Search

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.

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, its effectiveness in increasing bone mineral density (BMD) and in modulating biochemical skeletal markers upon previous treatments with bisphosphonates in a group of post-menopausal women affected by 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 effectiveness 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.

In an increasingly obese and aging population, metabolic chronic diseases, low bone mass, and osteoporotic fractures are major public health concerns. During the last decades, obesity and osteoporosis have become dramatic global health problems with an increasing prevalence worldwide. Interestingly, the belief that obesity is protective against osteoporosis has come into question, as demonstrated by recent epidemiologic and clinical studies, which have shown that high level of fat mass might be a risk factor for osteoporosis and fragility fractures, both in men and women. Several potential mechanisms have been proposed to explain the complex relationship between adipose tissue and bone. This chapter considers recent data in the literature to further evaluate the relationship between fat and bone tissue in men.

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 eval­uated 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.

Malnutrition is a frequent condition in the elderly especially in hospitals and in nursing homes, and even among the free-living elders the prevalence is not negligible (5-10%). Awareness towards malnutrition is still limited. The lack of time for nutritional assessment by the overcommitted healthcare personnel, including the general practitioners (GPs), may represent one possible explanation for limited recognition of malnutrition. Therefore, a self-administered instrument could be useful in raising alert on the GPs and allow early detection of malnutrition and early care provision. The aim of the present study was to analyze the validity of the Self-MNA that takes cue from the Mini Nutritional Assessment-Short Form (MNA-SF) and has been adapted to be self-administered by free-living elderly subjects. Participants were recruited from patients referring to the GP offices in Italy. Nutritional evaluation was performed through the administration of Full-MNA, MNA-SF and Self-MNA. The comorbidity level was assessed through the Cumulative Illness Rating Scale (CIRS). The level of difficulty in filling out the test was reported by the participants, and the time spent to complete the Self-MNA was also registered. A total of 226 subjects, 125 women and 101 men (75.1 ± 8 and 75.3 ± 8 years old, respectively; p=0.89) were enrolled, and 214 (94.7%) of them completed the Self-MNA. According with the Full-MNA test score, 8.4% of women and 3.5% of men were classified as malnourished, whereas 32.7% of women and 31.4% of men were at risk of malnutrition. Agreement between Self-MNA and Full-MNA, and Self-MNA vs. MNA-SF was classified as “moderate” (k = 0.476 and 0.496 respectively; p < 0.001). Self-MNA showed a fair predictive value compared to the Full-MNA and MNA-SF tests (76.6 and 79.9%, respectively) with a barely adequate sensitivity (70.9 and 75.4%, respectively). The analysis of the characteristics of FN (false negative: subjects who were considered at risk of malnutrition or malnourished at Full-MNA but not at Self-MNA) showed that the clinical and functional aspects of these subjects (age, comorbidity and severity, time necessary to complete the Self-MNA, decrease in food intake, severe illness in the past 3 months, dementia and depression, fluid intake, need for feeding assistance, arm and calf circumferences) were very similar to the characteristics of true positive subjects. Patients required 6.7 ± 4.5 minutes to complete the test and 25 subjects (11.7%) needed more than 10 minutes, up to a maximum of 30 minutes. Patients who stated a greater difficulty were older (79.8 ± 7 vs. 73.5 ± 7 years; p< 0.001), they were more «malnourished» at Full-MNA (10.7 vs. 1,7%; p= 0.006) and clinical status was characterized by a higher severity index (1.72 ± 0.6 vs. 1.41 ± 0.4; p= 0.008). In the present study we investigated the validity of the Self-MNA in a sample of free-living elderly subjects. The results obtained confirm the validity of the test that may represent a useful tool for the GPs, although some important limitations need to be considered, limiting its use in clinical practice.

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. 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. In this population, IGF-1 was inversely correlated with abdominal FM% (p

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.

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.

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/β-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 β-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/β-catenin-pathway, suggesting that a correct life style can improve skeletal metabolic alteration induced by obesity.

During the last decades, in industrialized countries was observed a significant increase in average life expectancy with a gradual aging of the population. The prolonged life expectancy, lifestyle and improper eating behaviors have contributed to increase the incidence of illnesses, often resulting of well-being, such as obesity, dysmetabolism, cardiovascular disease, osteoporosis, which contribute heavily to both quality of life of those affected and significant increase in social costs.

Background: Persistence is commonly considered a key factor for the successful management of osteoporosis and fragility fractures. Denosumab is the first biologic agent developed for the treatment of osteoporosis with satisfying data regarding the persistence with this therapy. Aim: The purpose of this multicenter observational real practice study was to evaluate the persistence with denosumab treatment in post-menopausal women affected by osteoporosis. Material/subjects and methods: Women were recruited in four specialized centers for the management of osteoporosis in North, Center and South of Italy. We included women with a diagnosis of post-menopausal osteoporosis, aged >50 years, able to obtain a prescription according to the Italian reimbursement criteria in force during the study period for anti-osteoporotic pharmacological treatment. They initiated a treatment with subcutaneous denosumab (Prolia ® ) 60 mg/every 6 months between November 2011 and May 2016. Women who had received aromatase inhibitors were excluded. Patients were assessed at baseline and every 6 months for all treatment length. Persistence data were evaluated for a total of 36 months. Results: Eight hundred seventy women were enrolled; mean aged 70 years, with a mean body mass index of 24.8 ± 4.1 kg/m 2 . At the Dual-energy X-ray absorptiometry assessment, the mean lumbar spine T-score was −2.76 ± 1.14 standard deviations (SD) and the mean femoral neck T-score was −2.49 ± 0.80 SD. During the study, the total persistence was 91.4%. Total dropouts were 75 (8.6%), higher within the initial 6-month period of treatment. Conclusions: Persistence to denosumab treatment in our observational real practice study was very high. These results suggest that factors such as frequency of visits, pharmacological schedule, and opportunity to call the doctor might play an important role in the persistence and adherence to treatment to obtain maximum therapeutic effect and avoid further fragility fractures. Background: Persistence is commonly considered a key factor for the successful management of osteoporosis and fragility fractures. Denosumab is the first biologic agent developed for the treatment of osteoporosis with satisfying data regarding the persistence with this therapy. Aim: The purpose of this multicenter observational real practice study was to evaluate the persistence with denosumab treatment in post-menopausal women affected by osteoporosis. Material/subjects and methods: Women were recruited in four specialized centers for the management of osteoporosis in North, Center and South of Italy. We included women with a diagnosis of post-menopausal osteoporosis, aged >50 years, able to obtain a prescription according to the Italian reimbursement criteria in force during the study period for anti-osteoporotic pharmacological treatment. They initiated a treatment with subcutaneous denosumab (Prolia®) 60 mg/every 6 months between November 2011 and May 2016. Women who had received aromatase inhibitors were excluded. Patients were assessed at baseline and every 6 months for all treatment length. Persistence data were evaluated for a total of 36 months. Results: Eight hundred seventy women were enrolled; mean aged 70 years, with a mean body mass index of 24.8 ± 4.1 kg/m2. At the Dual-energy X-ray absorptiometry assessment, the mean lumbar spine T-score was −2.76 ± 1.14 standard deviations (SD) and the mean femoral neck T-score was −2.49 ± 0.80 SD. During the study, the total persistence was 91.4%. Total dropouts were 75 (8.6%), higher within the initial 6-month period of treatment. Conclusions: Persistence to denosumab treatment in our observational real practice study was very high. These results suggest that factors such as frequency of visits, pharmacological schedule, and opportunity to call the doctor might play an important role in the persistence and adherence to treatment to obtain maximum therapeutic effect and avoid further fragility fractures.

Aims: Osteogenesis imperfecta (OI) is a rare inherited disorder causing low bone density and increased fragility. Bisphosphonates (BP) are a treatment of choice for OI. Few studies have investigated the long-term effects of BP in OI patients. Thus, aim of our study was to follow up adults affected by OI to evaluate changes in metabolic, clinical situation and safety of long-term neridronic acid therapy, BP authorized for OI treatment. Study design: Longitudinal observational study. Place and duration of the Study: Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition. Year: 2004 - October 2010. Methodology: 68 patients underwent clinical examination, laboratory endocrine/ metabolic, pro-inflammatory cytokines screening, ECG at baseline and every 3 months and bone mineral density evaluation, by DEXA, once a year. Results: Skeletal evaluation showed a significant increase of BMD through follow up. Patients were evaluated for metabolic and cardiovascular risk factors, which were unmodified by long-term therapy. Conclusion: Long-term neridronic acid treatment increases bone density, does not alter metabolic parameters indicating that this therapy can be considered safe and a valid therapeutic option for OI patients.

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.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.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).Reduced sleep duration negatively influences body composition, macronutrient intake, and QoL in obese subjects.

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 activityin 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/β-catenin molecular pathway, as demonstrated by the significant alteration of specific target genes expression and by alteredβ-catenin cellular compartmentalization and GSK3βphosphorylation. In conclusion our results show for the first time that sera of obese subjects with low bone mineral density and sarcopenia significantly alter osteoblasts homeostasisin vitro, indicating potential detrimental effects of trunk fat on bone formation and skeletal homeostasis.

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.

Several chronic metabolic alterations are present in obese subjects. While it is well known about the detrimental effect of abdominal adipose tissue on chronic metabolic clinical condition, less is known on the role of lean mass in obese subjects. Thus, the aim of our study was to evaluate the potential correlation of muscle mass, metabolic condition and inflammation status in obese individuals.The study included 426 obese subjects (86 men and 340 female; mean age 44.8 ± 14 years; BMI: 34.9 ± 6.1 kg/m(2)). Exclusion criteria were chronic medical conditions or use of medications affecting bone metabolism, alterations of hormonal and nutritional status, vitamin D supplementation, recent weight loss and prior bariatric surgery. Patients underwent measurements of bone mineral density (lumbar and hip) and body composition (lean mass, total and trunk fat mass) by dual X-ray absorptiometry and were evaluated for hormonal and metabolic profile and inflammatory markers.Higher lean body mass (LM%) was inversely correlated with homeostasis model assessment of insulin resistance (p0.0091; r(2) 0.03938) and associated with lower fibrinogen levels (p0.0001; r(2) 0.1263). Interestingly, in obese subjects, LM% was associated with higher levels of vitamin D (p0.0001, r(2) 0.1140), osteocalcin (p0.0001, r(2) 0.2401) and insulin-like growth factor-1 (IGF-1) (p0.0002, r(2) 0.1367).Our results show for the first time that in obese patients, higher amounts of lean mass are directly linked to a lower inflammatory profile and to better insulin sensitivity, but also to the presence of higher level of vitamin D and IGF-1. Moreover, these data suggest that higher levels of lean mass in obese people correlate with a better metabolic profile and, thus, strongly suggest the need to develop programs to facilitate an increase in physical activity in obese people.

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/m2) 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.