The effects of the inflammatory response on bone growth.

The inflammatory response is a process which forms a defence against the effects of trauma or invasion by foreign organisms or substances. Inflammation is mediated by local and systemic changes in expression of its activators and inhibitors. Many of these regulators of inflammation are also the controllers of normal cellular activity, so the effects of inflammation are due to changes in the amounts, ratios and timings of their expression, rather than de novo expression of specific mediators of inflammation. The effects of inflammation on bone growth are two-fold. Firstly, systemic inflammatory effects have consequences on hormone, mineral and nutrient metabolism which affect bone growth. Secondly, cytokine mediators of inflammation cause local changes in cell regulation to influence both endochondral processes in the growth plate, and modelling and remodelling activity associated with appositional growth. The complexity of the osteotropic influences responsible for maintaining normal bone development mean that inflammatory process will have different and unpredictable effects on linear growth at different times, and under different nutritional, biochemical, physical and psychological circumstances. This review will examine the effects of systemic and local changes in inflammation which have effects on bone growth and remodelling, focusing on systemic effects of the acute phase response, and the local actions of the eicosanoids and three cytokines with particularly potent actions on the metabolism of cells in bone and cartilage.