ESPE Abstracts

Background: Inflammatory diseases, such as inflammatory bowel disease or juvenile idiopathic arthritis may lead to growth retardation. One of the key players in inflammatory conditions is TNFa which also triggers other inflammatory cytokines exerting its growth suppressive effects locally at the growth plate level and systemically at the pituitary level leading to a suppression of the GH/IGF-1-axis. Mechanical loading has been regarded as one of the primary functional determinants of bone mass, architecture and elongation with the potential to treat bone growth disorders. However, to this date, no data is available on the direct effects of mechanical loading on bone growth in a model of inflammation-induced bone growth retardation.

Aim: The aim of this study was to investigate the potential for mechanical loading to rescue bone growth in a model of chronic inflammation where fetal rat femur bones are cultured ex vivo in the presence of pro-inflammatory cytokines.

Methods: Mechanical loading was applied every 2-3 days to fetal rat femur bones (E19.5) co-cultured for 12 days with TNFa and IL1-b. Bone growth over the 12-day-culture period of was calculated by analyzing bone length measurements performed on digital pictures captured at several time-points including at baseline and endpoint.

Results: When co-culturing femur bones with equal concentrations of TNFa and IL1-b, a dose dependent growth suppressive effect was observed. In bones exposed to mechanical loading, femur bone growth was significantly stimulated, both in the group exposed to TNFa and IL1-b at 1 ng/ml each (199 ± 31 mm vs 151 ±45 mm growth in loaded and unloaded bones, respectively; P <0.05) and in those exposed to both cytokines at 3 ng/ml (111 ± 52 mm vs 32 ± 31 mm growth; P <0.05).

Conclusion: Mechanical loading was found to stimulate femur bone growth in an ex vivo model of chronic inflammation. Further in vivo studies are needed to validate these findings.