Concerted actions of insulin-like growth factor 1, testosterone, and estradiol on peripubertal bone growth: A 7-year longitudinal study

Abstract

A better understanding of how bone growth is regulated during peripuberty is important for optimizing the attainment of peak bone mass and for the prevention of osteoporosis in later life. In this report we used hierarchical models to evaluate the associations of insulin-like growth factor 1 (IGF-1), estradiol (E 2 ), and testosterone (T) with peripubertal bone growth in a 7-year longitudinal study. Two-hundred and fifty-eight healthy girls were assessed at baseline (mean age 11.2 years) and at 1, 2, 3.5, and 7 years. Serum concentrations of IGF-1, E 2 , and T were determined. Musculoskeletal properties in the left lower leg were measured using peripheral quantitative computed tomography (pQCT). Serum levels of IGF-1, E 2 , and T increased dramatically before menarche, whereas they decreased, plateaued, or increased at a lower rate, respectively, after menarche. IGF-1 level was positively associated with periosteal circumference (PC) and total bone mineral content (tBMC) throughout peripuberty but not after adjustment for muscle cross-sectional area (mCSA). On the other hand, IGF-1 was associated with tibial length (TL) independently of mCSA before menarche. T was positively associated with TL, PC, tBMC, and cortical volumetric bone mineral density, independent of mCSA, before menarche but not after. E 2 was associated with TL positively before menarche but negatively after menarche. These findings suggest that during puberty, circulating IGF-1 promotes bone periosteal apposition and mass accrual indirectly, probably through stimulating muscle growth, whereas the effects of sex steroids on bone growth differ before and after menarche, presenting a biphasic pattern. Hence the concerted actions of these hormones are essential for optimal bone development in peripuberty. ß

Specific Bone Mass Acquisition in Elite Female Athletes

“…Various authors have reported that the peaks of bone gain and bone calcium deposition occur around menarche (ie, Ϫ0.6 to Ϫ0.8 mo before) and decrease afterward (ie, 2 y later) (1,26,42). The increase in IGF-1 and estradiol during this period has an essential concerted action on direct bone development in peripuberty (43). Moreover, the increase in estradiol may reduce the set point of the bone mechanostat and thus affect the relation between mechanical loading and bone strength (44,45).…”

Longitudinal Changes in Circulating Testosterone Levels Determined by LC-MS/MS and by a Commercially Available Radioimmunoassay in Healthy Girls and Boys during the Pubertal Transition

“…Longitudinal measurements of adrenal androgens including testosterone have previously been performed with immunoassays illustrating rising levels with increasing age and progression of puberty [15,16,17]. With the advent of a more sensitive LC-MS/MS method to measure testosterone, it is now possible to detect testosterone levels in girls and boys several years prior to onset of puberty.…”

Skeletal muscle and pediatric bone development

“…Whereas skeletal growth and maturation are under the control of various hormones and sex steroids, IGF-I is considered a major determinant of cortical bone development [50]. Circulatory IGF-I concentrations mirror hepatic origins and both the muscle and bone secrete IGF-I, which acts in an autocrine and/or paracrine manner [51][52][53].…”