Increased levels of biochemical markers of bone turnover in relation to persistent immune activation in common variable immunodeficiency

Background Based on the involvement of cytokines and growth factors in bone homeostasis, we hypothesised that patients with common variable immunodefi ciency (CVI), characterised by persistent immune activation in vivo, may ha ve disturbed bone metabolism as evaluated by biochemical markers of bone tu rnover. Materials and methods Serum levels of tumour necrosis factor a (TNFa), inte rleukin-6 (IL-6), bone-specific alkaline phosphatase (B-ALP), osteocalcin, carboxyterminal crosslinking telopeptide of type I collagen (CTX-I), insuli n-like growth factor (IGF)-I and IGF binding protein-3 (IGFBP-3) were measu red in 25 patients with CVI and compared to 25 age- and sex-matched healthy controls. Results Patients with CVI had significantly higher serum levels of CTX-I an d B-ALP, and significantly lower serum levels of IGF-I and IGFBP-3 compared to controls as shown in cross-sectional, and as for B-ALP and CTX-I, also during longitudinal testing. No differences were observed for osteocalcin b etween the two groups. The elevated B-ALP and decreased IGF-I and IGFBP-3 l evels were most pronounced in a subgroup of CVI patients characterised by p ersistent activation of proinflammatory cytokines in vivo. Raised B-ALP and decreased IGF-I and IGFBP-3 were also significantly correlated with enhanc ed IL-6 and TNF-a levels in these patients. Conclusions The present study suggests that persistent immune activation in vivo, with raised levels of proinflammatory cytokines, may be related to d isturbed bone homeostasis in CVI patients, further supporting an interactio n between immune related mediators and bone metabolism in humans.