title: Regulatory effect of parathyroid hormone on sRANKL-osteoprotegerin in hemodialysis patients with renal bone disease.
abstract: Receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin are newly identified molecules that contribute to the modulation of bone remodeling. RANKL activates osteoclast function by binding to RANK in either a soluble or membrane-bound form, whereas osteoprotegerin (OPG) neutralizes its effects. The aim of this study is the evaluation of soluble RANKL (sRANKL)-OPG in cohorts of hemodialysis patients and the establishment of possible correlations between their serum levels and those of other biochemical markers. We measured intact parathyroid hormone (iPTH), osteocalcin (OC), OPG, alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and sRANKL in 104 hemodialysis patients. The patients were studied as a whole and in two subgroups according to their bone turnover state. In patients with low serum levels of bone turnover markers (intact parathyroid hormone [iPTH] < 100 pg/mL, ALP < 100 U/L, TRAP < 4 U/L; 33 patients), the following correlations were found: (i) positive correlations of iPTH with RANKL (r = 0.394, P = 0.023) and RANKL/OPG ratio (r = 0.49, P = 0.004); (ii) a negative correlation between iPTH and OPG (r = -0.365, P = 0.037). The subgroup of patients with normal or high serum levels of bone turnover markers (iPTH >or= 150 pg/mL, ALP >or= 100 U/L, OC >or= 40 ng/mL; 19 patients) exhibited the following significant correlations: (i) a positive correlation between OPG and iPTH serum level (r = 0.649, P = 0.003); and (ii) a negative correlation between RANKL/OPG ratio and iPTH (r = -0.464, P = 0.045). In conclusion, the observation that PTH favors RANKL and inhibits OPG production was only demonstrated in the serum of hemodialysis patients in a low turnover state. The positive correlation between serum OPG and iPTH in normal or high turnover rates implies a homeostatic mechanism to limit bone resorption, probably associated with skeletal resistance to PTH.
authors.affiliation: Laboratory for Experimental Surgery and Surgical Research, Athens University, Athens, Greece. konsdoum@yahoo.gr
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Doumouchtsis
authors.forename: Despoina
authors.initials: D
authors.lastname: Perrea
authors.forename: Stergios
authors.initials: S
authors.lastname: Doumouchtsis
authors.forename: Marios
authors.initials: M
authors.lastname: Tziamalis
authors.forename: Maria
authors.initials: M
authors.lastname: Poulakou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vlachos
authors.forename: Alkis
authors.initials: A
authors.lastname: Kostakis
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000503:physiopathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D053244:Osteoprotegerin / Q000097:blood*; D010281:Parathyroid Hormone / Q000378:metabolism*; D053245:RANK Ligand / Q000097:blood*; D006435:Renal Dialysis; D000071681:Tartrate-Resistant Acid Phosphatase; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase