Bone Abstracts

Introduction: One third of patients in the long-term heparin therapy show reduction in bone density. We have shown that heparin binds to bone morphogenetic protein 6 (BMP6) and inhibits its osteogenic activity in vitro. Here we explored whether heparin effects BMP6 mediated bone efficacy in vivo.

Methods: We have used a mouse model of postmenopausal osteoporosis and tested the effect of heparin on BMP6 therapy and its osteogenic activity using DEXA and μCT of femur and tibia.

Results: We showed that BMP6 restored the quality and microarchitecture of osteoporotic bone. In combination with heparin, femur bone volume over tissue volume was reduced for 24% (tibia 30%) and the trabecular number by 29% (tibia 35%), while trabecular separation was increased by 25% (tibia 17%), as compared to BMP6 therapy alone. These results were supported by BMD values measured by DEXA. In heparin-induced osteoporosis model, BMP6 prevented heparin-induced osteoporosis when used simultaneously, but not after heparin therapy, as shown by BMD of femur and tibia. The results were confirmed by μCT, where BMP6 used simultaneously with heparin improved all measured parameters of trabecular bone.

Conclusion: We confirmed that heparin binds to BMP6 in vivo and prevents dose- and time-dependently its osteogenic activity, which might be the mechanism of heparin-induced bone loss.