title: Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) serum levels in patients on chronic hemodialysis.
abstract: The mechanisms underlying the skeletal resistance to PTH in patients on chronic hemodialysis (CHD) are not yet fully clarified. Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) modulate the genesis and activity of osteoclasts, however their role in renal osteodystrophy pathogenesis has not been clarified so far. The present study aimed to evaluate OPG and RANK-L serum levels in hemodialysis patients and whether OPG/RANK-L system could have a role in the skeletal resistance to PTH. In fasting blood samples obtained from 60 patients (36 males and 24 females) on CHD for at least 2 yr and from 40 healthy subjects of similar age and gender distribution as controls (CTRs), we measured serum OPG, RANK-L, bone alkaline phosphatase (B-ALP), N-terminal telopeptide of type I collagen (NTx), PTH(1-84), calcium and phosphate. In 30 of 60 hemodialysis patients, a blood sample was also drawn soon after the dialytic session. Serum levels of RANK-L, but not OPG, showed a slight but significant (p<0.05) decrease after the dialytic session. OPG resulted being about six times higher in CHD patients than in CTRs (38.7 +/- 16.2 vs 6.3 +/- 0.17 pg/ml), whereas RAN K-L serum levels were only slightly increased with respect to controls (0.88 +/- 0.47 vs 0.64 +/- 0.38 pmol/l). CHD patients showed serum PTH(1-84) and bone turnover higher than in CTRs. No correlation was found between OPG/RANK-L system and PTH or bone turnover markers. Instead, in the patients with high osteoclast activity (no.=21) OPG/RANK-L ratio was correlated (r=-0.41, p<0.01) with NTx serum levels, whereas in patients with decreased osteoclast activity (no.=39) no relationship was found. In conclusion, our findings showed that, although both OPG and RANK-L are accumulated in hemodialysis patients, only RANK-L and the balance between OPG and RANK-L seem to be related to osteoclast activity.
authors.affiliation: Department of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy. gonnelli@unisi.it
authors.forename: S
authors.initials: S
authors.lastname: Gonnelli
authors.forename: A
authors.initials: A
authors.lastname: Montagnani
authors.forename: C
authors.initials: C
authors.lastname: Caffarelli
authors.forename: A
authors.initials: A
authors.lastname: Cadirni
authors.forename: M S
authors.initials: MS
authors.lastname: Campagna
authors.forename: M B
authors.initials: MB
authors.lastname: Franci
authors.forename: B
authors.initials: B
authors.lastname: Lucani
authors.forename: E
authors.initials: E
authors.lastname: Gaggiotti
authors.forename: R
authors.initials: R
authors.lastname: Nuti
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001842:Bone and Bones / Q000201:enzymology; D002118:Calcium / Q000097:blood; D002352:Carrier Proteins / Q000097:blood*; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D010010:Osteoclasts / Q000502:physiology; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000097:blood; D010710:Phosphates / Q000097:blood; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D006435:Renal Dialysis
chemical_list: D002352:Carrier Proteins; D024042:Collagen Type I; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D010455:Peptides; D010710:Phosphates; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D000469:Alkaline Phosphatase; D002118:Calcium