Osteoporosis (OP) is a complex systemic disease characterized by a loss of bone density, leading to bone fragility and an increase risk of fractures of the hip, spine and wrist. The clinical therapeutic effect is still far from satisfactory. Thus, further studies are urgently needed to explore the pathogenesis of OP. In this study, our aim is to explore the underlying molecular mechanism of lncRNA H19/miR-29a-3p axis for regulating of inflammation, proliferation and apoptosis in OP. The expression of lncRNA H19 was significantly upregulated in OP samples compared with the health control. Subsequently, we found that miR-29a-3p is the target of lncRNA H19 in OP. Furthermore, the knockdown of lncRNA H19 was validated to promote the expression of pro-inflammatory mediators, repress cell proliferation and inhibit cell apoptosis in vitro. Moreover, the modulating effects of lncRNA-H19 on the expressions of pro-inflammatory mediators, cell proliferation and apoptosis in vitro were diminished after co-transfecting with miR-29a-3p inhibitor and siRNA-H19. Thus, we concluded that lncRNA H19/miR-29a-3p axis was involved in the development of OP. This study might provide a better understanding of OP development and a potential therapeutic target for OP intervention.