Risk Factors for Bone Fractures in Patients With Comorbid Pathology

Abstract

Patients with heart failure (HF) have elevated levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), leading to macrophage activation, impaired microvascular function, changes in muscle contraction and fibrosis development. In addition, these proinflammatory cytokines promote bone resorption, thereby increasing the incidence of bone fractures. The aim of the study is to evaluate the effect of tumor necrosis factor-alpha receptor types 1 and 2 (TNF-α-SR1 and TNF-α-SR2) on fracture probability in individuals with osteoporosis who have concurrent chronic heart failure (HF) and type 2 diabetes mellitus (T2DM). The study was conducted on 178 women aged 50 to 65 years. Among these women, 48 were in group 1 and had both heart failure and type 2 diabetes. Group 2 included 93 patients with osteoporosis and heart failure and group 3 included 37 women with osteoporosis, heart failure and type 2 diabetes. Thirty-five postmenopausal women without any clinical and instrumental signs of cardiovascular pathology or osteoporosis were selected as the control group. The levels of TNF-α-SR1 and TNF-α-SR2 receptors in patient groups 1-3 were significantly higher (p<0.01) than in the control group, as were their concentrations. In addition, it was found that the levels of both receptors were significantly higher in group 3 than in patients in groups 1 and 2. To evaluate the levels of TNF-α-SR1 and TNF-α-SR2, the data were divided into four quartiles (Q1-Q4) based on the increase in the concentrations of these markers. For TNF-α-SR2, an increasing risk gradient was observed, with the odds ratio (OR) for osteoporosis events increasing from 1.4 to 12.83, but the risk was statistically significant only for Q3-Q4. For Q4 TNF-α-SR1 levels, a significant increase in the risk of an adverse osteoporosis outcome at 36 months was also found (OR=5.25, p=0.038). In addition, the use of loop diuretics was found to be a predictor of high risk of osteoporotic fractures in patients with chronic HF (JR=6.29, 95% CI=1.45-17.26, p=0.015). Postmenopausal women with chronic HF and elevated levels of soluble TNF-α-SR1 and TNF-α-SR2 receptors are at higher risk for osteoporosis and adverse disease progression. In addition, the use of loop diuretics in these individuals is associated with an increased risk of osteoporotic fractures.