A total of 19 out of 31 compounds were accepted by Lipinski’s rule (Lipinski’s violations ≤ 1), TPSA (<140 Å2), and binding energy (<−6.0 kcal/mol), among which MD2-TLR4-IN-1 (PubChem ID: 138454798) (Figure 4), with the highest binding energy (−9.9 kcal/mol), was selected as the most important ligand to dampen comorbidity of RA and OP. This evidence concerns the gene TLR4 and rheumatoid arthritis.