Pause insertions during cyclic in vivo loading affect bone healing.

Fracture repair is influenced by the mechanical environment, particularly when cyclic loads are applied across the fracture site. However, the specific mechanical loading parameters that accelerate fracture healing are unknown. Intact bone adaptation studies show enhanced bone formation with pauses inserted between loading cycles. We hypothesized pause-inserted noninvasive external loading to mouse tibial fractures would lead to accelerated healing. Eighty mice underwent tibial osteotomies with intramedullary stabilization and were divided into four loading protocol groups: (1) repetitive loading (100 cycles, 1 Hz); (2) pause/time-equivalent (10 cycles, 0.1 Hz); (3) pause/cycle-equivalent (100 cycles, 0.1 Hz); and (4) no load control. Loading was applied daily for 2 weeks. Healing was assessed using histology, biomechanical bending tests, and microcomputed tomography. The pause-inserted, cycle-equivalent group had a greater percentage of osteoid present in the callus cross-sectional area compared with no-load controls, indicating more advanced early healing. The pause-inserted, cycle-equivalent group had a failure moment and stiffness that were 37% and 31% higher than the controls, respectively. All three loaded groups had smaller overall mineralized callus volumes than the control group, also indicating more advanced healing. At an early stage of fracture healing, pause-inserted loading led to more histologically advanced healing.