We first deciphered the significance of sympathetic control of bone through the downstream β-AR signaling.31 As the β3AR was excluded from regulation of the skeleton,13 to reliably and optimally mimick the physiological sympathetic tone, we accordingly applied ISO for bone regulation.4,10 Expectedly, micro-CT examination and corresponding tranbecular quantification demonstrated that daily intermittent injection of ISO for 1 month in mice induced remarkable osteopenia (Fig. 1a, b). The gene discussed is ADRB3; the disease is Osteopenia.