Circulating Estradiol and Osteoprotegerin as Determinants of Bone Turnover and Bone Density in Postmenopausal Women

Abstract

Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of NF kappa B ligand. OPG has been shown to be an important inhibitor of osteoclast differentiation and activation in rodent models. Estrogen is known to suppress bone resorption, and the action of estrogen on bone may be mediated by OPG. The relationship between endogenous estrogen and circulating OPG levels and bone status in human populations is unclear. Thus, the aim of this study was to investigate the relationship between biochemical markers of bone turnover and bone density and circulating OPG and endogenous estradiol levels in a population-based cohort of postmenopausal women. Subjects were 180 women ages 55-91 yr (mean age, 67 yr). Serum estradiol was measured using an auto-analyzer. Serum concentrations of OPG were determined by ELISA. Markers of bone formation and resorption were measured by standard methods. Bone mineral density at total body, total hip, femoral neck, and lumbar spine was measured by dual energy x-ray absorptiometry. There was a significant inverse relationship between estradiol and all bone turnover markers (r-values from -0.46 to -0.23; P < 0.05). Serum estradiol was positively related to absolute bone density at all sites and to change in bone density at the hip and femoral neck by univariate analysis (r-values from 0.15-0.29; P < 0.05). We observed a weak inverse association between OPG and serum-based bone turnover markers (r-values -0.18 and -0.16; P < 0.05). There was a significant positive relationship between OPG and bone mineral density at total body, total hip, and femoral neck (r-values from 0.17-0.2; P < 0.05) by univariate analysis, which was lost after adjustment for age and body mass index. There was a significant weak positive relationship between circulating OPG and serum estradiol (r = 0.18; P < 0.02). We observed no significant relationships between OPG and bone turnover markers measured in urine. We conclude that the variation in circulating endogenous estradiol levels is an important factor contributing to levels of bone turnover and bone density at the menopause. Our observations also suggest that circulating levels of OPG may reflect OPG activity in bone and are related to circulating endogenous levels of estradiol. We have previously reported high levels of variability in urine markers of bone resorption, and we suggest that this could account for the absence of a significant association between these markers and circulating OPG.

A common polymorphism in the 5'-untranslated region of the aromatase gene influences bone mass and fracture risk

“…In some cross-sectional studies, a relationship has been found between serum estrogens and bone mass (5). The role of aromatase has also been highlighted by experimental and clinical studies.…”

Increased serum osteoprotegerin values in long-lived subjects: different effects of inflammation and bone metabolism

“…OPG acts as a decoy receptor, binding RANKL and thereby inhibiting the interaction between RANKL and its receptor on the osteoclast surface (12). In humans, OPG seems to exert a protective role in postmenopausal osteoporosis (13,14) and other metabolic diseases characterised by bone loss (15,16). The OPG/RANKL system has also been involved in the pathogenesis of cardiovascular diseases, thus underlining the possible link between vascular biology and bone metabolism (17,18).…”

Correlation Between 25-Hydroxyvitamin D and Estradiol Serum Level in Determining Bone Density in Menopausal Women

“…Based on this study, it was found postmenopausal women with low bone density values, only 19.4% with normal bone density, and only 4 (11.1%) who have osteoporosis, seen from the fourth characteristic of this subject, entirely included in the category of obese and with higher estradiol levels, these results prove the relationship of body mass index on bone density [13], [14].…”

“…The lowest prevalence was found in Malaysia (11.3%), Thailand (12.0%), Sweden (12.7%), Brazil (15.2%), France (16.2%), and Chile (19.1 %). 11,13,14 Increasing public awareness about the negative effects of sunlight causes skin cancer has resulted in the fact that many people use sun protection and avoid sun exposure or conditions requiring to spend most of the time indoors. Lack of exposure to sunlight will cause the state of vitamin D deficiency Humans produce most of the vitamin D through exposure to the effects of UV rays on the skin.…”