original languageEnglish
Pages (from-to)en20141673
JournalEndocrinology
DOIs
Publication statusPublished - 5 Feb 2015

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