Increased Prevalence of Fractures in Congenital Adrenal Hyperplasia: A Swedish Population-based National Cohort Study

• Published in: The journal of clinical endocrinology and metabolism Vol. 107; no. 2; pp. e475 - e486
• Main Authors: Falhammar, Henrik, Frisén, Louise, Hirschberg, Angelica Lindén, Nordenskjöld, Agneta, Almqvist, Catarina, Nordenström, Anna
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 18.01.2022
• Subjects: Adolescent; Adrenal Hyperplasia, Congenital - complications; Adrenal Hyperplasia, Congenital - diagnosis; Adrenal Hyperplasia, Congenital - genetics; Adrenal Hyperplasia, Congenital - metabolism; Adult; Bone Density - genetics; Case-Control Studies; Child; Child, Preschool; Female; Fractures, Bone - epidemiology; Fractures, Bone - genetics; Fractures, Bone - metabolism; Fractures, Bone - prevention & control; Humans; Infant; Infant, Newborn; Male; Medicin och hälsovetenskap; Middle Aged; Neonatal Screening - organization & administration; Neonatal Screening - standards; Online Only; Prevalence; Registries - statistics & numerical data; Steroid 21-Hydroxylase - genetics; Steroid 21-Hydroxylase - metabolism; Sweden - epidemiology; Young Adult; Sweden; trauma; bone mineral density; 21-hydroxylase deficiency; fall; osteoporosis
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgab712

Low bone mineral density has been reported in individuals with congenital adrenal hyperplasia (CAH), but the prevalence of fractures is unclear. To study the prevalence of fractures in CAH. Patients with CAH (n = 714, all 21-hydroxylase deficiency) were compared with controls matched for sex and year and place of birth (n = 71 400). Data were derived by linking National Population-Based Registers. Number and type of fractures. Mean age was 29.8 ± 18.4 years. Individuals with CAH had more fractures compared to controls [23.5% vs 16.1%, odds ratio (OR) 1.61, 95% CI 1.35-1.91], and this was found in both sexes (females: 19.6% vs 13.3%, OR 1.57, 95% CI 1.23-2.02; males: 28.7% vs 19.6%, OR 1.65, 95% CI 1.29-2.12). Fractures were significantly increased in patients born before the introduction of neonatal screening but not in those born afterwards. Any major fracture associated with osteoporosis (spine, forearm, hip, or shoulder) was increased in all individuals with CAH (9.8% vs 7.5%, OR 1.34, 95% CI 1.05-1.72). The highest prevalence of fractures was seen in SV phenotype and I172N genotype while nonclassic phenotype and I2 splice genotype did not show increased prevalence. A transport accident as a car occupant and fall on the same level were more common in patients with CAH, both sexes, than in controls. Patients with CAH had an increased prevalence of both any fracture and fractures associated with osteoporosis (both sexes) but not for patients neonatally screened. We conclude that fracture risk assessment and glucocorticoid optimization should be performed regularly.