Heat-inactivated Lactobacillus casei strain GKC1 Mitigates osteoporosis development in vivo via enhanced osteogenesis

Osteoporosis, a significant bone disease predominantly affecting elderly and postmenopausal women, leads to increased bone fragility and fracture risk, presenting a major public health concern with substantial socioeconomic implications. This study investigated the therapeutic potential of Lactobacillus strains, known for their immunomodulatory properties, in an ovariectomy-induced osteoporosis mouse model. Among three tested strains Lactobacillus casei GKC1, Lactobacillus rhamnosus GKLC1, and Lactobacillus johnsonii GKJ2, GKC1 demonstrated superior efficacy in promoting osteogenesis-related gene expression, including alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2). In ovariectomized mice (n = 8/group), both live and heat-inactivated GKC1 (57 mg/kg) and fermented GKC1 (1000 mg/kg) were administered orally for 28 days, with alendronate (2.5 mg/kg) serving as a positive control. The treatment significantly improved bone mineral density and femoral microstructure parameters compared to the ovariectomized control group. For the first time, heat-inactivated GKC1 exhibited superior anti-inflammatory effects through reduction of IL-17A and enhanced bone microstructural integrity, suggesting its potential as a safe and effective therapeutic agent for postmenopausal osteoporosis management. These findings provide compelling evidence for the development of postbiotic-based interventions in osteoporosis treatment, offering a promising alternative to conventional therapeutics.