Anti-PTH monoclonal antibody, clone BGN/1F8

Homeostasis of calcium (Ca) and phosphate (P-i) is maintained by a concerted interplay of absorption and reabsorption via the gastrointestinal tract and the kidney and by storage and mobilization from the bone regulated mainly by parathyroid hormone (PTH), 1,25-dihydroxycholecalciferol and calcitonin. The present study aimed at characterizing the effects of dietary P restriction on bone, vitamin D metabolism and rumen fermentation traits reflecting the endogenous P cycle maintaining the ruminal P supply for microbial metabolism. The experiments were done in eleven female, non-pregnant, non-lactating four- to nine-year-old Black Headed Mutton sheep allotted to two feeding groups: "P-restricted" (0.11% P/kg DM and 0.88% Ca/kg DM) and "Control" (0.38% P/kg DM and 0.88% Ca/kg DM). Dietary P restriction did not lead to hypophosphataemia, probably due to a compensation by bone mobilization, demonstrated by increased serum concentrations of a resorption marker and altered gene expression in bone tissue. In addition, the RNA expression of fibroblast growth factor 23, a bone-derived factor involved in the regulation of vitamin D metabolism, was significantly reduced with dietary P restriction. Furthermore, several genes related to vitamin D metabolism and plasma concentrations of 1,25-(OH)(2)D were associated with serum concentrations of phosphate (P-i). In the parotid gland, the expression of the P(i)transporter NaPi2b was negatively associated with serum P(i)and positively with parathyroid PTH expression. Although P(i)concentrations in saliva and the gastrointestinal tract were significantly reduced, we found no adverse effects of the P-restricted ration on the production of short chain fatty acids, but slight differences in the production of butyrate as well as its relationship to rumen P(i)and ammonia concentrations that might indicate an impact on ruminal fermentation.

Purpose Hypoparathyroidism (HP) is a rare endocrine disorder characterized by absent or inappropriately low levels of circulating parathyroid hormone (PTH). Research indicates that HP patients on conventional therapy may have a reduced quality of life. The study's purpose was to develop a new disease-specific measure of the impacts of hypoparathyroidism on functioning and well-being and provide evidence for its content validity based on rigorous qualitative research methodologies for patient-reported outcomes development. Methods Semi-structured, individual concept elicitation (CE) interviews were conducted with 5 clinical experts and 42 adults in the USA with HP to identify impacts of relevance and importance to the target population. Transcripts were coded and analyzed using an adapted grounded theory approach common to qualitative research. Following item generation, the draft measure was cognitive debriefed in an independent sample of 16 adults with HP. Results Analyses identified four impact domains: physical functioning, including ability to exercise (n = 32, 76%) and mobility (n = 21, 50%); daily life, including ability to do things around the home (n = 33, 79%), and interference with work productivity (n = 18, 43%); psychological well-being, including feeling anxious/anxiety (n = 34, 81%) and frustrated (n = 27, 64%); and social, including ability to participate in social activities (n = 33, 79%) and relationships (n = 32, 76%). Twenty-seven impacts were identified and included in the preliminary measure. After the cognitive debriefing, a validation-ready, 26-item Hypoparathyroidism Patient Experience Scale-Impact (HPES-Impact) was generated. Conclusion Findings provide substantial evidence of content validity for the validation-ready HPES-Impact in adults with HP.