Differential inflammatory environment in patients with osteoporosis and type 2 diabetes mellitus

Abstract

Type 2 diabetes mellitus (DM2) and osteoporosis are diseases associated with a pro‐inflammatory environ‐ment, the prevention of which through new therapeutic strategies could prevent their development. However, there are few studies that evaluate the inflammatory profile of osteoporosis in patients with DM2. This study focuses on evaluating the inflammatory immune response through serum concentrations of nine cytokines, two of them anti‐inflammatory (IL‐10, IL‐5) and six pro‐inflammatory (IL‐2, IL‐6, IL‐12 (p70), IL‐17A, TNFα and IFNɣ) in 163 individuals with DM2 and 47 controls. A subpopulation, made up of 43 DM2 patients without osteoporosis, and 33 with osteoporosis, was analyzed in greater depth at the level of bone parameters. Furthermore, we have assessed the calciotropic hormones, bone remodeling markers, bone mineral density and vertebral fractures in the population, and we have analyzed the relationship of the cytokines tested with DM2, osteoporosis and prevalent vertebral fractures. Patients with DM2 had significantly higher serum concentrations of IL‐10 compared to the control group (0.5±1 vs. 0.14±0.3 pg/ml; p=0.016) and the levels of IL12 p70 were shown lower in patients with DM2 compared to controls (2.9±1.6 vs. 3.9±3.1 pg/ml; p=0.027). In the group of patients with DM2 and osteoporosis, the levels of the cytokine IL‐6 were elevated compared to the group with DM2 without osteoporosis (10.9±14.6 vs. 4.5±7.0; p=0.017). An association of IL‐5 was also observed, with its lowest levels in the DM2 group with osteoporosis (1.7±0.2 vs. 3.8±0.6; p=0.032). Furthermore, IL‐5 showed a direct correlation with the levels of the bone formation biomarker alkaline bone phosphatase (r=0.277, =0.004) in the subpopulation of patients with DM2. The rest of cytokines did not show significant differences. In conclusion, our findings indicate that in our study population, patients with DM2 compared to healthy subjects present an inflammatory profile opposite to what is expected in a hyperglycemic situation, probably as a compensatory response to the inflammation caused. The cytokine profile is modified in the subpopulation of diabetic patients, depending on the presence of osteoporosis. In this case, the inflammatory profile in the presence of osteoporosis is consistent with the expected response.