Biomarkers Consortium - Bone Quality Project

The Biomarkers Consortium’s Bone Quality Project aims to evaluate and to identify biomarkers of bone strength and quality changes by analyzing pooled imaging and biochemical data from multiple clinical studies to allow definition of better clinical endpoints. The goal is for these biomarkers to be utilized in future clinical studies and practice in osteoporosis, and ultimately be formally qualified by the U.S. Food and Drug Administration (FDA).

A major outcome of this project, once completed, will be to make recommendations to FDA to qualify the identified biomarkers for such purposes. This is a $2 million, 4-year project, with two subprojects to critically evaluate: 1) bone marker density and imaging-derived bone strength measurements to estimate bone strength and fracture risk; and 2) bone turnover markers (BTMs) to use as markers of anti-fracture efficacy in osteoporosis drug development and for patient management in clinical practice. The project launched in late 2013.

Goals

  • Assemble a data set of more than 170,000 subjects from 50 RCTs to re-evaluate existing imaging and serum and urine bone turnover marker data from antifracture trials that estimate bone strength to examine utility as bone strength biomarkers.
  • Apply newer techniques including QCT images using finite element analysis (FEA) to evaluate as an imaging biomarker for bone strength.

Results & Accomplishments

The Project Team has aggregated a data set of more than 170,000 patients for the project’s analyses and has submitted a Letter of Intent to the FDA to qualify total hip bone density as a fracture biomarker. Results have been published as several abstracts at annual meetings of the American Society of Bone Mineral Research (ASBMR).

Selected Abstracts

Change in BMD as a Surrogate for Fracture Risk Reduction in Osteoporosis Trials: Results from Pooled, Individual-level Patient Data from the FNIH Bone Quality Study. (ASBMR 2018)

Change in Bone Turnover as a Surrogate for Fracture Outcomes;: A Novel Individual-level Analysis of Pooled Anti-resorptive Trials from the FNIH Bone Quality Study (ASBMR 2018)

Design of the Foundation for NIH Bone Quality Project: Pooled individual-level measurements of BMD, bone strength, and bone turnover as surrogates for fracture risk reduction (ASBMR 2015)

Change in DXA Hip BMD on Treatment Can Reliably Estimate Reduction in Hip Fracture Risk in Osteoporosis Trials: A Meta-Regression (ASBMR 2015)

Treatment-related Changes in Bone Turnover are Associated with Vertebral, but not Non-vertebral or Hip, Fracture Risk Reduction in Bisphosphonate Trials: A Meta-Regression (ASBMR 2016)

Media

Medscape (October 3, 2018): Study Finds BMD Can Stand in for Fractures. Will the FDA Agree? by Marlene Busko

FNIH Announcement (July 13, 2016): Q&A with Dennis Black, Ph.D., Principal Investigator of the FNIH Biomarkers Consortium’s Bone Quality Project: 

Oral Presentations

Two oral presentations at ASBMR 2018 "Change in BMD as a Surrogate for Fracture Risk Reduction in Osteoporosis Trials: Results from Pooled, Individual-level Patient Data from the FNIH Bone Quality Project - Dennis Black" and "Change in Bone Turnover as a Surrogate for Fracture Outcomes: A Novel Individual-level Analysis of Pooled Anti-resorptive Trials from the FNIH Bone Quality Study - Doug Bauer"

 

Partners

Public-Sector Partners
National Aging Institute
National Institute on Arthritis and Musculoskeletal and Skin Diseases
U.S. Food and Drug Administration

Private-Sector Partners
AgNovos Healthcare*
American Society for Bone Mineral Research*
Amgen, Inc.*
Daiichi Sankyo, Inc.*
Dairy Research Institute*
Eli Lilly and Company*
Merck Sharp & Dohme Corp.*
Roche Diagnostics Corporation*

Academic Partners
University of California San Francisco

*Provides financial or in-kind support for this program

FNIH Contact

Helen Heymann, MMSc., Scientific Project Manager, Metabolic Disorders; hheymann@fnih.org