Implications of measuring soluble receptor activators of nuclear factor-kappaB ligand and osteoprotegerin in bone metabolism of elderly women.
OBJECTIVE
The discovery of a signaling system consisting of a soluble receptor activator of the NF-kappaB ligand (sRANKL) and its decoy receptor osteoprotegerin (OPG) has provided a valuable key to understanding the pathophysiology of the bone microenvironment. We conducted a cross-sectional study of the role of sRANKL and OPG levels as they relate to bone metabolism in elderly postmenopausal women with and without osteoporosis.


METHODS
Fifty-one elderly women with or without osteoporosis were enrolled in the study. Bone alkaline phosphatase, osteocalcin, urinary deoxypyridinoline and urinary type I collagen N-terminal telopeptide (NTx) were measured as bone metabolic markers. Serum levels of OPG and sRANKL were measured by sandwich enzyme-linked immunosorbent assay and the lumbar spine bone mineral density (LSBMD) with dual-energy X-ray absorptiometry. Furthermore, we compared the sRANKL and OPG levels in elderly women with and without vertebral fractures (VFs).


RESULTS
In elderly postmenopausal women, there was a significant positive association between OPG levels and the T score and Z score of LSBMD (r = 0.345 and p = 0.014 for T score; r = 0.438 and p = 0.001 for Z score). sRANKL levels were not significantly correlated with T score, Z score of LSBMD, or any of the four bone metabolic markers. There were no significant differences in the sRANKL levels among the three groups (normal bone mineral density, osteopenia, and osteoporosis), but a trend toward a higher value in the osteoporosis group. The sRANKL/OPG ratio was negatively correlated with the T score and Z score of LSBMD (r = -0.336, p = 0.017; r = -0.384, p = 0.006, respectively), but not with any of the four bone metabolic markers. OPG levels in elderly women with VFs were lower than in those without VFs (p = 0.05). Multiple regression analysis showed that OPG and NTx are contributing factors to bone loss in elderly women (p = 0.014 and 0.012, respectively).


CONCLUSIONS
The OPG level provides a good predictor of osteoporosis as well as NTx in elderly women; additionally, the findings suggest that OPG might protect elderly women from bone loss or fractures.
Chiba
Yuko
Y
Department of Endocrinology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
Onouchi
Tsuneko
T
Ikeda
Toru
T
Adachi
Junichiro
J
Tamura
Yoshiaki
Y
Horiuchi
Toshiyuki
T
D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism*; D024042:Collagen Type I / Q000097:blood; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae / Q000503:physiopathology; D010024:Osteoporosis / Q000097:blood*; D053244:Osteoprotegerin / Q000097:blood*; D010455:Peptides / Q000097:blood; D017698:Postmenopause / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000097:blood
D015415:Biomarkers; D024042:Collagen Type I; D053244:Osteoprotegerin; D010455:Peptides; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C052929:collagen type I trimeric cross-linked peptide