Osteoprotegerin in Childhood Nephrotic Syndrome: Relation To Glucocorticoids, Parathyroid Hormone And Markers of Bone Metabolism

ABSTRACT
Background: A new cytokine system secreted by osteoblast (osteoprotegerin “OPG”and its ligand “OPGL”) that regulates osteoclastogenesis has been recently discovered. OPG is an antiresorptive cytokine as it blocks the biological effects of OPGL which is the final effector of osteoclastogenesis. OPG is downregulated by glucocorticoids (GC). Thus, OPG downregulation may be an important factor contributing to increased bone resorption in steroid-treated patients with nephrotic syndrome (NS). Objective: This study aimed at assessing serum OPG levels in children with NS and to study its relation to the renal disease, steroid therapy, Parathyroid hormone (PTH) as well as markers of bone formation (Osteocalcin “OC” and alkaline phosphatase “ALP”) and resorption (24hours urinary calcium “Ca”). Methods: Thirty four patients with NS were studied in comparison to 34 healthy children serving as controls. Patients were classified into 3 groups; group 1 included 8 newly diagnosed patients who were studied before and after a short course (one month) of steroid therapy for the first time. Group 2 included 16 frequent relapsers (FR) and group 3 included 10 frequent relapsers (IFR). Beside full clinical evaluation, measurements of serum OPG (ELISA), OC (radioimmunoassay), PTH (immunoradiometric assay), ALP and 24 hours urinary Ca and proteins were performed. Results: Patients with NS, whether compiled in one group or classified into newly diagnosed patients prior to steroid therapy, FR and IFR had a significantly lower OPG and parameters of bone formation (OC and alp) and a significantly higher 24 hours urinary Ca than controls. A short course of GC therapy for one month received by the newly diagnosed patients with NS resulted in significant decrease of serum OPG , OC, ALP and a significant increase of 24 hours urinary Ca. In contrast, serum PTH was not significantly affected by this therapy. Patients who were FR had a significantly higher cumulative steroid dose than those who were IFR (P<0.0001). The former group had a significantly lower serum OPG, OC, ALP and a significantly higher 24 hours urinary Ca and serum PTH than the latter group. Serum OPG and OC were decrease in 85.3% and 76%, respectively of patients with NS. On the other hand, serum PTH and 24 hours urinary Ca were elevated in 61.8% and 79.4% of these patients, respectively. OPG had a significant negative correlation with markers of disease activity and severity (ESR, serum cholesterol, 24 urinary protein and cumulative steroid dose), PTH and 24 hours urinary Ca. On the other hand, OPG had a significant positive correlation with OC and ALP. Conclusions: Osteoporosis in NS could be attributed to both enhancement of bone resorption and suppression of bone formation. Low serum OPG expression, which could be attributed to the renal disease itself and steroid therapy, may be an important factor contributing to bone resorption in NS. Thus, OPG administration may be considered as a new hopeful therapeutic modality for osteoporosis in NS, especially in patients who are frequent relapsers and with high cumulative steroid dose. Further studied regarding the protective effects of OPG administration against bone loss in NS are warranted.