# Understanding the skeleton in Down Syndrome

> **NIH NIH R01** · TEXAS A&M AGRILIFE RESEARCH · 2024 · $581,694

## Abstract

SUMMARY/ABSTRACT
This new R01 application entitled “Understanding bone mass in Down Syndrome” is focused on determining
the cellular mechanism for the low bone turnover we have identified in people and mice with Down Syndrome
(DS), and on characterizing fracture healing responses in different DS mouse models to gain insight into how
to better target fracture healing in the DS population with increased propensity to fracture. This proposal will
determine the contribution of Regulator of calcineurin 1 (RCAN1) that impacts both NF-κB activity in
osteoclasts and Wnt signaling in osteoblasts/osteocytes to the inherently low bone mineral density (BMD) in
DS. The proposed experiments will also determine the impact of cessation of the current clinical bone anabolic
interventions in the setting of DS as well as define DS fracture healing. Aim 1 will elucidate the pathways
through which RCAN1 controls osteoclast and osteoblast differentiation and function. Aim 2 will provide the
first direct evidence of fracture healing and repair in the context of low bone accrual and DS. Aim 3 will
determine the effects of discontinuation of current pharmaceutical anabolic therapies (anti-sclerostin antibody
and intermittent PTH) on bone mass accrual in three preclinical mouse models of DS. The successful
completion of this study will lead to a paradigm shift in our understanding of the DS bone phenotype and a new
landscape of high-quality research that will provide clarification of the mechanisms that contribute to the low
bone mass in DS and more importantly, provide the basis for new directions for the treatment of the fractures
and profound osteopenia that affects this population.

## Key facts

- **NIH application ID:** 11070425
- **Project number:** 4R01HD102909-02
- **Recipient organization:** TEXAS A&M AGRILIFE RESEARCH
- **Principal Investigator:** LARRY J. SUVA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $581,694
- **Award type:** 4N
- **Project period:** 2024-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11070425

## Citation

> US National Institutes of Health, RePORTER application 11070425, Understanding the skeleton in Down Syndrome (4R01HD102909-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11070425. Licensed CC0.

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