Background <p>Accurate assessment of bone mineral density (BMD) is crucial for evaluating bone loss in elderly and oncologic patients. Quantitative computed tomography (QCT) enables noninvasive quantification of patient BMD and can be performed opportunistically during routine CT examinations using either conventional or multi-energy CT (MECT). While both methods are used clinically, MECT can address limitations of conventional CT-based QCT.</p> Purpose <p>This study addresses a critical gap in the literature by systematically evaluating commercially available calibration phantoms for use with MECT, assessing the impact of protocol variations, establishing a calcium-based material decomposition workflow for BMD quantification, validating phantom-derived metrics against patient data, and providing recommendations for integrating quality control (QC) into routine clinical workflows.</p> Methods <p>Five CT QC phantoms containing bone-approximating materials, including calcium (Phantom A), dipotassium phosphate (Phantom B), hydroxyapatite (Phantom C), and calcium carbonate (Phantoms D and E), were evaluated by determining the dual-energy ratio (DER) of inserts. Phantoms were scanned on two identical dual-source CTs at 90/150Sn and 100/150Sn kVp with dose levels of 10 and 20 mGy. Images were reconstructed using filtered back-projection and iterative reconstruction. Phantom DERs were compared with retrospective vertebral measurements from a 10-patient cohort.</p> Results <p>Phantom A provided the most suitable representation of patient data, exhibiting a DER of 1.55 [95%CI:1.54–1.57] at 100/150Sn kVp, compared with 1.44 [95%CI:1.37–1.50] in patients. kVp significantly influenced response, whereas radiation dose and reconstruction approach had minimal effect.</p> Conclusions <p>Phantom selection is critical for MECT-based QCT, and calcium-based phantoms are well-suited for clinical QC and BMD quantification workflows.</p>