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

Abstract

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.

Is Serum Serotonin Involved in the Bone Loss of Young Females with Anorexia Nervosa?

“…Only negative correlations between the serotonin level and aBMD at lumbar spine were observed in the controls, confirming previous results in normal-weight young women [17]. Nevertheless, the negative relationship between serotonin and CTx levels suggests that circulating serotonin may be involved in the regulation of bone turnover, as previously reported in TRP diet-depleted rats [13].…”

“…The dramatic drop in nutritional intake and therefore TRP intake may have a role in the lower serum serotonin levels (-28 %) observed in AN patients, a hypothesis supported by the positive correlation we observed between serum serotonin levels and nutritional markers such as weight, BMI, WB-FM, leptin, and IGF-1 when the patients and controls were pooled. Experimental studies have shown that reduced serotonergic stores due to chronic TRP depletion impairs bone metabolism or accrual in growing rats [11,13], while long-term TRP-supple-mented diet or serotonin administration improves bone microarchitecture in the rats [11,14]. The reduced serum serotonin we observed in AN patients may thus be involved in the low bone mass.…”

“…The reduced serum serotonin we observed in AN patients may thus be involved in the low bone mass. However, the discrepant results in both animals [13][14][15] and humans [16,17] point out the difficulty of interpreting the role of circulating serotonin in bone metabolism. Nevertheless, in line with our assumption, Wang et al [17] found that serum serotonin levels in normal-weight women were positively associated with aBMD at various bones sites, suggesting that high levels of serotonin may be beneficial for bone and lower levels detrimental [17].…”

Bone Formation in a Scaffold Composed of Cylindrical Hydroxyapatite and Tryptophan- or Lysine-Coated Sponge <i>in Vivo</i>

“…In the present study, L-tryptophan and L-lysine were selected as factors for bone formation and their effects were evaluated. L-tryptophan would be available as a factor for the proliferation or differentiation of stem cells to facilitate bone-like tissue formation with bone marrow cells [6]. L-lysine has been mentioned as having a desirable effect during the healing process for the improvement of bone fractures [7].…”

Use of SSRIs May Impact Bone Density in Adolescent and Young Women With Anorexia Nervosa

“…25,26 Furthermore, a chronic deficiency of tryptophan, an amino acid precursor to serotonin, impairs bone metabolism and accrual in rats. 27 Manipulations of serotonin levels in the CNS affect behavior and cognition, 19 and serotonergic pathways have been effectively targeted for pharmacologic therapies. The SSRIs represent a class of widely prescribed antidepressants that are commonly used in populations at risk of compromised bone health, including patients suffering from eating disorders [1][2][3][4]7 and major depressive disorders.…”