An innovative local strategy based on drug combined bone substitute

E. Verron, B. Bujoli, O. Gauthier, P. Janvier, J.M. Bouler

Keywords: bone substitute, drug delivery system, osteoporotic fracture


Reinforcing osteoporotic bone is a clinical challenge for prevention and treatment of bone fractures. Specificity of osteoporotic sites (femur and spine)justifies the use of a local approach for the prevention of osteoporotic fractures. We developed a local approach based on calcium phosphate (CaP) bone substitutes combined with bisphosphonate (BP) largelly used in the treatment of osteoporosis. Our local concept is doubly interesting since 1)CaP matrix implanted in the osteoporotic site will mechanically reinforce the weakened bone and will act as a bone substitute, which will serve as a support for new bone formation; and 2)the BP released in situ will locally regulate osteoclastic hyperactivity. The present study is related to the design and the biological evaluation of an injectable CaP cement loaded with BP. We developed a large animal model for simulating lumbar vertebroplasty on vertebrae presenting a standardized osteopenic bone defect that was filled with cements. Both 2D and 3D analysis of micro-architectural parameters demonstrated that implantation of BP loaded cement in such vertebral defects positively influenced microarchitecture of the adjacent trabecular bone. Injection of this combined cement could be a potential technological approach for the prevention of osteoporotic fractures.