Fig. 4: l-serine treatment normalizes the acceleration of bone loss caused by long-term fluoxetine use in both animal models and postmenopausal women.

a Metabolomic analysis of BMAT in rabbits followed by 3-D PLS-DA revealed the distinct metabolic features in response to L-serine treatment. N = 8 rabbits/group. b The intracellular S1P in BMATs was significantly increased after serine treatment. Data were mean ± sem (N = 8/group). ** P < 0.01. c The accelerated reduction of BMD caused by fluoxetine in rabbits with OVX was prevented by L-serine treatment. Data were mean ± sem (N = 8/group). **P < 0.01. d L-serine treatment corrected the acceleration of BMD decline in OVX-CUMS rats caused by long-term fluoxetine use. Data were mean ± sem (N = 8/group). **P < 0.01 and ns: nonsignificant difference. e The serum level of cross-linked C-telopeptide of type I collagen (CTX) was significantly lower in patients with L-serine treatment (Flx + Serine) than that in patients with placebo (Flx + placebo). Data were mean ± sem (N = 19 for Flx + serine group and N = 18 for Flx + placebo group). **P < 0.01. f L-serine treatment for 12 months significantly reduced fluoxetine-induced mean BMD decrease of the total lumbar spine in patients. The representative DEXA image of the lumbar spine with ROIs for L1–L4 (Left). The mean BMD reduction of total lumbar spine before and after the study (Right). N = 19 for Flx + serine group and N = 18 for Flx + placebo group. *P < 0.05. g The mean BMD reduction of the total hip was significantly smaller in patients with L-serine treatment compared with the placebo group. The representative DEXA image of the hip with ROIs highlighted in yellow (Left). The mean annual BMD reduction of the total hip (Right). N = 19 for Flx + serine group and N = 18 for Flx + placebo group. **P < 0.01. h The representative lumbar spine MRI images for patients with L-serine treatment and placebo. T1 weighted, T2 weighted, and STIR images (From left to right).