Effects of rhIGF-1 administration on surrogate markers of bone turnover in adolescents with anorexia nervosa.
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.
Misra
Madhusmita
M
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. mmisra@partners.org
McGrane
Jacob
J
Miller
Karen K
KK
Goldstein
Mark A
MA
Ebrahimi
Seda
S
Weigel
Thomas
T
Klibanski
Anne
A
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
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