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Reduced vitamin D levels may play a significant role in the development of fractures and musculoskeletal pains reported in patients on aromatase inhibitors (AIs) for breast cancer. In this study, we evaluated the vitamin D status in postmenopausal women with non-metastatic breast cancer who were about to start AI therapy. This study was conducted on community dwelling postmenopausal subjects, aged 35-80 years, with early non-metastatic breast cancer (up to stage IIIA), who were about to start therapy using third generation AIs. Symptoms of joint and muscle pains were obtained using a modified Leuven menopausal questionnaire. 25-hydroxyvitamin D [25(OH)D] was evaluated by radioimmunoassay while bone mineral density (BMD) of the lumbar spine and the proximal femur by dual energy x-ray absorptiometry (DXA). Of the 145 participants (mean age = 60.96 ± 0.88 years), 63 of 145 (43.5%) had baseline levels of 25(OH)D of <20 ng/mL (deficient), 50 of 145 (34.5%) had levels between 20 and 29 ng/mL (insufficient), and only 32 of 145 (22%) had ≥30 ng/mL (sufficient); thus, 113 of 145 (78%) had low 25(OH)D levels (i.e., <30 ng/mL). Arthralgias and myalgias were found in 61.3% and 43% of patients, respectively; and of those, 83.3% and 88.1% had 25(OH)D of <30 ng/mL, respectively. Prevalence of vitamin D deficiency is high in breast cancer women and this may increase the risk of bone loss and fractures in those who are going to start AIs. Moreover, musculoskeletal pains are common in breast cancer women, even before the initiation of AIs and in association with low vitamin D in the majority. Future studies may be needed to establish the contribution of low vitamin D, if any, on the prevalence of musculoskeletal pains in women on AIs. [ABSTRACT FROM AUTHOR] more...

In patients with chronic hepatitis C, rapid virological response (RVR) at week 4 of treatment seems to be strongly associated with a high probability of achieving a sustained virological response (SVR). The aim of this study was to investigate the outcome of different pegylated interferon-α2b (Peg-IFN-α2b) dosages plus ribavirin (RBV) in patients with RVR. Forty-five naïve patients chronically infected with hepatitis C virus (HCV)-1b started Peg-IFN-α2b (1.5 μg/kg/week) in combination with weight-based RBV doses (800–1200 mg/day). Thirty-one patients (68.9%) attained RVR at week 4 of therapy, while four further patients showed negative HCV-RNA values for the first time at week 12 and were considered early virological responders (EVR). The 31 RVR patients were randomized to receive either RBV plus 1.5 μg/kg/week (17 pts) or 1.0 μg/kg/week (14 pts) of Peg-IFN-α2b for the remaining 44 weeks. The two groups were matched for age, sex, baseline alanine aminotransferase levels, viral load and fibrosis score. After 6 months of post-treatment follow-up, the prevalence of SVR was 94.1% (16/17) among RVR patients treated with 1.5 μg/kg/week and 92.8% (13/14) in RVR patients treated with 1.0 μg/kg/week ( P = not significant). A high-baseline viral load ( P = 0.01) and bridging fibrosis/cirrhosis ( P = 0.02) negatively influenced the likelihood of achieving RVR. On the contrary, the ability of RVR patients to achieve SVR did not correlate with these baseline characteristics in either of the treatment group. Finally, the SVR rate among EVR patients who responded after more than 4 weeks of treatment was significantly lower than among RVR patients (1/4 = 25% vs 29/31 = 93.5%; P = 0.0058), because of a high prevalence of post-treatment relapse among patients with EVR. [ABSTRACT FROM AUTHOR] more...

Estrogen is a critical hormone for bone homeostasis in men, but no information is available on the role of estrogen metabolism among men. The aim of this study was to evaluate the effect of estrogen hydroxylation on male bone mineral density (BMD). Participants consisted of 61 healthy Caucasian males (mean age 66.6 +/- 1.0 years). Urinary estrogen metabolites were measured by enzyme-linked immunosorbent assay, serum estradiol by ultrasensitive radioimmunoassay, sex hormone binding globulin by radioimmunoassay, and BMD of the lumbar spine and the proximal femur by dual-energy X-ray absorptiometry. Active estrogen metabolites, 16alpha-hydroxyestrone (16alphaOHE(1)) and estriol (E(3)), positively correlated with adjusted BMD in all regions of the proximal femur (all P < 0.05) but not at the lumbar spine, and those in the highest tertile of urinary 16alphaOHE(1 )had the highest BMD. Free estradiol index (FEI) also positively correlated with BMD of the total hip, femoral neck, and intertrochanter (all P < 0.05), while there was no correlation between BMD with inactive metabolites (2-hydroxyestrone and 2-methoxyestrone) and serum testosterone. Multiple regression analysis showed 16alphaOHE(1), FEI, and body mass index are important independent predictors of BMD in all regions of the proximal femur. Estrogen metabolism may modulate BMD in men. Increased urinary 16alphaOHE(1) and E(3) levels are associated with high BMD at the proximal femur, and 16alphaOHE(1) appears to be a major determinant of BMD among the metabolites evaluated. [ABSTRACT FROM AUTHOR] more...

One of the most promising genetic approaches to dissecting a multifactorial disease is represented by genetically isolated population studies. We studied a genetic marker in a cohort of women living on the Mediterranean island of Lampedusa, a geographically isolated population. Lampedusa, located between the African coast and Sicily, consists of a young genetic isolate (<20 generations) with an exponential growth in the last generations. We analyzed the association between the FokI vitamin D receptor (VDR) gene polymorphism, previously proposed as a predictor of bone mass, with parameters of bone mass and turnover in a cohort of pre- and postmenopausal women living on Lampedusa. In 424 women (277 postmenopausal and 147 premenopausal), allelic frequencies were 49% for the F allele and 51% for the f allele. Using analysis of covariance, we found that subjects with ff genotype exhibited a significantly (P < 0.001) lower lumbar spine bone mass, by dual-energy X-ray absorptiometry, and lower values of bone ultrasonographic parameters (speed of sound and broadband ultrasound attenuation) relative to those with Ff and FF genotypes. Conversely, osteocalcin and serum cross-laps were significantly higher in ff and Ff compared to FF genotype. Our data suggest that FokI VDR polymorphism may contribute to the determination of bone mass and turnover in both pre- and postmenopausal women in this geographically isolated population. [ABSTRACT FROM AUTHOR] more...

Abstract: Adult thalassemic patients have reduced bone mass due to disturbances in several different mechanisms affecting bone turnover. To determine if vitamin D deficiency contributes to the low bone mass of adult thalassemic subjects, we studied serum 25-OH-vitamin D levels in 90 patients (age ranging between 21 and 48 years) affected with thalassemia major (TM) and 35 (age 21–56 years) with thalassemia intermedia (TI). TM patients had been receiving regular transfusions from the age of 2 years and had increased serum ferritin, glutamic oxalacetic transaminase, glutamic piruvic transaminase as well as low bone density (L1–L4 Z score −2.07 ± 0.2). TI patients did not receive transfusions, but their ferritin levels were increased as well (520.3 ± 138,1). 8 TM patients (10.1%) and 4 TI (11.4%) had serum 25-OH-vitamin D less than 10.4 ng/ml and were considered presenting an absolute deficiency of vitamin D. Mean 25-OH-vitamin D was significantly (P < 0.01) lower in both TM and TI patients (20.3 ± 0.7 ng/ml and 20.9 ± 2.3 ng/ml, respectively) than in 100 healthy control subjects of similar age (25.2 ± 1 ng/ml). 1,25-OH-vitamin D levels were in the normal–lower levels (45.15 ± 1.5 mg/dl), while 24 H urinary calcium was below the normal range (15.75 mg/dl). In TM patients, the 25-OH-vitamin D levels correlated negatively with age (P < 0.05) and with serum ferritin (P < 0.05). TM and TI patients with low 25-OH-vitamin D levels (<17.8 ng/ml) presented higher serum ferritin levels (P < 0.01) and higher PTH (P < 0.05) compared to those with normal vitamin D. Moreover, TM patients with low 25-OH-vitamin D levels were significantly older (P < 0.05) and had higher GPT (P < 0.05) than patients with normal vitamin D. In conclusion, calcium metabolism is frequently impaired in adult thalassemic patients. An early and effective medical treatment should be taken in consideration by the clinician in order to improve the bone health in these patients. [Copyright &y& Elsevier] more...

We studied bone mass and metabolism in 30 adult women (age 28.5 ± 1.3) with thalassemia major (TM) and evaluated whether prolonged hormone replacement therapy (HRT) was able to optimize bone accrual. TM patients had reduced bone mass, increased bone turnover and lower serum gonadotropin and estradiol levels compared with 10 normal women of similar age. A significant correlation was found between bone mass and sex hormone levels. Six TM patients with normal ovarian function had normal bone turnover markers and modestly low bone mass (lumbar spine -1.29 ± 0.31; femoral neck -0.60±0.21; Z-score). The other 24 TM women were hypogonadic and had significantly lower bone mass for age (lumbar spine -2.35 ± 0.2, femoral neck -1.83 ± 0.2) and increased bone turnover relative to eugonadal women. Of the hypogonadal patients, 13 had taken HRT since age 15 ± 1 years, but their bone mass and turnover markers were not different than untreated hypogonadal patients. In conclusion, while hypogonadism negatively affects bone mass acquisition in adult TM women, HRT at the standard replacement doses is not sufficient to secure optimal bone accrual. [ABSTRACT FROM AUTHOR] more...

B Background: b The modified Blumgart pancreatojejunostomy (mB-PJ) reduces the incidence of pancreatic fistula (POPF) in open pancreatoduodenectomy (PD), but no information is available for robotic PD. We present a propensity score-matched analysis of mB-PJ vs Cattell-Warren pancreatojejunostomy (CW-PJ) in robotic PD. CR-POPF occurred in no patient after mB-PJ and in 15 patients after CW-P (23.8%) (p=0.10, OR 0.12). [Extracted from the article] more...

A correction to the article "Taxonomy of Rare Genetic Metabolic Bone Disorders" that was published in the 2015 issue is presented.

Objective: We investigated whether supplementation of the active form of vitamin D (calcitriol) in recent-onset type 1 diabetes can protect beta-cell function evaluated by C-peptide and improve glycemic control assessed by A1C and insulin requirement.Research Design and Methods: Thirty-four subjects (aged 11-35 years, median 18 years) with recent-onset type 1 diabetes and high basal C-peptide >0.25 nmol/l were randomized in a double-blind trial to 0.25 microg/day calcitriol or placebo and followed-up for 2 years.Results: At 6, 12, and 24 months follow-up, A1C and insulin requirement in the calcitriol group did not differ from the placebo group. C-peptide dropped significantly (P < 0.001) but similarly in both groups, with no significant differences at each time point.Conclusions: At the doses used, calcitriol is ineffective in protecting beta-cell function in subjects (including children) with recent-onset type 1 diabetes and high C-peptide at diagnosis. [ABSTRACT FROM AUTHOR] more...

An correction to the article "Serum chitotriosidase in postmenopausal women with severe osteoporosis" that was published online in the January 19, 2016 issue is presented.

Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk. [ABSTRACT FROM AUTHOR] more...

Summary: We studied the relationships among strength, muscle mass, and bone mineral density (BMD) with lifestyle change. Lifestyle therapy consisted of exercise, diet, and diet plus exercise. Diet was by caloric restriction to induce and maintain a weight loss of 10 % from baseline body weight. Exercise attenuated weight loss-induced muscle and bone losses. Exercise improved strength despite muscle loss in patients on diet and exercise. Changes in strength did not correlate with changes in BMD. However, changes in thigh muscle volume correlated with, and predicted changes in hip BMD. Introduction: Losses of hip BMD and lean body mass are major complications of lifestyle therapy in frail, obese older adults; however, the contribution of mechanical strain loss from muscle loss is poorly defined. We determined the effect of changes in thigh muscle volume and muscle strength on BMD in frail, obese older adults undergoing lifestyle therapy aimed at intentional weight loss with or without exercise. Methods: One hundred seven obese older adults were randomized to control, diet, exercise, and diet-exercise groups for 1 year. Thigh muscle volume was measured by magnetic resonance imaging, BMD by DXA, knee strength by dynamometry, total strength by one-repetition maximum (1-RM), and bone markers by immunoassay. Results: Thigh muscle volume decreased in the diet group (−6.2 ± 4.8 %) and increased in the exercise group (2.7 ± 3.1 %), while it was not significantly different from the control in the diet-exercise group. Changes in hip BMD followed similar pattern as those in thigh muscle volume. Knee extension and flexion increased in the exercise group (23 ± 20 %; 25 ± 19 %) and diet-exercise group (20 ± 19 %; 20.6 ± 27 %) but were unchanged in the control and diet groups. Changes in thigh muscle volume correlated with changes in hip BMD ( r = 0.55, P = <0.001) and were an independent predictor of changes in hip BMD ( β = 0.12, P = 0.03) in the multiple regression analyses after accounting for demographic factors and changes in weight and physical activity. There were no correlations between BMD changes and knee strength, 1-RM, and sclerostin changes. Conclusions: Changes in thigh muscle volume predict hip BMD changes in obese older patients undergoing lifestyle therapy. The effect of exercise in attenuating thigh muscle loss when added to diet may in part account for the reduction in weight loss-induced bone loss in the diet-exercise group. [ABSTRACT FROM AUTHOR] more...

While bone mineral density (BMD) by dual-energy X-ray absorptiometry is the primary method of determining fracture risk, assessing bone turnover may add valuable information for the management of patients with low bone mass. Bone turnover markers (BTMs) are used in clinical trials where they can provide essential information on the biological efficacy of osteoporosis treatments. In such population-based studies, BTMs can predict fracture risk independent of BMD. When combined with BMD, they improve the fracture risk estimate above and beyond BMD alone in postmenopausal osteoporotic women. Since changes in bone turnover after the initiation of therapy with bone resorption inhibitors occur much more rapidly than changes in BMD, treatment efficacy could, in theory, be determined within weeks of using BTMs. However, such predictive value is limited by the large biological variability of these biochemical markers, even though newer automated methods have reduced their analytical variability. Consequently, widespread adoption as a means of predicting treatment efficacy in fracture prevention for individual patients cannot yet be recommended. BTMs may be useful for monitoring adherence to antiresorptive therapy and may aid in identifying patients for whom antiresorptive therapy is most appropriate. Thus, although BTMs are currently confined to clinical research applications, further improvement in assay precision may extend their diagnostic value in clinical settings. [ABSTRACT FROM AUTHOR] more...

Background: Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score‐matched analysis. Methods: An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan–Meier method and Cox regression analyses. Results: Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score‐matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy. Conclusion: Patients with resected ampullary adenocarcinoma may benefit from gemcitabine‐based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype. [ABSTRACT FROM AUTHOR] more...

Normal standards for peak oxygen consumption (VO 2 peak) are controversial because they tend to be population and protocol specific. This study was undertaken to examine the association between percentage of age-predicted VO 2 peak and all-cause hospital readmission in cardiac outpatients who were referred to an exercise-based secondary prevention program. Hospital readmission was assessed in 1283 male patients with coronary heart disease (CHD) three years after enrolment, and related to the age-predicted VO 2 peak derived from the Fitness Registry and the Importance of Exercise: A National Data Base equation (FRIEND %PRED). VO 2 peak was estimated using a moderate perceptually regulated 1-km treadmill-walking test. Readmission was also assessed during the fourth-to-sixth years as function of improvement in FRIEND %PRED in 845 patients who were re-evaluated 3 years after baseline. During the 3-years after baseline, readmission rate was lower across increasing tertiles of FRIEND %PRED. Compared to the lowest tertile, the adjusted hazard ratios (HRs) for the second and third tertile were 0.98 (95% CI 0.76–1.27, p = 0.90) and 0.71 (0.53–0.95, p = 0.002). The rate of readmission from the fourth-to-sixth years after baseline was lower across tertiles of improved FRIEND %PRED , with adjusted HRs 0.78 (0.60–1.03, p = 0.08) and 0.58 (0.42–0.75, p < 0.0001) for the intermediate and high tertiles vs the lowest tertile. After adjustment for confounders, every 1 unit % increase in FRIEND %PRED was associated with a 3% reduction in risk of readmission (HR 0.97, 0.95–0.98, p < 0.0001). Age-predicted VO 2 peak estimated by a moderate treadmill-walk predicts hospital readmission in outpatients with CHD undergoing secondary prevention. [ABSTRACT FROM AUTHOR] more...