title: The effect of leptin replacement on parathyroid hormone, RANKL-osteoprotegerin axis, and Wnt inhibitors in young women with hypothalamic amenorrhea.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The objective of the study was to investigate how metreleptin exerts its positive effect on bone metabolism in humans.
  
  
  METHODS
  This was a randomized, double-blinded, placebo-controlled study.
  
  
  METHODS
  The study was conducted at Beth Israel Deaconess Medical Center (Boston, Massachusetts).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Metreleptin treatment over 36 weeks decreases iPTH and RANKL to OPG ratio levels in hypoleptinemic women with HA.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism (J.-P.F., S.A.P., S.C., C.S.M.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215; Department of Endocrinology (A.D.A.), 424 General Military Hospital, 54006 Thessaloniki, Greece; and Section of Endocrinology (C.S.M.), Boston Veterans Affairs Healthcare System, Harvard Medical School, Boston, Massachusetts 02130.
authors.forename: Joo-Pin
authors.initials: JP
authors.lastname: Foo
authors.forename: Stergios A
authors.initials: SA
authors.lastname: Polyzos
authors.forename: Athanasios D
authors.initials: AD
authors.lastname: Anastasilakis
authors.forename: Sharon
authors.initials: S
authors.lastname: Chou
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000568:Amenorrhea / Q000097:blood / Q000188:drug therapy*; D019485:Bone Morphogenetic Proteins / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005819:Genetic Markers; D020249:Hormone Replacement Therapy; D006801:Humans; D007027:Hypothalamic Diseases / Q000097:blood / Q000188:drug therapy*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D020738:Leptin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D053244:Osteoprotegerin / Q000097:blood*; D010281:Parathyroid Hormone / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; C422903:SOST protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; C415771:metreleptin