osteoprotegerin and Amenorrhea

Recombinant leptin (metreleptin) treatment restores bone mineral density in women with hypothalamic amenorrhea (HA), a condition characterized by hypoleptinemia, which has adverse impact on bone health.. The objective of the study was to investigate how metreleptin exerts its positive effect on bone metabolism in humans.. This was a randomized, double-blinded, placebo-controlled study.. The study was conducted at Beth Israel Deaconess Medical Center (Boston, Massachusetts).. Women (n = 18) with HA and hypoleptinemia for at least 6 months were randomized to receive either metreleptin or placebo for 36 weeks. Serum samples were obtained at baseline and 12, 24, and 36 weeks of treatment.. Circulating levels of leptin, intact PTH (iPTH), receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), sclerostin, dickkopf-1, and fibroblast growth factor-23.. Metreleptin administration significantly increased leptin levels throughout the treatment period (P = .001). iPTH decreased over the 36 weeks of treatment (P = .01). There was a trend toward a decrease in serum RANKL and increase in serum OPG in the metreleptin-treated group. The RANKL to OPG ratio was significantly decreased within the metreleptin (P = .04) but not the placebo group. Metreleptin had no effect on serum sclerostin, dickkopf-1, and fibroblast growth factor-23.. Metreleptin treatment over 36 weeks decreases iPTH and RANKL to OPG ratio levels in hypoleptinemic women with HA.

Topics: Adaptor Proteins, Signal Transducing; Adolescent; Adult; Amenorrhea; Bone Morphogenetic Proteins; Double-Blind Method; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Genetic Markers; Hormone Replacement Therapy; Humans; Hypothalamic Diseases; Intercellular Signaling Peptides and Proteins; Leptin; Osteoprotegerin; Parathyroid Hormone; RANK Ligand; Treatment Outcome; Young Adult

Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) are key factors in bone remodeling in patients with anorexia nervosa (AN) and osteopenia. The purpose of this study was to investigate basal serum levels of OPG, RANKL and leptin, as well as bone mineral density (BMD) measured by DEXA at lumbar vertebrae L1-L4, and their evolution during one year in two groups of patients with AN.. Group I included 10 adolescent girls suffering from malnutrition and secondary amenorrhea with an evolution of more than one year at the beginning of the study who received oral estrogen treatment throughout the follow-up period. Group II comprised 10 girls with malnutrition and secondary amenorrhea with an evolution of less than one year who received nutritional treatment only. All parameters were compared with those of a control group of 19 healthy, age-matched girls with normal BMI and regular menstrual cycles.. The OPG/RANKL ratio was significantly decreased (p<0.05) after 1 year in group I, a fact that was due to an increase (p<0.05) in serum RANKL values. A correlation between OPG/RANKL and BMD was found in group I at the beginning of the study (r = 0.95; p<0.001). Patients in this group showed lower BMD values (p<0.01), both at diagnosis and at the end of the study, than those of group II patients, who showed normal BMD values.. The decrease in the OPG/RANKL ratio in girls with AN could partly explain the increase in bone loss that occurs in these patients.

Topics: Absorptiometry, Photon; Adolescent; Amenorrhea; Anorexia Nervosa; Biomarkers; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Bone Resorption; Enzyme-Linked Immunosorbent Assay; Estradiol; Female; Follow-Up Studies; Humans; Leptin; Lumbar Vertebrae; Malnutrition; Osteoprotegerin; Radioimmunoassay; RANK Ligand; Receptors, Leptin; Reference Values; Treatment Outcome