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Purpose: We evaluated the early effect of denosumab on circulating markers of atherosclerosis in women with postmenopausal osteoporosis. Methods: Denosumab (60?mg) was administered subcutaneously every 6 months (m) in 27 women (mean age 75?±?5 years) with postmenopausal osteoporosis and high cardiovascular risk for a total of 24 m. Zoledronic acid was administered in 6 age-matched women as a single intravenous dose. Serum levels of vascular cell adhesion protein 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E and P selectin, CD-40 ligand (CD40L), interleukin-6 (IL-6), matrix metalloproteinase (MMP) 1 and 9, monocyte chemoattractant protein-1 (MCP-1), fibrinogen (FBG), and high sensitivity C-reactive protein (hs-CRP) were measured at baseline, 15 days (d), 2, 6 and 12 m after dosing. In the denosumab group, observation was extended to 24 m as secondary endpoint. Results: Serum ICAM-1 levels showed significant increase in the zoledronic acid group (+18?±?0.1%; p?<?0.01) at 12 m. In the denosumab group, we observed a significant increase in serum CD40L (+2?±?0.8%; p?<?0.001), MMP-1 (+11?±?0.4%, p?<?0.02), and MMP-9 (+39.4?±?0.8%, p?<?0.01) at 24 m. There was a significant increase in serum FBG and hs-CRP in both groups at 12 m (denosumab:+2.2?±?0.2% and +50.3?±?1.6%; zoledronic acid: +9.4?±?0.1 and +81.8?±?0.8%; p?<?0.01). No significant between-group differences were found. Conclusions: 24-m treatment with denosumab has no effect on the circulating markers of atherosclerosis in women with postmenopausal osteoporosis. Fluctuation of serum ICAM-1, CD40L, MMPs, FBG and hs-CRP can be ascribed to perturbation of immunological mechanisms stimulated by denosumab and zoledronic acid.

Prostate cancer is the most common tumor in men. To the best of our knowledge a systematic assessment of bone and mineral abnormalities has not been performed in prostatic cancer patients consecutively enrolled. This study was therefore carried out to investigate changes of skeletal and mineral metabolism in patients with prostate cancer (n= 69). A population of patients with cancer of various origin was also investigated as a control group (n= 53), since a comparison with non-prostate cancer patients has not been previously reported. In the prostatic cancer group, one patient had extremely high values of C-terminal Fibroblast Growth Factor 23, low values of tubular reabsorption of phosphate and very high values of bone alkaline phosphatase, suggesting the diagnosis of oncogenic osteomalacia. We found nine patients with primary hyperparathyroidism in the group of prostate cancer vs. only one in cancer patients group (p<  0.026). We stratified the population on the basis of Gleason score, prostate specific antigen and hormonal therapy. Using a generalized linear model with a logit link to predict the probability of developing primary hyperparathyroidism, only Gleason score, C-terminal fibroblast growth factor 23 and hormonal therapy had a significant effect (p< 0.05). Controlling for other covariates, a rise in fibroblast growth factor 23 increases the odds of developing primary hyperparathyroidism by 2% (p= 0.017), while patients with higher values of Gleason score have a much greater probability of developing primary hyperparathyroidism (log-odds  =  3.6, p <  0.01). The probability decreases with higher values of Gleason score while on hormonal therapy; a further decrease was observed in patients on hormonal treatment and lower values of GS. Finally, lower grade of Gleason score without hormonal therapy have a significant protective factor (p<  0.01) decreasing the odds of developing primary hyperparathyroidism by 8%. We showed a remarkable prevalence of primary hyperparathyroidism in men with prostate cancer; the multivariate analysis demonstrates that higher aggressiveness of prostate cancer, as determined by Gleason score, is a significant predictor of increased risk of developing primary hyperparathyroidism.

We considered the case of small-medium enterprises (SMEs) in Italy introducing a new classifier to predict bankruptcy up to eight years prior to failure. We considered a stratified random sample of 100 non-listed Italian SMEs, 50 of which filed for bankruptcy during the years 2000 to 2011. Results suggest that the proposed method more than holds its own when compared with standard non-parametric classification techniques. The performance of the proposed method based on recognition rate, sensitivity and specificity shows that the proposed technique is effective in predicting the failure of a firm up to eight years prior to the event. The high specificity makes the proposed technique very effective as a warning signal to determine if a firm is in distress with a sufficient enough time to take proper actions. The performance assessment has been achieved via cross-validation to get unbiased estimates of the performances.

The “trabecular bone score” (TBS) indirectly explores bone quality, independently of bone mineral density (BMD). We investigated the effects of anthropometric and metabolic parameters on TBS in 87 overweight/obese men. We assessed BMD and TBS by DXA, and some parameters of glucose metabolism, sex-and calciotropic hormone levels. Regression models were adjusted for either age and BMI, or age and waist circumference, or age and waist/hip ratio, also considering BMI >35 (y/n) and metabolic syndrome (MS) (y/n). Correlations between TBS and parameters studied were higher when correcting for waist circumference, although not significant in subjects with BMI >35. The analysis of covariance showed that the same model always had a higher adjusted r-square index. BMD at lumbar spine and total hip, fasting glucose, bioavailable testosterone, and sex hormone-binding globulin are the only covariates having a significant effect (p< 0.05) on the variations of TBS. The presence of MS negatively affected only the association between TBS and BMD at total hip. We did not find any significant effect of BMI >35 on TBS values or significant interaction terms between each covariate and either BMI >35 or the presence of MS. Obesity negatively affected TBS, despite unchanged BMD. Alterations of glucose homeostasis and sex hormone levels seem to influence this relationship, while calciotropic hormones have no role. The effect of waist circumference on TBS is more pronounced than that of BMI.