A simulated weightlessness state diminishes cortical bone healing responses.

A state of chronic immobility resulting from extended spaceflight, bed rest or paralysis can present severe secondary complications for individuals confronted with long bone cortical fractures that fail to heal. These secondary complications can generally lead to a decreased quality of life and function for these individuals, and may potentially lead to a life-threatening situation. One potential cause of these failed fracture healing situations may be the prolonged state of nonweight-bearing (NWB) that chronically immobile individuals are exposed to. The research investigation of this clinical issue has been hampered to some extent by the inconsistent use of pre-clinical animal models of chronic immobility to study cortical bone fracture healing under a physiologically relevant NWB condition. In this brief report, we will provide some very recent pre-clinical findings concerning cortical bone healing in a simulated weightlessness rodent model exhibiting a physiologically relevant NWB condition in its hind limbs. Specifically, we will document that this rodent model of a NWB situation mimics the human condition of chronic immobility with respect to the high incidence of delayed or failed healing of cortical bone fractures. Further, we will provide evidence to substantiate a hypothesis that a long-term NWB condition acts to impair cortical bone healing by diminishing the number of functional bone progenitor cells at the repair site required to heal bone fractures. Data from our laboratory, and other previously published reports in the literature 1-4 , demonstrate that cortical bone healing in a rat NWB model (hind limb disuse resulting from tail suspension) mimics the diminished bone regeneration response in humans exposed to a prolonged state of NWB. Standardized bone trauma (0.2-mm wide osteotomies) was introduced into the fibulae of full weight-bearing (WB) and NWB rats (Figure 1), and the bone healing response monitored longitudinally via micro-computed tomography imaging 5 . We found that a middiaphyseal, 0.2-mm osteotomy in the fibulae of NWB rats exhibited an inferior healing response over a 5-week period as compared to full weight-bearing (WB) control animals (Figure 2). Specifically, NWB healing responses yielded poor hard callus formation that resulted in significantly decreased hard callus size, extent of bridging callus across the trauma site, and bridging callus strength as compared to full WB counterparts. Histological examination of the healing callus showed an inad