A combination of bisphosphonate and BMP additives in impacted bone allografts

OP-1 increases bone ingrowth distance of new bone into allografts (Tagil et al. 2000), but the bone density after incorporation may be reduced by an increase in resorption (Hostner et al. 2000). Bisphosphonates inactivate osteoclasts; and can be used to increase allograft bone density after incorporation (Aspenberg and Astrand 2002). A combination of locally-applied bisphosphonate and OP-1 in the graft could therefore be expected to increase both new bone ingrowth and density. We tested this by using a rat bone chamber model. OP-1 alone increased the ingrowth distance of bone. Clodronate increased final bone density greatly, but reduced the ingrowth distance of new bone into grafts that were extremely impacted. This reduction was improved by adding OP-1. Regardless of graft density, combinations of OP-1 and clodronate included a high final bone density, but the ingrowth distances were shorter than with OP-1 alone. These data indicate that new bone and tissue ingrowth into a compacted graft depends on resorption and that resorption is a prerequisite for the stimulating effect of OP-1 in this experimental set-up. Although the problems associated with the use of OP-1 in impaction grafting may be solved by adding a bisphosphonate, some of the benefits of OP-1 can be lost.