Cross-calibration of 45calcium kinetics against dynamic histomorphometry in a rat model to determine bone turnover

Techniques for assessing bone dynamic are in high demand. Calcium (Ca) kinetic studies are currently being used in our clinical studies of bone turnover in adolescents and elderly. The technique has rarely been compared to the standard method of bone dynamic histomorphometry. We perturbed bone turnover through ovariectomy and sub-optimal dietary Ca in a female rat model to cross-calibrate Ca kinetics against dynamic histomorphometry. Kinetic studies involved oral and intravenous administration of (45)Ca and monitoring the tracer in blood, urine, feces, and bone over a 3-day period as part of a metabolic Ca balance study. Histomorphometric indices of mineral apposition rate, mineralizing surface, and bone formation rate were obtained from proximal metaphysis and mid-diaphysis region of tibial bone. Bone mineralization and resorption rates at the whole skeletal level as evaluated by kinetic studies were significantly correlated with the volume-based bone formation rate (BFR/BV) evaluated by dynamic histomorphometry in metaphyseal trabecular bone (r=0.72 and r=0.61, respectively, p<0.001) and surface-based bone formation rate (BFR/BS) in tibial cortex (r=0.63, p<0.001 and r=0.59, p<0.01, respectively). Significant correlations were also demonstrated between bone resorption and mineralization rates at the whole skeletal level (r=0.91, p<0.001) using (45)Ca kinetic data. Ca kinetic modeling showed an increase (p<0.001) in skeletal resorption and formation rates in response to ovariectomy (27.6 vs. 13.8 mg/d for bone resorption and 42.7 vs. 28 mg/d for bone formation in ovariectomized vs. their Sham-operated control animals, respectively). Ca kinetic data also showed that bone formation decreased by 30% and whole bone balance by 50%, when dietary Ca level was reduced from 0.4% to 0.2% (34.2 vs. 23.8 mg/d and 10.4 vs. 5.1 mg/d, respectively, p<0.001). Our data suggest that Ca kinetic studies can be used reliably to rapidly detect changes in bone turnover at the whole skeletal level in response to interventions.