osteoprotegerin and Nephrotic-Syndrome

To observe serum osteoprotegerin (OPG) level in children with nephrotic syndrome (NS) and changes in serum OPG level after glucocorticoid therapy, with the aim of studying the role of OPG in the bone metabolism of children with NS.. Forty-four children with idiopathic NS were randomly selected as the study group, including 24 newly diagnosed, untreated patients and 20 who had relapsed during the process of glucocorticoid reduction (cumulative dose of glucocorticoid 28327±5879 mg/m2). Twenty-three age- and sex-matched healthy children served as the control group. Serum osteoprotegerin (OPG) level was measured using ELISA. Serum N-terminal midfragment of osteocalcin (N-MID osteocalcin) was determined using electrochemical luminescence immunoassays (ECLIA).. Serum levels of OPG (211±55 ng/L) and N-MID osteocalcin (46±14 ng/mL) in the untreated NS group were reduced compared with 470±57 ng/L (OPG) and 73±9 ng/ml (N-MID osteocalcin) in the control group (P<0.05). Serum levels of OPG (176±42 ng/L) and N-MID osteocalcin (29±10 ng/mL) in the NS relapsed group were lower than in the untreated NS and control groups (P<0.05).. Bone metabolism disorders are found in children with NS. High-doses of glucocorticoid therapy can aggravate these disorders. Serum OPG levels in children with NS may be affected by both the renal disease itself and steroid therapy, suggesting that OPG is expected to become a new biochemical indicator for predicting changes to the bone metabolism of children with NS.

Topics: Child; Glucocorticoids; Humans; Nephrotic Syndrome; Osteocalcin; Osteoprotegerin

A novel cytokine system secreted by osteoblast, osteoprotegerin (OPG) and its ligand (OPGL) regulates osteoclastogenesis. To determine the relation of the serum OPG levels in children with nephrotic syndrome (NS) to the renal disease, we studied 30 patients with NS in comparison with 30 healthy children serving as controls. The study patients were divided into three equal groups: group 1 included newly diagnosed patients who were studied before and after a short course (one month) of steroid therapy for the first time, group 2 included frequent relapsers (FR), and group 3 included infrequent relapsers (IFR). In addition to serum OPG (ELISA), osteocalcin (OC), parathormone (PTH), alkaline phosphatase (ALP), and 24- hour urinary Ca and proteins were measured. The NS patients revealed a significantly lower serum OPG and parameters of bone formation (ALP and OC) and a significantly higher 24- hour urinary Ca than controls. A short course of glucocorticoids therapy for one month resulted in a significant decrease of serum OPG, ALP and OC levels and a significant increase of 24- hour urinary Ca, while serum PTH levels were not significantly affected by this the- rapy; the FR revealed a significantly lower serum level and a significantly higher 24- hour urinary Ca and serum PTH than the IFR. OPG had significant negative correlations with markers of disease activity and severity (ESR, serum cholesterol, 24- hour urinary protein and cumulative steroid dose), PTH and 24- hour urinary Ca. On the other hand, OPG had significant positive correlations with ALP, OC, and serum albumin. Low serum OPG, which is attributed to the renal disease and/or steroid therapy, may be an important factor contributing to bone resorption in NS. Studies of the protective effect of OPG administration against bone loss in NS are warranted.

Topics: Alkaline Phosphatase; Child; Child, Preschool; Comorbidity; Female; Humans; Infant; Male; Nephrotic Syndrome; Osteocalcin; Osteoporosis; Osteoprotegerin; Parathyroid Hormone

Receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) play key roles in the pathogenesis of glucocorticoid-induced osteoporosis (GIO). The aim of our study was to determine whether the cumulative glucocorticoid dose (CGCS) in children with idiopathic nephrotic syndrome (INS) has any effect on the concentration of serum RANKL and OPG and the RANKL/OPG ratio. The study population consisted of 90 children with INS, aged 3-20 years, who were treated with GCS. These children were divided into two groups according to the CGCS: low (L)<1 g/kg body weight (BW) and high (H)>or=1 g/kg BW, respectively. The control group (C) consisted of 70 healthy children. RANKL concentration was observed to be significantly higher and OPG significantly lower in INS children than in the reference group: 0.21 (range 0.01-1.36) versus 0.15 (0-1.42) pmol/l (p<0.05), respectively, and 3.76 (1.01-7.25) versus 3.92 (2.39-10.23) pmol/l (p<0.05), respectively. The RANKL/OPG ratio was significantly higher in INS children (p<0.01). The concentration of RANKL, similar to the RANKL/OPG ratio, was significantly higher in Group H children than in Group L children: 0.46 (0.02-1.36 ) versus 0.19 (0.01-1.25) (p<0.01) and 0.14 (0.01-0.71) versus 0.05 (0.002-0.37) (p<0.01), respectively. The concentration of OPG was similar in both groups. There was a positive correlation between CGCS and the concentration of sRANKL as well as the RANKL/OPG ratio (in both cases r=0.33, p<0.05). Based on these results, we suggest that long-term exposure to GCS results in a dose-dependent increase in serum RANKL concentration and the RANKL/OPG ratio, but not in the level of serum OPG.

Topics: Adolescent; Bone Density; Child; Child, Preschool; Glucocorticoids; Humans; Nephrotic Syndrome; Osteoprotegerin; RANK Ligand; Young Adult