The differential effects of bisphosphonates, SERMS (selective estrogen receptor modulators), and parathyroid hormone on bone remodeling in osteoporosis

Osteoporosis is a skeletal metabolic disease characterized by a compromised bone fragility, leading to an increased risk of developing spontaneous and traumatic fractures. Osteoporosis is considered a multifactorial disease and fractures are the results of several different risk factors both extra- and intraskeletal. Thus bone fragility can be the end point of several different causes: a) failure to reach an optimal peak bone mass during growth; b) excessive bone resorption resulting in decreased bone mass and microarchitectural deterioration; c) inadequate formation upon an increased resorption during the process of bone remodeling. The pharmacological therapeutical options, available to date, are directed on prevention of fractures. The aim of this paper is to describe the activities and the mechanisms of action, as known at present, of the most used therapies for osteoporosis and their clinical implications. Improvement of knowledge in this field will allow us to further improve therapeutical choices and pharmacological interventions

Disability, Physical Inactivity, and Impaired Health-Related Quality of Life Are Not Different in Metabolically Healthy vs. Unhealthy Obese Subjects

BACKGROUND: Obesity represents a major health hazard, affecting morbidity, psychological status, physical functionality, quality of life, and mortality. The aim of the present study was to explore the differences between metabolically healthy (MHO) and metabolically unhealthy (MUO) obese subjects with regard to physical activity, disability, and health-related quality of life (HR-QoL). METHODS: All subjects underwent a multidimensional evaluation, encompassing the assessment of body composition, metabolic biomarkers and inflammation, physical activity level (IPAQ questionnaire), disability (TSD-OC test), and HR-QoL (SF-36 questionnaire). MHO and MUO were defined based on the absence or the presence of the metabolic syndrome, respectively. RESULTS: 253 subjects were included (54 men and 199 women; age: 51.7 ± 12.8 vs. 50.3 ± 11.7 years, p = 0.46; BMI: 38.1 ± 5.7 vs. 38.9 ± 6.7 kg/m², p = 0.37). No significant difference was observed in body composition. There was no difference between MHO and MUO considering inflammation (hs-CRP: 6517.1 ± 11,409.9 vs. 5294.1 ± 5612.2 g/L; p = 0.37), physical inactivity (IPAQ score below 3000 METs-min/week in 77.6% of MHO vs. 80% of MUO subjects; p = 0.36), obesity-related disability (TSD-OC score > 33%, indicating a high level of obesity-related disability, in 20.2% of MHO vs. 26.5% of MUO subjects; p = 0.28), and the HR-QoL (SF-36 total score: 60 ± 20.8 vs. 62.8 ± 18.2, p = 0.27). DISCUSSION AND CONCLUSION:The metabolic comorbidity and the impairment of functional ability and psycho-social functioning may have a different timing in the natural history of obesity. Alterations in the physical activity level and mobility disabilities may precede the onset of metabolic abnormalities. (Trial registration 2369 prot 166/12-registered 23 February 2012; Amendment 223/14-registered 13 February 2014)

Assessment of trabecular bone score (TBS) in overweight/obese men: effect of metabolic and anthropometric factors

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 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

Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization

PURPOSE: Phosphodiesterase type-5 inhibitor administration in diabetic men with erectile dysfunction (ED) is associated with reduced waist circumference. We evaluated potential effects of daily tadalafil administration on body composition and investigated its possible mechanism(s) of action in C2C12 skeletal muscle cells in vitro. METHODS: Forty-three men on stable caloric intake (mean age 48.5 ± 7; BMI 25.5 ± 0.9 kg/m2) complaining mild ED and/or low urinary tract symptoms (LUTS) were randomly assigned to receive tadalafil (TAD) 5 mg/daily (once-a-day=OAD-TAD; n = 23) or 20 mg on-demand (on-demand=OD-TAD; n = 20) for 2 months. Primary outcomes were variations of body composition measured by Dual-energy X-ray absorptiometry; secondary outcomes were ED/LUTS questionnaire scores along with hormone (testosterone, estradiol, insulin) and endothelial function (Endopat2000) variations. RESULTS: OAD-TAD increased abdominal lean mass (p < 0.01) that returned to baseline after 2 months withdrawal. LUTS scores improved (p<0.01) in OD-TAD while ED scores improved (p < 0.01) in both groups. We found significant improvements in endothelial function (p < 0.05) that directly correlated with serum insulin (p < 0.01; r = 0.3641) and inversely correlated with estradiol levels (p < 0.01; r = 0.3655) even when corrected for potential confounders. Exposure of C2C12 cells upon increasing tadalafil concentrations (10-7 to 10-6 M) increased total androgen receptor mRNA and protein expression as well as myogenin protein expression after 24 and 72 h (2.8 ± 0.4-fold and 1.4 ± 0.02-fold vs. control, respectively, p < 0.05). CONCLUSIONS: Daily tadalafil improved lean mass content in non-obese men probably via enhanced insulin secretion, estradiol reduction, and improvement of endothelial function in vivo. The in vitro increased myogenin and androgen receptor protein expression in skeletal muscle cells suggests a translational action of phosphodiesterase type-5 on this receptor

What is the best diet for cardiovascular wellness? A comparison of different nutritional models

Cardiovascular diseases (CVD) represent to date the leading cause of mortality in both genders in the developed countries. In this context, a strong need for CVD prevention is emerging through lifestyle modification and nutrition. In fact, several studies linked CVD with unhealthy nutrition, alcohol consumption, stress, and smoking, together with a low level of physical activity. Thus, the primary aim is to prevent and reduce CVD risk factors, such as impaired lipid and glycemic profiles, high blood pressure and obesity. Different types of diet have been, therefore, established to optimize the approach regarding this issue such as the Mediterranean diet, Dietary Approaches to Stop Hypertension diet (DASH), vegetarian diet, ketogenic diet, and Japanese diet. Depending on the diet type, recommendations generally emphasize subjects to increase vegetables, fruits, whole grains, and pulses consumption, but discourage or recommend eliminating red meat, sweets, and sugar-sweetened beverages, along with processed foods that are high in sugar, salt, fat, or low in dietary fiber. In particular, we evaluated and compared the peculiar aspects of these well-known dietary patterns and, thus, this review evaluates the critical factors that increase CVD risk and the potential application and benefits of nutritional protocols to ameliorate dietary and lifestyle patterns for CVD prevention

Sarcopenic Obesity: Correlation with Clinical, Functional, and Psychological Status in a Rehabilitation Setting

Obesity and sarcopenia combination, appropriately defined as sarcopenic obesity (SO), due to disproportionally reduced/low lean body mass compared to excess fat mass, may lead to disability. Aims: The aim of our study was to investigate the relationship among sarcopenic obesity, physical performance, disability, and quality of life in a rehabilitation setting. Methods: Participants were recruited among obese patients (BMI > 30 kg/m2) admitted to the rehabilitation facility at the Department of Experimental Medicine, Medical Physiopatology, Food Science and Endocrinology Section during a 1-year period. A multidimensional evaluation was performed through bioelectrical impedance analysis and anthropometry, handgrip strength test, Short Physical Performance Battery (SPPB), 6-minute walk test (6MWT) and blood chemistry parameters. Psychological status (SCL-90 questionnaire), quality of life, and comorbidity (Charlson comorbidity index score) were also evaluated. Obesity was diagnosed as increased fat mass by 35% in women and by 25% in men. Sarcopenia was defined if lean body mass (LBM) was <90% of the subject’s ideal LBM. Results: 79 patients (48 women and 31 men; mean age: 60.1 ± 11.5 years, and 58.6 ± 10.8 years, respectively) were enrolled. Results showed a high prevalence of SO (54.4%) in our samples of obese subjects. Sarcopenia was present not only among older obese adults but also among younger obese subjects, and was related to reduced functional performance, to inflammatory status and to worse psychological status and quality of life

Effect of paricalcitol vs calcitriol on hemoglobin levels in chronic kidney disease patients: a randomized trial

Recent studies suggest that vitamin D deficiency represents an additional cofactor of renal anemia, with several mechanisms accounting for this relationship. In line with it, the administration of vitamin D or its analogues has been associated with an improvement of anemia. There are no data, however, about a direct effect of paricalcitol on hemoglobin (Hb) levels. Therefore, we conducted a study to determine whether paricalcitol, compared to calcitriol, improves anemia in patients with chronic kidney disease (CKD)

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 B300 min/day. Results 137 subjects (105 women and 32 men), age: 49.8 ± 12.4 years, BMI: 38.6 ± 6.7 kg/m2, were enrolled. Sleep duration was B300 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 B300 min when compared to their counterparts (all p.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 B300 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 B300 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.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, R2 = 0.19, p = 0.012). Conclusion Reduced sleep duration negatively influences body composition, macronutrient intake, and QoL in obese subjects

Osteoporosis and Sarcopenia Increase Frailty Syndrome in the Elderly

Musculoskeletal aging is a major public health interesting and strain due to the significant demographic modifications in the population, and it is linked to high risk of falls, loss of autonomy in elderly individuals and institutionalization with small health outcomes. Thus, this pathological status is related to high morbidity and health care rates. Bone mass and muscle mass and strength increase during late adolescence and early adulthood but start to reduce noticeably from the fifth decade of life and are closely linked. Bone and muscle tissues were increasingly recognized, as endocrine target organs and endocrine organs themselves, interacting through paracrine and endocrine signals. During growth, bone mineral content closely correlates with muscle mass, and several evidences suggest that osteoporosis and sarcopenia present common pathophysiological factors and show the correlation between low bone mineral density and sarcopenia in both men and women. Then, sarcopenia and osteoporosis, typical features of aging, are often associated with each other and with the frailty syndrome. In particular, sarcopenia and osteoporosis are major contributors to disability and frailty and the common denominators are age-related chronic inflammation, changes in body composition and hormonal imbalance. Frailty syndrome is characterized by a reduced response to stress, triggering the decline of the physiological functioning of the various systems. Frailty syndrome, typical of the older people, is frequently associated with a reduction in the quality of life and mobility. Falls often are the basis of reduced mobility and ability to perform the common functions of daily life and the increase in the number of institutionalizations. Moreover, the reduction of muscle mass, associated with altered muscle composition, fat and fibrous infiltration and alterations in innervations, and the increase in fat mass, have a synergistic effect on the increase in cardiovascular risk. The aim of this review is to analyze the pathophysiological mechanisms underlying the frailty syndrome and its association with sarcopenia and osteoporosis, and investigate possible intervention measures