# Advancing Product Development for Hypoparathyroidism: A Prospective Natural History Study of the Clinical Outcomes and Regulation of Disordered Mineral Metabolism

> **NIH FDA R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $399,887

## Abstract

Hypoparathyroidism (HPT) is a rare disorder characterized by low parathyroid hormone (PTH) and calcium
levels. Patients suffer consequences of hypocalcemia, including paresthesias, arrhythmias, and seizures.
Conventional treatment to prevent these life-threatening events is calcium and active vitamin D. However,
complications of HPT, including kidney and cardiovascular disease, cataracts, basal ganglia calcifications and
neuropsychiatric disorders, occur despite, and possibly due to, conventional treatment. Although we found
increased bone calcification may be beneficial to the skeleton, calcification of end-organs may be fully or partially
responsible for these complications. Registry, retrospective, and claims studies have reported vascular
calcifications in HPT patients; we noted brain calcifications, and observational data document coronary artery
calcifications. Other HPT-associated metabolic derangements may also be contributory. Unfortunately, the
pathogenesis, epidemiology, natural history, and links between HPT, end-organ diseases, vascular
calcifications, and other derangements are unclear. This represents a significant scientific gap and impedes the:
(1) diagnosis, monitoring, mitigation, and prevention of HPT associated complications; (2) development, study,
and implementation of new strategies to prevent HPT-associated end-organ damage; and (3) ability to conduct
studies leading to advances in the HPT treatment paradigm. These gaps are particularly relevant in light of PTH
treatment, a developing off-label therapeutic for HPT. PTH treatment had pro-calcific side effects reported in
FDA registry trials for osteoporosis and its possible role in calcification and end-organ diseases in HPT are not
clear. Indeed, although studies reported that HPT managed with conventional treatment was associated with
kidney function decline, we found that kidney function did not decline in patients managed with PTH instead of
conventional therapy. Also, our data suggest a link between altered bone gene expression and dysregulation of
calcium. We identified circulating microRNAs highly associated with low bone turnover, a major risk factor for
extra-skeletal calcification. Data suggest these same miRs may be involved in vascular calcification
development. This application will provide a rigorous standardized approach to longitudinal data collection in
HPT on end-organ damage and calcification propensity. Our central hypothesis is that a natural history cohort of
HPT enables the study of end-organ complications. We also hypothesize that end-organ disease is related to
calcification propensity and severity. The Aims are to: 1) Build a prospective cohort of longitudinally followed
HPT patients to study the epidemiology and clinical impact of end-organ damage; 2). Determine the organ-
specific physiologic consequences of HPT; 3). Elucidate determinants of HPT-associated end-organ damage
from biochemical testing and calcification imaging. For the first time, ...

## Key facts

- **NIH application ID:** 10891413
- **Project number:** 5R01FD007629-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** THOMAS L. NICKOLAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2024
- **Award amount:** $399,887
- **Award type:** 5
- **Project period:** 2022-09-15 → 2026-08-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891413

## Citation

> US National Institutes of Health, RePORTER application 10891413, Advancing Product Development for Hypoparathyroidism: A Prospective Natural History Study of the Clinical Outcomes and Regulation of Disordered Mineral Metabolism (5R01FD007629-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10891413. Licensed CC0.

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