title: Osteoprotegerin and parathyroid hormone as markers of high-turnover osteodystrophy and decreased bone mineralization in hemodialysis patients.
abstract: Osteoprotegerin (OPG) has a profound inhibitory effect on osteoclast differentiation and bone resorption. Because high-turnover renal osteodystrophy (ROD) is characterized by increased osteoclast activity, serum OPG concentrations might be used to distinguish between forms of ROD. Twenty-six patients on maintenance hemodialysis therapy underwent a transiliac crest biopsy for evaluation of histopathologic characteristics and histomorphometric studies. ROD was diagnosed as type II (normal or low turnover) or type III (high turnover plus osteoidosis) disease. Bone mineralization density distribution (BMDD) was characterized by measuring the mean trabecular calcium concentration in the biopsy specimen with quantitative backscattered electron imaging. Patients underwent additional dual-energy x-ray absorptiometry (DEXA) of the spine and hip and measurement of such biochemical markers of bone turnover as OPG, intact parathyroid hormone (iPTH), osteocalcin, calcitonin, bone alkaline phosphatase, and cross-laps. OPG levels were significantly reduced in patients with ROD III compared with ROD II (118 +/- 38 versus 204 +/- 130 pg/mL; P < 0.05) and correlated with BMDD (r = 0.43; P < 0.05). Patients with ROD III showed significantly lower BMDD compared with healthy controls (21.42% +/- 0.12% versus 22.17% +/- 0.81% weight; P < 0.01). Besides iPTH, which showed significantly greater levels in patients with ROD III than ROD II (382 +/- 322 versus 136 +/- 156 pg/mL; P < 0.05), none of the serological markers or DEXA was useful in separation of the groups. Discriminant function analysis showed that a combination of OPG and iPTH correctly classifies ROD II in 72% and ROD III in 88% of patients. We conclude that OPG in combination with iPTH can be used as a marker for noninvasive diagnosis of ROD in hemodialysis patients. Furthermore, OPG serum levels might be used to estimate trabecular bone mineralization in these subjects.
authors.affiliation: Department of Internal Medicine III, Division of Nephrology, University Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Haas
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Leko-Mohr
authors.forename: Paul
authors.initials: P
authors.lastname: Roschger
authors.forename: Josef
authors.initials: J
authors.lastname: Kletzmayr
authors.forename: Christoph
authors.initials: C
authors.lastname: Schwarz
authors.forename: Christoph
authors.initials: C
authors.lastname: Domenig
authors.forename: Thomas
authors.initials: T
authors.lastname: Zsontsich
authors.forename: Klaus
authors.initials: K
authors.lastname: Klaushofer
authors.forename: Günter
authors.initials: G
authors.lastname: Delling
authors.forename: Rainer
authors.initials: R
authors.lastname: Oberbauer
mesh_terms: D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015519:Bone Density; D001862:Bone Resorption; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology*; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000097:blood*; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D006435:Renal Dialysis / Q000009:adverse effects*; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D006023:Glycoproteins; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human