Allograft bone in hip revision: the effect of locally applied pharmacological treatment

Sammanfattning: The clinical success of primary hip replacement is paramount but the need for revisions will continue to increase due to the increasing number of operated individuals. In Sweden, the number of hip revisions in 2012 exceeded 2,300. During implant loosening, some of the bone in the femur is lost, which can make the revision more difficult. One way of handling bone loss has been the impaction technique. Allograft bone is morsellised and impacted into the defect before a prosthesis is inserted. Mechanically, the allograft bone immediately contributes to prosthetic stability. Biologically, the graft triggers an inflammatory response with ingrowth of fibrous tissue and blood vessels, accompanied by osteoclasts from the host. Parts of the graft bone are resorbed and degraded, and are eventually at least partially replaced with new living bone. In our first hypothesis, we suggested that resorption of the allograft that is too fast could reduce stability and result in implant loosening. We believed that this could be inhibited by local treatment of the graft with a bisphosphonate. Our second hypothesis was that by adding bone-inductive BMP-7 to the bisphosphonate, new bone formation would also be stimulated, leading to an increase in stability.
In papers I and II, the effect of the bisphosphonate zoledronate and BMP-7 on allografts was investigated in a bone conduction chamber in rats. We found a strong synergism of the combined treatment compared to the saline control. Local treatment with the bisphosphonate was efficient but it also tended to inhibit bone formation. In paper III, the same drugs were evaluated in a more clinically relevant prosthetic model in rabbits. A knee prosthesis was inserted into the tibia, which had been filled with impacted, morsellised allograft soaked in BMP-7 and/or zoledronate. Micro-CT showed increased bone density after zoledronate treatment relative to the saline control, but by histology the bone surrounding the prosthesis had a more unstable structure when BMP-7 was used combined with zoledronate. In paper IV, 30 patients had their femoral hip implant revised with the impaction bone grafting technique, and were randomised to have the bone graft soaked in either clodronate—a bisphosphonate— or saline. DXA scans were performed postoperatively and at 3 and 12 months to evaluate the effect of the study drug. Radiostereometry (RSA) was performed postoperatively, after 6 weeks, and after 3 and 12 months, to measure implant micromotion. Bone density and implant motion were similar in both groups and no significant differences were found.
In conclusion, we found that local administration of bisphosphonate is effective in inhibiting bone graft resorption in animal models and that the mode of application may matter. The addition of BMP-7 may lead to reduced stability and cannot be recommended. Finally, we were unable to show any effect of the bisphosphonate clodronate on bone density or implant motion in our clinical study on hip revision with impaction bone grafting.