Bone Properties in Hypoparathyroidism: Effects of PTH

Whereas much information is known about the properties of bone in primary
hyperparathyroidism, a disorder of parathyroid hormone (PTH) excess, virtually nothing is
known about the skeleton in hypoparathyroidism, a disorder in which PTH is absent. The
purpose of this research project is to test the hypothesis that the skeleton in
hypoparathyroidism is abnormal in its metabolic, densitometric, geometric, biomechanical and
microarchitectural features. We will also test the hypothesis that the skeleton is dependent
upon PTH for normal structure and function. Using non-invasive approaches as well as direct
analysis of bone itself, the human hypoparathyroid skeleton will be thoroughly
characterized. With each patient serving as his/her own control, we will determine how, to
what extent, and in what ways the administration of PTH restores skeletal dynamics and
structure to the hypoparathyroid skeleton. In this way, we will identify those structural
and dynamic elements of the skeleton that are influenced by or dependent upon PTH. Methods
to be utilized include dual energy X-ray absorptiometry, quantitative central and peripheral
computed tomography, geometry and size quantification, histomorphometry by standard and
microCT methods, finite element analysis, biochemical bone markers, quantitative back
scattered electron imaging, and Fourier Transform Infrared Spectroscopy. This research
project will extend our knowledge of the skeletal effects of PTH to its deficient range and
thus complete our understanding of PTH action on bone gained by our many years of studying
PTH overexpression in primary hyperparathyroidism. This investigation may also provide
insight into the means by which PTH helps to restore the skeleton when it is used to treat
osteoporosis.