Elsevier

Bone

Volume 32, Issue 6, June 2003, Pages 681-686
Bone

Original article
Serum levels of osteoprotegerin increase with age in a healthy adult population

https://doi.org/10.1016/S8756-3282(03)00090-5Get rights and content

Abstract

Regulation of the balance of osteoblastic and osteoclastic activity is critical for the understanding of normal cell biology and forms the basis of metabolic bone diseases. Our study reports about influences of age and gender on serum levels of osteoprotegerin (OPG) and its association to other clinical parameters of bone metabolism in a precisely determined cohort of 1134 healthy subjects at 17 Austrian outpatient bone clinics, aged between 19 and 96 years (females n = 687, 50 ± 21 years, 19–94, and males n = 447, 52 ± 13.5 years, 24–96). Mean OPG serum levels for all participants were 50.83 ± 51.47 pg/ml (n = 1134; median 36, 2–584) and we observed a sharp increase in females after 60 years and in males after 70 years of age. OPG serum levels increased significantly by age, 2.1 pg/ml in females and 1.9 pg/ml in males for every year (P < 0.0001). Correlation of OPG serum levels and several bone parameters of bone metabolism showed that OPG negatively correlated with serum iPTH (r = −0.14; P < 0.001) and with serum estradiol in females (r = −0.16, P < 0.0001). Bone mineral density measured by DXA method at the spine and at the hip did not correlate with OPG serum levels, except a borderline negative correlation at the trochanteric region (r = −0.1, P < 0.05) in females only. Our results show a significant increase of osteoprotegerin with age in healthy females and males but fluctuations do not predict bone mineral density under in vivo conditions.

Introduction

A variety of local growth factors regulate the differentiation and the activity of the osteoblastic and osteoclastic lineage [1], [2], [3]. The discovery of osteoprotegerin (OPG; osteoclastogenesis inhibitory factor), a soluble member of the tumor necrosis factor (TNF) receptor superfamily, and subsequent identification of RANKL (receptor activator of nuclear factor-kappaB ligand and osteoprotegerin, osteoclast differentiation factor) has provided new insights into the regulation of osteoclastogenesis [4], [5], [6].

OPG acts as a soluble secreted receptor for RANKL that prevents it from binding to and activating RANK (receptor activator of nuclear factor-kappaB) on the osteoclast surface. The impressive antiresorptive effects of OPG have been shown in several in vivo studies as transgenic mice overexpressing OPG have osteopetrosis with narrowing of the bone marrow cavities. In vitro studies have suggested that estrogen stimulates OPG expression, whereas parathyroid hormone (PTH) inhibits OPG and stimulates the expression of RANKL [7], [8]. Because OPG is expressed in the media of large arteries in wild type mice, it may also play a role in vascular biology [9], [10]. Interestingly, the degrees of vascular calcification and osteoporosis are correlated in aging women which might have future therapeutic implications [11].

Only a few studies examined an association of OPG serum levels with clinical parameters. Influences of age and gender on serum levels of OPG and association to other clinical parameters of bone metabolism have not been thoroughly investigated in normal subjects. We therefore have investigated a well-defined normal population of Austria; these data might serve as reference ranges for further clinical evaluations.

Section snippets

Subjects and methods

Overall approximately 5000 addresses were selected by chance from a population-based register and contacted by a standard written invitation. The study was effectuated free of charge in the months of December to April 1998/1999 and 1999/2000. Exclusion criteria for the study were chronic diseases or any medication effecting bone metabolism, e.g., glucocorticosteroids, anticonvulsants, and/or thyroid hormones. Women who were on hormone replacement therapy (HRT) were excluded, except those with

Results

Females (n = 687) and males (n = 447) were comparable for age (50 ± 21 years, 19–94 vs 52 ± 13.5 years, 24–96). Mean serum calcium levels were 2.39 ± 0.17 mg% (1.06–3.3). Within the normal range of 2.2–2.7 mg% were 89% (n = 1009); subjects with hypercalcemia (2.5%) were not included for further statistical evaluation to exclude any case suspicious for primary hyperparathyroidism, and another 8.5% were hypocalcaemic. Serum levels of 25(OH) vitamin D (20.9 ± 13.3 ng/ml; range, 2.2–99 ng/ml) and

Discussion

Recently, several authors have investigated serum osteoprotegerin levels in diseases affecting bone metabolism, e.g., prostate cancer and rheumatism and even diabetes and stroke [14], [15], [16]. Our study is the first investigating a normative range for OPG serum levels in a large representative cohort of females and males. As apparently healthy blood donors might suffer from unknown underlying diseases we decided to use a population-based registry and exclude those with evidence of diseases

Acknowledgements

We are grateful for the grant of MSD Austria (Mag. Gabriele Herpel-Grohm) to the Austrian Society of Bone and Mineral Research. This study was also supported by a grant from the Jubiläumsfond der Österreichischen Nationalbank (Project No. 8128).

The Austrian Study Group: G. Leb, K. Weber, A. Fahrleithner, A. Hoffmann (Universität LKH Graz, Endokrinologie und Nuklearmedizin); A. Kowatsch (Inst. für Hormonerkrankungen, Graz); G. Klima, Th. Lauermann (Steiermärkisch Gebietskrankenkasse, Graz); H.

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