Bone health in adolescents with congenital adrenal hyperplasia: exploring the interplay between glucocorticoid therapy, hormonal imbalance and puberty

Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive disorders requiring lifelong glucocorticoid (GC) therapy. Skeletal health remains incompletely characterized, particularly during adolescence. The pubertal transition represents a critical window for peak bone mass acquisition, during which chronic GC exposure, altered pubertal timing and abnormal sex steroid exposure may exert lasting effects on bone density, and quality. This mini-review examines current evidence on bone health in adolescents with CAH, focusing on the complex interplay among GC therapy, alterations in androgen levels and pubertal maturation. Most available data derive from patients with 21-hydroxylase deficiency and reveal heterogeneous bone mineral density outcomes, largely influenced by cumulative GC exposure, bone age advancement and body composition. Notably, studies adjusting bone density for age demonstrate impaired bone accrual masked by accelerated skeletal maturation. Emerging longitudinal data suggest that puberty does not fully compensate for early skeletal deficits and that divergence from reference populations may progress. Evidence regarding rarer CAH forms remains scarce. In 11 β -hydroxylase deficiency, pronounced androgen excess is associated with advanced bone maturation, yet data on bone density and fracture risk are lacking. Conversely, 17 α -hydroxylase/17,20-lyase deficiency is characterized by profound sex steroid deficiency, delayed puberty and distinct alterations in bone microarchitecture. Overall, adolescents with CAH are at risk of suboptimal peak bone mass acquisition. Optimizing skeletal outcomes requires individualized GC replacement, careful monitoring of pubertal progression and bone age-adjusted assessment of bone density. Longitudinal, phenotype-specific studies incorporating advanced imaging are needed to better define fracture risk and guide evidence-based management across the lifespan.