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.

A detailed description of the methods used in this study include the following: direct analysis of bone itself. skeletal dynamics and structure such as 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.

Trabecular width was obtained from histomorphometric assessment of percutaneous iliac crest bone biopsy. Trabecular width is the thickness of individual pieces of the spongy bone section. The structure and microscopic organization of a small piece of biopsied pelvic bone was analyzed.

trabecular number done on histomorphometric assessment of percutaneous iliac crest bone biopsy. Trabecular number is the number of individual pieces of the spongy bone section. The structure and microscopic organization of a small piece of biopsied pelvic bone was analyzed.

Cortical porosity done on histomorphometric assessment of percutaneous iliac crest bone biopsy. Cortical Porosity measures how many tiny holes there are in the solid bone section. The structure and microscopic organization of a small piece of biopsied pelvic bone was analyzed.

Mineralizing surface done on histomorphometric assessment of percutaneous iliac crest bone biopsy. Mineralizing surface measures how much of bone is getting new mineral put on it. The structure and microscopic organization of a small piece of biopsied pelvic bone was analyzed.

Rubin MR, Zhou H, Cusano NE, Majeed R, Omeragic B, Gomez M, Nickolas TL, Dempster DW, Bilezikian JP. The Effects of Long-term Administration of rhPTH(1-84) in Hypoparathyroidism by Bone Histomorphometry. J Bone Miner Res. 2018 Nov;33(11):1931-1939. doi: 10.1002/jbmr.3543. Epub 2018 Aug 16.