1. Development of new kinetic models. a. Using results from isotope dilution experiments with intravenous 42Ca in humans, a three hour test has been developed to measure the short-term clearance of calcium. This clearance reflects bone uptake and the state of local calcium dynamics at the bone surface. In studies of 91 normal female subjects, ages 4-50 years as well as 41 subjects with various forms of metabolic bone disease, results of this approach have been found to correlate with bone accretion measured from classical calcium kinetic studies with a correlation coefficient of 0.721, significant at p<0.005. b. A second novel model to describe calcium isotope dilution observations is a generalized non-Markovian model describing the long-term kinetics of calcium interaction with bone. In this model the reversible component of calcium flow to bone is modeled by a retention function. Using children with juvenile dermatomyositis, reversible loss to bone is found to be the same between the steroid and non-steroid treated subjects while irreversible tracer loss from plasma to bone is found to be statistically reduced (p=0.049) in glucocorticoid-treated patients relative to those untreated. 2. Ultrasonic imaging of the calcaneus has been performed as a potential alternative imaging approach to bone histomorphomorphometry of cancellous bone. Measurements in 142 healthy male and female subjects in the age range 18 months-84 years show a clear falloff in scattered ultrasound intensity in both males and females after the age of 35. The rate of fall in females is more pronounced than that of males. 3. The dynamic equilibrium calcium atom exchange between solution and crystal was studied using a slurry of CaCl2 and NaH2PO4 mixed with 50fm diam hydroxyapatite crystals in which initially 5% of the Ca ions in solution were 42Ca. The time course of the isotope both in solution and on the crystals was measured for 24 hrs using thermal ionization and ion microprobe mass spectrometry respectively. Isotope disappeared from the filterable portion of the slurry in the time of the study, diminishing by about 20% during the day, and at the same time, isotope was seen to accrete on the surface of the crystalline material isolated by filtering, with the isolated crystals -being found uniformly labelled on their surfaces.
