medwireNews: Children and young adults with congenital adrenal hyperplasia (CAH) may be at long-term risk of low bone mineral density (BMD), with the greatest risk found in boys and young men, Italian researchers have found.
“This may put them at risk of developing osteoporosis early in life”, say Stefano Mora (IRCCS San Raffaele Hospital, Milan) and co-authors in The Journal of Clinical Endocrinology & Metabolism.
The team measured prepubertal lumbar spine and whole-body BMD in 26 boys and 30 girls aged a median of 8 years who were diagnosed with classic salt-wasting CAH within a month of being born (n=47) or classic simple virilizing CAH within their first 4 years (n=9). The children were treated with hydrocortisone three times per day and mineralocorticoids once or twice per day.
Compared with 35 boys and 25 girls without CAH, the patients tended to be taller, heavier and have a greater BMI, but the differences did not reach statistical significance, the researchers say. The boys with CAH had a median 1-year advance on their bone age whereas the girls with CAH had median bone age in line with chronological age.
The patients with CAH had significantly greater lumbar spine and whole-body BMD than controls. For the boys, the lumbar spine measurements were 32.8 versus 29.6 cm2 and the whole-body measurements were 1365.0 versus 1212.6 cm2. For the girls, the corresponding measurements were 30.1 versus 27.9 cm2 and 1152.8 versus 1085.8 cm2.
However, after adjusting for sex, age, bone area and skeletal age, whole-body BMD was significantly lower in boys and girls with CAH than in controls, with no significant differences between children with and without CAH for lumbar spine BMD.
Mora et al report that there was no significant relationship between lumbar spine or whole-body BMD and glucocorticoid dose for boys or girls, but they note that the “small size of population and the fact that we chose to consider just the average [glucocorticoid] dose of the year preceding BMD measurement does not permit to reach a definite conclusion.”
The team also examined the BMD of 19 young men and 17 young women with CAH who were assessed before (median age 7.0–8.6 years) and after puberty (median age 18.1–19.0 years).
The team notes that the median height standard deviation score fell after puberty, with a significant difference over time noted for the young men (0.14 to –0.04 cm).
Moreover, Z-scores were significantly lower in young men after puberty for both whole-body BMD (decreasing from 0.8 before to 0.4 after) and lumbar BMD (0.5 to –0.6), and these measurements also “decreased markedly” in young women (0.3 to –0.3 and 0.0 to –0.2, respectively).
Multivariate analysis comparing the young adults with CAH with 20 healthy men and 31 healthy women, adjusting for age and height, showed that young men with CAH had significantly lower least squares mean measurements for lumbar spine BMD than controls, but the measurements were comparable for whole-body BMD. Young women with CAH had comparable BMD to the controls for both measurements.
Mora and co-authors note that glucocorticoid dosing did not significantly differ between young men and young women with CAH, and there were comparable distributions of testosterone, 17-hydroxyprogesterone, androstenedione and dehydroepiandrosterone sulphate (DHEAS).
“However, poor hormonal control was evidenced in both sexes”, they highlight.
Overall, 84% and 74% of young men and young women had 17-hydroxyprogesterone levels above the reference range, respectively, 48% of young men and 33%% of young women had androstenedione levels above the reference range, and 100% of all CAH patients had DHEAS suppression. The ratio of androstenedione to testosterone was above 1 in 37% of the young men and 20% were hypogonadal, and 20% of young women had testosterone levels above the reference range.
The researchers hypothesize that low testosterone and hypogonadism “could be one of the most important factor[s]” influencing lumbar BMD in boys and young men with CAH, and say that “further studies are needed to better understand the role of [glucocorticoid] therapy and hormonal control on these patients.”
They continue: “The equilibrium between exogenous glucocorticoids and endogenous production of androgens is critical for the maintenance of a balanced bone metabolism and, considering these data, we could assume that this age group may need a lower daily [glucocorticoid] dosage, closer to physiological production, to maintain a good hormonal control and avoid side effects on BMD.”
By Lynda Williams
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