In the Journals

Aromatase inhibitor therapy slows bone age advancement in congenital adrenal hyperplasia

The aromatase inhibitor anastrozole effectively slowed bone age advancement in children with congenital adrenal hyperplasia during 5 years of treatment without changes in bone mineral density or body composition, suggesting the therapy could serve as a useful add-on therapy to glucocorticoid replacement, according to findings published in Clinical Endocrinology.

Kyriakie Sarafoglou

“Our study found that bone age maturation slowed in children with congenital adrenal hyperplasia (CAH) treated with anastrozole,” Kyriakie Sarafoglou, MD, associate professor and director of the Center for Congenital Adrenal Hyperplasia and Disorders of Sex Development at the University of Minnesota Masonic Children’s Hospital, told Endocrine Today. “Before treatment with anastrozole, the average bone-age z score was 4.3 standard deviations (SDs). While on anastrozole, the average bone-age z score decreased to 1.9 SDs at the time of the DXA exam. There were no significant changes in bone density or body composition measures — including visceral adipose tissue — between children treated with anastrozole and glucocorticoids vs. children with CAH treated with glucocorticoids alone.”

Third-generation aromatase inhibitors, such as anastrozole and letrozole, are used as adjuvant therapy for estrogen receptor-positive breast cancer, to slow bone maturation in children with puberty disorders and in men with idiopathic short stature or growth hormone deficiency, Sarafoglou and colleagues wrote in the study background. However, the use of aromatase inhibitors in children and adolescents remains limited and off-label, they wrote.

In a retrospective study, Sarafoglou and colleagues analyzed data from 25 children with CAH treated with 1 mg anastrozole daily in addition to glucocorticoid therapy (mean age, 11 years; 56% boys) and 31 children with CAH not treated with anastrozole (mean age, 14 years; 29% boys). Participants underwent a pubertal exam, X-rays to determine bone age and DXA scans. Researchers used linear regression analysis to compare BMD and body composition measures in treated vs. untreated children, adjusting for age, pubertal status, sex, CAH type, duration of hydrocortisone therapy, BMI z score and bone-age z score.

Among children treated with anastrozole, 40% were diagnosed with simple-virilizing CAH, 32% had nonclassic CAH and 28% had salt-wasting CAH. Among children not treated with anastrozole, 68% had salt-wasting CAH, 19% had simple-virilizing CAH and 13% had nonclassic CAH. Mean duration of anastrozole therapy was 5.2 years.

In the anastrozole group, average bone-age z score decreased from a mean of 4.3 SD before initiating treatment to 1.9 SD at the time of most recent DXA exam (P = .0004), according to researchers. After 5 years of anastrozole therapy, there were no between-group differences in bone-age z score, total body BMD z score or L2 to L4 BMD z score. Visceral adipose tissue, subcutaneous abdominal fat and total fat also did not differ between treated and untreated groups, according to researchers.

“Although it is reassuring that BMD and visceral adipose tissue were not adversely affected in children with CAH treated with anastrozole when compared to children with CAH not treated with anastrozole, a prospective, multicenter, longitudinal study to evaluate BMD, bone strength and vertebral morphology is needed in children with CAH treated with aromatase inhibitors to better understand long-term effects,” Sarafoglou said. – by Regina Schaffer

For more information:

Kyriakie Sarafoglou, MD, can be reached at the Center for Congenital Adrenal Hyperplasia’s Hospital, 2450 Riverside Ave., East Building, Room MB671, Minneapolis, MN 55454; email: saraf010@umn.edu.

Disclosures: The authors report no relevant financial disclosures.

The aromatase inhibitor anastrozole effectively slowed bone age advancement in children with congenital adrenal hyperplasia during 5 years of treatment without changes in bone mineral density or body composition, suggesting the therapy could serve as a useful add-on therapy to glucocorticoid replacement, according to findings published in Clinical Endocrinology.

Kyriakie Sarafoglou

“Our study found that bone age maturation slowed in children with congenital adrenal hyperplasia (CAH) treated with anastrozole,” Kyriakie Sarafoglou, MD, associate professor and director of the Center for Congenital Adrenal Hyperplasia and Disorders of Sex Development at the University of Minnesota Masonic Children’s Hospital, told Endocrine Today. “Before treatment with anastrozole, the average bone-age z score was 4.3 standard deviations (SDs). While on anastrozole, the average bone-age z score decreased to 1.9 SDs at the time of the DXA exam. There were no significant changes in bone density or body composition measures — including visceral adipose tissue — between children treated with anastrozole and glucocorticoids vs. children with CAH treated with glucocorticoids alone.”

Third-generation aromatase inhibitors, such as anastrozole and letrozole, are used as adjuvant therapy for estrogen receptor-positive breast cancer, to slow bone maturation in children with puberty disorders and in men with idiopathic short stature or growth hormone deficiency, Sarafoglou and colleagues wrote in the study background. However, the use of aromatase inhibitors in children and adolescents remains limited and off-label, they wrote.

In a retrospective study, Sarafoglou and colleagues analyzed data from 25 children with CAH treated with 1 mg anastrozole daily in addition to glucocorticoid therapy (mean age, 11 years; 56% boys) and 31 children with CAH not treated with anastrozole (mean age, 14 years; 29% boys). Participants underwent a pubertal exam, X-rays to determine bone age and DXA scans. Researchers used linear regression analysis to compare BMD and body composition measures in treated vs. untreated children, adjusting for age, pubertal status, sex, CAH type, duration of hydrocortisone therapy, BMI z score and bone-age z score.

Among children treated with anastrozole, 40% were diagnosed with simple-virilizing CAH, 32% had nonclassic CAH and 28% had salt-wasting CAH. Among children not treated with anastrozole, 68% had salt-wasting CAH, 19% had simple-virilizing CAH and 13% had nonclassic CAH. Mean duration of anastrozole therapy was 5.2 years.

In the anastrozole group, average bone-age z score decreased from a mean of 4.3 SD before initiating treatment to 1.9 SD at the time of most recent DXA exam (P = .0004), according to researchers. After 5 years of anastrozole therapy, there were no between-group differences in bone-age z score, total body BMD z score or L2 to L4 BMD z score. Visceral adipose tissue, subcutaneous abdominal fat and total fat also did not differ between treated and untreated groups, according to researchers.

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“Although it is reassuring that BMD and visceral adipose tissue were not adversely affected in children with CAH treated with anastrozole when compared to children with CAH not treated with anastrozole, a prospective, multicenter, longitudinal study to evaluate BMD, bone strength and vertebral morphology is needed in children with CAH treated with aromatase inhibitors to better understand long-term effects,” Sarafoglou said. – by Regina Schaffer

For more information:

Kyriakie Sarafoglou, MD, can be reached at the Center for Congenital Adrenal Hyperplasia’s Hospital, 2450 Riverside Ave., East Building, Room MB671, Minneapolis, MN 55454; email: saraf010@umn.edu.

Disclosures: The authors report no relevant financial disclosures.