In this study we evaluated the role of cytokines and insulin-like growth fa
ctor (IGF) system in mediating the skeletal changes that occur during puber
ty by determining the relationship between serum levels of cytokines and IG
F system components vs. 1) bone formation and resorption parameters in seru
m and urine, 2) bone density, and 3) metacarpal bone indexes in 65 pubertal
girls. Lumbar bone mineral density and metacarpal width increased signific
antly both between Tanner stages (TS) II and III and between TS III and TV,
whereas metacarpal length and serum levels of stimulatory IGF system compo
nents increased significantly only between TS II and III. Biochemical marke
rs of bone turnover were significantly less in TS IV girls than in TS II an
d III girls. In general, serum levels of IGF system components showed a sig
nificant positive correlation to bone density in TS II and III girls, where
as bone resorption markers corrected for creatinine showed a significant ne
gative correlation to bone density in TS III and TV girls. Serum levels of
IGF system components showed a significant positive correlation to serum os
teocalcin levels as well as metacarpal width in TS II girls, whereas urinar
y levels of bone resorption markers showed a significant negative correlati
on to metacarpal width in TS ni girls. Serum levels of interleukin-6 were d
ecreased during late puberty and were negatively correlated with bone densi
ty in TS III and TV girls. Our data are consistent with a model in which th
e sex steroid hormone-induced increase in the IGF system leads to an increa
se in longitudinal growth and periosteal bone expansion, whereas the sex st
eroid hormone-induced reduction in bone turnover (possibly via cytokines) l
eads to an increase in cortical thickness via endosteal regulation.