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Background  To provide a low-toxicity and high-efficacy clinical treatment for osteoporosis via a novel combination of LiCl and LY294002.    Methods  The protein levels of p-AKT, AKT, p-GSK3β, GSK3β, β-catenin, p-β-catenin, and NFATC1 were measured in osteoblasts and osteoclasts by Western blot. ALP activity and TRACP activity were measured using the corresponding kit. The levels of BALP, PINP, CTX, and TRACP-5b were determined in accordance with the requirements of the ELISA kits. Microstructural analysis was performed on the left distal femur using microcomputed tomography.    Results  Treatment with the combination of LiCl and LY294002 led to a markedly increased osteoblast activity but significantly decreased osteoclast differentiation and bone absorption capacity compared with the treatment with LiCl or LY294002 alone ( P  < 0.01). In serum, the low-dose combination of LiCl and LY294002 significantly enhanced BALP levels ( P  < 0.01) and significantly decreased PINP, TRACP-5b, and CTX levels ( P  < 0.01) compared with the application of either drug alone.    Conclusions  This study indicates that drug combinations directed at multiple targets could be used for osteoporosis treatment by promoting osteoblast proliferation and inhibiting differentiation with high efficiency.

Combined low-dose LiCl and LY294002 for the treatment of osteoporosis in ovariectomized rats