Assessment of the relationship between melatonin, hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes, and osteoprotegerin and its ligand sRANKL in girls with anorexia nervosa

Abstract

It has been suggested that disturbances in melatonin (MEL) secretion might play a role in osteoporosis development in females with anorexia nervosa (AN). It might be hypothesized that changes in the levels of hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes might mediate the potential relationship between MEL and bone tissue. We investigated whether a relationship existed between MEL and LH, FSH-E2, TSH-FT3, FT4 and ACTH-cortisol axes in girls with AN. We also aimed to establish whether such a relationship might adversely affect the balance of the OPG/sRANKL system. Eighty-six girls with AN and 21 healthy subjects aged 12.6 to 18.2 years participated in the study. The serum levels of hormones as well as OPG and sRANKL were determined by radioimmunoassay (RIA), immunoradiometric assay (IRMA) or enzyme-linked immunosorbent assay (ELISA) methods. Our study participants with AN showed a significant reduction in body mass and body mass index (BMI), a decrease in LH, E2 and FT3 concentrations, increased MEL concentration at 02.00 hours and increased amplitude between its nocturnal and morning levels (Δ MEL2.00/9.00) as well as an increase in cortisol concentration. These changes were associated with a significant increase of OPG and sRANKL levels and a decrease in the OPG/sRANKL ratio. BMI values correlated positively with LH, FSH, E2, FT3 and the OPG/sRANKL ratio while the correlation between BMI and cortisol was negative. Δ MEL2.00/9.00 correlated positively with cortisol and negatively with LH, FSH, E2, FT3 concentrations and the OPG/sRANKL ratio. A positive correlation was observed between LH, E2 and the OPG/sRANKL ratio as well as between cortisol and sRANKL while the correlation between LH and OPG as well as between cortisol and the OPG/sRANKL ratio was negative. E2 and LH were shown to be significant and independent predictors of Δ MEL2.00/9.00. LH turned out to be a significant and independent predictor of OPG, cortisol and FT3 were significant and independent predictors of sRANKL, while LH, E2, Δ MEL2.00/9.00 and FT3 were significant predictors of the OPG/sRANKL ratio. Alterations in OPG and sRANKL levels observed in girls with AN are associated with changes in nocturnal MEL secretion, the circadian rhythm of MEL, and LH, E2, FT3 and cortisol levels. Dysregulation of the relationships between MEL and LH, E2, FT3 and cortisol found in girls with AN might affect the balance of the OPG/sRANKL system. Low values of the OPG/sRANKL ratio associated with high OPG and sRANKL levels suggest some defect in the mechanism compensating for bone remodeling disturbances.