Abstract
Improving periprosthetic bone is essential for implant fixation and reducing peri-implant fracture risk. This studied examined the individual and combined effects of iPTH and mechanical loading at the cellular, molecular, and tissue level for periprosthetic cancellous bone. Adult rabbits had a porous titanium implant inserted bilaterally on the cancellous bone beneath a mechanical loading device on the distal lateral femur. The right femur was loaded daily, the left femur received a sham loading device, and half of the rabbits received daily PTH. Periprosthetic bone was processed up to 28 days for qPCR, histology, and uCT analysis. We observed an increase in cellular and molecular markers of osteoblast activity and decrease in adipocytic markers for both treatments, with small additional effects in the combined group. Loading and iPTH led to a decrease and increase, respectively, in osteoclast number, acting through changes in RANKL/OPG expression. Changes in SOST and beta-catenin mRNA levels suggested an integral role for the Wnt pathway. We observed strong singular effects on BV/TV of both loading (1.53 fold) and iPTH (1.54 fold). Combined treatment showed a small additive effect on bone volume. In conclusion, loading and iPTH act through a pro-osteoblastic/anti-adipocytic response and through control of bone turnover via changes in the RANKL/OPG pathway. These changes led to a small additional, but not synergistic, increase in bone volume with the combined therapy.
