Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system are associated with bone metabolism in middle-aged males.
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-kappaB 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.


METHODS
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.
Oh
Ki Won
KW
Department of Internal Medicine, Hallym University, Chunchon, Korea. okwendo@yahoo.co.kr
Rhee
Eun Jung
EJ
Lee
Won Young
WY
Kim
Sun Woo
SW
Baek
Ki Hyun
KH
Kang
Moo Il
MI
Yun
Eun Joo
EJ
Park
Cheol Young
CY
Ihm
Sung Hee
SH
Choi
Moon Gi
MG
Yoo
Hyung Joon
HJ
Park
Sung Woo
SW
D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D015519:Bone Density; D016723:Bone Remodeling; D001842:Bone and Bones / Q000502:physiology*; D002352:Carrier Proteins / Q000097:blood*; D024042:Collagen Type I; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004958:Estradiol / Q000097:blood; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007723:Korea; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D053244:Osteoprotegerin; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides; D011347:Procollagen / Q000097:blood; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D012044:Regression Analysis; D013739:Testosterone / Q000097:blood
D015415:Biomarkers; D002352:Carrier Proteins; D024042:Collagen Type I; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I