Evaluation of the Role of Interleukin 6 in Paget’s Disease of Bone

Abstract

Raised levels of serum interleukin 6 (IL-6) have been found in some studies of Paget’s disease of bone (PDB), and this cytokine has been suggested to act as a mediator of increased osteoclast activity in the disease. Here weevaluated serum IL-6 in two cohorts of patients with PDB and controls and related serum IL-6 levels in PDB patients to clinical features of the disease. Serum IL-6 was measured by ELISA in 553 individuals with PDB from the PIP study (n =  165), the PRISM study (n = 388) and 533 population-based controls. In the PDB cases, we studied associations between IL-6 and disease extent, pain, previous bisphosphonate therapy, and biochemical markers of bone turnover. Serum IL-6 was correlated with age (r = 0.256, p < 0.001) and serum creatinine (rho = 0.148, p < 0.001) but values did not differ in males and females. Following adjustment for age and serum creatinine, there was no significant difference in IL-6 between PIP cases and controls (p = 0.268) or PRISM cases and controls (p = 0.399) nor was there a significant correlation between serum IL-6 and number of affected bones in PDB or bodily pain. Serum IL-6 was correlated with total alkaline phosphatase (rho = 0.174, p < 0.001), and PINP (rho = 0.095, p < 0.05) but not with the bone resorption marker CTX. In summary, we found no difference between circulating IL-6 values in PDB and controls but serum IL-6 was related to alkaline phosphatase and PINP. These observations do not support a role for raised circulating IL-6 values as an important driver of osteoclast activity in PDB.