Objective To explore the effect of methylprednone on the occurrence of osteoporosis in immunoglobulin A(IgA)nephropathy model rats and the possible mechanism.Methods 36 SD rats were randomly divided into control group,model group(IgA nephropathy model was established and normal saline was injected into tail vein),administration group(IgA nephropa-thy model was established and 30 mg/kg methylprednone was injected into tail vein),with 12 rats in each group.The urine of each group was collected for 24 h,and the urine protein was detected by automatic urine analyzer.Abdominal arterial blood was collected and serum was separated.The serum creatinine(CRE)and urea nitrogen(BUN)levels were detected by automatic biochemical analyzer,and the serum tartrate-resistant acid phosphatase-5b(TRACP-5b)content was detected by ELISA.The histopathological changes of kidney and femur were observed by HE staining.The expression of TRACP in femoral tissue was detected by immuno-histochemical staining.The expression of Toll-like receptor 4(TLR4)/nuclear factor κB(NF-κB)pathway-related proteins in fe-mur tissues of rats in each group was detected by Western Blot.Results Compared with the control group,urine protein of model group was significantly increased(P<0.05),the levels of CRE and BUN in serum were significantly increased(P<0.05),glo-meruli and renal tubules were significantly injured in renal tissue,while serum TRACP-5b content was not significantly changed(P>0.05),and the trabecular structure of femur tissue was intact,TRACP expression level and relative expression levels of TLR4,NF-κB and p-NF-κB protein were not significantly changed(P>0.05).Compared with the model group,urine protein and CRE and BUN in serum in the administration group were significantly decreased(P<0.05),the lesions of glomeruli and renal tu-bules were significantly reduced,the number of interstitial inflammation cells was decreased,but the content of TRACP-5b in the serum was significantly increased(P<0.05),the bone trabecular structure in the femur tissue was sparse and thin and osteoblasts were decreased,TRACP expression level was significantly increased(P<0.05),and the relative expression level of TLR4 and p-NF-κB protein was significantly up-regulated(P<0.05).Conclusion Methylprednone can improve kidney injury in IgA ne-phropathy model rats,but promote the expression of TRACP leading to osteoporosis,which may be related to the activation of TLR4/NF-κB.