Linking chronic tryptophan deficiency with impaired bone metabolism and reduced bone accrual in growing rats

There is increasing evidence that serotonin may regulate bone metabolism. However, its role remains to be clarified. Serotonin seems to be either beneficial or detrimental for bone tissues depending on the pharmacological manipulation used. In this study we evaluated the impact of a reduction of serotonergic stores induced by chronic tryptophan (TRP) depletion on various bone parameters in growing rats. For this purpose rats received a TRP-free diet for 60 days. Bone mass, mineral content and density were measured by DXA and by pQCT in the appendicular skeleton. Bone metabolic markers included urinary deoxypyridinoline and serum osteocalcin measurements. IGF-I levels were also evaluated. In TRP-free diet rats, we found a decrease in body weight, a delayed femoral bone growth and bone mineral content as measured by DXA. pQCT analysis showed that these effects were related to a reduction of both cortical and trabecular bone and are associated with a reduction of bone strength. These effects are due to a negative shift in the balance between bone formation and resorption with a significant decrease in bone formation as evidenced by a reduction both in osteocalcin and IGF-I levels. The present data extend our overall knowledge on the participation of serotonin in the regulation of growing bone and could be of interest in studying the impairment of bone growth in depressed subjects under particular condition of rapid bone accrual such as childhood and adolescence.