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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK069350-02
Application #
7117277
Study Section
Skeletal Biology Development and Disease Study Section (SBDD)
Program Officer
Malozowski, Saul N
Project Start
2005-09-01
Project End
2010-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$580,734
Indirect Cost
Name
Columbia University (N.Y.)
Department
Dentistry
Type
Schools of Dentistry
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Cipriani, Cristiana; Abraham, Alice; Silva, Barbara C et al. (2017) Skeletal changes after restoration of the euparathyroid state in patients with hypoparathyroidism and primary hyperparathyroidism. Endocrine 55:591-598
Misof, Barbara M; Roschger, Paul; Dempster, David W et al. (2016) PTH(1-84) Administration in Hypoparathyroidism Transiently Reduces Bone Matrix Mineralization. J Bone Miner Res 31:180-9
Zhou, Bin; Zhang, Zhendong; Wang, Ji et al. (2016) In Vivo Precision of Digital Topological Skeletonization Based Individual Trabecula Segmentation (ITS) Analysis of Trabecular Microstructure at the Distal Radius and Tibia by HR-pQCT. Pattern Recognit Lett 76:83-89
Cusano, Natalie E; Nishiyama, Kyle K; Zhang, Chengchen et al. (2016) Noninvasive Assessment of Skeletal Microstructure and Estimated Bone Strength in Hypoparathyroidism. J Bone Miner Res 31:308-16
Rubin, Mishaela R; Cusano, Natalie E; Fan, Wen-Wei et al. (2016) Therapy of Hypoparathyroidism With PTH(1-84): A Prospective Six Year Investigation of Efficacy and Safety. J Clin Endocrinol Metab 101:2742-50
Rubin, Mishaela R; Zwahlen, Alexander; Dempster, David W et al. (2016) Effects of Parathyroid Hormone Administration on Bone Strength in Hypoparathyroidism. J Bone Miner Res 31:1082-8
Cusano, Natalie E; Rubin, Mishaela R; Bilezikian, John P (2015) Parathyroid hormone therapy for hypoparathyroidism. Best Pract Res Clin Endocrinol Metab 29:47-55
Silva, Barbara C; Bilezikian, John P (2015) Parathyroid hormone: anabolic and catabolic actions on the skeleton. Curr Opin Pharmacol 22:41-50
Cusano, Natalie E; Rubin, Mishaela R; Zhang, Chiyuan et al. (2014) Parathyroid hormone 1-84 alters circulating vascular endothelial growth factor levels in hypoparathyroidism. J Clin Endocrinol Metab 99:E2025-8
Cusano, Natalie E; Rubin, Mishaela R; McMahon, Donald J et al. (2014) PTH(1-84) is associated with improved quality of life in hypoparathyroidism through 5 years of therapy. J Clin Endocrinol Metab 99:3694-9

Showing the most recent 10 out of 29 publications