# Leveraging modeling-based bone formation for osteoporosis treatment

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $420,449

## Abstract

Project Summary
The healthy skeleton continuously renews itself throughout the lifespan via closely coupled bone resorption
and remodeling-based bone formation. In contrast, modeling-based bone formation, i.e., de novo bone
formation without prior activation of bone resorption, is less commonly found in the adult skeleton, but has
been identified as an important mechanism by which anabolic agents for osteoporosis, e.g., intermittent
parathyroid hormone (PTH) and PTH related peptide (PTHrP), and sclerostin antibody (Scl-Ab), rapidly elicit
new bone formation. By developing a novel imaging platform that enables reliable identification of MBF and
RBF and subsequent tissue-level mechanical testing in adult rat bone, we discovered that MBF responds
faster than RBF to anabolic treatments. Moreover, bone tissue resulting from MBF has a greater resistance to
anabolic treatment withdrawal-induced bone loss and increased heterogeneity of elastic modulus compared to
pre-existing bone and bone tissue resulting from RBF. These exciting preliminary data provide a strong
scientific premise to support our central hypothesis that MBF is a highly efficient regenerative mechanism that
leads to sustainable therapeutic benefits on bone tissue quantity and quality, and whole bone strength.
Furthermore, our data suggest that, upon early withdrawal from anabolic treatment, ongoing bone formation
continues at MBF sites, forming an “anabolic window” that retains the treatment effect; In contrast, the majority
of bone tissue formed at RBF sites were resorbed following treatment withdrawal. Therefore, we propose that a
cyclic and sequential treatment regimen with alternating anabolic and anti-resorptive treatments will lead to
increased mineral deposition and number of MBF, improved retention of bone tissue at RBF and quiescent
bone surface, and improved tissue heterogeneity and whole bone strength. The overall objective of this study
is to elucidate the cellular mechanisms (Aim 1a) and mechanical consequences (Aim 2a) of MBF and RBF,
and to evaluate the new treatment regimen which leverages MBF to improve and extend treatment efficacy
(Aim 2a and 2b) using a rat model. By combining our innovative imaging and image analyses with tissue-level
mechanical testing approaches, this proposed research project will fill the critical knowledge gap of long-term
mechanical consequences of bone tissue formed through MBF and RBF, and provide important insight for the
clinical design and optimization of treatment strategies that modulate MBF, a highly efficient but often
overlooked regenerative mechanism.

## Key facts

- **NIH application ID:** 10366040
- **Project number:** 5R01AR077598-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Xiaowei Sherry Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $420,449
- **Award type:** 5
- **Project period:** 2021-03-05 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10366040

## Citation

> US National Institutes of Health, RePORTER application 10366040, Leveraging modeling-based bone formation for osteoporosis treatment (5R01AR077598-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10366040. Licensed CC0.

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