Ki Won Oh and Eun Jung Rhee contributed equally to this reported work and all authors should be considered as first authors.
Circulating osteoprotegerin and receptor activator of NF-κB ligand system are associated with bone metabolism in middle-aged males
Article first published online: 3 DEC 2004
Volume 62, Issue 1, pages 92–98, January 2005
How to Cite
Oh, K. W., Rhee, E. J., Lee, W. Y., Kim, S. W., Baek, K. H., Kang, M. I., Yun, E. J., Park, C. Y., Ihm, S. H., Choi, M. G., Yoo, H. J. and Park, S. W. (2005), Circulating osteoprotegerin and receptor activator of NF-κB ligand system are associated with bone metabolism in middle-aged males. Clinical Endocrinology, 62: 92–98. doi: 10.1111/j.1365-2265.2004.02179.x
This work was partly supported by the Research Grant from Hallym University and the Samsung Grant No. SBRI C-A3-223–1.
- Issue published online: 3 DEC 2004
- Article first published online: 3 DEC 2004
- (Received 23 July 2004; returned for revision 22 August 2004; finally revised 25 September 2004; accepted 26 October 2004)
Objective Osteoporosis is a growing health problem in males as well as in females. Sex hormones and insulin-like growth factor-I (IGF-I) have been shown to be the major determinants in male bone metabolism. Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of NF-κB ligand (RANKL). OPG and RANKL have been shown to be important regulators of osteoclastogenesis. However, the relationship between the OPG-RANKL system and male bone status in human populations are unclear. Thus, the aim of this study was to investigate the relationship between the OPG-RANKL system and bone mineral metabolism in males.
Patients and Measurements Serum concentrations of OPG, RANKL, oestradiol, total testosterone and IGF-I and bone mineral density (BMD) were measured in 80 Korean males aged 42–70 (mean age, 54·5 year). Enzyme-linked immunosorbent assays were used to determine the serum concentrations of OPG and RANKL. Serum concentrations of oestradiol, total testosterone, IGF-I and bone turnover markers were determined using standard methods. BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry.
Results We observed a significant negative correlation between the serum OPG levels and lumbar spine BMD (r =−0·259, P < 0·05) in Spearman correlation analysis. Serum OPG levels and RANKL/OPG ratios were found to be significantly correlated to the serum osteocalcin levels (r =− 0·254, P < 0·05; r = 0·264, P < 0·05) in Spearman correlation analysis. Serum OPG levels were found to be negatively correlated with serum oestradiol levels (r =−0·319, P < 0·01) in Spearman correlation analysis. In addition, a significant positive correlation was found between serum RANKL/OPG ratios and oestradiol levels (r = 0·374, P < 0·001) in Spearman correlation analysis. In contrast, Serum total testosterone and IGF-I levels were not correlated with serum OPG levels or RANKL to OPG ratios in Spearman correlation analysis. In a multiple regression analysis, age, body mass index (BMI), and serum OPG levels were identified as a significant predictor for lumbar spine BMD, and age, BMI, serum OPG and RANKL levels for femoral neck BMD. In another multiple regression analysis, only serum oestradiol level was identified as a significant predictor for serum OPG or RANKL levels. In contrast, Serum total testosterone and IGF-I levels were not correlated with serum OPG or RANKL levels in multiple regression analysis.
Conclusions Our data show that the circulating OPG-RANKL system is associated with bone metabolism in the male populations. Also, our data suggest that OPG and RANKL may be mediators of the effects of oestradiol in male bone metabolism.