Bone Abstracts

Sclerostin, a Wnt signaling antagonist encoded by the SOST gene, negatively regulates osteoblasts and inhibits bone formation. Mechanical loading, which induces bone formation, leads to a decrease in sclerostin levels. Recently, neutralizing antibodies against sclerostin were tested successfully for the treatment of osteoporosis in rodents. However, sclerostin is not the only signal involved in mechanotransduction. Therefore we investigated whether treatment with sclerostin antibodies (ScAb) can be improved by the addition of mechanical loading in a mouse model for postmenopausal osteoporosis.

Fourty 15-week-old C57BL/6 mice were subjected to bilateral ovariectomy. Treatment with ScAb (100 mg/kg, i.v. weekly) respective vehicle and mechanical loading of the 6th caudal vertebra of 8 or 0 N was started 5 weeks later for 4 weeks. Cyclic loading was applied via steel pins inserted in the 5th and 7th caudal vertebra (10 Hz, 3000 cylces, three times/week). The loaded vertebra was scanned by in vivo micro-CT (vivaCT 40, Scanco Medical AG, Brüttisellen, Switzerland) at week 15, 20, 22, and 24. Static as well as dynamic parameters were evaluated.

While the controls showed continuous bone loss, treatment with ScAb (0 N) as well as loading increased trabecular bone volumes fraction (BV/TV) by 13%. The combination of loading and ScAb led to a further increase by 28%. The increase in BV/TV was caused by thickening of trabeculae while loss in trabecular number could not be stopped by any treatment. The combined treatment increased bone formation rate by 100% as compared to ScAb (0 N) alone and by 200% as compared to untreated and unloaded (0 N) mice while bone resorption rate was significantly reduced by 50% as compared to ScAb (0 N) and by 75% as compared to untreated (0 N) mice.

Our results show that mechanical loading is able to increase bone volume independently of sclerostin antibody treatment.