Are activated T cells regulators of bone metabolism in children with Crohn disease?

Objectives

To test the hypothesis that circulating activated T cells may release cytokines that decrease bone turnover in children with Crohn disease.

Study design

Newly diagnosed Crohn disease and healthy controls of similar age were compared for bone age, bone mineral content and density, markers of bone remodeling, and serum concentration and in vitro T-cell production of receptor activator of nuclear factor κB ligand (RANKL), interferon (INF)-γ, and osteoprotegerin (OPG).

Results

Newly diagnosed children with Crohn disease (n = 23) had similar bone mineral density (BMD) z-scores and body mass index as the controls (n = 40). Biochemical markers of bone remodeling indicated a state of low bone turnover in the Crohn disease patients compared with controls. Serum OPG (pmol/L; mean ± SD, median) was higher (4.24 ± 1.74, 3.98 vs 3.38 ± 0.83, 3.41; P < .05), and serum RANKL (pmol/L) was lower in the Crohn disease patients (0.50 ± 0.86, 0.28 vs 1.02 ± 1.63, 0.49; P < .01), consistent with decreased bone resorption. Activated T cells from Crohn disease patients produced a higher concentration of INF-γ (ng/μg protein) than those from controls (20.03 ± 26.39, 8.70 vs 9.76 ± 14.10, 6.17; P < .05).

Conclusions

The newly diagnosed children with Crohn disease exhibited reduced bone remodeling, possibly due to T-cell INF-γ and OPG.

Abbreviations: BAP, Bone alkaline phosphatase, BMC, Bone mineral content, BMD, Bone mineral density, CCMC, Connecticut Children’s Medical Center, CICP, Collagen type 1 C-terminal propeptide, DPD, deoxypirridoline, ELISA, Enzyme-linked immunosorption assay, IFN, Interferon, IGF, Insulin-like growth factor, OPG, Osteoprotegerin, PCDAI, Pediatric Crohn disease activity index, RANKL, Receptor activator of nuclear factor κB ligand, sRANKL, Soluble receptor activator of nuclear factor κB ligand