Bone Health Should Be an Important Concern in the Care of Patients Affected by 21 Hydroxylase Deficiency (original) (raw)
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European Journal of Endocrinology, 2008
Objective: It remains controversial whether long-term glucocorticoids are charged of bone demineralization in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The aim of this study was to know whether cumulative glucocorticoid dose from the diagnosis in childhood to adulthood in patients with CAH had a negative impact on bone mineral density (BMD). Design: This was a retrospective study. Methods: Thirty-eight adult patients with classical and non-classical CAH were included. BMD was measured in the lumbar spine and femoral neck. Total cumulative glucocorticoid (TCG) and total average glucocorticoid (TAG) doses were calculated from pediatric and adult files. Results: We showed a difference between final and target heights (K0.82G0.92 S.D. for women and K1.31G0.84 S.D. for men; P!0.001). Seventeen patients (44.7%) had bone demineralization (35.7% of women and 70% of men). The 28 women had higher BMD than the 10 men for lumbar (K0.26G1.20 vs K1.25G1.33 S.D.; PZ0.02) and femoral T-scores (0.21G1.30 S.D. versus K1.08G1.10 S.D.; PZ0.007).
Glucocorticoid-Induced Osteoporosis in Children with 21-Hydroxylase Deficiency
BioMed Research International, 2013
21-Hydroxylase de�ciency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH), resulting from deletions or mutations of the P450 21-hydroxylase gene (CYP21A2). Children with 21-OHD need chronic glucocorticoid (cGC) therapy, both to replace congenital de�cit in cortisol synthesis and to reduce androgen secretion by adrenal cortex. GC-induced osteoporosis (GIO) is the most common form of secondary osteoporosis that results in an early, transient increase in bone resorption accompanied by a decrease in bone formation, maintained for the duration of GC therapy. Despite the con�icting results in the literature about the bone status on GC-treated patients with 21-OHD, many reports consider these subjects to be at risk for osteoporosis and fractures. In bone cells, at the molecular level, GCs regulate various functions including osteoblastogenesis, osteoclastogenesis, and the apoptosis of osteoblasts and osteocytes. In this paper, we focus on the physiology and biosynthesis of endogenous steroid hormones as well as on the effects of GCs on bone cells, highlighting the pathogenetic mechanism of GIO in children with 21-OHD.
Clinical Endocrinology, 2020
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 16yrs. 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, non-classical n=25) in which BMD and bloods were available. Clinical and hormonal data at age 16yrs was 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/cm 2 ; p<0.050), whole femur T-score (-0.87±1.08 vs-0.16±1.24; p<0.05) and lumbar T-score (-0.81±1.34 vs 0.09±1.3; p<0.050). 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<0.050). In women lumbar spine BMD correlated negatively with hydrocortisoneequivalent dose per body surface (r 2 =0.695, p<0.001). Furthermore, BMI at age 16yrs correlated positively with lumbar spine T-score (r 2 =0.439, p=0.003) and BMD (r 2 =0.420, p=0.002) in women. The androstenedione/testosterone ratio at age 16yrs correlated positively with lumbar spine Z-score in women (r 2 =0.284, p=0.024) and trochanter Zscore in men (r 2 =0.600, p=0.025). 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.
Clinical Endocrinology, 2009
Objective It remains controversial if glucocorticoid replacement therapy impairs bone mineral density (BMD) in young patients with 21-hydroxylase deficiency. We aimed to analyze the impact of treatment variables, phenotype and genotype on BMD and bone metabolism in these patients. Design Cross-sectional study. Measurements Twenty-eight Caucasian patients with classical 21-hydroxylase deficiency (5-39 years). Clinical parameters, hormonal status, osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), genotype and lumbar BMD (Z-scores) were assessed. Cumulative and mean hydrocortisone equivalent doses were calculated for the entire treatment period. Results Patients with severely reduced BMD Z-scores (£-2AE5 SD) had significantly higher mean/cumulative glucocorticoid doses compared to patients with moderately reduced (P ¼ 0AE003/ P ¼ 0AE026) and normal Z-scores (>-1 SD) (P ¼ 0AE005/P ¼ 0AE011). Mean hydrocortisone equivalent doses > 20 mg/m 2 /day led to significantly lower lumbar BMD Z-scores (-2AE16 ± 1AE4 SD) vs. doses £ 20 mg/m 2 /day (-0AE59 ± 1AE25 SD) (P ¼ 0AE008). BMD correlated negatively with mean/cumulative glucocorticoid doses and treatment duration. OC (86AE45 ± 37AE45 ng/ml) and CTX (1AE45 ± 0AE43 ng/ml) were significantly increased compared to an age-and sex-matched control group in patients with active growth; only CTX was slightly increased in patients who completed growth. Conclusions High cumulative and mean glucocorticoid doses negatively impact on BMD in children and young adults with classical 21-hydroxylase deficiency. Substitution therapy should be adapted particularly at this life period to prevent bone loss.
Frontiers in Endocrinology
Background: Decreased bone mineral density (BMD) is a concern in patients with congenital adrenal hyperplasia (CAH) due to lifelong glucocorticoid replacement. Studies till date have yielded conflicting results. We wanted to systematically evaluate the available evidence regarding BMD in adult patients with CAH. Methods: We searched Medline, Embase and Cochrane Central Register of Controlled Trials to identify eligible studies. Studies comparing BMD in CAH patients with age-and sex-matched controls were included. Age <16 years and absence of controls were exclusion criteria. Two authors independently reviewed abstracts, read full-text articles, extracted data, assessed risk of bias using Newcastle-Ottawa scale, and determined level of evidence using Grading of Recommendations Assessment, Development, and Evaluation methodology. Results: Nine case-control studies with a total sample of 598 (cases n = 254, controls n = 344) met eligibility criteria. Median age was 31 years (IQR 23.9-37) and 65.7% were female. Total body BMD (Mean Difference [MD]-0.06; 95%CI −0.07, −0.04), lumbar spine BMD (MD −0.05; 95%CI −0.07, −0.03) and femoral neck BMD (MD −0.07; 95%CI −0.10, −0.05) was lower in cases compared to controls. Lumbar spine T-scores (MD −0.86; 95%CI −1.16, −0.56) and Z-scores (MD −0.66; 95%CI −0.99, −0.32) and femoral neck T-scores (MD −0.75 95%CI −0.95, −0.56) and Z-scores (MD −0.27 95%CI −0.58, 0.04) were lower in cases. Conclusion: BMD in adult patients with CAH was lower compared to controls. Although insufficient data precludes a dose-response relationship between glucocorticoid dose and BMD, it would be prudent to avoid overtreatment with glucocorticoids.
Journal of Bone and Mineral Metabolism, 2003
Glucocorticoids are essential in the treatment of patients with congenital adrenal hyperplasia (CAH). The opposite actions of glucocorticoids and androgens in bone mass achievement justify a study of bone mineral density (BMD) in these patients. We evaluated BMD in patients with CAH due to classic 21-hydroxylase (CYP21A2) deficiency and investigated the involvement of clinical and laboratory factors in the BMD. This study assessed the clinical and laboratory factors involved in BMD of 45 patients at the Pediatric Unit of Endocrinology, UNICAMP, who had been diagnosed as having classical CAH due to CYP21A2 deficiency including molecular characterization. The sample consisted of 28 females and 17 males; 23 salt-wasting (SW) and 22 simple virilizing (SV) cases, with average of 9.9 years (ranges, 5.1–16.3 years) when bone densitometry was performed. The DEXA method was used for calculating the areal BMD Z score in L2–L4. The variables were analyzed with reference to the BMD for chronological age (BMD/CA), height age (BMD/HA), and bone age (BMD/BA). The mean Z score for BMD/CA was 0.08 ± 1.21 (−2.55 to 2.64); it was 0.29 ± 1.33 (−2.01 to 4.00) for BMD/HA, and −0.90 ± 1.24 (−3.41 to 1.92) for BMD/BA. The BMD/CA was significantly lower in females and in patients on treatment for a long period and of more advanced chronological age. Weight and body mass index (BMI) Z scores showed a positive correlation with advanced BA. The higher the weight and BMI Z scores, the higher the BMD/HA. The BMD/BA values were significantly higher in the group in which BA was closer to CA. The BMD/BA value was significantly lower when compared to the value obtained with height and chronological ages. Sex, duration of treatment, weight, BMI, and bone age have an effect on areal BMD in patients with CAH due to CYP21A2 deficiency, which may be underestimated when evaluated in relation to CA and HA.
Annals of Internal Medicine, 1994
Objectives: 1) To evaluate the effects of glucocorticoid (GC) doses on bone mineral density (BMD) in children with congenital adrenal hyperplasia (CAH), 2) Investigate other factors infl uencing BMD. Methods: Twenty-six children with CAH and 11 healthy controls included in the study. All of the patients were examined with dual-energy X-ray absorptiometry (DXA) using a Hologic QDR 1000/W densitometer. The metabolic control state, age at diagnosis GC dose (mg/m 2 /day), pubertal status, 17 hydroxyprogesterone (17 OHP) levels, bone age (BA), and lumber BMD were evaluated in all cases. BMD (g/cm 2), BMD z-score corrected to National Standards (cNS-BMD z-score), BMD z-score corrected to BA (cBABMD), bone mineral content (BMC), BMC corrected to puberty (cPBMC), and bone area (BAR) values were determined. Patients were grouped according to mean on-therapy serum 17 OHP levels as tight control (17 OHP < 10 nmol/L) (n:13) and poor control (17 OHP > 10 nmol/L) (n:13). All groups were compared with each other. Results: The age range was 2.1-15.7 years and the mean age (± SD) 9.3 (± 3.5) years. There were no signifi cant differences between the groups in terms of GC doses, lumbar BMD values [BMD (g/cm 2), BMD z-score corrected to National Standards (cNS-BMD z-score), BMD z-score corrected to BA (cBABMD), bone mineral content (BMC), BMC corrected to puberty (cPBMC), and bone area (BAR)]. However, the BMI value was higher in children with CAH than normal healthy controls. The BA of the poor control, late diagnosed groups and male patients were higher than tight control, early diagnosed group and female patients, respectively. BMC and BA were lower than the control group in tight control with early diagnosed patients. The cBABMD z-score was lower in males with poor control than males with tight control. There were no similar results in female patients. Conclusions: Although GC treatment seems not to infl uence BMD in CAH patients in our study, further studies are needed to