Bone remodeling is regulated by inner ear vestibular signals

Abstract

Bone remodeling allows the conservation of normal bone mass despite constant changes in internal and external environments. The adaptation of the skeleton to these various stimuli leads credence to the notion that bone remodeling is a true homeostatic function, and as such is under the control of specific centers in the central nervous system (CNS). Hypothalamic and brainstem centers, as well as the sympathetic nervous system (SNS), have been identified as regulators of bone remodeling. However, the nature of the afferent CNS stimuli that may modulate CNS centers involved in the control of bone remodeling, with the exception of leptin, remains unclear. Based on the partial efficacy of exercise and mechanical stimulation regimens to prevent microgravity-induced bone loss and the known alterations in vestibular functions associated with space flights, we hypothesized that inner ear vestibular signals may contribute to the regulation of bone remodeling. Using an established model of bilateral vestibular lesions and microtomographic and histomorphometric bone analyses, we show here that induction of bilateral vestibular lesion in rats generates significant bone loss, which is restricted to weight-bearing bones and associated with a significant reduction in bone formation, as observed in rats under microgravity conditions. Importantly, this bone loss was not associated with reduced locomotor activity or metabolic abnormalities, was accompanied with molecular signs of increased sympathetic outflow, and could be prevented by the b-blocker propranolol. Collectively, these data suggest that the homeostatic process of bone remodeling has a vestibulosympathetic regulatory component and that vestibular system pathologies might be accompanied by bone fragility.

Vestibular loss disrupts daily rhythm in rats

“…Here we confirm that global locomotor activity in the days after transtympanic injection was similar in BVL and SO rats according to one of our recent papers using a similar vestibular lesion model by arsanilate (61). In that previous work we showed that diurnal and nocturnal locomotor activity independently remained at the same level in both groups, whereas rats with BVL suffered from a vestibular syndrome maximal between day 2 and day 7 after lesion compared with unharmed control rats (60).…”

“…Consequently, if rats with BVL suffer from a vestibular syndrome, their diurnal/nocturnal global locomotor activity remained similar to that of rats in the SO group, but it was more divided within the first days after lesion. This suggests that the sleep/wake state was probably more fragmented; however, the total sleep time might not have changed, and thus would not influence the daily rhythms of Temp and Act (60,61).…”

“…vestibular system; biological rhythms; temperature; locomotor activity; rats LOCATED IN THE TEMPORAL BONES, the vestibular system is composed of three semicircular canals that encode head rotation velocity and two otolithic macula that encode linear acceleration and gravity force. The vestibular system is primarily involved in gaze stabilization and postural control (23), but its influence has been expanded to autonomic and bone regulation (11,61,63), spatial learning and memory (5, 6, 56), and spatial orientation and perception of gravitational verticality (37). Studies carried out in environments in which gravity is altered have shown evidence of a possible influence of the vestibular system on hypothalamic circadian function in rats (27) and mice (18,46…”

“…The vestibular system is primarily involved in gaze stabilization and postural control (23), but its influence has been expanded to autonomic and bone regulation (11,61,63), spatial learning and memory (5,6,56), and spatial orientation and perception of gravitational verticality (37). Studies carried out in environments in which gravity is altered have shown evidence of a possible influence of the vestibular system on hypothalamic circadian function in rats (27) and mice (18,46); disruption of circadian rhythms of temperature (Temp) and locomotor activity (Act) have been similarly observed in both species for about 7 days in a 2 G environment generated by a centrifuge.…”

Reduced bone formation markers, and altered trabecular and cortical bone mineral densities of non-paretic femurs observed in rats with ischemic stroke: A randomized controlled pilot study

“…Our observations of group differences in bone volume and density at the distal femur and a reduction of bone formation marker P1NP in animals with stroke–despite similar physical activity patterns between groups—suggest that stroke may suppress bone formation. Based on human stroke studies [10,29], evidence from hind-limb immobilization and unloading in neurologically intact rats [5–7], and the neural control of bone metabolism [11,12,30], it was hypothesized that MCAo would compromise the microstructure of femurs on the left (paretic) leg. There was no effect of stroke observed on the primary outcome (trabecular bone volume fraction of left femurs), but there were a number of changes in secondary outcomes that may prove to be important findings and should be considered for inclusion in future studies.…”