AIM: To analyse the effect of systemic application of N-methyl pyrrolidone (NMP) on the pulp-dentine complex and on the jawbone of ovariectomized rats. METHOD: Female Sprague Dawley rats were randomly divided into a Sham-operated group (Sham n = 6) and an oestrogen depletion by ovariectomy (OVX n = 12) group. In 6 of the ovariectomized animals, N-methyl pyrrolidone (NMP) in phosphate-buffered saline (PBS) was administered systemically weekly by intraperitoneal injection (i.p.); the other 6 were injected with PBS (Veh). After 15 weeks of injections, the jaw bones were collected and pulps extracted from the incisors teeth. Histology was used to determine pre-dentine thickness in teeth and radiography to determine alveolar bone mass. Immunohistological staining and RT-PCR were performed to verify the presence and localization of the odontoblast-specific dentine sialoprotein and to quantify its expression in the dentine-pulp complex. Mandibular cortical width and mandibular height were evaluated by means of X-ray analysis. Statistical analysis was performed with analysis of variance (anova). RESULTS: Both pre-dentine (P = 0.029) and alveolar bone structures (P = 0.049) were significantly reduced due to oestrogen deficiency in OVX Veh and OVX. NMP treatment normalized these parameters to the Sham level. DSPP expression in OVX NMP animals was significantly higher (P = 0.046) than in OVX Veh. X-ray analysis confirmed that ovariectomy significantly reduced the mandibular cortical width in the OVX Veh group compared to the Sham Veh and OVX NMP (P = 0.020). CONCLUSION: N-methyl pyrrolidone (NMP) had a remarkable anti-osteoporotic ability preserving activity in the pulp-dentine complex and preventing jawbone loss. These effects make NMP a promising candidate for the preservation of the activity of the pulp-dentine complex and jawbone thickness in post-menopausal females.