Objective To evaluate the value of serum levels of transforming growth factor β (TGF-β), interleukin-6 (IL-6) and ferrimodulin in bone health status in patients with osteoporosis. Methods 102 patients with osteoporosis diagnosed in our hospital from April 2022 to March 2024 were included in the experimental group. In addition, 100 patients who underwent physical examination in our hospital during the same period were included in the control group. Serum levels of TGF-β, IL-6, ferrimodulin, OC, P1NP and β-CTX were detected and compared between the control group and the experimental group. The linear correlation between TGF-β, IL-6, sideromodulin and bone metabolism indexes in patients with osteoporosis was analyzed by Pearson correlation. The efficacy of serum TGF-β, IL-6 and sideromodulin in single and combined assessment of bone health status was analyzed. Results Compared with the control group, the levels of TGF-β, ferrimodulin, OC and P1NP in the experimental group were significantly decreased, while the levels of IL-6 and β-CTX in the serum were significantly increased (P < 0.05). According to Pearson correlation analysis, serum TGF-β in osteoporosis patients was positively correlated with OC and P1NP (r =0.407, 0.450, P < 0.05), and negatively correlated with β-CTX (r =-0.422, P < 0.05). Serum ferritin was positively correlated with OC and P1NP (r =0.399, 0.410, P < 0.05), and negatively correlated with β-CTX (r =-0.384, P < 0.05). Serum IL-6 was negatively correlated with OC and P1NP (r =-0.500, -0.493, P < 0.05), and positively correlated with β-CTX (r =0.459, P < 0.05). The sensitivity, specificity and accuracy of TGF-β, IL-6 and ferriregulation combined assessment of bone health status were 85.00%, 88.00% and 86.50%, respectively, which were significantly higher than the single evaluation efficacy of the three indexes (P < 0.05). Conclusion Serum TGF-β, IL-6 and sideromodulin levels play an important role in the regulation of bone metabolism in osteoporosis, and their combined assessment of bone health is more effective.