Two-week longitudinal survey of bone architecture alteration in the hindlimb-unloaded rat model of bone loss: sex differences

Abstract

Vico. Two-week longitudinal survey of bone architecture alteration in the hindlimb-unloaded rat model of bone loss: sex differences. Am J Physiol Endocrinol Metab 290: E440 -E447, 2006; doi:10.1152/ajpendo.00293.2004.-The goal of this study was to determine, through a longitudinal follow-up, whether sex influences bone adaptation during simulated weightlessness. Twelve-week-old male and female Wistar rats were hindlimb unweighted for 2 wk, and the time course of bone alteration was monitored in vivo by means of densitometry and unbiased three-dimensional quantitative microcomputed tomography at 7 and 14 days. Compared with male rats, female rats had twice more cancellous bone volume at the proximal tibia at baseline, and this bone volume continued to increase, whereas in males it stabilized. Conversely, cortical area was greater in males than in females, and in both sexes cortical bone was still expanding. Hindlimb unloading resulted in larger reductions in males than in females in both cortical and cancellous compartments. In females, trabecular thickness and number decreased mildly, whereas in males trabecular number was dramatically reduced. In both sexes, the trabecular network became less connected and more rod-like shaped. Bone cellular activities evaluated by histomorphometry showed decreased bone formation rate in both sexes and increased resorption activity only in males. In conclusion, in female rats unloaded-related cancellous alterations reversed the growing process, whereas in males, which show lower growth process, it induced an accentuation of age-related cancellous bone changes for most of the parameters.in vivo microcomputed tomography; dual-energy X-ray absorptiometry; histomorphometry; cancellous; cortical GROWTH AND DEVELOPMENT OF RATS encompasses a broad range of research including the bone field. Rodent partial immobilization by tail suspension, originally a model of simulated hypogravity, is now one of the most used for inducing regional bone loss. It has been extensively used in parallel to the Russian unmanned Biocosmos flight series comprising male Wistar rats (24,25). These studies showed ample evidence of pathophysiological functional and structural alterations in muscle, bone, cardiovascular, and related body fluid shift responses. In the skeleton, unloading induced both cortical and cancellous bone loss in the hindlimbs (11,29). Longitudinal elongation rate was found either diminished or unchanged (8,27). However, as male rats were more often used in space missions, they were also more often involved in this simulated weightlessness model compared with females. The gold standard bone loss model in females is ovariectomy-induced bone loss, and it was proposed that postmenopausal osteoporosis per se would be a failure of the bone's adaptation to functional loading (22). However, in rats, it has been recently shown that estrogens suppress the responsiveness of the female skeleton to mechanical loading (19). Sex-specific response during immobilization has been poorly investigated. To o...

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