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

Abstract

Context Low bone mineral density has been reported in individuals with congenital adrenal hyperplasia (CAH), but the prevalence of fractures is unclear. Objective To study the prevalence of fractures in CAH. Design, Setting, and Participants: 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. . Main Outcome Measures Number and type of fractures. Results Mean age was 29.8±18.4 years. Individuals with CAH had more fractures compared to controls (23.5% vs. 16.1%, 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 non-classic 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. Conclusions Patients with CAH had an increased prevalence of both any fracture and fractures associated with osteoporosis (both sexes) but not for patient neonatally screened. We conclude that fracture risk assessment and glucocorticoid optimization should be performed regularly.

Characteristics of In2G Variant in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

“…As far as the metabolic outcomes and complications such as obesity, cardiovascular complications, and bone fragility, they are mostly associated with the therapy; therefore, delineating the influence of genotype is very complicated due to different treatment regimens and length of therapy. However, the risk is generally increased as compared with controls ( 92 – 95 ). In one large epidemiological study, only obesity and venous thromboembolism were significantly more common in patients with In2G than in controls, while patients with null variants had more cardiometabolic risk ( 96 ).…”

Management challenges and therapeutic advances in congenital adrenal hyperplasia

“…A meta-analysis of nine case–control studies ( n = 254 patients with CAH and 344 control individuals) showed a lower BMD in patients with CAH; however, a relationship with glucocorticoid dose was not found 90 . A population-based Swedish study ( n = 714 patients with CAH and 71,400 control individuals) found an increased risk of fragility fractures in patients with CAH 91 . Overall, BMD studies in CAH are limited to either small cohorts or heterogeneous cohorts lacking hormonal data, thereby highlighting the need for rigorous prospective studies.…”

Long-Term Outcomes of Congenital Adrenal Hyperplasia

“…In a meta-analysis, including individuals with glucocorticoid replacement therapy, treatment increased the fracture risk [ 57 ]. Recent epidemiological studies on the presence of fractures in patients with CAH have been reported [ 33 , 58 ]. A Swedish study identified more fractures in the patient group already at a young age compared to the general population (OR, 1.61; mean age of the CAH group 29.8 years) [ 58 ].…”

“…Recent epidemiological studies on the presence of fractures in patients with CAH have been reported [ 33 , 58 ]. A Swedish study identified more fractures in the patient group already at a young age compared to the general population (OR, 1.61; mean age of the CAH group 29.8 years) [ 58 ]. However, in a Korean study, more fractures were only found in patients aged 40 years and older (OR, 1.4) [ 33 ].…”

“…However, in a Korean study, more fractures were only found in patients aged 40 years and older (OR, 1.4) [ 33 ]. In the Swedish study, only those with classic CAH had an increased fracture rate in contrast to individuals with NC CAH who had a fracture rate similar to matched controls [ 58 ]. This is in accordance with the findings of a United States study where patients with NC CAH had a lower fracture rate than patients with classic CAH [ 49 ].…”