Prepubertal Healthy Children’s Urinary Androstenediol Predicts Diaphyseal Bone Strength in Late Puberty

Abstract

During the physiological process of adrenarche, the adrenal glands of healthy children secrete increasing amounts of weak androgenic steroids partly metabolized to potent sex steroids. The aim of the study was to examine whether adrenal androgen metabolite excretion rates before the onset of puberty may be prospectively associated with late-pubertal diaphyseal bone strength. We conducted the study in an auxological and metabolic child nutrition research facility. The sample included 45 healthy adolescents who underwent proximal forearm bone and muscle area measurements by peripheral quantitative computed tomography at the age of 16 yr (SD 1.5) and who had collected a 24-h urine sample 8 yr earlier, allowing to quantify the prepubertal urine metabolome. Prepubertal hormonal predictors quantified by gas chromatography-mass spectrometry were: dehydroepiandrosterone, its 16-hydroxylated downstream metabolites, 5-androstene-3beta,17beta-diol (androstenediol), sums of total androgen and glucocorticoid metabolites, cortisol, and 6beta-hydroxycortisol. Proximal forearm radius was measured. Of all prepubertal hormones analyzed, only sex- and age-specific androstenediol levels significantly predicted pubertal stage-, height-, and muscularity-adjusted diaphyseal bone modeling (periosteal circumference, beta = 0.67, P = 0.002; cortical area, beta = 2.15, P = 0.02), bone mineral content (beta = 2.2; P = 0.04), and polar strength strain index (beta = 12.2; P = 0.002). Androstenediol explained 5-10% of the late-pubertal diaphyseal radius variability. Our prospective profiling of urinary steroid metabolites in 24-h urine samples collected before puberty suggests that androstenediol is an early predictor of the diaphyseal bone strength in late puberty. This predominantly peripheral conversion product of adrenarchal dehydroepiandrosterone by 17beta-hydroxysteroid dehydrogenase may hence be involved in a sustained improvement of radial bone accretion during growth.