Abstract: Objective To analyze the regulatory effect of denosumab on the bone metabolic microenvironment in patients with rheumatoid arthritis (RA) complicated by osteoporosis (OP). Methods Eighty-two patients with RA and OP admitted to Liaocheng Second Hospital Affiliated to Shandong First Medical University between February 2023 and October 2024 were divided into an intervention group and control group by random number table method, with 41 cases in each group. The control group received risedronate sodium based on conventional treatment, while the intervention group received denosumab based on conventional treatment. The clinical efficacy, joint mobility, health status, and bone metabolism indicators were compared between the two groups. Results Compared with the control group, the intervention group showed a higher total effective rate (P＜0.05). After 1 and 6 months of treatment, the intervention group demonstrated significantly better outcomes compared to the control group, evidenced by significantly lower Disease Activity Score in 28 Joints (DAS28) score, Health Assessment Questionnaire (HAQ) score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibody (anti-CCP antibody), and rheumatoid factor (RF) levels, as well as significantly higher levels of 25-hydroxyvitamin D (25-OH-VD) and osteocalcin (OCN), and significantly greater bone mineral density at the femoral neck and lumbar spine (P＜0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P＞0.05). Conclusion Denosumab has a significant therapeutic effect in patients with RA and OP, effectively improving bone metabolism, joint mobility, and bone mineral density, while reducing the inflammatory response.