CLINICAL AND MOLECULAR STUDIES RELATIVE TO BONE METABOLISM IN PATIENTS WITH CONGENITAL ADRENAL HYPERPLASIA

MARTÍN S, MUÑOZ L, PÉREZ A, SOBRERO G, PICOTTO G, OCHETTI M, CARPENTIERI A, SILVANO L, DÍAZ DE BARBOZA G, SIGNORINO M, RUPÉREZ C, BERTOLOTTO P, ULLA M, PELLIZAS C, MONTESINOS M, TOLOSA DE TALAMONI N, MIRAS M

JOURNAL OF PEDIATRIC ENDOCRINOLOGY AND METABOLISM

Gruyter

Año: 2014 vol. 27 p. 1161 - 1166

2191-0251

Background: Patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) need a life-long glucocorticoid (GC) replacement therapy. GC may interfere with growth and alter bone mineral metabolism. This is still a matter of controversy a clear pattern of bone metabolic markers and, moreover, their relationship with components of the GH-IGF1 axis. Different polymorphisms of candidate genes related to bone metabolism have been associated with variations in bone homeostasis and therefore, GC treatment might show different impact on bone metabolism according to their genotypes. Objectives: In the present study we analyzed clinical and biochemical parameters and different polymorphisms of candidate genes associated with BMD as possible indicators of osteopenia development in CAH patients. Possible associations of the polymorphisms with markers of bone turnover, BMD and IGF system were also evaluated. Material and methods: CAH patients with 21 OHD deficency, treated with GC, and healthy controls were studied. CAH patients were divided in WC (well controlled) and PC (poorly controlled) groups. Anthropometric parameters, biochemical markers of bone turnover and BMD were evaluated. Polymerase chain reaction technique was used to genotype different candidate genes. Statistical analyses were performed using the statistical software R 4.14.2 for Windows, χ2 test, Pearson?s chi-square, Wilcoxon or Kruskal Wallis test (significance at p < 0.05). Results and discussion: Age, height and BMI were similar in both WC and PC groups and no differences were found in the concentration of IGF-I and IGFBP3 or in bone turnover markers. Genotype distributions were similar in the healthy group and CAH patients. The 192-192 genotype frequency (IGF-I) was significantly lower in PC patients than that from controls. In CAH patients, FF genotype (VDR) appeared to correlate with lower lumbar spine BMD and also, there was a significant association between the 0-0 genotype (IGF-I) and the high values of -CrossLaps and a low total BMD. Conclusions: This study contributes to understand the association of genetic determinants of BMD with the variable response to GC treatment in CAH patients and may help to demonstrate the usefulness of these genetic polymorphisms as indicators of a lower BMD in this group of patients.