Introduction: Primary osteoporotic pain (POPP) seriously affects the life of patients. Although chronic pain is associated with altered central nervous activity, the central pathological mechanism of POPP is still unclear. This study aimed to explore the differences of brain activity between POPP patients and healthy controls (HCs), as well as the correlations between altered brain regions and pain. Method: Magnetic resonance imaging data (MRI) and visual analogue scale (VAS) scores of subjects were collected. MRI data were preprocessed and then regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) values of brain regions were calculated. ReHo and ALFF values were compared between groups. Result: (1) Compared with HCs, reduced ReHo values were found in the left medial superior frontal gyrus, middle frontal gyrus, opercular part of inferior frontal gyrus and right dorsolateral superior frontal gyrus of POPP patients. (2) Reduced ALFF values were identified in the left dorsolateral superior frontal gyrus, medial superior frontal gyrus, orbital part of middle frontal gyrus, opercular part of inferior frontal gyrus and right dorsolateral superior frontal gyrus. (3) Negative correlations were identified between ReHo values of the left middle frontal gyrus and VAS scores in the patient group. Conclusion：The prefrontal dysfunction may be related to the occurrence of POPP. In addition, the left middle frontal gyrus can be used as an indicator to evaluate the severity of pain in patients with POPP. These findings help us to further understand the pathogenesis of POPP from the perspective of neuroimaging.