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The objective of this study was to develop a new calibration method that enables calibration of Hounsfield units (HU) to bone mineral densities (BMD) without the use of a calibration phantom for fracture risk prediction of femurs with metastases using CT-based finite element (FE) models. Fifty-seven advanced cancer patients (67 femurs with bone metastases) were CT scanned atop a separate calibration phantom using a standardized protocol. Non-linear isotropic FE models were constructed based on the phantom calibration and on two phantomless calibration methods: the “air-fat-muscle” and “non-patient-specific” calibration. For air-fat-muscle calibration, peaks for air, fat and muscle tissue were extracted from a histogram of the HU in a standardized region of interest including the patient’s right leg and surrounding air. These CT peaks were linearly fitted to reference “BMD” values of the corresponding tissues to obtain a calibration function. For non-patient-specific calibration, an average phantom calibration function was used for all patients. FE failure loads were compared between phantom and phantomless calibrations. There were no differences in failure loads between phantom and air-fat-muscle calibration (p = 0.8), whereas there was a significant difference between phantom and non-patient-specific calibration (p<0.001). Although this study was not designed to investigate this, in four patients who were scanned using an aberrant reconstruction kernel, the effect of the different kernel seemed to be smaller for the air-fat-muscle calibration compared to the non-patient-specific calibration. With the air-fat-muscle calibration, clinical implementation of the FE model as tool for fracture risk assessment will be easier from a practical and financial viewpoint, since FE models can be made using everyday clinical CT scans without the need of concurrent scanning of calibration phantoms. [ABSTRACT FROM AUTHOR]