title: Bone mass in subjects with Klinefelter syndrome: role of testosterone levels and androgen receptor gene CAG polymorphism.
abstract: BACKGROUND
  Klinefelter syndrome (KS) is a chromosomal alteration characterized by supernumerary X-chromosome(s), primary hypogonadism, decreased pubertal peak bone mineral density (BMD), and accelerated bone loss during adulthood. Decreased bone mass has been traditionally related to low testosterone levels. However, testosterone replacement therapy does not necessarily increase bone mass in these patients, and low BMD can be observed also in patients with normal testosterone levels. The androgen receptor (AR) gene CAG polymorphism seems to modulate the sensitivity to testosterone and previous studies have related it to some clinical aspects of KS, to include BMD, gynecomastia, testes and prostate volume, and hemoglobin concentration.
  
  
  OBJECTIVE
  To analyze the relation between bone mass, testosterone, and AR CAG polymorphism in men with KS.
  
  
  METHODS
  Cross-sectional cohort study.
  
  
  METHODS
  University department.
  
  
  METHODS
  One hundred twelve consecutive treatment-naïve 47,XXY Klinefelter patients (mean age 33.5 ± 4.7 yr) and 51 age-matched normal male controls.
  
  
  METHODS
  Dual-energy x-ray absorptiometry, CAG repeat length polymorphism, X-chromosome inactivation, and testosterone levels.
  
  
  RESULTS
  Forty-nine of 112 KS subjects (42.5%) had low bone mass (osteopenia or osteoporosis). Lumbar and/or femoral T-scores were lower in KS patients compared with controls. No significant relationship was observed between testosterone levels and bone parameters, and the prevalence of osteopenia/osteoporosis was similar in subjects with normal and low testosterone levels (43.7% and 40.5%, respectively). The mean CAG repeat length calculated after X-chromosome inactivation analysis showed no differences between patients with normal and low bone mass.
  
  
  CONCLUSIONS
  Testosterone levels and AR CAG polymorphism are not associated with bone mass phenotype in KS.
authors.affiliation: Department of Histology, Section of Clinical Pathology and Centre for Male Gamete Cryopreservation, University of Padova,35121 Padova, Italy. carlo.foresta@unipd.it
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferlin
authors.forename: Mirko
authors.initials: M
authors.lastname: Schipilliti
authors.forename: Cinzia
authors.initials: C
authors.lastname: Vinanzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Garolla
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Mambro
authors.forename: Riccardo
authors.initials: R
authors.lastname: Selice
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.forename: Carlo
authors.initials: C
authors.lastname: Foresta
mesh_terms: D000328:Adult; D015519:Bone Density / Q000502:physiology; D001842:Bone and Bones / Q000473:pathology*; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D006801:Humans; D007713:Klinefelter Syndrome / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D008297:Male; D009929:Organ Size; D011110:Polymorphism, Genetic / Q000502:physiology; D011944:Receptors, Androgen / Q000235:genetics* / Q000502:physiology; D013739:Testosterone / Q000097:blood* / Q000502:physiology; D018911:Trinucleotide Repeats / Q000235:genetics; D055815:Young Adult
chemical_list: D011944:Receptors, Androgen; D013739:Testosterone