Analysis of mechanism of treating short stature with large bone age by letrozole combined with growth hormone based on miR-874-3p/SMAD3 axis

Pan Jie; Wang Zhu-jun; Zhang Ya-jun

doi:10.3969/j.issn.1672-8157.2025.01.040

Abstract：Objective To investigate the mechanism of letrozole combined with growth hormone in the treatment of short stature boys with large bone age based on miR-874-3p/SMAD3 axis.Methods A retrospective analysis was performed on 80 short stature boys with large bone age admitted to Wuhan Eighth Hospital from January 2021 to February 2024.According to the differ-ence in treatment methods,they were divided into the study group(n=41)and control group(n=39).The patients in the control group were treated with growth hormone while those in the study group with letrozole on the basis of the regimen in the control group.The levels of bone metabolism indexes(serum osteocalcin,bone alkaline phosphatase,β-collagen degradation products(β-CTX)),growth indexes(height,bone age,growth rate),blood glucose indexes(blood glucose,glycosylated hemoglobin),serum insu-lin-like growth factor 1,insulin-like growth factor binding protein 3 and miR-874-3p/SMAD3 axis-related mRNA were compared between the two groups before and after treatment.The incidence of adverse reactions was also compared between the two groups.Results In the study group,the levels of height,bone age,growth rate,osteocalcin,bone alkaline phosphatase,insulin-like growth factor 1,insulin-like growth factor binding protein 3,miR-874-3pmRNA,SMAD3 mRNA and β-CTX after treatment were(122.70±2.62)cm,(8.52±0.33)years old,(9.13±2.06)cm·year-1,(85.96±13.09)μg·L-1,(172.98±39.20)μg·L-1,(168.52±15.06)ng·mL-1,(6.87±0)72)µg·mL-1,(1.63±0.21),(1.85±0.30),(0.43±0.10)µg·L-1,respectively.In the control group,they were(117.09±7.13)cm,(8.12±0.76)years old,(7.16±1.85)cm·year-1,(72.09±12.51)μg·L-1,(131.09±35.02)μg·L-1,(151.08±13.96)ng·mL-1,(6.15±0.60)μg·mL-1,(1.30±0.23),(1.53±0.36),(0.62±0.16)μg·L-1,respectively.They were significantly higher in the study group than in the control(t=4.716,3.079,4.492,4.840,5.031,5.365,4.846,6.707,4.328,6.403,all P<0.05).There were no significant differenc-es in levels of blood glucose and glycosylated hemoglobin and incidence of adverse reactions between the two groups(P>0.05).Conclusion Letrozole combined with growth hormone can effectively improve bone metabolism and elevate IGF-1 and IGFBP-3 levels in short stature boys with long bone age to promote the growth and development of children.The mechanism of which may be related to the regulation of miR-874-3p/SMAD3 axis.