title: Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic athletes and non-athletes and are associated with bone density and strength estimates.
abstract: Irisin and FGF21 are novel hormones implicated in the "browning" of white fat, thermogenesis, and energy homeostasis. However, there are no data regarding these hormones in amenorrheic athletes (AA) (a chronic energy deficit state) compared with eumenorrheic athletes (EA) and non-athletes. We hypothesized that irisin and FGF21 would be low in AA, an adaptive response to low energy stores. Furthermore, because (i) brown fat has positive effects on bone, and (ii) irisin and FGF21 may directly impact bone, we hypothesized that bone density, structure and strength would be positively associated with these hormones in athletes and non-athletes. To test our hypotheses, we studied 85 females, 14-21 years [38 AA, 24 EA and 23 non-athletes (NA)]. Fasting serum irisin and FGF21 were measured. Body composition and bone density were assessed using dual energy X-ray absorptiometry, bone microarchitecture using high resolution peripheral quantitative CT, strength estimates using finite element analysis, resting energy expenditure (REE) using indirect calorimetry and time spent exercising/week by history. Subjects did not differ for pubertal stage. Fat mass was lowest in AA. AA had lower irisin and FGF21 than EA and NA, even after controlling for fat and lean mass. Across subjects, irisin was positively associated with REE and bone density Z-scores, volumetric bone mineral density (total and trabecular), stiffness and failure load. FGF21 was negatively associated with hours/week of exercise and cortical porosity, and positively with fat mass and cortical volumetric bone density. Associations of irisin (but not FGF21) with bone parameters persisted after controlling for potential confounders. In conclusion, irisin and FGF21 are low in AA, and irisin (but not FGF21) is independently associated with bone density and strength in athletes.
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Pediatric Endocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Vibha
authors.initials: V
authors.lastname: Singhal
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Lawson
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Division of Sports Medicine, Boston Children's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Ackerman
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Pouneh K
authors.initials: PK
authors.lastname: Fazeli
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Hannah
authors.initials: H
authors.lastname: Clarke
authors.affiliation: Department of Biostatistics, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Harris Center, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Kamryn
authors.initials: K
authors.lastname: Eddy
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Marengi
authors.affiliation: Endocrine Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Derrico
authors.affiliation: Endocrine Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Bouxsein
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Pediatric Endocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Madhusmita
authors.initials: M
authors.lastname: Misra
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D000328:Adult; D000568:Amenorrhea / Q000097:blood*; D056352:Athletes; D015519:Bone Density / Q000502:physiology*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000502:physiology*; D016022:Case-Control Studies; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D005353:Fibronectins / Q000097:blood*; D006801:Humans; D008598:Menstruation / Q000097:blood / Q000502:physiology; D055815:Young Adult
chemical_list: C577593:FNDC5 protein, human; D005353:Fibronectins; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors