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.

Objectives: 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.

Subjects and 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.

Conclusion: Short-term administration of rhIGF-1 causes an increase in a surrogate bone formation markers in girls with AN without significant side effects.

Figures

Fig. 1

Percent change in levels of PINP and CTX in girls with anorexia nervosa who did (black bars) or did not (gray bars) receive rhIGF-1. A significant increase occurred in PINP following 7–9 days of rhIGF-1 administration in girls receiving rhIGF-1. In contrast, a significant increase occurred in CTX over the study duration in girls who did not receive rhIGF-1. *p < 0.05.