Enrica Fila

Oxidative Stress and Bone Resorption Interplay as a Possible Trigger for Postmenopausal Osteoporosis

The underlying mechanism in postmenopausal osteoporosis (PO) is an imbalance between bone resorption and formation. This study was conducted to investigate whether oxidative stress (OxS) might have a role in this derangement of bone homeostasis. In a sample of 167 postmenopausal women, we found that increased serum levels of a lipid peroxidation marker, hydroperoxides, were negatively and independently associated with decreased bone mineral density (BMD) in total body (r = −0.192, P < 0.05), lumbar spine (r = −0.282, P < 0.01), and total hip (r = −0.282, P < 0.05), as well as with increased bone resorption rate (r = 0.233, P < 0.05), as assessed by the serum concentration of C-terminal telopeptide of type I collagen (CTX-1). On the contrary, the OxS marker failed to be correlated with the serum levels of bone-specific alkaline phosphatase (BAP), that is, elective marker of bone formation. Importantly, multiple regression analysis revealed that hydroperoxides is a determinant factor for the statistical association between lumbar spine BMD and CTX-1 levels. Taken together, our data suggest that OxS might mediate, by enhancing bone resorption, the uncoupling of bone turnover that underlies PO development.

Metabolic transitions at menopause: In post-menopausal women the increase in serum uric acid correlates with abdominal adiposity as assessed by DXA

OBJECTIVES The present study aimed to investigate any associations between parameters of body fat mass distribution and levels of serum uric acid (sUA), a well-documented cardiovascular risk factor, among non-obese women ranging from pre- to post-menopausal status. METHODS In this cross-sectional population-based study we assessed body fat distribution by dual-energy-X-ray absorptiometry (DXA), and sUA levels in 101 pre- and 134 post-menopausal non-obese apparently healthy women. RESULTS Multivariate stepwise regression analysis revealed that sUA was independently associated to the indicators of overall fatness, i.e. body mass index (β=0.339, p<0.001) and DXA-assessed total and percentage body fat (β=0.366, p<0.001 and β=0.412, p<0.001, respectively), only among post-menopausal women. Within this sample subset, trunk (i.e. central) fat mass emerged as a strong predictor of sUA (β=0.408, p<0.001), after taking the potential confounders (including body mass index) into account. CONCLUSION Central fat accumulation was found to be independently associated with higher sUA levels among non-obese women in post- but not among those in pre-menopause.

Association between circulatory levels of adipokines and bone mineral density in postmenopausal women

Objective:Epidemiological evidence indicates that excess fat may be beneficial for bone health, offering protective effects against the onset of postmenopausal osteoporosis. Experimental data suggest that this link might be due to the direct effect of adipokines on bone tissue. Confirmatory evidence of this association, however, remains limited. Methods:The levels of a panel of selected adipokines including interleukin (IL)-6, -8, -1&bgr;, adipsin, lipocalin-2/neutrophil gelatinase-associated ipocalin, tumor necrosis factor alpha, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, hepatocyte growth factor, resistin, leptin, and adiponectin in a group of osteopenic and osteoporotic postmenopausal women were compared with those of unaffected women (n = 127). Results:Univariate analysis revealed that leptin and adiponectin were significantly correlated with bone mineral density (BMD). In particular, leptin was positively associated with BMD of the spine (r = 0.22, P < 0.05), femoral neck (r = 0.23, P < 0.05), trochanter (r = 0.20, P < 0.05), and total hip (r = 0.27, P < 0.01), whereas adiponectin was inversely correlated with BMD at the trochanter (r = −0.21, P < 0.05). No correlations were, however, significant after adjusting for body fat variables. Stratification of the sample according to IL-6 levels revealed that adiponectin remained significantly inversely associated with BMD, regardless of fat levels and age (&bgr;=−0.29, P < 0.05; r2 = 0.198) in the subgroup of participants with low levels of IL-6. Conclusions:Our data suggest that circulating adiponectin is inversely associated with markers of bone health in postmenopausal women, and that the interaction is influenced by IL-6 levels.

Waist circumference and dual-energy X-ray absorptiometry measures of overall and central obesity are similarly associated with systemic oxidative stress in women

Abstract Growing evidence suggests that overall and abdominal obesity might lead to oxidative stress (OxS), which, in turn, plays a key role in the pathogenesis of a wide spectrum of diseases. In this study, for the first time, we compared the correlations of indirect, i.e. anthropometric, and direct, by dual energy X-ray absorptiometry (DXA), measures of body fat with circulatory OxS markers in women. To address this issue, we assessed central and total body fat mass (FM) by DXA, and serum levels of advanced oxidation protein products (AOPP), thiols and hydroperoxides in 275 healthy women (age 21–65 years; body mass index [BMI] 21.1–32.0 kg/m2; waist circumference [WC] 60.1–109.9 cm). Among the markers considered in the study, only hydroperoxides levels, i.e. by-products of lipid peroxidation, were significantly (p < 0.05 for all) and positively correlated to body fat accumulation after controlling for confounding factors. In particular, this marker was found to be similarly associated with DXA-derived total FM, total FM % and trunk FM as well as with WC. Of note, hydroperoxides appeared to be correlated with abdominal but not with general obesity, as classified according to standard WC and BMI cut-offs, respectively. In conclusion, taken together our data demonstrated that, at least in women, the measurement of body FM by DXA has no advantage over the simpler and cheaper WC with regard to their associations with systemic OxS markers. Moreover, WC emerged as a superior potential predictor of OxS compared to the other most commonly used anthropometric measures (including BMI and waist to hip ratio).

Accumulation of central fat correlates with an adverse oxidative balance in non-obese postmenopausal women.

Abstract The aim of the present study was to investigate whether accumulation of central fat is correlated with systemic oxidative stress (OxS) in non-obese apparently healthy postmenopausal women. Serum parameters of OxS (hydroperoxides and non-enzymatic antioxidants) along with body fat distribution, as assessed by dual-energy-X-ray absorptiometry (DXA), were evaluated in 134 non-obese postmenopausal women. Multiple regression analysis showed that central (trunk) fat significantly correlated with both markers of OxS independently of confounding factors (i.e. BMI, smoking, age, hypertension, legs and arms fat mass). In specific, the standardized regression coefficient was positive for hydroperoxides (β = 0.324, p < 0.05) and negative for antioxidants (β = −0.495, p < 0.01) level. In conclusion, the current data showed that the increase in central fat is an independent predictor of OxS condition among non-obese women in postmenopausal status. The possible pro-oxidant effects of the excess in central adiposity might be more harmful among post- than among pre-menopausal women, due to the postulated ability of E2 to contrast oxidative challenge and the related diseases.

Higher Urinary Levels of 8-Hydroxy-2'-deoxyguanosine Are Associated with a Worse RANKL/OPG Ratio in Postmenopausal Women with Osteopenia.

Postmenopausal osteoporosis (PO) is a major public health issue which affects a large fraction of elderly women. Emerging in vitro evidence suggests a central role of oxidative stress (OxS) in postmenopausal osteoporosis (PO) development. Contrariwise, the human studies on this topic are still scarce and inconclusive. In the attempt to address this issue, we sought to determine if OxS, as assessed by 8-hydroxy-2-deoxyguanosine (8-OHdG), may influence the level of receptor activator of nuclear factor-κb ligand (RANKL)/osteoprotegerin (OPG) ratio (a central regulator of bone metabolism) in a sample (n = 124), including postmenopausal women with osteoporosis, osteopenia and normal bone mass density (BMD). The most striking result that emerged in our study was the independent and positive (beta = 0.449, p = 0.004, and R 2 = 0.185) association between the OxS marker and RANKL/OPG ratio which was found in osteopenic but not in the other 2 sample groups. If confirmed by longitudinal studies, our findings would suggest that OxS is implicated in the derangement of bone homeostasis which precedes PO development. In line with these considerations, antioxidant treatment of postmenopausal women with moderately low BMD might contribute to preventing PO and related complications.