Osteogenic potentials with joint-loading modality

Abstract

Osteogenic potentials with a novel joint-loading modality were examined, using mouse ulnae as a model system. Load-induced deformation of rigid bone is known to generate interstitial fluid flow and stimulate osteogenesis. However, in most of the previous studies, loads were applied to cortical bone. In the current study, we addressed the question of whether deformation of the epiphysis underneath the joint would enhance bone formation in the epiphysis and the diaphysis. In order to answer the question, we applied lateral loads to a mouse elbow and conducted a bone histomorphometric analysis, as well as measurements of strains and streaming potentials. Compared to the no-loading control, the histomorphometric results showed that 0.5-N loads, applied to the elbow at 2 Hz for 3 min/day for 3 consecutive days, increased the mineralizing surface (two- to threefold), the rate of mineral apposition (three- to fivefold), and the rate of bone formation (six- to eightfold) in the ulna. Strain measurements indicated that strains of around 30 µstrain, induced with the joint-loading modality, were under the minimum effective strain of around 1000 µstrain, which is considered necessary to achieve strain-driven bone formation. To evaluate the induction of fluid flow with the joint-loading modality, streaming potentials were measured in separate experiments, using mouse femurs ex vivo. We found that the streaming potentials correlated to the magnitude of the load applied to the epiphysis (r² = 0.92), as well as the flow speed in the medullary cavity (r² = 0.93). Taken together, the findings of the current study support the idea of joint-loading driven osteogenesis, through a mechanism that involves the induction of fluid flow in cortical bone.