Proinflammatory cytokines and the risk of osteoporotic fractures in postmenopausal breast cancer patients

Despite the increased risk of bone fractures in patients with malignant neoplasms (MN), especially breast cancer (BC), bone health assessment and preventive treatment of osteoporosis (OP) still remain understudied. The aim of our work was to investigate the significance of systemic inflammatory markers in relation to 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. Patients and methods: The study included 85 postmenopausal women with different malignancies, including 40 BC patients. All patients with BC underwent dual-energy X-ray absorptiometry, the 10-year probability of fracture was assessed by FRAX. IL-1β, IL-6, and TNFα were measured by quantitative enzyme-linked immunosorbent assay. The mean time since diagnosis of MN until referral for osteoporosis (OP) was 3 (2.0-4.0) years. 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 documented in 16 patients, OP, in 19 cases. Adjuvant chemotherapy was performed in 42.5% of cases among breast cancer patients, and adjuvant hormonal therapy was performed in 87.5% of cases (different postmenopausal hormone therapies were used). When comparing the cytokine levels in BC subgroups with presence (47.5%) or absence of OP, we have found that IL-1β was higher in patients with OP as compared to both normal persons and osteopenic patients (p = 0.027 and p = 0.029, respectively); IL-6 was higher only in patients with OP compared to normal subjects (p = 0.011); TNFα in OP and osteopenia exceeded those values in OP-free cases (p = 0.001 and p = 0.039, respectively). TNFα levels correlated with the risk score for large osteoporotic fractures (FRAX:MOF) (rS = 0.33, p = 0.036) and IL-6 (rS = 0.55). A higher 10-year risk of vertebral fractures (p = 0.003) was observed in the group of BC patients with ‘high’ ( median) TNFα levels. In summary, proinflammatory cytokines seem to be involved in bone resorption processes. Postmenopausal BC patients have an increased estimated 10-year risk of low-energy spine fractures associated with high TNFα levels.