The overall goal in this SCOR grant is to study aspects of interaction of PTH and estrogen in the pathogenesis and treatment of osteoporosis. The function of the Core is to provide the technical tools to investigators to answer the questions posed. The Biochemistry Core has served this purposed in the last grant funding period and will continued, in concert with the other Cores, to provide investigators with the state-of-the-art tools to understand and solve this insidious disease. While the improvement in the precision and accuracy of bone mass measurement in recent years has enabled the investigator to make the diagnosis, and follow the progress of the disease with certain confidence, a relatively long period of time is still needed to observe changes. Histomorphometric measurements provide significant insight into the state of bone turnover, however, the invasive nature of bone biopsy, and the limitations on the frequency of follow up samples, restricts the use of this technique. In recent years, biochemical markers, relevant to the bone loss process, have become readily available. Some of these markers have been correlated to histomorphometric parameters of bone turnover. Although a single determination of these markers cannot generally be used to replace bone mass measurement, a series of marker determinations from the same individual within a short period of time has proven to be very useful in monitoring the efficacy of drug intervention or degree of compliance. In addition, the use of biochemical markers in conjunction with bone mass has enhanced the ability to predict fracture risk. In this application, the Biochemistry Core will perform calcium metabolism, bone turnover markers, and cytokine assays for each of the projects. Cytokines will be used to aid the study of subcellular mechanism of PTH action in a mouse models, pathogenesis and treatment of hyperparathyroidism in humans and has a main tool to study the efficacy of short term intermittent PTH treatment, its subsequent withdrawal and rechallenge.