title: Effects of rhIGF-1 administration on surrogate markers of bone turnover in adolescents with anorexia nervosa.
abstract: BACKGROUND
  Adolescents with anorexia nervosa (AN) have low bone density and low levels of surrogate markers of bone formation. Low bone density is a consequence of hormonal alterations that include hypogonadism and decreases in IGF-1, a bone trophic factor. Although IGF-1 is key to pubertal bone accretion, and effects have been demonstrated in adults, there are no data regarding the effect of recombinant human (rh) IGF-1 administration in adolescents with AN.
  
  
  OBJECTIVE
  We hypothesized that rhIGF-1 would cause an increase in PINP, a bone formation marker, in girls with AN, without any effect on CTX, a bone resorption marker.
  
  
  METHODS
  RhIGF-1 was administered at a dose of 30-40 mcg/k twice daily to 10 consecutive girls with AN 12-18 years old for 7-9 days. Ten age-matched girls with AN were followed without rhIGF-1 for a similar period. IGF-1, PINP and CTX levels were measured.
  
  
  RESULTS
  RhIGF-1 administration caused an increase in IGF-1 from day-1 to day-4/5 (p<0.0001) and day-1 to day-8/9 (p<0.0001). Simultaneously, PINP increased from day-1 to day-4/5 (p=0.004) and day-1 to day-8/9 (p=0.004), with a smaller increase from day-4/5 to day-8/9 (p=0.048). CTX levels did not change with rhIGF-1 administration. No changes occurred in IGF-1 or PINP levels in girls not receiving rhIGF-1; however, CTX levels increased significantly (p=0.01). Percent change in PINP was significantly higher (p=0.02) and percent change in CTX was significantly lower (p=0.006) in girls who received rhIGF-1 compared to those who did not receive any intervention. RhIGF-1 was well tolerated without hypoglycemia.
  
  
  CONCLUSIONS
  Short-term administration of rhIGF-1 causes an increase in a surrogate bone formation markers in girls with AN without significant side effects.
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. mmisra@partners.org
authors.forename: Madhusmita
authors.initials: M
authors.lastname: Misra
authors.forename: Jacob
authors.initials: J
authors.lastname: McGrane
authors.forename: Karen K
authors.initials: KK
authors.lastname: Miller
authors.forename: Mark A
authors.initials: MA
authors.lastname: Goldstein
authors.forename: Seda
authors.initials: S
authors.lastname: Ebrahimi
authors.forename: Thomas
authors.initials: T
authors.lastname: Weigel
authors.forename: Anne
authors.initials: A
authors.lastname: Klibanski
mesh_terms: D000293:Adolescent; D000856:Anorexia Nervosa / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D024042:Collagen Type I / Q000097:blood; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010012:Osteogenesis; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D011994:Recombinant Proteins; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D007334:Insulin-Like Growth Factor I