Efficacy of Denosumab Therapy Following Treatment with Bisphosphonates in Women with Osteoporosis: A Cohort Study.

Denosumab is a human monoclonal antibody that neutralizes RANKL, a cytokine able to interact with the RANK receptor on preosteoclasts and osteoclasts, decreasing their recruitment and differentiation, leading to a decreased bone resorption. The aim of this observational real-life study was to analyze adherence to denosumab therapy and assess its efficacy in increasing bone mineral density (BMD) and modulating biochemical skeletal markers following previous treatments with bisphosphonates in a group of post-menopausal women with osteoporosis. Women were recruited in the specialized center from March 2012 to September 2019. Biochemical markers were recorded at baseline and every six months prior to subsequent drug injection. Dual X-ray absorptiometry was requested at baseline and after 18/24 months. Comparing BMD at baseline and after denosumab therapy in naive patients and in those previously treated with bisphosphonates, a positive therapeutic effect was observed in both groups. The results of our real-life study demonstrate, as expected, that BMD values significantly increased upon denosumab treatment. Interestingly, denosumab showed an increased efficacy in patients previously treated with bisphosphonates. Moreover, biochemical markers data indicate that osteoporotic patients, without other concomitant unstable health conditions, could be evaluated once a year, decreasing the number of specialistic center access.

Estimated need for anthelminthic medicines to control soil-transmitted helminthiases in school-aged children, 2020-2030.

BACKGROUND: Soil-transmitted helminthiases (STH) are part of the group of neglected tropical diseases traditionally treated with preventive chemotherapy interventions. In recent years, drug donations have been essential to expanding preventive chemotherapy and achieving progressive control of morbidity from STH. This study aims to evaluate the need for anthelminthic medicines during 2020-2030. METHODS: To estimate the need for anthelminthic medicines, we considered three different scenarios: (1) the control programmes continues to expand coverage and maintains the frequency of drug administration established at baseline; (2) the programmes continues to expand coverage but adapts the frequency of drug administration when the STH prevalence is reduced and (3) the STH programme becomes self-sustainable in some endemic countries. RESULTS: We estimate that the number of anthelmintic medicines needed to treat school-aged children will increase by 40% by 2025 and by 52% by 2030 if countries do not change the frequency of preventive chemotherapy (scenario 1); that the number of tablets needed will reduce by 32.4% by 2025 and by 49.1% in 2030 if endemic countries reduce the frequency of preventive chemotherapy (scenario 2); and drug donations could be reduced by 54.4% by 2025 and 74.4% by 2030 if some endemic countries could become independent in drug procurement (scenario 3). CONCLUSIONS: The number of anthelmintic medicines needed to achieve elimination of morbidity due to STH in school-aged children will decline during 2020-2030. The decline will be substantial if a number of "upper-middle income" countries in which STH are endemic procure, as expected, anthelminthic medicines independently.

Effects of Acute Whole-Body Vibration Practice on Maximal Fat Oxidation in Adult Obese Males: A Pilot Study.

OBJECTIVE: Whole-body vibration (WBV) training has been established as a useful method to improve physical fitness in obese individuals. However, the effects of WBV exercise on maximal fat oxidation (MFO) have not been examined in obese subjects yet. METHOD: MFO was eval-uated during a cardiopulmonary exercise test (CPET) on a treadmill in 12 adult obese males (BMI = 34.9 ± 3.3 kg/m2) after three different warm-up conditions: static half squat plus WBV (HSV), static half squat without WBV (HSWV), and rest (REST). Cortisol levels were evaluated before and after the warm-up, and 1 min (T1), 10 min (T10), and 30 min (T30) of the recovery phase. RESULTS: MFO was significantly higher in HSV (p = 0.013; 569.4 ± 117.9 mg/min) and HSWV (p = 0.033; 563.8 ± 142.9 mg/min) than REST (445.5 ± 117.9 mg/min). Cortisol concentrations at T1 were significantly higher in HSV (p = 0.023) and HSWV (p = 0.015) than REST. Moreover, cortisol concentrations were significantly lower at T30 than T1 in HSWV (p = 0.04). No differences were found between T30 and T1 in HSV. CONCLUSIONS: Active warm-up increases MFO; however, vibration stimulus during half squatting does not increase MFO during a CPET in obese subjects. The lack of significant differences of cortisol concentrations in HSV during the recovery phase might suggest a long-term effect of WBV on the endocrine system.

Sustained preventive chemotherapy for soil-transmitted helminthiases leads to reduction in prevalence and anthelminthic tablets required.

BACKGROUND: The goal of soil-transmitted helminthiases (STH) control programmes is to eliminate STH-associated morbidity in the target population by reducing the prevalence of moderate- and heavy-intensity infections and the overall STH infection prevalence mainly through preventive chemotherapy (PC) with either albendazole or mebendazole. Endemic countries should measure the success of their control programmes through regular epidemiological assessments. We evaluated changes in STH prevalence in countries that conducted effective PC coverage for STH to guide changes in the frequency of PC rounds and the number of tablets needed. METHODS: We selected countries from World Health Organization (WHO)'s Preventive Chemotherapy and Transmission control (PCT) databank that conducted ≥5 years of PC with effective coverage for school-age children (SAC) and extracted STH baseline and impact assessment data using the WHO Epidemiological Data Reporting Form, Ministry of Health reports and/or peer-reviewed publications. We used pooled and weighted means to plot the prevalence of infection with any STH and with each STH species at baseline and after ≥5 years of PC with effective coverage. Finally, using the WHO STH decision tree, we estimated the reduction in the number of tablets needed. RESULTS: Fifteen countries in four WHO regions conducted annual or semi-annual rounds of PC for STH for 5 years or more and collected data before and after interventions. At baseline, the pooled prevalence was 48.9% (33.1-64.7%) for any STH, 23.2% (13.7-32.7%) for Ascaris lumbricoides, 21.01% (9.7-32.3%) for Trichuris trichiura and 18.2% (10.9-25.5%) for hookworm infections, while after ≥5 years of PC for STH, the prevalence was 14.3% (7.3-21.3%) for any STH, 6.9% (1.3-12.5%) for A. lumbricoides, 5.3% (1.06-9.6%) for T. trichiura and 8.1% (4.0-12.2%) for hookworm infections. CONCLUSIONS: Countries endemic for STH have made tremendous progress in reducing STH-associated morbidity, but very few countries have data to demonstrate that progress. In this study, the data show that nine countries should adapt their PC strategies and the frequency of PC rounds to yield a 36% reduction in drug needs. The study also highlights the importance of impact assessment surveys to adapt control strategies according to STH prevalence.

Female infertility: which role for obesity?

Obesity is associated with infertility in women through multiple and complex mechanisms. Briefly, the adipose tissue through the production of many factors, such as leptin, free fatty acids (FFA), and cytokines may affect both ovarian and endometrium functions, with a final alteration in oocyte maturation and endometrial epithelium receptivity. In addition, through the development of peripheral insulin resistance obesity produces a condition of functional hyperandrogenism and hyperestrogenism that contribute to produce anovulation and to reduce endometrial receptivity and, therefore participate to cause infertility. Weight loss is able to restore fertility in most cases, but there are no practical indications to guide the clinician to choice the best method among increased physical activity, diet, drugs, and bariatric surgery.

Relationship between individual ventilatory threshold and maximal fat oxidation (MFO) over different obesity classes in women.

OBJECTIVE: The use of the Individual Ventilatory Threshold (IVT), as parameter to prescribe exercise intensity in individuals with obesity, has become more frequent during the last years. This study aimed to evaluate the relationship between IVT and Maximal Fat Oxidation (MFO) in women with obesity. METHODS: Fifty-two obese female adults (age = 43.6±10.9 years; BMI = 38.5±5.2 kg/m2) were included in this study. According to the BMI classification, subjects were divided into three groups: Obese Class I (OBI, n = 16); Obese Class II (OBII, n = 20) and Obese Class III (OBIII, n = 16). All subjects performed an incremental graded exercise test to evaluate peak oxygen uptake (VO2peak), IVT and MFO. MFO was evaluated using a stoichiometric equation. Fat max zone was determined for each subject within 10% of fat oxidation rates at MFO. For each HR, %HRmax, VO2 and %VO2peak variable, Pearson's correlation test was done between IVT and MFO exercise intensity. When statistical correlation was found we used a comparative statistical analysis to assess differences between IVT and MFO. Statistical significance was set at P ≤ 0.05. RESULTS: For each HR, %HRmax, VO2 and %VO2peak variable there was a positive significant correlation (P<0.01) between IVT and MFO. No significant differences were found for HR, %HRmax, and VO2 between IVT and MFO. %VO2peak was significantly higher at IVT than at MFO (P = 0.03). MFO rates were significantly higher in OBIII women than in women of the other two classes. In all subjects, IVT was within the fat max zone. CONCLUSION: The use of HR and VO2 corresponding to IVT could be a useful parameter not only to improve cardiorespiratory fitness but also to prescribe physical activity that maximize fat oxidation in obese subjects.

Effects of body weight loss program on parameters of muscle performance in female obese adults.

BACKGROUND: Body weight loss program may lead to a decrease in lean body mass affecting negatively muscle performance in obese subjects. Thus, the aim of this study was to examine the effect of weight loss on muscle performance in female obese subjects. METHODS: Eighty obese female adults were enrolled for a 2-month unsupervised aerobic training (UAT) plus nutritional program. In the pre- and postintervention body composition was evaluated by hand-to-foot bioelectrical impedance method, body strength using handgrip test, and lower muscle power was assessed by a 5-repetition chair stand test (CST) and 30-s chair stand test (30sCST) wearing a dynamometer. RESULTS: Thirty-six subjects completed the protocol, 39% had high compliance (HC), while 61% had low compliance (LC) to exercise prescription. HC group showed a significant decreased body weight, percent of fat mass and lean muscle mass after training. Both groups significantly increased CST performance while only HC significantly increased 30sCST. No differences were found in CST muscle power in both groups between pre- and post-training. However, evaluation of muscle power during 30sCST showed significantly higher value in HC group than LC group after training. CONCLUSIONS: The results of our study show that although total lean muscle mass decreased after UAT, lower body muscle efficiency increased while muscle power did not change suggesting that in obese patients UAT can help to optimize weight loss and body efficiency. The data might be helpful for exercise professionals to evaluate correctly the muscle performance in obese adults after weight loss programs.

Insulin growth factor-1 correlates with higher bone mineral density and lower inflammation status in obese adult subjects.

PURPOSE: Obesity is a severe public health problem worldwide, leading to an insulin-resistant state in liver, adipose, and muscle tissue, representing a risk factor for type 2 diabetes mellitus, cardiovascular diseases, and cancer. We have shown that abdominal obesity is associated with homeostasis derangement, linked to several hormonal and paracrine factors. Data regarding potential link between GH/IGF1 axis, bone mineral density, and inflammation in obesity are lacking. Thus, aim of this study was to evaluate correlation among IGF-1, BMD, and inflammation in obese individuals. METHODS: The study included 426 obese subjects, mean age 44.8 ± 14 years; BMI 34.9 ± 6.1. Exclusion criteria were chronic medical conditions, use of medications affecting bone metabolism, hormonal and nutritional status, recent weight loss, and prior bariatric surgery. Patients underwent measurements of BMD and body composition by DEXA and were evaluated for hormonal, metabolic profile, and inflammatory markers. RESULTS: In this population, IGF-1 was inversely correlated with abdominal FM% (p < 0.001, r 2 = 0.12) and directly correlated with osteocalcin (OSCA) (p < 0.002, r 2 = 0.14). A negative correlation was demonstrated between IGF-1 levels and nonspecific inflammatory index, such as fibrinogen (p < 0.01, r 2 = 0.04) and erythrocyte sedimentation rate (p < 0.0001, r 2 = 0.03). IGF-1 was directly correlated with higher BMD, at both lumbar (p < 0.02, r 2 = 0.03) and femoral site (p < 0.04, r 2 = 0.03). CONCLUSIONS: In conclusion, our results show that higher levels of serum IGF-1 in obese patients correlate with lower inflammatory pattern and better skeletal health, as demonstrated by higher BMD and osteocalcin levels. These results lead to speculate the existence of a bone-adipose-muscle interplay modulating energy homeostasis, glucose, bone metabolism, and chronic inflammation in individuals affected by abdominal obesity.

Preventive chemotherapy in one year reduces by over 80% the number of individuals with soil-transmitted helminthiases causing morbidity: results from meta-analysis.

The morbidity due to Ascaris lumbricoides and Trichuris trichiura is caused by infections of moderate and heavy intensity while hookworm infections of all intensities are recognized to cause morbidity. This study aims to evaluate the effect of repeated rounds of preventive chemotherapy on the proportion of soil-transmitted helminth (STH) infections causing morbidity. We identified studies from 17 countries, reporting changes in the proportion of STH infection causing morbidity between baseline and follow-up. In the studies identified, the average proportion of individuals with STH infections of moderate and heavy intensity was of 14% at baseline and was on average reduced to 2% by the intervention (i.e., 85% reduction). There was an average reduction of 73% after the first year of treatment, which reached almost 80% after 5 years and over 95% in 10 years of deworming interventions. The reduction in hookworm prevalence was 57% after 12 months reaching 78% after 5 years. We consider the results presented in this study especially useful for decision makers as it demonstrates the effectiveness of preventive chemotherapy in reducing STH prevalence and morbidity. We encourage the implementation of deworming programs to achieve the goal, set by WHO for 2020, to eliminate STH morbidity in children.

Physical activity and hypocaloric diet recovers osteoblasts homeostasis in women affected by abdominal obesity.

Obesity is a multifactorial disease linked to metabolic chronic disorders such as diabetes, and hypertension. Also, it has recently been associated with skeletal alterations and low bone mineral density. We previously demonstrated that exposure of osteoblasts to sera of sedentary subjects affected by obesity alters cell homeostasis in vitro, leading to disruption of intracellular differentiation pathways and cellular activity. Thus, the purpose of the present study has been to evaluate whether sera of sedentary obese women, subjected to physical activity and hypocaloric diet, could recover osteoblast homeostasis in vitro as compared to the sera of same patients before intervention protocol. To this aim, obese women were evaluated at time 0 and after 4, 6, and 12 months of individualized prescribed physical activity and hypocaloric diet. Dual-energy-X-ray absorptiometry measurements were performed at each time point, as well as blood was collected at the same points. Cells were incubated with sera of subjects before and after physical activity as described: obese at baseline and after for 4, 6, and 12 months of physical activity and nutritional protocol intervention. Osteoblasts exposed to sera of patients, who displayed increased lean and decreased fat mass (from 55.5 ± 6.5 to 57.1 ± 5.6% p ≤ 0.05; from 44.5 ± 1.1 to 40.9 ± 2.6% p ≤ 0.01 respectively), showed a time-dependent increase of Wnt/ß-catenin signaling, versus cells exposed to sera of obese patients before intervention protocol, suggesting recovery of osteoblast homeostasis upon improvement of body composition. An increase in ß-catenin nuclear accumulation and nuclear translocation was also observed, accompanied by an increase in Adiponectin receptor 1 protein expression, suggesting positive effect on cell differentiation program. Furthermore, a decrease in sclerostin amount and an increase of type 1 procollagen amino-terminal-propeptide were depicted as compared to baseline, proportionally to the time of physical activity, suggesting a recovery of bone remodeling modulation and an increase of osteoblast activity induced by improvement of body composition. In conclusion, our results show for the first time that sera of obese sedentary women who increased lean mass and decreased fat mass, by physical activity and hypocaloric diet, rescue osteoblasts differentiation and activity likely due to a reactivation of Wnt/ß-catenin-pathway, suggesting that a correct life style can improve skeletal metabolic alteration induced by obesity.

Reduced sleep duration affects body composition, dietary intake and quality of life in obese subjects.

PURPOSE: Sleep duration has emerged as a crucial factor affecting body weight and feeding behaviour. The aim of our study was to explore the relationship among sleep duration, body composition, dietary intake, and quality of life (QoL) in obese subjects. METHODS: Body composition was assessed by DXA. "Sensewear Armband" was used to evaluate sleep duration. SF-36 questionnaire was used to evaluate quality of life (QoL). A 3-day dietary record was administered. Subjects were divided into 2 groups: sleep duration > and ≤300 min/day. RESULTS: 137 subjects (105 women and 32 men), age: 49.8 ± 12.4 years, BMI: 38.6 ± 6.7 kg/m(2), were enrolled. Sleep duration was ≤300 min in 30.6 % of subjects. Absolute and relative fat mass (FM) (40.5 ± 9 vs. 36.5 ± 9.1 kg; 40.2 ± 4.7 vs. 36.9 ± 5.6 %), and truncal fat mass (19.2 ± 6.1 vs. 16.6 ± 5 kg; 38.6 ± 5.3 vs. 35.2 ± 5.5 %) were higher in subjects sleeping ≤300 min when compared to their counterparts (all p < 0.05), whereas just a tendency towards a higher BMI was observed (p = 0.077). Even though energy intake was not different between groups, subjects sleeping ≤300 min reported a higher carbohydrate consumption per day (51.8 ± 5.1 vs. 48.4 ± 9.2 %, p = 0.038). SF-36 total score was lower in subjects sleeping ≤300 min (34.2 ± 17.8 vs. 41.4 ± 12.9, p = 0.025). Sleep duration was negatively associated with FM (r = -0.25, p = 0.01) and SF-36 total score (r = -0.31, p < 0.001). The inverse association between sleep duration and SF-36 total score was confirmed by the regression analysis after adjustment for BMI and fat mass (R = 0.43, R (2) = 0.19, p = 0.012). CONCLUSION: Reduced sleep duration negatively influences body composition, macronutrient intake, and QoL in obese subjects.

Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects.

Aim of the study was to examine cardiorespiratory parameters at individual ventilatory threshold (IVT) and peak exercise capacity ([Formula: see text]) in outpatient diabetic and sarcopenic obese subjects. Seventeen obese subjects (BMI: 36.6 ± 4.1 kg·m(-1)) and sixteen SO subjects (BMI: 37.0 ± 7.3 kg·m(-1)) were compared with sixteen T2DM subjects (BMI: 37.7 ± 5.6 kg·m(-1)). All groups performed an incremental exercise test on a treadmill according to their physical ability. [Formula: see text], %HRmax, and maximal metabolic equivalent (METmax) were evaluated at maximal effort. Moreover, [Formula: see text], %[Formula: see text], %HRmax, %HRR, ΔHR, and METivt were assessed at IVT. No significant differences were found in any physiological parameters at maximal effort ([Formula: see text], %HRmax, and METmax) in all groups. On the contrary, [Formula: see text], %[Formula: see text], %HRmax, %HRR, ΔHR, and METivt were significantly lower in T2DM subjects as compared to OB and SO subjects at IVT (p < 0.05). Our results show that while at maximal effort there are no differences among groups, at IVT the physiological parameters are lower in T2DM subjects than in OB and SO subjects. Therefore, due to the differences observed in the groups, we suggest usng the IVT as a useful parameter to prescribe aerobic exercise in obese with sarcopenia or diabetes mellitus conditions.

Psoriasis and bone mineral density: implications for long-term patients.

Psoriasis is a chronic inflammatory disease associated with several comorbidities. Osteoporosis is defined as a reduction in bone mineral density with impaired bone microarchitecture. Several mechanisms may be implicated as a possible cause for the association between psoriasis and osteoporosis, such as systemic inflammation, anti-psoriatic drug intake and joint dysfunction for psoriatic arthritis (PsA). The aim of the present study was to assess bone mineral density (BMD) in patients with psoriasis, correlating the prevalence of osteopenia/osteoporosis with Psoriasis Area and Severity Index (PASI) score, mean duration of psoriatic disease, PsA and previous treatments for psoriasis. Forty-three consecutive patients with psoriasis, 19 of whom were affected by the arthropathic form, were enrolled. We evaluated the severity of psoriasis as measured by PASI score, the CASPAR criteria and ultrasounds of the joints to verify the diagnosis of PsA and the age of psoriasis onset to estimate mean disease duration. Patients underwent a bone density scan of the lumbar spine and femoral neck by dual-energy X-ray absorptiometry to measure BMD. Patients with osteopenia/osteoporosis showed a statistically significant longer average duration of psoriatic disease (17 years), compared to patients affected by psoriasis with normal T-score (8.8 years) (P = 0.04). The linear logistic regression confirms a significant relation between mean psoriatic disease duration and BMD alterations (P = 0.04). Our results suggest the necessity of an early diagnostic evaluation of bone metabolism in patients with psoriasis, especially if characterized by longer disease duration.

Abdominal Fat and Sarcopenia in Women Significantly Alter Osteoblasts Homeostasis In Vitro by a WNT/ ß -Catenin Dependent Mechanism.

Obesity and sarcopenia have been associated with mineral metabolism derangement and low bone mineral density (BMD). We investigated whether imbalance of serum factors in obese or obese sarcopenic patients could affect bone cell activity in vitro. To evaluate and characterize potential cellular and molecular changes of human osteoblasts, cells were exposed to sera of four groups of patients: (1) affected by obesity with normal BMD (O), (2) affected by obesity with low BMD (OO), (3) affected by obesity and sarcopenia (OS), and (4) affected by obesity, sarcopenia, and low BMD (OOS) as compared to subjects with normal body weight and normal BMD (CTL). Patients were previously investigated and characterized for body composition, biochemical and bone turnover markers. Then, sera of different groups of patients were used to incubate human osteoblasts and evaluate potential alterations in cell homeostasis. Exposure to OO, OS, and OOS sera significantly reduced alkaline phosphatase, osteopontin, and BMP4 expression compared to cells exposed to O and CTL, indicating a detrimental effect on osteoblast differentiation. Interestingly, sera of all groups of patients induced intracellular alteration in Wnt/ ß -catenin molecular pathway, as demonstrated by the significant alteration of specific target genes expression and by altered ß -catenin cellular compartmentalization and GSK3 ß phosphorylation. In conclusion our results show for the first time that sera of obese subjects with low bone mineral density and sarcopenia significantly alter osteoblasts homeostasis in vitro, indicating potential detrimental effects of trunk fat on bone formation and skeletal homeostasis.

Negative association between trunk fat, insulin resistance and skeleton in obese women.

AIM: To evaluate the potential interference of trunk fat (TF) mass on metabolic and skeletal metabolism. METHODS: In this cross-sectional study, 340 obese women (mean age: 44.8 ± 14 years; body mass index: 36.0 ± 5.9 kg/m(2)) were included. Patients were evaluated for serum vitamin D, osteocalcin (OSCA), inflammatory markers, lipids, glucose and insulin (homeostasis model assessment of insulin resistance, HOMA-IR) levels, and hormones profile. Moreover, all patients underwent measurements of bone mineral density (BMD; at lumbar and hip site) and body composition (lean mass, total and trunk fat mass) by dual-energy X-ray absorptiometry. RESULTS: Data showed that: (1) high TF mass was inversely correlated with low BMD both at lumbar (P < 0.001) and hip (P < 0.01) sites and with serum vitamin D (P < 0.0005), OSCA (P < 0.0001) and insulin-like growth factor-1 (IGF-1; P < 0.0001) levels; (2) a positive correlation was found between TF and HOMA-IR (P < 0.01), fibrinogen (P < 0.0001) and erythrocyte sedimentation rate (P < 0.0001); (3) vitamin D levels were directly correlated with IGF-1 (P < 0.0005), lumbar (P < 0.006) and hip (P < 0.01) BMD; and (4) inversely with HOMA-IR (P < 0.001) and fibrinogen (P < 0.0005).Multivariate analysis demonstrated that only vitamin D was independent of TF variable. CONCLUSION: In obese women, TF negatively correlates with BMD independently from vitamin D levels. Reduced IGF-1 and increased inflammatory markers might be some important determinants that account for this relationship.