NIH grant: A novel MRI method for noninvasive imaging of bone quality in type 2 diabetes (1K99AR086311-01A1)

retained text

NIH grant 1K99AR086311-01A1: A novel MRI method for noninvasive imaging of bone quality in type 2 diabetes
Institute: {'code': 'AR', 'abbreviation': 'NIAMS', 'name': 'National Institute of Arthritis and Musculoskeletal and Skin Diseases', 'admin_org_id': '12500006', 'admin_funding_url': ''}. PI: Soo Hyun  Shin. Award: $117426.
Start: 2026-06-18T00:00:00.
ABSTRACT:
Type 2 diabetes mellitus (T2DM) affects 500 million of the global population, which is expected to increase to
800 million in 20 years. One of the multiple complications involved with T2DM is the significantly increased bone
fracture risk and post-fracture mortality. Dual-energy X-ray absorptiometry (DXA) scans are routinely performed
to measure bone mineral density (BMD) and associated fracture risk. However, T2DM patients often show
preserved or even elevated BMD despite the significantly increased fracture risk. This mismatch between the
BMD measurement and actual fracture risk hampers the accurate assessment of fracture risk and the
appropriate treatment of T2DM that considers patient bone health. The lack of an accurate fracture risk
assessment tool also confounds the evaluation of the bone health effect of antidiabetic drugs, including recently
highlighted glucagon-like peptide-1 receptor agonists (e.g., semaglutide) and sodium-glucose cotransporter-2
inhibitors. Previous studies have suggested that bone quality, rather than bone quantity, as represented by BMD,
is a crucial factor contributing to fracture risk in T2DM settings. Collagen crosslinking via advanced glycation
end-products (AGEs) in cortical bone has been identified as a distinctive bone quality characteristic of T2DM
patients, which explains the increased bone fragility. Although this finding is highly promising for improving the
bone health management of T2DM patients, currently, no non-invasive method can monitor collagen crosslinking
in the bones. This proposal aims to develop an ultrashort echo time (UTE) MRI-based method for measuring the
degree of bone collagen crosslinking by quantifying magnetization transfer between water and collagen in the
bone. This method, termed UTE-quantitative magnetization transfer (UTE-qMT) MRI, measures not only the
quantity of macromolecules (e.g., collagen) in the bone but also the rates of exchange between water and
macromolecular protons, which are related to the degree of collagen crosslinking. The proposal will develop and
optimize the accelerated UTE-qMT method for reliably measuring the exchange rate in Aim 1. The optimized
technique will be validated by correlating exchange rates with AGE-driven collagen crosslinking and subsequent
compromise of bone mechanical properties in Aim 2. Finally, the optimized UTE-qMT MRI method will be
translated to animal and human studies to demonstrate its clinical feasibility for investigating the effect of
antidiabetic drugs on bone health in patients with T2DM in Aim 3. The successful completion of these aims will
enable rapid and accurate assessment of bone fracture risk in patients with T2DM. Furthermore, noninvasively
probing bone quality can also accurately assess the effect of antidiabetic drugs on bone health and aid in
screening novel T2DM therapeutics for their impact on bone health.

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