External validation of a novel HR-pQCT based fracture risk assessment tool (FRAC) in a Male Cohort: The Osteoporotic Fractures in Men (MrOS) Study

Annabel R Bugbird; Andrew J Burghardt; Lisa Langsetmo; Kristine E Ensrud; Mary L Bouxsein; Douglas P Kiel; Steven K Boyd; Danielle E Whittier

doi:10.1093/jbmr/zjaf187

External validation of a novel HR-pQCT based fracture risk assessment tool (FRAC) in a Male Cohort: The Osteoporotic Fractures in Men (MrOS) Study

J Bone Miner Res. 2025 Dec 31:zjaf187. doi: 10.1093/jbmr/zjaf187. Online ahead of print.

Authors

Annabel R Bugbird¹, Andrew J Burghardt², Lisa Langsetmo³, Kristine E Ensrud³, Mary L Bouxsein⁴, Douglas P Kiel⁵, Steven K Boyd¹, Danielle E Whittier¹

Affiliations

¹ McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary AB, Canada.
² Department of Radiology & Biomedical Imaging, University of California, San Francisco, CA, USA.
³ University of Minnesota, Department of Medicine, Minneapolis VA Health Center, MN, USA.
⁴ Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
⁵ Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

PMID: 41474190
DOI: 10.1093/jbmr/zjaf187

Abstract

Introduction: Fracture risk estimates can be used clinically to inform treatment decision-making in osteoporosis. Current fracture risk assessment tools have a low sensitivity in predicting fractures in males. This study aims to evaluate and validate the performance of a new fracture prediction tool - the Microarchitecture Fracture Risk Assessment Calculator (FRAC) - in a multi-centre cohort (MrOS) of older community-dwelling men.

Methods: The performance of FRAC was assessed in a population of 1586 men aged $\geq 77$ years in the US. All participants underwent HR-pQCT scanning (61 m) of the distal radius and distal tibia. Incident fracture information was collected every 4 months from the study visit. The FRAC 5-year and 10-year risk of major osteoporotic fracture (MOF) and any osteoporotic fracture (AOF) was calculated for all participants. The model calibration was assessed by fitting Fine Gray competing risk regression models. The model discrimination was assessed using receiver operator characteristic curves (ROCs) and area under the curve (AUCs).

Results: Over the 10-year follow-up period, 129 men experienced an incident major osteoporotic fracture. The FRAC models showed good generalizability of the 5-year risk estimates (regression slope 0.8-1.1) to MrOS cohort. The FRAC models displayed an improved model performance (AUC = 0.685-0.703) relative to reference models of FRAX (AUC = 0.641) and FN aBMD alone (AUC = 0.636) for the 5-year MOF risk estimates. A sub-analysis on individuals classified as moderate risk by FRAX (10-20% MOF risk) found that FRAC aided in stratifying risk, particularly for the 5-year risk estimates (FRAC AUC = 0.691-0.706).

Conclusion: The FRAC models demonstrated strong performance and generalizability to an external cohort of older men. This validation of FRAC suggests its potential use as an alternate assessment tool for osteoporotic fracture risk and may have value in targeting moderate-risk subgroups to aid treatment decisions.

Keywords: FRAC; FRAX; Fracture risk assessment; high resolution peripheral quantitative computed tomography; osteoporosis.

Plain language summary

The Microarchitecture Fracture Risk Assessment Calculator ($\mu $FRAC) was developed to predict osteoporotic fracture risk using direct measures of bone microarchitecture. This study externally validated $\mu $FRAC in a cohort of older men. The tool demonstrated good short-term calibration and its performance was improved compared to currently established fracture prediction tools. This highlights the potential use of $\mu $FRAC as an alternate assessment tool for osteoporotic fracture risk particularly in cases where conventional risk assessment tools that are based on clinical risk factors are not able to concretely discern fracture risk.