We investigated the impact of human demineralized bone matrix (hDBM) plus adipose-derived stem cells (hADS) plus photobiomodulation (PBM) on a critical-sized femoral defect (CSFD) in ovariectomy induced osteoporosis in rats. There were 6 groups as follows. In group 1 (control, C), only CSFDs were created. Groups 2-6 were implanted with DBM into the CSFD (DBM-CSFD). In group 2 (S), only DBM was transplanted into the CSFD. In group 3 (S + PBM), the DBM-CSFDs were treated with PBM. In group 4, the DBM-CSFDs were treated with alendronate (S + ALN). In group 5, ADSs were seeded into DBM-CSFD (S + ADS). In group 6, ADSs were seeded into DBM-CSFD and the CSFDs were treated with PBM (S + PBM + ADS). At week eight (catabolic phase of bone repair), the S + ALN, S + PBM + ADS, S + PBM, and S + ADS groups all had significantly increased bone strength than the S group (ANOVA, p = 0.000). The S + PBM, S + PBM + ADS, and S + ADS groups had significantly increased Hounsfield unit than the S group (ANOVA, p = 0.000). ALN, ADS, and PBM significantly increased healed bone strength in an experimental model of DBM-treated CSFD in the catabolic phase of bone healing in osteoporotic rats. However, ALN alone and PBM plus ADS were superior to the other protocols. (C) 2020 Elsevier Inc. All rights reserved.