The decreased cancellous bone volume/total volume (BV/TV) observed in Notch2tm1.1Ecan was significantly increased in the context of the Hes1 inactivation associated with increased connectivity and trabecular number so that the osteopenia of Notch2tm1.1Ecan mice was ameliorated in CtskCre/WT;Notch2tm1.1Ecan;Hes1Δ/Δ mice (Fig. 2). The gene discussed is HES1; the disease is Osteopenia.