# The cell metabolism basis for bone complications in type I diabetes

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $441,570

## Abstract

Abstract
Compelling clinical evidence has linked diabetes with increased fracture risks and impaired bone healing.
Suppressed bone turnover is a common feature in both type I and type II diabetes. Therefore, use of
bisphosphonates, which are the main stay of osteoporosis treatment but further suppress bone turnover, may
exacerbate bone quality deterioration in the long term. The current bone anabolic drugs however have limited
use in diabetic patients, particularly diabetic children, due to black box warnings. Thus, there remain
tremendous unmet needs for safe and effective bone anabolic drugs. A thorough understanding of cellular
metabolism in diabetic bone is essential for rational designs of novel bone therapies, but research in this area
has been hampered by the lack of adequate knowledge about normal metabolism in bone cells. In recent years
we and others have uncovered new details about the metabolic signatures of osteoblasts and osteoclasts,
therefore providing a solid foundation for investigating the potential dysregulation of bone cell metabolism in
the context of diabetes. As type 1 diabetes (T1D) is the most common form of newly diagnosed diabetes in
childhood, we focus our present study on T1D by employing the Akita mouse that harbors a spontaneous point
mutation in the Ins2 gene causing postnatal apoptosis of pancreatic ß cells. We propose to test the central
hypothesis that type I diabetes disrupts normal osteoblast metabolism and that enhancement of
glucose metabolism in osteoblasts can mitigate diabetic bone defects. We test the hypothesis in three
specific aims. Aim 1 will characterize the bone defects at the cellular level in the diabetic mouse. Aim 2 will
detail the metabolic defects in osteoblasts caused by diabetes, and specifically investigate the role of insulin.
Finally, in Aim 3 we will test genetically whether stimulation of glycolysis ameliorates the bone defect in the
diabetic mouse. Successful completion of the proposal is likely to open a new avenue for developing bone-
enhancing drugs.

## Key facts

- **NIH application ID:** 10839341
- **Project number:** 5R01DK125498-04
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Fanxin Long
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $441,570
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839341

## Citation

> US National Institutes of Health, RePORTER application 10839341, The cell metabolism basis for bone complications in type I diabetes (5R01DK125498-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10839341. Licensed CC0.

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