GnRHa therapy poses no BMD risk for children with CAH

medwireNews: Gonadotropin-releasing hormone agonist (GnRHa) therapy in children with congenital adrenal hyperplasia (CAH) does not compromise bone mineral density (BMD), US researchers say.

The team found that patients who did and did not receive GnRHa therapy had comparable BMD on attaining their adult height, prompting the investigators “to conclude that GnRHa therapy can be used safely to delay central puberty for children with CAH who experience early puberty.”

However, Deborah Merke (Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland) and co-workers also identified an “overall downtrend” in BMD between attainment of adult height and early adulthood in the overall cohort instead of the usual increase experienced by healthy individuals.

“Although we did not find an association between lower BMD and higher glucocorticoid doses, we hypothesize that there may still be an underlying glucocorticoid effect driving this overall BMD decline”, they write in The Journal of Clinical Endocrinology & Metabolism.

The investigators reviewed data for 61 patients with classic CAH caused by 21-hydroxylase deficiency, the majority (70%) of whom had the salt-wasting phenotype. Sixteen boys and four girls had received GnRHa therapy for at least 1 year (mean 4.5 years) on evidence of early puberty, and all patients received hydrocortisone prior to achieving their adult height. Early adulthood data were available for 34 patients including whole-body scans for 29 individuals that were taken at an average of 24.4 years of age.

Adult height was attained when bone age was greater than 15 years in girls and 17 years in boys and the rate of growth was less than 1.5 cm/year.

Of note, use of GnRHa therapy was associated with a significant improvement in final adult height versus predicted height at start of puberty compared with nonuse (0.795 vs 0.028 SD increase on predicted adult height, respectively)

At the time of reaching adult height, patients who did and did not receive GnRHa therapy had comparable BMD z-scores for the whole body, lumbar spine, femoral neck, total hip and distal radium, although receipt of GnRHa therapy was associated with a significantly lower BMD z-score at the femoral neck at the start of puberty.

However, BMD z-scores for all the measurement sites in the full patient population significantly decreased from time of adult height attainment to early adulthood, the researchers report.

In addition, sex-adjusted BMD at the femoral neck fell from 0.877 g/cm2 to 0.842 g/cm2 between reaching adult height and early adulthood, although no changes were noted for lumbar spine and total hip BMD over this period, and an increase was identified for whole body and distal radius BMD.

Multivariate analysis indicated that poor BMD z-score trends for distal radius and lumbar spine were significantly associated with the salt-wasting CAH phenotype and male sex, while BMI was positively associated with BMD z-scores for the total hip.

Receipt of dexamethasone was also associated with a trend towards lower whole-body and lumbar spine BMD compared with use of short-acting hydrocortisone, and with lower lumbar spine BMD when compared with prednisone use.

“Importantly, we conclude that the CAH population is at risk for early-onset low bone mass, especially given the decline in z-scores observed overtime and in early adulthood, regardless of GnRHa treatment”, Merke et al write.

“The impact of declining BMD on clinical outcomes including risk for osteoporosis and fractures in late adulthood and prevention strategies should be the focus of future studies.”

By Lynda Williams

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group

J Clin Endocrinol Metabol 2023; doi:10.1210/clinem/dgad514
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