Increased Prevalence of Fractures in Congenital Adrenal Hyperplasia: A Swedish Population-based National Cohort Study
Related Experiment Video
Updated: Oct 18, 2025
Scanning Skeletal Remains for Bone Mineral Density in Forensic Contexts
Published on: January 29, 2018
Henrik Falhammar1,2, Louise Frisén3,4, Angelica Lindén Hirschberg5,6
1Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
Insights
Individuals with congenital adrenal hyperplasia (CAH) experience a higher prevalence of fractures, particularly those linked to osteoporosis. Early screening and optimized glucocorticoid treatment are crucial for managing fracture risk in CAH patients.
Area of Science:
- Endocrinology and Metabolism
- Bone Health and Osteoporosis
- Genetics and Rare Diseases
Background:
- Congenital adrenal hyperplasia (CAH) is associated with low bone mineral density, but fracture prevalence remains unclear.
- Understanding fracture risk is crucial for managing long-term health in CAH patients.
Purpose of the Study:
- To determine the prevalence of fractures in individuals with congenital adrenal hyperplasia (CAH).
- To compare fracture rates in CAH patients with a matched control population.
Main Methods:
- A population-based register study comparing 714 patients with 21-hydroxylase deficiency CAH to 71,400 matched controls.
- Fracture data, including type and number, were analyzed.
- Subgroup analysis was performed based on birth era (pre/post-neonatal screening) and CAH phenotype/genotype.
Main Results:
- CAH patients exhibited a significantly higher prevalence of fractures (23.5% vs 16.1%, OR 1.61).
- Increased fracture risk was observed in both males and females, with major osteoporotic fractures also elevated (9.8% vs 7.5%, OR 1.34).
- Fracture rates were higher in patients born before neonatal screening and specific CAH phenotypes (SV, I172N).
Conclusions:
- Congenital adrenal hyperplasia is linked to an increased risk of fractures, including those associated with osteoporosis.
- Neonatal screening appears to mitigate this increased risk.
- Regular fracture risk assessment and glucocorticoid management are recommended for CAH patients.
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%, 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.
Conclusions:
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.
Related Concept Videos
01:27Adrenal Gland Disorders
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
01:29Bone Disorders
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
01:09Changes in the Appendicular Skeleton with Age
Initially, the limb buds consist of a core of mesenchyme covered by a layer of ectoderm. The ectoderm at the end of the limb bud thickens to form a narrow crest called the apical ectodermal ridge. This ridge stimulates the underlying...
01:27Fractures: Bone Repair
Minor fractures with no bone displacement are treated by immobilizing the fractured bone using a cast or splint. However, in the case of fractures with displaced bones, the broken bones are repositioned before immobilization to ensure successful healing without deformation and loss of function. The realignment of fractured bone ends is performed through a process called reduction. If the...