Osteoporosis is caused by a combination of factors leading to increased risk of fracture. Postmenopausal estrogen deficiency, the major cause in aging women globally contributes to the biggest burden of the disease and presently worsened by the lack of osteogenic therapy. In search of Nigerian plants with osteogenic potentials, we evaluated crude extracts or compounds of the eastern Nigerian mistletoe, a known antidiabetic plant traditionally claimed as a putative panacea for post-menopausal syndromes. Crude methanolic extracts of mistletoe harvested from three host tress; Kola acuminata, Citrus spp and Garcinia kola and five abundant isolated compounds including 3, 4, 5-trimethoxybenzoate (KH), lupeol (LP), 7α, 15β-dihydroxy lupeol palmitate (DLP), friedelin (FRD) and 3-methoxy quercetin (QD) were evaluated for their osteogenic potentials using osteogenic models. Results showed that the crude extracts (0.2 – 1.6 µg/ml concentrations) exhibited significant increase in the alkaline phosphatase activity of osteoblasts compared to control cells, exhibiting EC50 values of 52.60-, 2.72- and 637.00 µg/ml respectively for Kola acuminata, Citrus spp and Garcinia kola. None of the extracts had cytotoxicity to osteoblasts at the concentrations tested. The compounds (100pM-100nM concentrations) except FRD produced 3 – 5 folds increase in alkaline phosphatase activity and significantly enhanced mineralization (> 2-fold) of cultured osteoblasts compared to control osteoblasts with very low EC50 values (QD-0.001µM, KH-0.0028µM, DLP-0.97µM, LP-2.98µM, FRD-8.11µM). All compounds strongly induced the expression of key osteogenic genes including BMP-2 and RUNX2. In conclusion, the crude extract and compounds from the mistletoes species possess potent in vitro osteogenic activities and may be developed as safer alternative(s) in the management of diseases where bone loss is the pathology. Reference: [1] Omeje, E.O., et al. (2011a), Phtyo. lett, – DOI: 10.1016/j.phytol.2011.07.011.