Abstract The primary aim of this work is to investigate the potential of nonlinear ultrasound for microdamage detection in human bone. Microdamage evaluation in human bone is of great importance, because it is considered a significant parameter for characterizing fracture risk. Experiments employing nonlinear acoustic vibro-modulation were carried out in human femoral trabecular specimens removed during surgery. A frequency mixing (inter-modulation) was observed between an ultrasound wave, propagating in the bone, and a low-frequency vibration applied directly to the bone specimens. The appearance of side frequencies, which are related to the vibrational excitation, around the fundamental ultrasound frequency manifests the modulation nonlinear phenomenon. Instead of inducing microdamage by mechanical fatigue loading, specimens with different degree of osteoporosis were used. The experiments demonstrated that osteoporotic bone exhibits stronger nonlinearity compared to healthy bone presenting significant increase of the modulation amplitude with increasing degree of osteoporosis. The obtained results indicate that, in contrast to conventional hysteretic nonlinearity, dissipative acoustic nonlinearity can be of significance in the generation of nonlinear modulation effects. In the proposed technique the size and the shape of samples are not crucial compared to nonlinear resonant ultrasound spectroscopy (NRUS). Furthermore, the method is sensitive to the presence of microdamage, non-invasive, easy to implement and most important, it can be proved valuable tool for in vivo bone damage characterization.