Hypoparathyroidism: clinical features, skeletal microstructure and parathyroid hormone replacement

Abstract

Objective: Hypoparathyroidism is a disorder in which parathyroid hormone is deficient in the circulation due most often to immunological destruction of the parathyroids or to their surgical removal. The objective of this work was to define the abnormalities in skeletal microstructure as well as to establish the potential efficacy of PTH(1-84) replacement in this disorder.

Subjects and methods: Standard histomorphometric and microCT analyses were performed on iliac crest bone biopsies obtained from patients with hypoparathyroidism. Participants were treated with PTH(1-84) for two years.

Results: Bone density was increased and skeletal features reflected the low turnover state with greater BV/TV, Tb. Wi and Ct. Wi as well as suppressed MS and BFR/BS as compared to controls. With PTH(1-84), bone turnover and bone mineral density increased in the lumbar spine. Requirements for calcium and vitamin D fell while serum and urinary calcium concentrations did not change.

Conclusion: Abnormal microstructure of the skeleton in hypoparathyroidism reflects the absence of PTH. Replacement therapy with PTH has the potential to correct these abnormalities as well as to reduce the requirements for calcium and vitamin D.

Figure 1

Figure 1A. A representative photomicrograph of an iliac crest biopsy from a normal control (left) as compared to a hypoparathyroid subject (right). Figure 1B. 3-D μCT image of iliac crest biopsy in a representative hypoparathyroid subject (left) and a normal control (right).

Figure 2

Figure 2A. Scatter plots of the five BMDD parameters measured in 19 hypoparathyroid patients. The patients are distinguished by categories, gender, and etiology. Grey band and dotted line in the background indicate SD and mean of the reference values. Figure 2B. FTIRI measurements in biopsies from the hypoparathyroid patients (n = 19). Collagen cross link ratio (pyr/deH-DHLNL) were assessed in trabecular bone (HypoPT_collx) and compared with a normal reference population (NL_collx).

Figure 3

Changes in Calcium (3A) and 1,25-dihydroxyvitamin D (3B) Supplementation. Calcium requirements decreased at 3, 9, 12, 18 and 24 months from baseline, while 1,25-dihydroxyvitamin D requirements decreased by 1 month. Data are mean ± SD; * p < 0.05 as comparison to baseline.

Figure 4

BMD Changes with PTH (1-84) therapy of hypoparathyroidism.