Endocrine Abstracts (2003) 6 P52


S Jabbar1,2, C Weston1, J Drury1 & J Varey2

1South Tees Acute Trust 1, Division of Pathology, The James Cook University Hospital, Middlesborough, TS4 3BW; 2Northumbria University 2 , School of Applied Sciences, Ellison Building, Newcastle, NE1 8ST.

The importance of the sRANK-L / RANK / Osteoprotegerin (OPG) system in osteoclast function has clearly been demonstrated in the rat. Activating and inactivating mutations lead to severe disturbances of bone remodelling.

Since this early animal work, there have been several studies designed to assess the importance of sRANK-L / RANK / OPG in diseases of the human skeleton. sRANK-L and OPG are measurable in blood.

This cross-sectional study measured the plasma concentrations of both sRANK-L and OPG in blood samples from 185 osteoporotic women (mean age 62.4 years), with bone mineral density (BMD) more than 2.5 SD below the young adult value, and 185 age-matched controls with normal bone mineral density.

BMD was measured by LUNAR DEXA. sRANK-L and OPG were measured by Biochemica Gruppe ELISA assays supplied by Quidel Diagnostics.

Osteoporotic women have a significantly increased concentration of both sRANK-L (mean 0.664 pmol/L and 0.371pmol/L, t = 2.55, P = 0.01) and OPG (18.70 pmol/L and 10.44pmol/L, t= 2.315, P =0.02) in their plasma compared with the age matched non-osteoporotic women

A positive correlation was shown between OPG and age in osteoporotic women (r = 0.190, P<0.01). There was no correlation between age & OPG in controls.

No correlation was found between age & sRANK-L in osteoporotic and control women.

This study is the first to report that there is a detectable difference in the plasma sRANK-L in osteoporotic and non-osteoporotic women. Activation of RANK by RANK-L is considered to be the principle cell surface receptor mechanism leading to osteoclast activation. The increased sRANK-L concentrations seen in the osteoporotic women supports the hypothesis that this system is part of the aetiology of excessive bone resoption in this group.

Increased levels of OPG have been proposed as a compensatory response to increased osteoclast activity and these results do not reject that hypothesis.

This study indicates that measurement of these members of the TNF family may present new insights into the pathophysiology and diagnosis of common bone diseases.

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