Relationship between Bone Metabolism and Plasma Cytokine Levels in Patients at Risk of Post-Transplantation Bone Disease after Bone Marrow Transplantation

Abstract

Bone marrow transplant recipients may carry an increased risk of bone diseases, involving numerous factors that affect bone mineral metabolism. Interleukin-6 is a potent stimulator of bone resorption in vivo. The soluble fraction of interleukin-6 receptor is reported to trigger osteoclast formation by interleukin-6 in vitro. In a cross-sectional study we measured serum bone alkaline phosphatase concentrations and the urinary excretion of pyridinium cross-links in 21 patients after bone marrow transplantation, and investigated the relationship between these values and those for the plasma levels of interleukin-6 and soluble interleukin-6 receptor. Following bone marrow transplantation female--but not male--patients showed higher serum bone alkaline phosphatase values than age- and sex-adjusted controls (p < 0.05). Both female and male patients were characterized by increased urinary excretion values of pyridinium cross-links (p < 0.05). In contrast to a marked increase of interleukin-6 plasma levels (p < 0.001) no significant difference in the soluble interleukin-6 receptor levels was found between patients and apparently healthy persons (p = 0.838). Multiple regression analysis (taking into account different variables of the immunosuppressive regimen applied) revealed the plasma concentration of interleukin-6 as an independent predictor of the urinary excretion of pyridinium cross-links (p < 0.05). In conclusion, in patients following bone marrow transplantation, these findings indicate (a) an increase of bone formation in female--but not in male--patients possibly reflecting primary ovarian failure and (b) an enhancement of bone resorption possibly mediated by circulating interleukin-6.