Inertial measurement units (IMUs) need sensor-to-segment calibration to measure human kinematics. Multiple methods exist, but, when assessing populations with locomotor function pathologies, multiple limitations arise, including holding postures (limited by joint pain and stiffness), performing specific tasks (limited by lack of selectivity) or hypothesis on limb alignment (limited by bone deformity and joint stiffness). We propose a sensor-to-bone calibration based on bi-plane X-rays and a specifically designed fusion box to measure IMU orientation with respect to underlying bones. Eight patients undergoing total hip arthroplasty with bi-plane X-rays in their clinical pathway participated in the study. Patients underwent bi-plane X-rays with fusion box and skin markers followed by a gait analysis with IMUs and a marker-based method. The validity of the pelvis, thigh and hip kinematics measured with a conventional sensor-to-segment calibration and with the sensor-to-bone calibration were compared. Results showed (1) the feasibility of the fusion of bi-plane X-rays and IMUs in measuring the orientation of anatomical axes, and (2) higher validity of the sensor-to-bone calibration for the pelvic tilt and similar validity for other degrees of freedom. The main strength of this novel calibration is to remove conventional hypotheses on joint and segment orientations that are frequently violated in pathological populations.