Bone Health in Youth with Congenital Adrenal Hyperplasia: Abdominal and Total Adiposity is Associated with Bone Mineral Density.

Introduction: Patients with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency require lifelong glucocorticoid treatment, often at supraphysiologic doses, which increases their risk for obesity starting in early childhood and osteoporosis later in life. While obesity and inflammation have been shown to negatively impact bone health in the general population, the relationship between bone mineral density (BMD) and abdominal adiposity in youth with CAH remains unclear. We examine the association between BMD, adiposity, inflammation, and adrenal androgens in youth with CAH.

Methods: Thirty-five youth with CAH (12.33±3.20 years; 12 males) and 38 age- and sex-matched controls (12.70±2.83 years; 14 males) underwent dual-energy X-ray absorptiometry (DXA) for BMD, MRI for abdominal adiposity [visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT)], and bone age X-ray. Linear regression models assessed associations between whole body and lumbar areal height-adjusted BMD-z (WB aBMDHAZ, LS aBMDHAZ), adiposity, hormones, and inflammatory markers, adjusting for GC dose and BMI-z.

Results: Adiposity measures were significantly higher in CAH patients (SAT, VAT, total % body fat, Ps <0.01). LS aBMDHAZ negatively correlated with SAT (β= -1.21; 95% CI:-2.17, -0.24; P=0.014), VAT (β= -0.38; 95% CI:-0.77, 0.02; P=0.061), and total % body fat (β= -0.63; 95% CI:-1.23, -0.03; P=0.039) in youth with CAH, independent of BMI-z and GC dose. In controls, only VAT (β= -0.39; 95% CI:-0.77, -0.01; P=0.044) was negatively associated with LS aBMDHAZ. Areal BMDHAZ remained within normal limits for both groups, but in CAH patients, LS aBMDHAZ declined with age. No associations were found between BMDHAZ and adrenal hormones or MCP-1.