Implications of Measuring Soluble Receptor Activators of Nuclear Factor-κB Ligand and Osteoprotegerin in Bone Metabolism of Elderly Women

Abstract

Background/Aim: The discovery of a signaling system consisting of a soluble receptor activator of the NF-κB 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. Subjects and 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). Conclusion: 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.

Levels of osteoprotegerin (OPG) and receptor activator for nuclear factor kappa B ligand (RANKL) in serum: Are they of any help?

“…These findings are discussed to reflect an increased pool of osteoblasts or osteoblast precursor cells, which produce OPG; some authors explain the OPG increase as a response of bone to the elevated turnover status in order to normalize it. Again, data remain controversial, as there are some papers that failed to prove any association of OPG with turnover markers [43][44][45].…”

“…The Danish twin studies revealed only a small weak correlation of OPG and sRANKL with BMD in a healthy population [28]. In patients with osteoporosis, there was an inverse relation between OPG and BMD [18,24,27,39,44,[46][47][48][49] a fact that is commonly interpreted as reduced OPG (and mineral) content in osteoporosis; yet, some authors described a positive correlation between OPG and BMD [25,42,45] as a kind of endogenous protective mechanism against bone loss. Serum RANKL levels seem to be independent of BMD [18,27,30,50].…”

“…These findings, however, have not yet been confirmed elsewhere. Low serum OPG has been associated with prevalent vertebral fractures in postmenopausal women with osteoporosis [23,45]; in cardiac transplant patients, low OPG serum levels also predicted vertebral fractures [47]. In patients with liver cirrhosis [44] as well as in a cohort of liver transplant recipients, there were no differences in OPG serum levels between patients with or without fractures [40].…”

The RANK/ RANKL/ OPG interaction in the repair of autogenous bone grafts in female rats with estrogen deficiency

“…However, the literature presents conflicting results concerning the period after menopause, when bone loss is related to favoring RANKL activity over that of OPG. In a cohort study, Mezquita-Raya et al 21 and Chiba et al 22 found no correlation between OPG and bone resorption markers in women, regardless of their menopause status. According to the results, this study also demonstrated that the expression of bone markers during repair of autogenous bone grafts was not altered by estrogen deficiency.…”

Osteoprotegerin, RANKL and bone turnover in postmenopausal osteoporosis

“…Stern et al found that the plasma level of RANKL rose significantly with age and was inversely associated with BMD in men only 17. In contrast, a number of studies have been unable to demonstrate any significant correlation between serum RANKL and BMD in postmenopausal women 14 18 19…”