Bone mineral density and fractures in congenital adrenal hyperplasia: Findings from the dsd‐LIFE study

Abstract

Background In patients with congenital adrenal hyperplasia (CAH) type and doses of glucocorticoids used as well as sex hormone secretion during puberty have important actions on bone mineral density (BMD) in adulthood. Aim To evaluate BMD in adult CAH patients depending on current glucocorticoid therapy and on androgen levels in adulthood and at age 16 years. Methods We included 244 CAH patients from the dsd‐LIFE cohort (women n = 147, men n = 97; salt‐wasting n = 148, simple‐virilizing n = 71, nonclassical n = 25) in which BMD and bloods were available. Clinical and hormonal data at age 16years were retrieved from patients' files. Results Simple‐virilizing women showed lower BMD compared to salt‐wasting women at trochanter (0.65 ± 0.12 vs 0.75 ± 0.15 g/cm2; P < .050), whole femur T‐score (−0.87 ± 1.08 vs −0.16 ± 1.24; P < .05) and lumbar T‐score (−0.81 ± 1.34 vs 0.09 ± 1.3; P < .050). Fracture prevalence did not differ significantly between the CAH groups. Prednisolone vs. hydrocortisone only therapy caused worse trochanter Z‐score (−1.38 ± 1.46 vs −0.47 ± 1.16; P < .050). In women lumbar spine, BMD correlated negatively with hydrocortisone‐equivalent dose per body surface (r2 = 0.695, P < .001). Furthermore, BMI at age 16years correlated positively with lumbar spine T‐score (r2 = 0.439, P = .003) and BMD (r2 = 0.420, P = .002) in women. The androstenedione/testosterone ratio at age 16years correlated positively with lumbar spine Z‐score in women (r2 = 0.284, P = .024) and trochanter Z‐score in men (r2 = 0.600, P = .025). Conclusion Higher glucocorticoid doses seemed to cause lower BMD especially in women. Prednisolone appeared to have more detrimental effects on BMD than hydrocortisone. Higher glucocorticoid doses (lower androstenedione/testosterone ratio) during adolescence may cause lower BMD in adulthood.

Bone Mineral Density in Adults With Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis

“…One study reported that the fractures had often occurred during sport activities, however, the underlying trauma was not recorded systematically (37). There are also other studies reporting on fractures in CAH but then there was no control group making it difficult to assess the risk (19,39,44,62). Thus, future studies examining fractures, how they occurred (fragility vs. traumatic fractures) in patients with CAH compared to controls are required.…”

“…However, there have been conflicting results in the published literature regarding BMD in CAH patients. Some studies reported normal BMD (21)(22)(23)(24)(25)(26)(27) while other studies reported low BMD in all or some sites (3,(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44) or even high BMD (45). Thus, the aim of this systematic review and meta-analysis was to review the available literature to assess if adult patients with CAH are at risk of decreased BMD compared to age-and sex-matched controls.…”

The contribution of serum cortisone and glucocorticoid metabolites to detrimental bone health in patients receiving hydrocortisone therapy

“…We believe this has significant clinical implications with regard to the timing of glucocorticoid dosing, as patients (particularly those taking thrice-daily regimens) may be recommended to take their final hydrocortisone dose of the day in the late afternoon/ early evening and some patients with congenital adrenal hyperplasia have historically received glucocorticoids late at night to impact on the nocturnal rise in adrenal androgens in response to the nocturnal ACTH surge. If glucocorticoids are taken later in the day it may lead to higher levels of cortisol/ cortisone during night-time hours and thus have a greater negative impact on bone metabolism [ 56 ].…”

The contribution of serum cortisone and glucocorticoid metabolites to detrimental bone health in patients receiving hydrocortisone therapy

“…We believe this has significant clinical implications with regard to the timing of glucocorticoid dosing, as patients (particularly those taking thrice-daily regimens) may be recommended to take their final hydrocortisone dose of the day in the late afternoon/ early evening and some patients with congenital adrenal hyperplasia have historically received glucocorticoids late at night to impact on the nocturnal rise in adrenal androgens in response to the nocturnal ACTH surge. If glucocorticoids are taken later in the day it may lead to higher levels of cortisol/ cortisone during night-time hours and thus have a greater negative impact on bone metabolism (54).…”