Search Results

You are looking at 1 - 2 of 2 items for

  • Author: Dirk De Bacquer x
Clear All Modify Search
Free access

Patricia Crabbe, Stefan Goemaere, Hans Zmierczak, Inge Van Pottelbergh, Dirk De Bacquer and Jean-Marc Kaufman

Objective: Across studies it has been suggested that leptin intervenes as a regulator of bone metabolism. This study assesses the contribution in elderly men of leptin and the Gln223Arg leptin receptor gene (LEPR) polymorphism to the variation in bone homeostasis, in relation to body composition and free estradiol as major confounders.

Design: We performed cross-sectional (n = 270) and longitudinal (mean follow-up 3.4 years, n = 214) evaluations in elderly men.

Methods: Serum leptin, LEPR genotype, baseline bone mineral density (BMD), longitudinal BMD changes at the hip and forearm, and biochemical markers of bone turnover were determined.

Results: In cross-sectional analyses absolute fat mass was the index of body composition most strongly associated with leptin (r = 0.74; P < 0.001). LEPR genotypes and serum leptin were not associated. Serum bone-specific alkaline phosphatase (S-BAP) was associated with LEPR genotypes (P = 0.05) and urinary C-terminal telopeptides of type I collagen (U-CTX) were associated with leptin levels (P = 0.03), independently from age, fat mass and free estradiol. Baseline BMD at the hip and forearm was neither associated with leptin nor with LEPR genotypes. Prospectively assessed BMD loss was not associated with serum leptin at the hip, whereas BMD loss was positively associated with leptin at the forearm (P = 0.01), independently from age, fat mass and free estradiol. Longitudinal changes in hip or forearm BMD were not associated with LEPR genotypes.

Conclusion: The findings suggest a possible role for leptin as determinant of bone homeostasis in elderly men, but with only modest impact independently from body composition and free estradiol.

Free access

Veerle Bogaert, Griet Vanbillemont, Youri Taes, Dirk De Bacquer, Ellen Deschepper, Kristel Van Steen and Jean-Marc Kaufman

Objective

The human androgen receptor (AR) contains a polyglutamine and a polyglycine stretch which are highly polymorphic and are coded respectively by a CAG and GGN repeat in exon 1 of the AR gene. Although the in vitro studies indicated a possible effect of the GGN repeat polymorphism on the AR gene transcription and clinical observations suggest that it might modulate the androgen action, its functional significance remains unclear. We wanted to assess whether the GGN repeat affects the serum testosterone levels in healthy men, which is the expected outcome through feedback regulation if it influences androgen action as has been shown to be the case for the CAG repeat.

Design and patients

A population based cross-sectional cohort study including 1476 healthy young, middle-aged, and elderly men.

Measurement

Testosterone and LH levels were determined by immunoassay; free testosterone (FT) levels were calculated. Genotyping of the GGN repeat was performed using the sequencing technique.

Results

The GGN repeat number was significantly associated with circulating testosterone and FT levels (P=0.017 and P=0.013 respectively). However, taking into account that age, body mass index, and CAG are already in the regression model, the GGN repeat could explain only a small part of the variation of both testosterone and FT.

Conclusion

To our knowledge, this study is the first to demonstrate a significant positive association between the GGN repeat and androgen levels in a large cohort of healthy men. Although the present study thus adds credence to the view that the polyglycine tract in the AR can modulate AR action, this effect appears to be only small so that its clinical relevance remains questionable.