In the JournalsPerspective

Glucocorticoid therapy may reduce bone density in congenital adrenal hyperplasia

Higher glucocorticoid doses for adults with congenital adrenal hyperplasia may be associated with lower bone mineral density, especially among women and those prescribed prednisolone, according to findings published in Clinical Endocrinology.

“It is well known that chronic treatment with glucocorticoids influences bone homeostasis by direct suppression of osteoblastic activity, inhibits intestinal calcium absorption with secondary hyperparathyroidism, and increases bone resorption by osteoclasts,” Marcus Quinkler, MD, an endocrinologist with Endocrinology in Charlottenburg in Berlin, and colleagues wrote in the study background. “This will ultimately increase the risk for fractures. Since congenital adrenal hyperplasia patients receive glucocorticoid therapy, the type and doses of glucocorticoid as well as adequate sex hormone secretion during puberty may have important actions on bone mineral content and metabolism.”

Quinkler and colleagues analyzed data from 244 adults with congenital adrenal hyperplasia (CAH; 147 women) participating in dsd-LIFE, an international study with 14 medical recruitment centers specialized in the treatment of disorders of sex development in France (n = 4), Germany (n = 4), Poland (n = 2), Sweden (n = 1), the Netherlands (n = 2) and the United Kingdom (n = 1). Researchers reviewed clinical and hormonal data at study participation and at age 16 years when available. The phenotype of 21-hydroxylase deficiency was classified into salt-wasting (n = 148), simple-virilizing (n = 71), and non-classical CAH (n = 25), based on clinical and hormonal criteria. For analysis, the dose of glucocorticoid was converted into milligrams of hydrocortisone equivalent (1 mg dexamethasone = 70 mg hydrocortisone; 1 mg prednisolone = 6 mg hydrocortisone). Daily hydrocortisone equivalent intake was corrected for body surface area. BMD was measured via DXA.

Fracture wrist or osteoporosis 2019 
Higher glucocorticoid doses for adults with congenital adrenal hyperplasia may be associated with lower bone mineral density, especially among women and those prescribed prednisolone.
Source: Adobe Stock

Researchers found that women with simple-virilizing CAH had lower BMD compared with women with salt-wasting CAH at the trochanter (mean, 0.65 vs. 0.75 g/cm2; P < .05), whole femur T-score (mean, –0.87 vs. –0.16; P < .05) and lumbar T-score (mean, –0.81 vs. 0.09; P < .05). There were no between-group differences in fracture prevalence.

Prednisolone vs. hydrocortisone-only therapy was associated with a worse trochanter z score (mean, –1.38 vs. –0.47; P < .05). Among women, lumbar spine BMD correlated negatively with hydrocortisone equivalent dose per body surface (P < .001). Additionally, BMI at age 16 years correlated positively with lumbar spine T-score (P = .003) and BMD (P = .002) among women.

The androstenedione/testosterone ratio at age 16 years correlated positively with lumbar spine z score for women (P = .024) and trochanter z score for men (P = .025).

“We believe that in the treatment of adult CAH patients, it is important to avoid long-acting glucocorticoid preparations, such as prednisolone and dexamethasone, and the use of these preparations should be used only for certain time periods or situations, eg, for fertility treatment,” the researchers wrote. “In general, the treatment with hydrocortisone should aim [for] the imitation of physiological cortisol secretion profiles as long as delayed-release hydrocortisone preparation[s] are not readily available.”

The researchers added that long-acting glucocorticoid doses after 6 p.m. and the total suppression of adrenal androgens should be avoided. – by Regina Schaffer

Disclosures: The authors report no relevant financial disclosures.

Higher glucocorticoid doses for adults with congenital adrenal hyperplasia may be associated with lower bone mineral density, especially among women and those prescribed prednisolone, according to findings published in Clinical Endocrinology.

“It is well known that chronic treatment with glucocorticoids influences bone homeostasis by direct suppression of osteoblastic activity, inhibits intestinal calcium absorption with secondary hyperparathyroidism, and increases bone resorption by osteoclasts,” Marcus Quinkler, MD, an endocrinologist with Endocrinology in Charlottenburg in Berlin, and colleagues wrote in the study background. “This will ultimately increase the risk for fractures. Since congenital adrenal hyperplasia patients receive glucocorticoid therapy, the type and doses of glucocorticoid as well as adequate sex hormone secretion during puberty may have important actions on bone mineral content and metabolism.”

Quinkler and colleagues analyzed data from 244 adults with congenital adrenal hyperplasia (CAH; 147 women) participating in dsd-LIFE, an international study with 14 medical recruitment centers specialized in the treatment of disorders of sex development in France (n = 4), Germany (n = 4), Poland (n = 2), Sweden (n = 1), the Netherlands (n = 2) and the United Kingdom (n = 1). Researchers reviewed clinical and hormonal data at study participation and at age 16 years when available. The phenotype of 21-hydroxylase deficiency was classified into salt-wasting (n = 148), simple-virilizing (n = 71), and non-classical CAH (n = 25), based on clinical and hormonal criteria. For analysis, the dose of glucocorticoid was converted into milligrams of hydrocortisone equivalent (1 mg dexamethasone = 70 mg hydrocortisone; 1 mg prednisolone = 6 mg hydrocortisone). Daily hydrocortisone equivalent intake was corrected for body surface area. BMD was measured via DXA.

Fracture wrist or osteoporosis 2019 
Higher glucocorticoid doses for adults with congenital adrenal hyperplasia may be associated with lower bone mineral density, especially among women and those prescribed prednisolone.
Source: Adobe Stock

Researchers found that women with simple-virilizing CAH had lower BMD compared with women with salt-wasting CAH at the trochanter (mean, 0.65 vs. 0.75 g/cm2; P < .05), whole femur T-score (mean, –0.87 vs. –0.16; P < .05) and lumbar T-score (mean, –0.81 vs. 0.09; P < .05). There were no between-group differences in fracture prevalence.

Prednisolone vs. hydrocortisone-only therapy was associated with a worse trochanter z score (mean, –1.38 vs. –0.47; P < .05). Among women, lumbar spine BMD correlated negatively with hydrocortisone equivalent dose per body surface (P < .001). Additionally, BMI at age 16 years correlated positively with lumbar spine T-score (P = .003) and BMD (P = .002) among women.

The androstenedione/testosterone ratio at age 16 years correlated positively with lumbar spine z score for women (P = .024) and trochanter z score for men (P = .025).

“We believe that in the treatment of adult CAH patients, it is important to avoid long-acting glucocorticoid preparations, such as prednisolone and dexamethasone, and the use of these preparations should be used only for certain time periods or situations, eg, for fertility treatment,” the researchers wrote. “In general, the treatment with hydrocortisone should aim [for] the imitation of physiological cortisol secretion profiles as long as delayed-release hydrocortisone preparation[s] are not readily available.”

The researchers added that long-acting glucocorticoid doses after 6 p.m. and the total suppression of adrenal androgens should be avoided. – by Regina Schaffer

Disclosures: The authors report no relevant financial disclosures.

    Perspective
    Richard Auchus

    Richard Auchus

    This is a well-done retrospective study that points out that chronic exposure to greater than physiologic doses of glucocorticoids causes problems over time. Even though people may seem fine as young adults, 30 years from now, what is going to happen to them? These findings highlight the need for better treatments in congenital adrenal hyperplasia that will reduce the need to give these excessive doses of glucocorticoids.

    • Richard Auchus, MD, PhD
    • Professor of Pharmacology and Internal Medicine
      Division of Metabolism, Endocrinology and Diabetes
      The University of Michigan

    Disclosures: Auchus reports he has conducted contract research for Neurocrine Bioscience and Spruce Biosciences, and has received consulting fees from Adrenas Therapeutics, Neurocrine Biosciences, Spruce Biosciences, and Quest Diagnostics.