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 μCT 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.

New understanding and treatments for osteoporosis

“…Standard treatment regimens include the administration of calcium and vitamin D. Hypoparathyroidism is the only classic endocrine deficiency disease for which the deficient hormone (i.e., PTH) is not approved for replacement therapy. A number of studies, however, show that both teriparatide or PTH(1-84) provide good calcemic control, while reducing the intake of calcium and vitamin D in these individuals [43][44][45]. In addition, urinary calcium excretion falls.…”

Low bone turnover and increase of bone mineral density in a premenopausal woman with postoperative hypoparathyroidism and thyroxine suppressive therapy

“…While there are promising results on teriparatide and intact parathyroid hormone therapy [12,18,19], hypoparathyroidism remains the last endocrinopathy not routinely treated by substitution of the missing hormone. Fig.…”

Repurposing a novel parathyroid hormone analogue to treat hypoparathyroidism

“…Alternatively, treatment with calcitriol and/or vitamin D supplementation can restore serum calcium, but there are risks of hypercalciuria-related complications in the kidney (Moses et al, 1976;Langdahl et al, 1996). Calcium and/or vitamin D supplementation also do not appear to address abnormalities in bone microarchitecture or increased risk of certain fractures, despite increased BMD in HP patient groups (Rubin and Bilezikian, 2010;Mendonca et al, 2013;Underbjerg et al, 2015). Both PTH (1-84) and PTH (1-34) have been evaluated in a number of clinical studies in adults and children with various forms of HP (Rubin and Bilezikian, 2010;Winer et al, 2010;Winer et al, 2012;Cusano et al, 2013;Mannstadt et al, 2013;Winer et al, 2014;Santonati et al, 2015;Upreti et al, 2017).…”