The infrared (IR) and Raman spectra of the osteoporosis drug alendronate in the monosodium trihydrate alendronate crystal were measured. In order to interpret them, density functional theory (DFT) calculations for the solvated alendronate molecule were performed following the structural features revealed by X-ray data. A comparison between the DFT-calculated IR and Raman of the converged species and the measured spectra unveils relevant phosphate group signatures in the 400–1400 cm−1 wavenumber range, especially IR absorption bands at 1015, 1049, 1067, 1131, 1177, and 1235 cm−1, which were related to CP and OP bond length stretching, and Raman lines at 449, 661, and 969 cm−1, involving phosphate scissors and bond length vibrations. A comparison with experimental data of alendronate incorporated into hydroxyapatite (HAP) indicates that, for wavenumbers below 1500 cm−1, the interaction of alendronate with HAP does not affect significantly the alendronate vibrational spectra, while for the 1600–3000 cm−1 interval the interaction with HAP changes the normal mode wavenumbers by about −100 cm−1. Copyright © 2014 John Wiley & Sons, Ltd.