The role of osteoprotegerin and sclerostin in bone metabolism in children with congenital adrenal hyperplasia

Introduction and aim: The aim of this study was to evaluate the bone metabolism of children with Congenital Adrenal Hyperplasia (CAH) who were followed up, examined and treated in Karadeniz Technical University (KTU) Farabi Hospital, Department of Pediatric Endocrinology, to determine the role of osteoprotegerin (OPG) and sclerostin in bone metabolism, to determine the bone mineral density and glucocorticoid (GC) dose and The aim of this study is to determine the relationship between GC duration and to evaluate the effect of GC use on OPG and sclerostin levels in these patients. Material and method: Thirty one pediatric patients between the ages of 5-18, who were diagnosed with CAH and who were using GC for at least six months, who were being followed up in the KTU Faculty of Medicine Farabi Hospital Pediatric Endocrinology outpatient clinic, participated in the group. Thirty one sex- and age-matched children were included in the healthy control group. Blood was taken from the patient and control groups for the measurement of serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), parathormone (PTH), 25-hydroxy vitamin D (25OHD), OPG, and sclerostin. In addition, 17-hydroxy progesterone (17OHP) levels were also studied in the patient group. Lumbar 1-4 (L1-4) bone mineral density (BMD) and L1-4 BMD Z-score were measured by Dual-X Ray Absorptiometry (DXA) according to the height age of the patient and control groups. Results: The study was conducted with 31 patients with CAH and 31 healthy controls. There was consanguineous marriage in 12 (39%) patients. Of the patient group, 25 (81%) had 21-hydroxylase enzyme deficiency (21OHD), and 6 (19%) had 11-β hydroxylase enzyme deficiency (11βOHD). Of the patients, 19 (61%) were female and 12 (39%) were male. The age at diagnosis of the patient group was 1.35±2.76 years (0-9.6). At the time of diagnosis, 30 (97%) patients were in the prepubertal period and 1 (3%) patient was in the pubertal period. There was no significant difference between the birth weights and birth heights of the patient group and the control group. At the time of enrollment, the age of the patient group was 11.58±3.71 years, and the control group was 11.47±3.45 years. Serum 25OHD and OPG levels of the patient group were significantly higher than the control group. Although serum sclerostin levels of the patient group were higher than the control group, it was not significant (p>0.05). However, serum sclerostin levels in patients in pubertal period were significantly higher than pubertal control group (p<0.05). The sclerostin level of the prepubertal control group was significantly higher than the pubertal control group (p<0.05). However, the sclerostin level of the prepubertal control group was found to be significantly higher than the pubertal control group, while L1-4 BMD was found to be significantly lower (p<0.05). Glucocorticoid dose of the patients was 15.18±4.25mg/m²/day (8.8-26.5). There was no significant difference between GC doses of female and male patients. As the duration of GC use increased, serum P and ALP levels decreased and L1-4 BMD increased. 25-hydroxy vitamin D levels were significantly higher in prepubertal girls in the control group compared to pubertal girls (p<0.05). In addition, serum 25OHD levels; While it was <15µg/l in 11 (35%) patients, it was <15µg/l in 20 (64%) children in the control group. Serum OPG levels of the patient and control groups; OPG levels of patients were higher than controls in three different subgroups with serum 25OHD <15µg/l, between 15-20µg/l and >20 µg/l (p<0.05). In addition, the pubertal patient group; serum 25OHD, OPG levels were higher than pubertal controls (p<0.05). When evaluated according to pubertal status, serum OPG levels of prepubertal patients were higher than prepubertal controls and serum OPG levels of pubertal patients were higher than pubertal controls (p<0.05), while serum sclerostin levels were found to be higher only in pubertal patients compared to pubertal controls (p<0.05). When evaluated according to gender; serum OPG levels were higher in girl patients than in control girls and in boy patients compared to control boys (p<0.05). However, no significant difference was found between serum OPG and sclerostin levels when boys and girls were compared in both groups (p<0.05). A positive correlation was found between serum OPG and sclerostin levels in the patient group. There was no correlation between serum OPG or sclerostin levels in the patient group and serum Ca, P, ALP, PTH, 25OHD, L1-4 BMD and L1-4 BMD Z-score, duration of use of GC, GC dose and age. There was a negative correlation between serum ALP and OPG levels in the control group, and a negative correlation between serum OPG and sclerostin levels. Conclusion: Our study is the first to investigate the role of sclerostin in bone metabolism in patients with CAH, as well as the first to evaluate serum sclerostin and osteoprotegerin together with other bone metabolism parameters in patients with CAH. Higher OPG levels in our patient group compared to the control group were thought to be the result of a compensation mechanism against the tendency to increase in bone resorption secondary to both chronic disease and GC use. In our control group, sclerostin levels decreased in the pubertal period, as stated in the literature, in line with advancing age. In the patient group, the expected decrease in serum sclerostin levels with puberty was not observed and serum sclerostin levels of pubertal patients were found to be higher than pubertal controls. This was also indirectly evaluated as an indicator of susceptibility to bone destruction in patients with CAH. In addition, the concomitant increase in serum sclerostin and OPG levels in the patient group was thought to be a reflection of increased bone turnover in CAH, especially in the pubertal period. Keywords: Congenital adrenal hyperplasia in children, bone metabolism, sclerostin, osteoprotegerin, secondary osteopenia-osteoporosis