Provided are methods for treating a pathological condition associated with unbalanced osteoclast differentiation by providing an AQP-9 modulator. The modulator can be an AQP-9 inhibitor or an AQP-9 inducer. Also provided are methods for modulating osteoclast differentiation, methods for treating pathological conditions associated with unbalanced osteoclast differentiation, as well as pharmaceutical composition including such modulators.