Biomarkers Consortium - Bone Quality Project

Accelerating development of treatments for osteoporosis and other bone diseases

The Problem
Patients with osteoporosis, other bone diseases or increased risk for bone fractures have diminished bone strength and quality, yet researchers lack the tools needed to assess these characteristics during drug development.
The Solution
The Bone Quality Project will evaluate the ability of existing biomarkers, and explore the potential of novel biomarkers, to characterize bone strength and quality to inform osteoporosis drug development efforts.

Overview

The Biomarkers Consortium’s Bone Quality Project will analyze pooled imaging and biochemical data from multiple clinical studies, aiming to identify and evaluate biomarkers of bone strength and changes in bone quality, to allow definition of improved endpoints for clinical trials. This project will ultimately seek formal FDA qualification of its biomarkers, so that the biomarkers can be utilized in future clinical studies as well as in clinical practice to address osteoporosis.

This $2 million, 4-year project (launched in 2013)  includes two subprojects that will evaluate (1) bone marker density and imaging-derived bone strength measurements to estimate bone strength and fracture risk and (2) bone turnover markers for use as markers of anti-fracture efficacy in osteoporosis drug development and for patient management in clinical practice.

Goals

  • Assemble a dataset of more than 170,000 subjects from 50 randomized controlled antifracture trials and reevaluate existing imaging, serum and urine bone turnover marker data to assess the utility of these measures as biomarkers of bone strength.
  • Apply newer techniques, including using finite element analysis (FEA), to evaluate quantitative computed tomography (QCT) images as potential biomarkers for bone strength.

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

Results & Accomplishments

Aggregated Data

The Project Team has aggregated data from more than 170,000 patients for its analyses.

Dissemination of Results

Results from this project have been published in several peer-reviewed scientific publications (listed above) and as abstracts for several annual meetings of the American Society of Bone Mineral Research (ASBMR).

FDA Approval for Biomarker Qualification

The Bone Quality Team obtained FDA approval for its Letter of Intent (LOI) to qualify hip bone density as a fracture biomarker and is proceeding with its Biomarker Qualification Plan. This LOI was the first LOI ever approved for a surrogate endpoint biomarker (DXA) under the 21st Century Cures Act.

Scientific Publications

  • Treatment-related changes in bone mineral density as a surrogate biomarker for fracture risk reduction: meta-regression analyses of individual patient data from multiple randomised controlled trials. Black D. et al. The Lancet Diabetes & Endocrinology. 2020 Aug. 8(8): 649-730 Read more
  • No more fracture trials in osteoporosis? Reid I. The Lancet Diabetes & Endocrinology. 2020 Aug 8(8):650-651 Read more
  • Change in Bone Density and Reduction in Fracture Risk: A Meta-Regression of Published Trials. Bouxsein ML, Eastell R, et al; J Bone Miner Res; 2019 Apr. 34(4):632-642 Read more
  • Treatment-Related Changes in Bone Turnover and Fracture Risk Reduction in Clinical Trials of Anti-Resorptive Drugs: A Meta-Regression. Bauer DC, Black DM, et al; J Bone Miner Res; 2018 Apr;33(4):634-642. Read more

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) Read more
  • 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) Read more
  • 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

FNIH Social Media on Lancet Publication (September 2020)

  • Medscape (October 3, 2018): Study Finds BMD Can Stand in for Fractures. Will the FDA Agree? by Marlene Busko Read more:
  • FNIH Announcement (July 13, 2016): Q&A with Dennis Black, Ph.D., Principal Investigator of the FNIH Biomarkers Consortium’s Bone Quality Project:  Read more

ASBMR 2018 Oral Presentations

  • "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"
  • "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"