Analysis of whole skeleton 3H-tetracycline loss as a measure of bone resorption in maturing rats.

Several modifications of the 3H-tetracycline bone labeling method for measuring whole skeleton bone resorption were tested. Under steady state conditions of whole skeleton resorptive activity, bone labeling for intervals longer than 2 weeks prior to experimentation did not significantly alter the urinary 3H-tetracycline loss curve. The utilization of nonlinear regression analysis showed that the urinary loss of 3H-tetracycline was best described by double exponential equations, indicating the loss of label from two distinct and independent exchangeable bone compartments. This conclusion was supported by the finding that soft tissues were effectively depleted of 3H-tetracycline by 24 hours after the final injection of label. Hence, it was concluded that approximately 40% of the 3H-tetracycline loss from skeletal bone is associated with a "fast" compartment which is depleted within 6 or 7 days after label loading. The size and rate of 3H-tetracycline loss from the fast compartment decreased (40%) with age such that the depletion time remained constant between 8 and 24 weeks of age in both male and female rats. The remaining 60% of 3H-tetracycline loss from a "slow" compartment which was depleted in about 70 days in young (8 week) rats. This compartment, which is believed to reflect cell-mediated resorption of calcified bone; decreased in size with age in both male (50%) and female (30%) rats. The rate of label loss from this compartment, however, remained relatively high so that the depletion time decreased (approximately 35%) between 8 and 24 weeks of age. By determining whole skeletal mass and calculating these parameters on the basis of skeletal mass, we were further able to demonstrate significantly higher resorptive activity in female than in male rats by 24 weeks of age.