Original Investigations
Osteoprotegerin and parathyroid hormone as markers of high-turnover osteodystrophy and decreased bone mineralization in hemodialysis patients*,**,*

https://doi.org/10.1053/ajkd.2002.31409Get rights and content

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. © 2002 by the National Kidney Foundation, Inc.

Section snippets

Patients

Twenty-six patients (11 women; age, 56 ± 21 years) on maintenance hemodialysis therapy for a median of 38 months (interquartile range, 9 to 67 months) were recruited immediately before kidney transplantation, after informed consent was obtained. These patients were taking part in an ongoing randomized controlled trial of bisphosphonate versus placebo therapy in posttransplantation osteodystrophy, in which 32 patients were calculated to be necessary to detect a 40% difference in bone resorption

OPG

The median OPG plasma level in patients on hemodialysis therapy was significantly greater than that in age- and sex-matched healthy controls (Table 1).After dividing patients into ROD types II and III according to histomorphometric results, we found significantly lower OPG levels in patients with high-turnover bone disease compared with those with ROD II (Table 1). Moreover, there was a trend toward a negative correlation between OPG and osteoblast and osteoclast surface area (r = 0.42; P =

Discussion

We investigated biochemical markers of bone turnover to accurately diagnose ROD and mineralization deficiency in patients on maintenance hemodialysis therapy. OPG in combination with iPTH are the best biochemical markers to discriminate between ROD II and III. In addition, OPG can be used as a noninvasive measure for the diagnosis of trabecular bone mineralization. Other noninvasive, but widely used, diagnostic procedures, such as DEXA, were not helpful in the diagnosis and discrimination of

Acknowledgements

The authors thank Sonja Grois and Phaedra Messmer (Ludwig Boltzmann Institute of Osteology, Vienna) for expert technical assistance.

References (26)

  • A Gerakis et al.

    Correlation of bone mineral density with the histological findings of renal osteodystrophy in patients on hemodialysis

    J Nephrol

    (2000)
  • C Canavese et al.

    Correlations between bone histopathology and serum biochemistry in uremic patients on chronic hemodialysis

    Int J Artif Organs

    (1998)
  • S Franke et al.

    PICP as bone formation and NTx as bone resorption marker in patients with chronic renal failure

    Eur J Med Res

    (1998)
  • Cited by (0)

    *

    Supported in part by a grant from Novartis.

    **

    Address reprint requests to Rainer Oberbauer, MD, Klinik für Innere Medizin III, Abteilung für Nephrologie und Dialyse, Währinger Gürtel 18-20, A-1090 Vienna, Austria. E-mail: [email protected]

    *

    0272-6386/02/3903-0015$35.00/0

    View full text