Effects of surgical holes in mouse tibiae on bone formation induced by knee loading

Loads applied directly to the knee (knee loading) have recently been demonstrated to induce anabolic responses in femoral and tibial cortical bone. In order to examine the potential role of intramedullary pressure in generating those knee loading responses, we investigated the effects of drilling surgical holes that penetrated into the tibial medullary cavity and thereby modulated pressure alteration. Thirty-nine C57/BL/6 female mice in total were used with and without surgical holes, and the surgical holes were monitored with micro CT and histology. The left knee was loaded for 3 days, and the contralateral limb was treated as a sham-loaded control. Mice were sacrificed for bone histomorphometry 2 weeks after the last loading. Although the surgical hole induced bone formation in both loaded and non-loaded tibiae, due to regional and systemic acceleratory phenomenon the anabolic effect of knee loading was substantially diminished. Without the holes, knee loading significantly elevated cross-sectional cortical area, cortical thickness, mineralizing surface, mineral apposition rate, and bone formation rate on the periosteal surface. For example, the rate of bone formation was elevated 2.1 fold (p<0.001; middle diaphysis--50% site from the knee along the length of tibiae) and 2.7 fold (p<0.01; distal diaphysis--75% site). With the surgical holes, however, knee loading did not provide significant enhancement either at the 50% or 75% site in any of the histomorphometric measurements (p>0.05). The results support the idea that alteration of intramedullary pressure is necessary for knee loading to induce bone formation in the diaphysis.