Systemic effects of ulna loading in male rats during functional adaptation

Abstract

Functional skeletal adaptation is thought to be a local phenomenon controlled by osteoctyes. However, the nervous system also may have regulatory effects on adaptation. The aim of this study was to determine the effects of loading of a single bone on adaptation of other appendicular long bones and whether these responses were neuronally regulated. Young male Sprague-Dawley rats were used. The right ulna was loaded to induce a modeling response. In other rats, a second regimen was used to induce bone fatigue with a mixed modeling/remodeling response; a proportion of rats from each group received brachial plexus anesthesia to induce temporary neuronal blocking during bone loading. Sham groups were included. Left and right long bones (ulna, humerus, tibia, and femur) from each rat were examined histologically 10 days after loading. In fatigue- and sham-loaded animals, blood plasma concentrations of TNF-α, RANKL, OPG, and TRAP5b were determined. We found that loading the right ulna induced an increase in bone formation in distant long bones that were not loaded and that this effect was neuronally regulated. Distant effects were most evident in the rats that received loading without bone fatigue. In the fatigue-loaded animals, neuronal blocking induced a significant decrease in plasma TRAP5b at 10 days. Histologically, bone resorption was increased in both loaded and contralateral ulnas in fatigue-loaded rats and was not significantly blocked by brachial plexus anesthesia. In young, growing male rats we conclude that ulna loading induced increased bone formation in multiple bones. Systemic adaptation effects were, at least in part, neuronally regulated. © 2010 American Society for Bone and Mineral Research.

Mechanical loading causes site-specific anabolic effects on bone following exposure to ionizing radiation

“…An alternative, if speculative, explanation for the lack of a persistent radiation decrement is that axial loading has systemic effects to improve cancellous microarchitecture of the nonloaded, contralateral limb of irradiated mice. Similar systemic effects of axial ulnar loading reportedly occur in rats [66]. Further work is needed to understand better the late effects of radiation exposure on skeletal integrity in the adult.…”

Vertical ground reaction forces diminish in mice after botulinum toxin injection

“…This result suggested that bone loss due to a loss of muscle activity is mediated by the nervous system. In addition, Sample et al (2008Sample et al ( , 2010 found that unilateral loading triggered an osteogenic response in the contralateral side that was mitigated when neural signals were blocked. These combined results indicate that the nervous system may play a key role in the interaction between muscle and bone.…”

In Vivo Axial Loading of the Mouse Tibia

“…A separate experiment must be performed to ensure that tibial loading does not cause systemic effects, which have been both confirmed and refuted in the literature (19, 20). Confirm that paired contralateral control limbs from loaded mice are not different from control limbs obtained from separate nonloaded animals.…”