Information for Researchers
The SABRE Proposed
Surrogate Biomarker:
24 Month "% Change in Total Hip BMD (Active - Placebo)"
*from HORIZON Pivotal Fracture Trial
Black, et al. NEJM 2007
Summary of Data Compilation (as of May 2025)
Includes pivotal trials for
all osteoporosis drugs
approved in U.S.
53 studies
176,750 individuals
Primary Analysis (per FDA):
Meta-Regression of 2-Year Total Hip BMD
vs. % Change vs. Fracture Reductions
Correlation between changes in BMD are high enough to support surrogacy*
*FDA agreed
adapted from Black, et al. Lancet Diab & Endocrinol 2020
How to Use Change in BMD % Future Drug Approvals?
Establish a threshold for Change in THBMD% above which the drug would have a 95% chance of reducing fracture risk.
Surrogate Threshold Effect (STE)
1
If a future trial of a drug showed a THBMD% >2.04%, then the drug almost certainly (95%) would reduce all clinical fracture risk and could be approved.
1 - Ciani et al. Nature Rev Discovery 2016
2 - Black et al. Lancet Diab & Endocrinol 2020; Eastell et al. JBMR 2021
BMD as a surrogate will transform approval of new osteoporosis treatments