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Glucocorticoids can cause decreased bone density in congenital adrenal hyperplasia
Women with the salt-losing form of congenital adrenal hyperplasia had higher risk.
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Adult women treated with long-term glucocorticoids for classical congenital adrenal hyperplasia have a higher risk for decreased bone mineral density compared to controls.
Women with the salt-losing form of congenital adrenal hyperplasia (CAH) appear to have a higher risk than women with the simple virilizing form.
Congenital adrenal hyperplasia results from a deficiency of one of five enzymes required for the synthesis of cortisol in the adrenal cortex. “Management of this disorder consists of lifelong glucocorticoid supplementation to reduce excess levels of adrenal androgens,” investigators wrote in the Journal of Clinical Endocrinology and Metabolism. “Concern has been raised regarding the potential impact of long-term glucocorticoid use on bone mineral density [BMD] in women with CAH.”
Jeremy A. King, MD, a clinical fellow at Johns Hopkins School of Medicine, and colleagues conducted a study assessing the impact of long-term glucocorticoid use on BMD in 26 women with CAH compared with the unaffected sisters of these patients. Eleven women had the salt-losing form and 15 women had the simple virilizing form of CAH.
Treatment initiation
All women were over 21 years old at the time of the study; all those with the salt-losing form of CAH had started glucocorticoid in infancy, while those with the simple virilizing form began treatment anywhere from infancy through 22 years of age.
Researchers measured whole body and lumbar spine BMD with dual-energy x-ray absorptiometry.
At baseline, the only significant difference between the salt-losing, simple virilizing and control groups was in height (153 cm vs. 148 cm vs 159 cm, respectively).
“Although not reaching statistical significance, there was a trend for the [unaffected sisters] to have lower BMI” compared with the other groups, the investigators wrote. Twelve of the CAH patients and four control patients had completed menopause.
Five women in the salt-losing group (45%) and two of the women in the simple virilizing group (13%) had osteopenia, which was defined as a T-score between -1 and -2.5; only one woman in the control group was osteopenic (P<.001).
Researchers adjusted for age and BMI; differences in z-score, T-score and lumbar spine BMD measurements remained statistically significant.
Comparing only the salt-losing and the simple virilizing groups, researchers found a trend toward lower T-scores, z-scores and lumbar spine measurements in the salt-losing patients.
Endocrinological outcomes
Levels of several hormones were also measured, and serum 17-hydroxyprogesterone and dehydroepiandrosterone (DHEA) levels were found to be significantly lower among both CAH groups vs. the control group.
DHEA and DHEA sulfate levels were also lower among CAH patients with osteopenia vs. those without osteopenia.
Notably, all women with low levels of adrenal hormones but without osteopenia were postmenopausal.
King told Endocrine Today that while this study could not prove a causal relationship between adrenal oversuppression and BMD loss, “the differences in adrenal steroid levels between the subjects with normal BMDs and osteopenia certainly suggest oversuppression as a potential mechanism.”
Barbara P. Lukert, MD, a professor in the department of medicine at the University of Kansas School of Medicine in Kansas City, wrote an editorial in the same journal about the dangers of glucocorticoid replacement and how best to manage this therapy.
“The valuable lessons to be learned from [King and colleagues’] work may be to recognize the need for finding ways of predicting which patient will be most susceptible to the adverse effect of glucocorticoids on bone and the need for biochemical markers for monitoring glucocorticoid adequacy vs. excess,” she wrote.
King said that future studies should focus on determining dosages and specific steroids to provide optimal control of adrenal androgen production without significant lowering of BMD.
“Now that women with congenital adrenal hyperplasia are able to live long lives, we want to avoid adding iatrogenic conditions to their list of medical problems,” he said. – by Dave Levitan
For more information:
- King JA, Wisniewski AB, Bankowski BJ, et al. Long-term corticosteroid replacement and bone mineral density in adult women with classical congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2006;91:865-869.