Three-dimensional analysis of the musculoskeletal system typically involves measurements of ground reaction forces and moments (GRF&Ms) with floor-mounted force plates and segment kinematics measured with optical cameras that are expensive and inconvenient to use in the field. Recent advances in inertial motion capture (IMC) provides new opportunities of full-body motion capture in any working environment. Also, newly developed methods allow the prediction of GRF&Ms with only full-body segment kinematic as input to a musculoskeletal model. In the present study, a novel analysis approach was investigated to estimate the internal loading on the lumbar spine exclusively with input from IMC. Validation of the IMC model was done comparing GRF&Ms and L4-L5 joint reaction forces (JRFs) for 13 subjects during common manual materials handling (MMH) tasks with a standard laboratory model. Pearson’s correlation coefficients, relative and root-mean-square error, magnitude and phase error were calculated to compare GRF&Ms and L4-L5 JRFs. The results generally showed best agreement for vertical GRFs, sagittal GRMs, frontal GRMs, L4-L5 axial compression forces, and anteroposterior shear forces. The present study proposed a novel method to investigate spine loading in the field using only IMC and musculoskeletal modelling.