| Both physical activity and steroid hormone levels decrease during aging and contribute to bone loss and osteoporosic fracture risk. Mechanical loading might offer a site-specific treatment free from the side effects of current pharmacologic therapies. Functional adaptation has been studied extensively in mid-shaft diaphyseal cortical bone, but not in cancellous bone. However, the adaptive response in corticocancellous sites at the ends of long bones is more relevant to osteoporosis. The main hypothesis of this research is that bone adaptation to controlled mechanical loading increases bone mass and alters architectural. A method for cyclically loading the mouse tibia in vivo was developed to study functional bone adaptation. In two separate studies compressive cyclic loads were applied daily to the 10-week-old, male C57BL/6 mouse tibia for up to 6 weeks. One study consisted of normal, intact male mice. The other study utilized both orchidectomized (surgically castrated) and sham-operated (intact) mice. Adaptation was quantified at the completion of mechanical loading by directly comparing volumetric bone mass and architectural measures between loaded and contralateral limbs by the three-dimensional, x-ray attenuation technique of microcomputed tomography. The results of these experiments indicated that functional bone adaptation to daily, cyclic, axial loading of the mouse tibia increased the cancellous bone volume fraction and average trabecular thickness in the proximal tibia in both intact and castrated mice, with a site-specific response that was greater in the corticocancellous metaphysis (proximal end) than the cortical mid-shaft diaphysis. The response depended on the level of loading in the intact mouse and was nearly complete 2 weeks after onset. The applied loading also reversed the bone mass loss created by sex-steroid depletion. A method was also developed for combining techniques to label new bone formation and measure net bone mineral by microcomputed tomography to provide information on the accumulation of mineral in bone. The increases in bone mass and reversal of bone loss at a cancellous bone site motivate further exploration of the use of mechanical loading to attain greater peak bone mass and combat the increased osteoporotic fracture risk associated with reduced activity and sex-steroid levels. |
