The effects of simulated weightlessness on bone maturation.

In earlier studies we showed that elevating the hind limbs of growing rats for up to 2 weeks results in a temporary cessation of bone growth in the hind limbs and a transient fall in the serum levels of 1,25-dihydroxyvitamin D. To determine whether such skeletal unloading also retards the maturation of bone, as seen in vitamin D-deprived animals, we fractionated by density the tibiae from rats whose hind limbs had been elevated for up to 15 days. These fractions were analyzed for dry weight, calcium content, and calcium and proline uptake. The most dense fraction (fraction 4) had the highest degree of mineralization (ratio of calcium to dry weight) and comprised 82% of the total dry weight of the control tibiae. The total incorporation of [3H]proline administered in vivo 24 h before removing the tibiae was evenly distributed among all of the fractions, although it was highest in the least dense fraction (fraction 1) when normalized to dry weight. Total incorporation of 45Ca was highest in fraction 4, although when normalized to dry weight it was highest in fraction 3. With skeletal unloading, the proportions of bone and 45Ca incorporation in fraction 4 decreased, while the proportions in less dense fractions increased. [3H]Proline incorporation fell in all fractions. These effects were maximal after 10 days of unloading and returned toward the control values after that time. We conclude that skeletal unloading transiently reduced bone formation and retarded mineralization in the growing rat, which resulted in a decrease in mature bone.