Cortical bone gain following loading is site-specifically enhanced by prior and concurrent disuse in aged male mice

The primary aim of bone anabolic therapies is to strategically increase bone mass in skeletal regions likely to experience high strains. This is naturally achieved by mechanical loading of the young healthy skeleton. However, these bone anabolic responses fail with age. Here, we applied site specificity analysis to map regional differences in bone anabolic responses to axial loading of the tibia (tri-weekly, for two weeks) between young (19-week-old) and aged (19-month-old), male and female mice. Loading increased bone mass specifically in the proximal tibia in both sexes and ages. Young female mice gained more cortical bone than young males in specific regions of the tibia. However, these site-specific sex difference were lost with age such that bone gain following loading was not significantly different between old males and females. Having previously demonstrated that prior and concurrent disuse enhances bone gain following loading in old females, we established whether this “rescue” is sex-specific. Old male mice were subjected to sciatic neurectomy or sham surgery, and tri-weekly loading was initiated four days after surgery. Disuse augmented cortical bone gain in response to loading in old male mice, but only in the regions of the tibia which were load-responsive in the young. Increased understanding of how locally-activated load-responsive processes lead to site-specific bone formation, and how the age-related diminution of these processes can be site-specifically enhanced by disuse, may lead to the next generation of strategic bone anabolic therapies.HighlightsSex differences in cortical tissue area of young and old mice are not site-specificThe loading response in young, but not old, mice is sex- and site-specificThe cortical loading response is site-specifically enhanced by disuse in old mice of both sexesThe trabecular loading response can be rescued by disuse in old male, but not female, mice

Raman Spectroscopic Analysis to Detect Reduced Bone Quality after Sciatic Neurectomy in Mice

Bone mineral density (BMD) is a commonly used diagnostic indicator for bone fracture risk in osteoporosis. Along with low BMD, bone fragility accounts for reduced bone quality in addition to low BMD, but there is no diagnostic method to directly assess the bone quality. In this study, we investigated changes in bone quality using the Raman spectroscopic technique. Sciatic neurectomy (NX) was performed in male C57/BL6J mice (NX group) as a model of disuse osteoporosis, and sham surgery was used as an experimental control (Sham group). Eight months after surgery, we acquired Raman spectral data from the anterior cortical surface of the proximal tibia. We also performed a BMD measurement and micro-CT measurement to investigate the pathogenesis of osteoporosis. Quantitative analysis based on the Raman peak intensities showed that the carbonate/phosphate ratio and the mineral/matrix ratio were significantly higher in the NX group than in the Sham group. There was direct evidence of alterations in the mineral content associated with mechanical properties of bone. To fully understand the spectral changes, we performed principal component analysis of the spectral dataset, focusing on the matrix content. In conclusion, Raman spectroscopy provides reliable information on chemical changes in both mineral and matrix contents, and it also identifies possible mechanisms of disuse osteoporosis.

Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice

The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic neurectomy- (NTX-) induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects andviaan increase in protein synthesis and a decrease in protein degradation.