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Am J Physiol Endocrinol Metab 276: E62-E69, 1999;
0193-1849/99 $5.00
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Vol. 276, Issue 1, E62-E69, January 1999

Bone and hormonal changes induced by skeletal unloading in the mature male rat

Walter Dehority1, Bernard P. Halloran1, Daniel D. Bikle1, Tracy Curren2, Paul J. Kostenuik1, Thomas J. Wronski3, Ying Shen3, Brian Rabkin2, Abderrahman Bouraoui1, and Emily Morey-Holton2

1 Departments of Medicine and Physiology, University of California and Division of Endocrinology, Veterans Affairs Medical Center, San Francisco 94121; 2 Life Sciences Division, National Aeronautics and Space Administration-Ames Research Center, Moffett Field, California 940351; and 3 Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida 32610

To determine whether the rat hindlimb elevation model can be used to study the effects of spaceflight and loss of gravitational loading on bone in the adult animal, and to examine the effects of age on bone responsiveness to mechanical loading, we studied 6-mo-old rats subjected to hindlimb elevation for up to 5 wk. Loss of weight bearing in the adult induced a mild hypercalcemia, diminished serum 1,25-dihydroxyvitamin D, decreased vertebral bone mass, and blunted the otherwise normal increase in femoral mass associated with bone maturation. Unloading decreased osteoblast numbers and reduced periosteal and cancellous bone formation but had no effect on bone resorption. Mineralizing surface, mineral apposition rate, and bone formation rate decreased during unloading. Our results demonstrate the utility of the adult rat hindlimb elevation model as a means of simulating the loss of gravitational loading on the skeleton, and they show that the effects of nonweight bearing are prolonged and have a greater relative effect on bone formation in the adult than in the young growing animal.

aging; disuse osteoporosis; mechanical loading of bone


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