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Pennisi P.,University of Catania | Russo E.,Geriatric Unit | Gaudio A.,University of Catania | Veca R.,Istituto Ricerca Medica Ambientale | And 6 more authors.
Maturitas | Year: 2010

Atherosclerosis and osteoporosis appear to be epidemiologically correlated. Most (but not all) animal and clinical studies suggest that osteoprotegerin (OPG) may represent a possible molecular link between bone loss and vascular calcification. The aim of this study was to investigate the association of OPG with bone mineral density (BMD) and vascular plaques, in order to contribute to a better understanding of the link between atherosclerosis and osteoporosis. The study population consisted of 100 consecutive postmenopausal women referred for routine osteoporosis screening. BMD was evaluated by dual-energy X-ray absorptiometry. Presence of carotid or femoral plaques was examined by ultrasonography. OPG was measured by enzyme immunoassay. Seventy-two subjects had low bone mass and were categorized as osteopenic (32) or osteoporotic (40). Fifty-two subjects had one or more atherosclerotic plaques at carotid or femoral level. Both lumbar spine and femoral BMD were associated with the number of plaques (r = -0.5370; p < 0.0001, and r = -0.4423; p = 0.0012, respectively), however only spine BMD remained significantly associated with the number of plaques after adjustment. OPG serum values showed a significant association with age (r2 = 0.057; p = 0.042). The association between OPG and the number of plaques was significant only in patients with concomitant involvement of carotid and femoral districts (r2 = 0.758; p < 0.0001). © 2010 Elsevier Ireland Ltd. All rights reserved.

Gaudio A.,University of Catania | Pennisi P.,University of Catania | Bratengeier C.,Biomarker Design Forschungs GmbH | Torrisi V.,Istituto Ricerca Medica Ambientale | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Context: Sclerostin, a Wnt signaling antagonist on the osteoblasts produced by osteocytes, is regulated by mechanical strain and is implicated in the pathogenesis of disuse bone loss. There are no data on sclerostin in humans. Objective: The aim of the study was to evaluate sclerostin in patients immobilized after stroke, compared with control subjects, and to analyze its relationship with markers of bone formation and resorption. Design: This was a cross-sectional study. Setting and patients: We studied 40 postmenopausal women immobilized after a single episode of stroke 6 months or longer after onset, and 40 postmenopausal women from the general community. Bone status was assessed by quantitative ultrasound measurements at the calcaneus. Bone alkaline phosphatase (b-AP), carboxy-terminal telopeptide of type I collagen (CrossLaps), and sclerostin were evaluated by ELISA. We also used ELISA to measure serum levels of Dickkopf-1, another soluble inhibitor of Wnt/β-catenin signaling, highly expressed by osteocytes. Results: Immobilized patients had higher sclerostin serum levels (median 0.975 ng/ml; 25th to 75th percentiles 0.662-1.490) than controls (median 0.300 ng/ml; 25th to 75th percentiles 0.165-0.400: P< 0.0001) and an increased bone turnover with a more significant rise inboneresorption (CrossLaps)than formation (b-AP) markers. Sclerostin correlated negatively with b-AP (r = -0.911; P < 0.0001) and positively with CrossLaps (r = 0.391; P = 0.012). Dickkopf-1 did not significantly differ between the groups. Patients alsohadquantitative ultrasoundmeasurementsindex lower than controls (P<0.001). Conclusions: This study shows for the first time that long-term immobilized patients present hypersclerostinemia associated with reduced bone formation, and suggests that sclerostin could be a link between mechanical unloading and disuse osteoporosis in humans. Copyright © 2010 by The Endocrine Society.

Gaudio A.,University of Catania | Privitera F.,University of Catania | Battaglia K.,University of Catania | Torrisi V.,Istituto Ricerca Medica Ambientale | And 5 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signaling. Objectives: The aim of the study was to evaluate the circulating β-catenin levels in T2DM patients and to analyze their relationship with sclerostin and bone turnover markers. Design: This was a cross-sectional study. Setting and Patients: The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (bone mineral density) and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostinand β-catenin were evaluated by an immunoenzymetric assay. Results: Consistent with previous reports in T2DM subjects, we found sclerostin levels higher and bone turnover markers lower than controls. In our cohort of T2DM patients, β-catenin levels are significantly lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50-2.80; and median 4.25 pg/ml, 25th to 75th percentiles 2.20-7.62, respectively; P = 0.0002). β-Catenin correlated negatively with sclerostin (P < 0.0001) and positively with bone alkaline phosphatase (P =0.0030) only in T2DM patients and negatively with age in both groups. Eight of the 40 T2DM patients had vertebral fractures. Conclusions: These results show for the first time that T2DM patients have serum concentrations of β-catenin lower than controls. The negative association of β-catenin with sclerostin suggests a biological effect of increased sclerostin on the Wnt signaling, which appears impaired in T2DM. Copyright © 2012 by The Endocrine Society.

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