Journal of Bone and Mineral Research · Dec 31, 2025

External validation of a novel HR-pQCT based fracture risk assessment tool (μFRAC) in a male cohort: the osteoporotic fractures in men (MrOS) study

By Bugbird AR, Burghardt AJ, Langsetmo L et al.

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 ($\mu $FRAC)-in a multicentre cohort (MrOS) of older community-dwelling men. The performance of $\mu $FRAC was assessed in a population of 1586 men aged $\geq 77$ years in the United States. All participants underwent HR-pQCT scanning (61 $\mu $m) of the distal radius and distal tibia. Incident fracture information was collected every 4 months from the study visit. The $\mu $FRAC 5-year and 10-year risk of major osteoporotic fracture and any osteoporotic fracture were 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 and area under the curve (AUCs). Over the 10-year follow-up period, 129 men experienced an incident major osteoporotic fracture. The $\mu $FRAC models showed good generalizability of the 5-year risk estimates (regression slope 0.8-1.1) to MrOS cohort. The $\mu $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 major osteoporotic fracture (MOF) risk estimates. A sub-analysis on individuals classified as moderate risk by FRAX (10%-20% MOF risk) found that $\mu $FRAC aided in stratifying risk, particularly for the 5-year risk estimates ($\mu $FRAC AUC = 0.691-0.706). The $\mu $FRAC models demonstrated strong performance and generalizability to an external cohort of older men. This validation of $\mu $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.

doi.org/10.1093/jbmr/zjaf187Open accessPubMed 41474190Biomarkers