Osteoporosis leading to fracture and other sequelae is a common medical problem which often results in serious financial costs, limitations on lifestyle, and even death. While a variety of techniques have been utilized to attempt to prevent bone loss and resultant fracture, there is little information on the change in the quality of osteoporotic bone before and after such treatments. Bone "quality", measured by bone architecture, mineral properties (crystal size, orientation, composition, and content), and matrix content, is a principal factor in determining bone strength. These studies will evaluate the mineral and matrix constituents of osteoporotic bone before and after treatment, using Fourier transform infrared microspectroscopy (FTIRM) to concurrently provide quantitative information about each of the determinants of bone quality with the exception of architecture. FTIRM is a technique in which a light microscope coupled to an infrared spectrometer permits examination of tissue sections at 10-20 upsilon m resolution. FTIRM analyses of osteoporotic and control human and primate bones will be used to test four hypotheses. First, the study will look at a series of synthetic apatites to verify the finding that different types of substitution in the apatite lattice affect the spectral parameters of the mineral in different ways. Then FTIRM, polarization FTIRM, and two dimensional FTIRM techniques will be used to map the mineral and matrix changes in osteoporosic lamellar, trabecular, and osteonal bone. The hypotheses to be tested by FTIRM will be that: (I) Significant differences in both mineral and matrix content and mineral composition occur between osteoporotic and normal bones. (2) Site and time dependent changes in osteoporotic mineral composition and quality depend on the rate of turnover of the bone. (3) Differences in fracture rate between patients treated with NaF and calcium and those treated with slow release NaF and calcium are due to differences in resultant mineral and matrix quality and composition. (4) Different drug regimens variously influence the restoration of "normal,, bone quality in osteoporotic humans and animals. Treatments to be considered include: bisphosphonates, estrogens, PTH, and calcitonin. Results of these FTIRM analyses will provide insight into the basis for the loss of bone strength in osteoporosis, and may suggest which treatments are most desirable.