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Trauma

BONE VOLUME IS NOT ALTERED WITH UNLOADING, BUT INCREASES WITH LOADING, IN THE HOMOZYGOUS SCLEROSTIN KNOCKOUT MOUSE

International Society for Fracture Repair (ISFR)



Abstract

Introduction

Canonical Wnt inhibitor Sclerostin (SOST) may be a key mechanotransduction regulator.

Methods

Unloading/loading 10 week old Sost−/− and WT mice. Unloading: Quads and calf muscles injected each with 0.5U botulinum toxin (BTX, Allergan) caused tibial unloading. Loading: 1200 cycles of tibial axial loading, 1200μe on mid-shaft, 4Hz, 5 days/week. Treated and control tibiae μCT scanned (Skyscan 1174) at 2 weeks.

Results

Unloading the WT tibiae significantly decreased cortical bone volume (−5%) and thickness (−7%) compared to WT control (p<0.01). Larger bone volume loss (−25%) was seen in the trabecular compartment (p<0.01), along with 10% and 22% decreases in trabecular thickness and number (p<0.01). These parameters were not altered between unloaded and control Sost−/− tibiae.

Tibial loading increased cortical bone volume in WT (18%) and Sost−/− (25%) mice (p<0.01). Cortical thickness was also increased in WT (19%) and Sost−/− (17%) mice (p<0.01). The trabeculae of the WT loaded tibiae showed significant thickening (15%, p<0.01) not seen in the Sost−/− tibiae. Metaphyseal cortical bone volume increased in both loaded WT (13%) and Sost−/− (31%) tibiae compared to their controls (p<0.01), suggestive of metaphyseal corticalisation.

Conclusion

SOST knockout inhibited unloading-induced bone loss, but not loading-induced bone gain. SOST may have an important role in bones response to unloading, but may not be essential for the response to loading.