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Postmenopausal osteoporosis is a systemic skeletal disease of fragility fractures due to the loss of the mass and the deterioration of the microarchitecture of bone. This study aimed to assess the effects of raloxifene hydrochloride nanosuspensions (RLX-NSps) on ovariectomized (OVX)-induced osteoporotic rats, and the underlying mechanisms were also investigated in vivo and ex vivo. RLX-NSps were successfully prepared, and the obtained RLX-NSps had a mean particle size of (91.17 ± 0.73) nm, PDI value of 0.201 ± 0.03 and zeta potential of (36.3 ± 1.8) mV. RLX-NSps showed a clear colloidal solution with light yellow opalescence. RLX-NSps were stable in artificial intestinal fluid, artificial gastric fluid, PBS, isotonic glucose and physiological saline. The OVX mice were administered an RLX-NSps or RLX solution for 3 weeks. The bone micro-tomographic histomorphometry and bone mineral density (BMD) were assessed by micro-CT, and the biochemical markers procollagen type I N-terminal propeptide (P1NP) and beta-isomerized C-telopeptide (β-CTX) were determined from serum. Finally, primary bone marrow stromal cells (BMSCs) were isolated from the tibia and cultured to evaluate cell proliferation and osteogenic differentiation. The results demonstrated that the RLX-NSp group had a better effect on the bone microarchitecture than the RLX solution group. Therefore, RLX-NSps could partially attenuate bone loss more effectively than RLX solution in OVX mice by inhibiting bone resorption and improving the ability of BMSCs to proliferate and their osteogenic differentiation to some extent. Based on these results, nanosuspensions (NSps) may be a promising delivery system for postmenopausal osteoporosis therapy.
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