A randomized trial of nasal spray salmon calcitonin in men with idiopathic osteoporosis: Effects on bone mineral density and bone markers

In a 12-month randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover. Twenty-eight men with idiopathic osteoporosis aged 27-74 years (mean, 52.4 years) were randomized to receive either nasal SCT (200 IU) or a nasal placebo daily for a period of 1 year. All the men received a daily supplement of 0.5 g of calcium. The men who received SCT had a mean (+/-SEM) increase in BMD of 7.1 +/- 1.7% at the lumbar spine. In contrast, the men who received the placebo had an increase of 2.4 +/- 1.5% (p > 0.05) for the comparison with baseline. The increase in lumbar BMD in the calcitonin group was significantly greater than that in the placebo group (p < 0.05). There were no significant changes in the femoral neck, trochanter, or Ward’s triangle relative to both baseline and placebo after 12 months. Treatment with nasal SCT resulted in a significantly pronounced suppression of bone resorption markers (urinary deoxypyridinoline [DPD], type I cross-linked N-telopeptide [NTX], and type I cross-linked C-telopeptide [CTX]) and to a lesser extent in bone formation markers (serum bone-specific alkaline phosphatase [BALP], osteocalcin [OC], serum C-terminal procollagen type I extension peptides [PICP], and serum N-terminal procollagen type I extension peptides [PINP]), whereas the placebo did not. Therapy was tolerated well and there were no treatment-related adverse events. We conclude that intranasal SCT (200 IU daily) is safe and effective in increasing lumbar BMD and reducing bone turnover in men with idiopathic osteoporosis

Patient radiation exposure measurements during interventional procedures: A prospective study

This is a prospective study with the purpose of assessing patient radiation dose and stochastic risk (risk for fatal cancer) in a patient population undergoing interventional radiological (IR) procedures. Measurements were performed on 36 consecutive patients undergoing percutaneous transluminal angioplasty (PTA, n = 18), transjugular intrahepatic portosystemic shunt (TIPS, n = 3), diagnostic angiography (DA, n = 6), arterial embolization (AE, n = 3), and hepatic neoplasm chemoembolization (HCE, n = 6). Kerma area product (KAP) was used as a measure of x-ray exposure to the patient. Mean KAP value per procedure was 79 ± 50 Gy cm for PTA, 139 ± 55 Gy cm for TIPS, 110 ± 44 Gy cm for DA, 325 ± 145 Gy cm for AE, and 150 ± 76 Gy cm for HCE. Forty-six percent of total KAP value was attributed to fluoroscopy. In conclusion, we showed that a linear correlation between effective dose and KAP was found (r = 0.84), which could be used for estimating patient effective dose using KAP measurements. Small changes to the number of digital frames acquired result in substantial change of the total KAP in interventional radiological procedures. Stochastic risk from IR procedures is quite low for the patient. Measuring KAP is a simple and accurate method, which provides the interventional radiologist with a good estimation of the patient's relative risk for stochastic effects. Copyright © 2006 Health Physics Society

Impact of prenatal and postnatal nutritional manipulation on bone quality in adult Wistar rats offspring

Background and aims: We aimed to evaluate the impact of perinatal food manipulation on skeletal characteristics and insulin levels of Wistar rats at the age of 1 year. Methods: Sixty-seven first-time pregnant rats were randomized, to either normally fed (Control Diet, CD), food-restricted (FR), or fat-fed (FF), from the 12th gestational day, and gave birth on the 21st day of pregnancy. Pups born to FR-mothers were divided into: fetal growth restricted (FGR) and non-FGR, based on their birth weight. Maternal food manipulation continued through the lactation period. Following delivery, all neonates were cross-fostered until the 25th day postpartum; the offspring of normally-fed mothers were lactated by FR-, FF- or CD-fed mothers. A similar process was followed for the offspring of mothers FF- or FR-during pregnancy. On the 26th day postpartum, all pups were weaned to the diet of their foster mother until one year old. Bone density was assessed by peripheral quantitative computed tomography. Results: FF/FF rats had lower values of total bone density and total/subcortical area compared to CD/CD. FF/FR showed lower subcortical density compared to FF/FF group. FGR/CD showed lower values of all assessed skeletal parameters compared to those receiving CD throughout the experiment. Non-FGR/FF rats had higher values of all assessed skeletal parameters compared to those food restricted postnatally. FGR-pups that were fat-fed postnatally had higher insulin vs rats FF/FR. Similar insulin levels were identified in rats fat-fed postnatally, irrespective of prenatal food-restriction or high-fat diet. Conclusions: Perinatal food manipulation is associated with distinct skeletal acquisition and insulin levels’ profiles in Wistar rats at the first year of life. © 2021 The Author

Effect of rhythmic gymnastics on volumetric bone mineral density and bone geometry in premenarcheal female athletes and controls

Context and Objective: Weight-bearing exercise during growth exerts positive effects on the skeleton. Our objective was to test the hypothesis that long-term elite rhythmic gymnastics exerts positive effects on volumetric bone mineral density and geometry and to determine whether exercise-induced bone adaptation is associated with increased periosteal bone formation or medullary contraction using tibial peripheral quantitative computed tomography and bone turnover markers. Design and Setting: We conducted a cross-sectional study at a tertiary center. Subjects: We studied 26 elite premenarcheal female rhythmic gymnasts (RG) and 23 female controls, aged 9-13 yr. Main Outcome Measures: We measured bone age, volumetric bone mineral density, bone mineral content (BMC), cortical thickness, cortical and trabecular area, and polar stress strength index (SSIp) by peripheral quantitative computed tomography of the left tibia proximal to the distal metaphysis (trabecular) at 14, 38 (cortical), and 66% (muscle mass) from the distal end and bone turnover markers. Results: The two groups were comparable according to height and chronological and bone age. After weight adjustment, cortical BMC, area, and thickness at 38% were significantly higher in RG (P < 0.005-0.001). Periosteal circumference, SSIp, and muscle area were higher in RG (P < 0.01-0.001). Muscle area was significantly associated with cortical BMC, area, and SSIp, whereas years of training showed positive association with cortical BMC, area, and thickness independent of chronological age. Conclusions: RG in premenarcheal girls may induce positive adaptations on the skeleton, especially in cortical bone. Increased duration of exercise is associated with a positive response of bone geometry. Copyright © 2010 by The Endocrine Society

MYC copy gain, chromosomal instability and PI3K activation as potential markers of unfavourable outcome in trastuzumab-treated patients with metastatic breast cancer

Background: There is an unmet need for more efficient patient stratification for receiving trastuzumab in the metastatic breast cancer (mBC) setting, since only part of such patients benefit from the addition of this agent to chemotherapy. The aim of this study was to investigate the prognostic value of biomarkers including MYC and MET in mBC patients treated with trastuzumab-based regimens. Methods: mBC patients, locally tested as HER2-positive, treated with trastuzumab and chemotherapy between 1998 and 2010 were evaluated. Paraffin tumors (n = 229) were retrospectively centrally assessed by immunohistochemistry (IHC) for HER2, ER, PgR and Ki67; fluorescence in situ hybridization (FISH) for HER2, TOP2A and centromere (CEN) 17, MYC and CEN8, MET and CEN7; qPCR for MYC, MET copy number (CN); and, for PI3K activation (PIK3CA mutations; PTEN and phospho-mTOR protein expression). Increased CEN CN was assessed based on normal cut-offs. Time to progression (TTP) and survival were evaluated from the initiation of trastuzumab as first line treatment. Results: Among all tumors, 90 were HER2-negative upon central testing (ambiguous HER2) and the rest were true HER2-positive. Further, 156 patients presented with mBC upon relapse of pre-treated disease (R-mBC) and 65 were diagnosed at stage IV (de novo mBC). Concordance between FISH and qPCR on gene CN status was fair for MYC (Kappa = 0.458) and absent for MET. The presence of MYC CN gain with qPCR and the absence of PI3K activation were infrequent events (7 and 8 % of evaluable tumors, respectively), while 41 % of tumors had increased CEN CN in one or more chromosomes, indicative of chromosomal instability. The most consistent finding in the entire cohort and in the above patient subgroups with respect to outcome was the unfavourable effect of MYC CN gain, which was retained upon multivariable analysis (e.g., survival in the entire cohort, HR 6.02; 95 % CI 2.67-13.6; p < 0.001). Further unfavourable prognosticators were increased CEN CN in one chromosome in R-mBC but not in de novo mBC (multivariable interaction p = 0.048), PI3K activation in R-mBC (multivariable p = 0.004) and increased Ki67 for patient TTP. Conclusions: MYC gene copies, centromere status and PI3K activation may adversely impact trastuzumab treated mBC patient outcome and seem worthy validating in larger series. © 2016 The Author(s)

Prognostic implications of mismatch repair deficiency in patients with nonmetastatic colorectal and endometrial cancer

Background The clinical relevance of mismatch repair (MMR) status in patients with nonmetastatic cancer across tumour types remains unclear. Our goal was to investigate the prognostic role of MMR deficiency in patients with stage I-III colorectal and endometrial cancer. Methods Patients with nonmetastatic colorectal and endometrial cancer with tumour tissue available for analysis were identified through the Hellenic Cooperative Oncology Group (HeCOG)'s tumour repository. Patients had been referred to Departments of Medical Oncology affiliated with HeCOG. MMR protein expression was evaluated by immunohistochemistry. The primary outcome measure was overall survival (OS). Results From May 1990 to September 2012, 1158 patients with nonmetastatic colorectal (N = 991) and endometrial cancer (N = 167) were identified (median age: 64 years, men: 544). All patients with colorectal and 109 (65%) with endometrial cancer had received adjuvant treatment. MMR deficiency was observed in 114 (11.5%) of colorectal and 80 (47.9%) of endometrial tumours. More commonly deficient proteins were PMS2 (69 patients, 7%) and MLH1 (63 patients, 6.5%) in colorectal cancer and MSH2 (58 patients, 34.7%) in endometrial cancer. Colorectal MMR-deficient (dMMR) tumours were more likely to be right sided (65 % dMMR vs 27 % proficient MMR, pMMR; p < 0.001), high grade (31% vs 15%, Ï ‡ 2, p < 0.001) and with a mucinous component (64% vs 42%, p < 0.001). Endometrial dMMR tumours were more often of endometrioid histology (51.4 % endometrioid vs 20 % serous/clear cell, p = 0.020). Compared with MMR proficiency, MMR deficiency was associated with improved OS in patients with endometrial cancer (HR = 0.38, 95% CI 0.20 to 0.76, p = 0.006), but not in patients with colorectal cancer (HR = 0.73, 95% CI 0.49 to 1.09, p = 0.130). After adjusting for age, stage and grade, MMR deficiency maintained its favourable prognostic significance in patients with endometrial cancer (HR = 0.42, 95% CI 0.20 to 0.88, p = 0.021). Conclusions DMMR was associated with improved outcomes in patients with nonmetastatic endometrial cancer, but not in patients with nonmetastatic colorectal cancer who received adjuvant chemotherapy. © 2019 BMJ Publishing Group Limited. No commercial re-use. See rights and permissions. Published by BMJ