# Denosumab and sequential zoledronic acid to prevent bone loss and maintain bone mass after spinal cord injury

> **NIH NIH R34** · NORTHWESTERN UNIVERSITY · 2024 · $279,354

## Abstract

The current R34 proposal in response to NIAMS PAR-22-205 will provide us the time and resources to
complete the detailed clinical trial planning necessary to meet NIAMS and NIH standards and regulatory
requirements prior to submitting a U01 application for funding. Activities included in this proposal include
initiating clinical, operational and regulatory activities; developing a data safety monitoring plan; identifying
and vetting clinical sites; developing and testing training materials, obtaining investigational drug; establishing
data collection, management and data analysis plans; and developing a final budget; and submission of a U01
application for funding. The study being proposed will evaluate the use of denosumab and sequential
zoledronic acid therapy to prevent bone loss after acute SCI. Bone loss after acute spinal cord injury (SCI)
occurs rapidly and is profound in magnitude, with 50% of bone mass or more being lost in the lower extremities
of non-weightbearing individuals, resulting in an elevated risk of fracture and limiting access to weight-bearing
rehabilitation. Bone loss is driven primarily by increased bone resorption, and the use of bisphosphonates to
prevent bone loss has slowed but not prevented significant bone loss. In contrast, an initial small clinical trial of
denosumab, a more potent anti-resorptive agent, has reported efficacy in preventing DXA-determined bone loss
after SCI, particularly at skeletal sites around the knee, the most common site of fracture. These data need to be
replicated in a larger and more diverse SCI population with bone loss evaluated by accurate CT imaging
technology and serum bone markers. And importantly, as the skeletal benefits of denosumab have been shown
to be rapidly lost after its discontinuation, an additional intervention to prevent this loss of efficacy after
denosumab discontinuation needs to be considered. Intravenously administered zoledronic acid has been shown
to be effective in this setting, and we have recently shown in a larger clinical trial that zoledronic acid is
effective in reducing bone loss at knee skeletal sites after SCI, providing further support for its use in this
setting. Additionally, our data have also demonstrated a significant interaction between zoledronic acid
treatment and a measure of ambulatory ability, WISCI, strongly suggesting that weight-bearing can impact
skeletal outcomes after zoledronic acid treatment and be an important factor for clinical decision making
regarding who should be treated. Thus, the overall goal of this study is to assess the efficacy, safety and
durability of sequential treatment with denosumab and zoledronic acid to prevent and maintain bone loss after
acute SCI. We will utilize the setting of a double-blind, randomized clinical trial, with initial denosumab and
placebo treatment for 12 months (dosing at baseline and at 6 months) after acute SCI, followed by
randomization at that point of the group receiving denosumab, stratif...

## Key facts

- **NIH application ID:** 10854271
- **Project number:** 1R34AR082859-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** THOMAS JACK SCHNITZER
- **Activity code:** R34 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $279,354
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10854271

## Citation

> US National Institutes of Health, RePORTER application 10854271, Denosumab and sequential zoledronic acid to prevent bone loss and maintain bone mass after spinal cord injury (1R34AR082859-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10854271. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*