This project will employ high resolution quantitative computed x-ray tomography to evaluate and compare the effects of two treatments (human calcitonin and pamidronate) on the healing process and bone mineral redistribution in Paget's disease of bone. The applicants will characterize these processes using radiographic techniques with higher spatial resolution than has been previously applied to this disease. Quantitation of bone mineral densities for many small (4 microliter) volumes will permit statistical analysis of density distribution and subtle redistribution of bone mineral. The applicants will also investigate possible differences between two treatments, one which required chronic application, and another which produces alterations in the pathological remodeling process after a single treatment. They will also determine whether the type of treatment affects the rate or pattern of healing of lytic lesions and remodeling of sclerotic areas, and whether the effects of pamidronate are dose-dependent. The relationship between reduction in the heterogeneity of visual densities and the reduction in biochemical markers of disease activity will also be analyzed. As a part of this study, improved techniques for the serial measurement of bone density in small volumes will be developed. This should have clinical impact in the study of a variety of bone disorders. Improvements in serial data alignment and three dimensional subtraction techniques will provide the precision required for a more thorough utilization of the acquired density data. The proposed work will complement, but not duplicate, ongoing studies relating bone structure to biology in other conditions.
