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Background The capacity for bone healing reportedly is limited in osteoporosis with a less than ideal environment for healing of bone grafts. We therefore developed a composite bone substitute with rhBMP-2 loaded gelatin microsphere (GM) and calcium phosphate cement (CPC) to use in osteoporosis. Questions/purposes We asked whether (1) controlled release of rhBMP-2 could be improved in this composite bone substitute and (2) increasing factors released from the bone substitute could accelerate osteoporotic bone healing. Methods We soaked rhBMP-2/GM/CPC and rhBMP-2/ CPC composites in simulated body fluid for 28 days and then determined the amount of rhBMP-2 released. Both composites were implanted in bone defects of osteoporotic goats and left in place for 45 and 140 days; the specimens then were evaluated mechanically (pushout test) and morphologically (CT scanning, histology). Results The in vitro study showed the new composite released more rhBMP-2 compared with rhBMP-2/CPC. CT showed the defects healed more quickly with new grafts. The bone mineralization rate was greater in rhBMP-2/GM/ CPC than in rhBMP-2/CPC after 45 days of implantation and the pushout test was stronger after 45 and 140 days of implantation. Conclusions The new graft composite released more loaded factors and appeared to repair osteoporotic bone defects. Clinical Relevance These preliminary data suggest the new composite can be used as a bone substitute to accelerate healing of fractures and bone defects in osteoporosis.

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