OR11-03 Assessment Of Bone Microarchitecture In Patients With 21-hydroxylase Deficiency By High-resolution Peripheral Quantitative Computed Tomography (HRpQCT)

Abstract Disclosure: L.B. Farias: None. L.A. Gross: None. R. Nolasco: None. J.S. Rossi: None. F.A. Barbosa: None. C.E. Kater: None. M.D. Walker: None. J.P. Bilezikian: None. M. Lazaretti-Castro: None. Introduction: 21-Hydroxylase Deficiency (21OHD) is an autosomal recessive disorder characterized by variable degrees of cortisol deficiency and androgen excess. It’s the main cause of congenital adrenal hyperplasia, and according to the pathogenic variation affecting the CYP21A2 gene, 21OHD will manifest in two clinical forms: Classic (CL) and non-classic (NC). The former is a more severe and even fatal condition if not correctly treated. In the latter, symptoms of hyperandrogenism may appear during infancy or adulthood, notably in girls. Management of both forms requires glucocorticoids (GC), often at supraphysiologic doses. While GC negatively impacts bone, high androgen levels may be protective. However, data on skeletal involvement in 21OHD are controversial and limited. Objective: This study aims to evaluate bone health of patients with 21OHD on chronic GC therapy, using high-resolution peripheral quantitative computed tomography (HRpQCT) to assess volumetric (v) BMD, microarchitecture, and mechanical properties of the tibia and radius. We hypothesized androgens may mitigate the deleterious effects of GC on bone. Materials and Methods: Cross-sectional study of patients with CL and NC 21OHD. DXA and HRpQCT were performed, and groups were compared to matched controls (CT). Mean±SE is shown. Results: 33 patients (26 CL, 7 NC) and 66 CT (age: CL 33±2, NC 37±4, CT 35±1 years, p=0.56; 73-86% female) were compared. 21OHD patients were shorter (CL 154±0.02; NC 154±0.03, CT 162±0.01 cm, p<0.001), and weight was higher in CL vs NC (73±3 vs 61±5 kg, p<0.04) with no difference to CT (68±2 kg). Compared to other groups, CL patients had higher BMI (CL 30.5±0.9, NC 25.5±1.8, CT 25.7±0.6 kg/m2, p<0.001), and fat indices by DXA: Body Fat +16% vs NC and +21% vs CT, p<0.004; Fat Mass Index +42% vs NC, +41% vs CT, p<0.0004. The GC dose was 44% higher in CL vs NC (p<0.05). Compared to CT, NC had lower BMD at the spine and hip (-10.3% to -19.5%; all p<0.04) with no difference from the CL group. At the radius, 21OHD patients had lower trabecular (Tb) bone volume fraction, TbvBMD, and Tb area, and greater Tb separation (11-13% for CL vs CT and 13-29% for NC vs CT, all p≤0.03; no difference between 21OHD groups). At the tibia, patients had lower Tb bone volume fraction, TbvBMD, Tb area, and total area (9-14% for CL vs CT and 15-20% for NC vs CT, all p≤0.02; no difference between 21OHD groups). Compared to CT, CL and NC had 13% higher cortical thickness (p<0.03), and higher cortical vBMD at the radius (+2% for CL vs CT, +5% for NC vs CT, p<0.02) and tibia (+3% for CL vs CT, +4% for NC vs CT, p=0.002) with no difference between 21OHD groups. Conclusion: Patients with 21OHD, regardless of severity, exhibit trabecular deterioration despite preserved cortical bone. These findings may suggest compartment-specific alterations reflecting opposing effects of chronic GC exposure and androgen excess on the skeleton. Presentation: Saturday, July 12, 2025