MRI Biomarkers of Bone Quality in DMD
Abstract
Need for Bone Biomarkers in DMD: Osteoporosis, broken bones, and poor bone health affect a majority of teens and men with Duchenne muscular dystrophy (DMD). Poor bone health and fractures cause pain, increase disability, and decrease quality of life for many people with DMD. Monitoring bone health and treating poor bone health in DMD is an important focus for clinicians. There is an urgent need for studies to test which osteoporosis drugs work best to prevent and treat poor bone health in DMD, and whether new muscle drugs can also protect bone. However, measuring the effectiveness of these drugs is challenging. It is most important that the drugs can reduce the frequency of broken bones in individuals with DMD, but using this as a clinical trial outcome would require either a very large study with thousands of participants, or a very long study where participants are followed for many years. Neither of these are realistic in a rare and progressive disease like DMD, particularly if they include a placebo group who is not receiving treatment. There is a need for biomarkers of bone quality, which can be used to measure differences between treatment and placebo groups over realistic time frames and which are related to fracture risk. Right now, the most commonly used biomarker for bone in DMD is bone mineral density measured by dual-energy X-ray absorptiometry (DXA). Because bone mineral density isn’t a strong predictor of who will break a bone, its value is limited in clinical trials. Magnetic resonance imaging (MRI) can accurately measure bone quality and help to predict fracture risk in other populations, but isn’t currently being used in clinical trials involving people with DMD. Objectives of This Study: The objective of this study is to develop MR measures of bone quality in individuals with DMD as biomarkers for clinical trials of bone drugs in DMD. Specifically, we will measure cortical and trabecular bone in the femur (thigh bone) and trabecular bone in the spine in 7- to 18-year-old males with and without DMD. We hypothesize that we will be able to measure both cortical and trabecular bone quality reliably, that bone quality will be worse in people with DMD than in unaffected people, and that bone will deteriorate significantly over 12 months in people with DMD. We also hypothesize that there will be significant relationships between MRI measures of bone quality and factors known or thought to affect fracture risk in DMD, including age, ambulatory status, and muscle health. This project addresses multiple focus areas for the Fiscal Year 2020 Translational Research Partnership Award, specifically, “Clinical studies designed to improve care and quality of life in endocrinology” and “Assessment of clinical tools and outcome measures.” Outcomes of the Research: The ultimate goal of this research is to provide tools for endocrinologists to use to test different therapies to prevent and treat fragile bones in DMD. If this study is successful, the tools can move into clinical trials quickly: the measurements we make are done on a standard clinical MRI scanner, and our team has tremendous practical experience implementing MRI measures in clinical trials for DMD. In the last 6 years, we have performed muscle biomarker measurements in 7 clinical trials, with over 30 sites across the US, Canada, and Europe. Being able to measure the effect of drugs on bone quality without relying solely on DXA or waiting for trial participants to develop fractures will make it possible to plan and conduct realistic trials to evaluate treatment of poor bone health in DMD. Studies are needed to evaluate oral and IV bisphosphonates, denosumab, teriparatide, new drugs like those being developed by Mesentec, and muscle-targeted drugs like Vamorolone. Clinical trials are critically important to make sure that there is evidence for the effectiveness of the drugs patients receive – currently, clinicians mostly prescribe treatments based on the res
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110566
Entities
People
- Rebecca Willcocks
Organizations
- United States Army
- University of Florida