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Osteoporosis is a well-known complication of Crohn's disease (CD). Osteoprotegerin (OPG) concentration is elevated in patients with CD compared to healthy controls. Long-term infliximab (IFX) maintenance therapy improves the patients' bone mineral density. The effect of IFX on bone metabolism has not yet been clarified. Our aim was to evaluate IFX effects on bone pathology in CD patients.Twenty-nine patients were treated with IFX as an induction therapy according to international guidelines at weeks 0, 2, and 6. Serum concentrations of biochemical markers of bone formation (osteocalcin, OC) and bone resorption (beta-crosslaps, bCL), and serum concentrations of OPG and receptor activator of nuclear factor kappa B ligand (sRANKL) were measured before every treatment at days 1, 14, and 42.Serum levels of OC and sRANKL increased after treatment. OC concentrations were 28.93 ± 14.95 ng/mL versus 36.33 ± 20.05 ng/mL (P < 0.005) at days 1 and 42, respectively; sRANKL concentrations were elevated from 0.0112 ± 0.028 ng/mL to 0.0411 ± 0.123 ng/mL (NS) by the end of the study. The concentrations of both bCL and OPG decreased. bCL concentrations were 0.636 ± 0.594 versus 0.519 ± 0.235 (NS) at days 1 and 42, respectively, while OPG concentration decreased from 3.739 ± 1.485 to 3.491 ± 1.618 (P < 0,05).IFX therapy decreased the OPG concentration in CD patients significantly. In parallel, the serum bone resorption marker (bCL) also decreased. Concentrations of bone formation marker (OC) and sRANKL increased during the same period; however, those changes were not statistically significant. Elevated OPG in CD could be a counter-regulatory response to inflammatory cytokines or may reflect T-cell activation.