PRO-INFLAMMATORY CYTOKINES AND THE RISK OF OSTEOPOROTIC FRACTURES IN POSTMENOPAUSAL BREAST CANCER PATIENTS

Abstract

Despite the increased risk of fracture in patients with malignant neoplasms (MN), especially breast cancer (BC), bone health assessment and preventive treatment of osteoporosis (OP) remain partial. Pro-inflammatory cytokines - interleukin(IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α) - confirm their importance in the development of bone fragility and fractures. The aim of the study: to investigate the influence of systemic inflammatory markers on the severity of osteoporotic changes and to evaluate their association with the estimated 10-year risk of low-energy fractures determined by FRAX in postmenopausal patients with breast cancer. The study included 85 postmenopausal women with MN of various localizations, including 40 patients with BC. All of patients with BC underwent dual-energy X-ray absorptiometry, assessed the 10-year probability of fracture by FRAX, and measured IL-1β, IL-6, and TNF-α by quantitative enzyme-linked immunosorbent assay. The mean time since diagnosis of MN before referral for OP was 3[2.0;4.0] years and differed significantly between groups of individuals with BC (1[1.0;2.0] year) and other MN (4[3.0;5.0] years; p<0.001), indicating physicians‘ wariness of osteoporotic complications of BC and patients’ awareness of fracture risks. In patients with MN, OP was diagnosed in 51.2% of cases, and osteopenia - in 37.2%. In the group of BC patients, osteopenia was noted in 16 patients, OP - in 19 patients. Adjuvant chemotherapy was performed in 42.5% of cases in the group of breast cancer patients, and adjuvant hormonal therapy was performed in 87.5% of cases (different regimens of postmenopausal hormone therapy were used). When comparing the cytokine indices in the groups of patients with BC in the presence (47.5%) or absence of OP, it was found: IL-1β was higher in patients with OP both compared to normal and compared to osteopenia (p=0.027 and p=0.029, respectively); IL-6 was higher only in patients with OP compared to normal (p=0.011); TNF-α in OP and osteopenia exceeded those without osteoporotic disorders (p=0.001 and p=0.039, respectively). TNF-α levels correlated with the risk score for large osteoporotic fractures (FRAX:MOF) (r_S=0.33, p=0.036) and IL-6 (r_S=0.55). A higher 10-year risk of vertebral fractures (p=0.003) was observed in the group of BC patients with ‘high’ (> median) TNF-α levels. In summary, proinflammatory cytokines are actively involved in bone resorption processes, and postmenopausal patients with RA have an increased estimated 10-year risk of low-energy spine fractures in the presence of high TNF-α levels. Patients with BC should be seen by a rheumatologist for OP and low-energy fractures, and active preventive measures should be implemented as early as possible.