Osteoprotegerin levels in hyperthyroidism and postmenopausal osteoporosis : relationship with BMD and bone markers

Abstract EN

Thyrotoxicosis increases bone turnover in favor of net bone resorption.

There is much evidence to suggest that binding ofTs to its nuclear receptors directly stimulates osteoblasts.

Osteoprotegerin (OPG) is a secreted member of the TNF receptor superfamily, has been identified as an osteoblast-derived regulator of bone resorption and bone mass.

Recently, osteoprotegerin (OPG) has been implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic bone diseases.

The contribution of OPG to the pathogenesis of bone diseases in humans has remained incompletely understood.

The aim of the present work is to, 1) determined levels of OPG inpatients with hyperthyroidism and postmenopausal osteoporosis ; and 2) investigated the relationship of OPG levels to the markers of bone turnover and bone density.

Material and Methods : The study comprised 80 subjects divided into three groups.

Group I : thirty patients, premenopausal women (age 36 + 8.5 years) with Graves' disease.

Group II: twenty healthy age matched (35 + 9 years) females as a normal control group.

Group III : thirty patients, postmenopausal osteoporosis (age 57 ± 3.5 years).

The following measurements were made for all subjects : FT4, FT3, TSH, Osteocalcin (OC), bone alkaline phosphatase (BAP), Urinary deoxypyridinoline (UDPD), 25-hydroxycholecalciferol (2SOHvit.D3), Parathyroid hormone (PTH), and Osteoprotegerin (OPG).

Bone mineral densitometry (BMD) measurement of the spine (lumbar vertebrae 2-4) and femoral neck (FN) was measured using dual-energy x-ray absorptiometry (DXA).

Results: The BMD in the hyperthyroid were highly significantly low compared to the control group (p < 0.001).

Tfie mean serum values of OC and BAP, were all significantly higher in hyperthyroid and postmenopausal osteoporosis patients than in normal controls [15.8 + 2.1 and 22.

7 + 4.3 vs 7.1 + 2.5 mmolA and 36+8 and 57.7 + 9.1 vs 17 + 6u / lrespectively, p < 0.001).

UDPD levels were markedly elevated in hyperthyroid and postmenopausal osteoporosis patients compared to the control group [10.7+2.4 and 20.2 + 5.6 vs 4.2 + l.lnmol / mmol cr, p < 0.001].

In the hyperthyroid group, there was a significant positive correlation between UDPD levels and serum FT4 (r = 0.385, p < 0.05) and FT3 (r = 0.495, p < 0.01).

Serum OPG values were significantly higher in hyperthyroid and postmenopausal osteoporosis patients compared to control group (6.3 + 3.2 and 11.3 + 3.4 vs 3.1 ± 1.8pmolA, p <0.001).

OPG serum concentrations were positive correlated with UDPD (r = 0.479, p < 0.01, in hyperthyroid group) and (r = 0.513, P < 0.05 in postmenopausal osteoporosis group).

Conclusion : There is an increase in circulating OPG concentrations in patients with hyperthyroidism and in patients with postmenopausal osteoporosis.

The significant positive correlations of OPG serum levels with thyroid hormones as well as the positive correlations with UDPD suggest that OPG may act as an important paracrine mediator of bone metabolism in hyperthyroidism.