Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: Rationale, design and patient baseline characteristics for the PIONEER 6 trial.

AIMS: To assess the cardiovascular (CV) safety of oral semaglutide, the first tablet formulation of a glucagon-like peptide-1 receptor agonist. MATERIALS AND METHODS: PIONEER 6 is a multinational, randomized, placebo-controlled, double-blind trial in patients with type 2 diabetes at high risk of CV events (defined as being aged ≥50 years and having established CV disease [CVD] or moderate [stage 3] chronic kidney disease [CKD], or being aged ≥60 years with ≥1 other CV risk factor). Patients were randomized to once-daily oral semaglutide (up to 14 mg) or placebo added to standard of care. The primary composite endpoint is time to first occurrence of CV death or non-fatal myocardial infarction or non-fatal stroke. The primary hypothesis was to exclude an excess in CV risk with oral semaglutide by assessing non-inferiority versus placebo for the primary endpoint (non-inferiority margin of 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio). PIONEER 6 is event-driven, with follow-up continuing until accrual of at least 122 primary outcome events. There is no pre-defined minimal duration. RESULTS: Overall, 3183 patients have been enrolled (mean age 66.1 years, 31.6% females) in 214 sites across 21 countries. At baseline, the mean duration of diabetes was 14.9 years, mean glycated haemoglobin concentration was 66 mmol/mol (8.2%), and 84.6% of patients had established CVD/moderate CKD. CONCLUSIONS: PIONEER 6 will provide evidence regarding the CV safety of oral semaglutide in patients with type 2 diabetes and high CV risk.

Effects of live music during chemotherapy in lymphoma patients: a randomized, controlled, multi-center trial.

PURPOSE: Chemotherapy is associated with both somatic and psychological side effects. Music might ease these problems. Several randomized controlled trials have investigated the effect of music, but the results are inconclusive. We aimed to examine whether live or pre-recorded music listening decreases anxiety during chemotherapy in newly diagnosed lymphoma patients. METHODS: A total of 143 patients with non-Hodgkin and Hodgkin lymphomas were randomly assigned into three groups receiving either 30 min of patient-preferred live music (n = 47), 30 min of patient-preferred pre-recorded music (n = 47), or standard care (n = 49) during up to five outpatient chemotherapy sessions. The primary endpoint was anxiety measured by the Spielberger's State Anxiety Inventory. Secondary endpoints included blood pressure, pulse rate, nausea and vomiting, serum catecholamine levels pre- and post-intervention to measure arousal levels, and health-related quality of life. The Musical Ability Test was used to link musical ability to the primary endpoint. RESULTS: When adjusting for age, sex, diagnosis, number of sessions, and baseline anxiety, the linear mixed model showed a borderline statistically significant reduction in the primary outcome anxiety in the live music group compared to standard care (7% (95% CI, - 14% to 0%, p = 0.05), while the effect of pre-recorded music was non-significant (5% (95% CI, - 12% to + 3%, p = 0.18). No intervention effects were seen in secondary outcomes. CONCLUSION: Our findings suggest that patient-preferred live music reduces anxiety among patients with malignant lymphomas undergoing chemotherapy. Musical ability among this group of cancer patients seems not to be a determining factor for effect of music intervention.

Kind of blue: A systematic review and meta-analysis of music interventions in cancer treatment.

OBJECTIVES: Music may be a valuable and low-cost coping strategy for cancer patients. We conducted a systematic review and meta-analysis to identify the psychological and physical effects of music interventions in cancer treatment. METHODS: We included randomized, controlled trials with adult patients in active cancer treatment exposed to different music interventions versus control conditions. Qualitative studies and systematic reviews were excluded. We identified a total of 2624 records through 2 systematic searches (June 2015 and September 2016) in PubMed, Scopus, EMBASE, Cinahl, Web of Science, Cochrane, and PsycINFO and used Risk of Bias Assessment, GRADE and Checklist for Reporting Music-Based Interventions to evaluate the music applied and quality of the studies. We conducted meta-analyses using Review Manager (version 5.3). PROSPERO reg. no. CRD42015026024. RESULTS: We included 25 RCT's (N = 1784) of which 20 were eligible for the meta-analysis (N = 1565). Music reduced anxiety (SMD -0·80 [95% CI, -1.35 to -0.25]), pain (SMD -0.88 [95% CI -1.45 to -0.32]), and improved mood (SMD -0.55 [95% CI, -0.98 to -0.13]). However, studies were hampered by heterogeneity with I2 varying between 54% and 96%. Quality of the studies ranged from very low to low. The most effective mode of music intervention appeared to be passive listening to self-selected, recorded music in a single session design. CONCLUSIONS: Music may be a tool in reducing anxiety, pain, and improving mood among patients with cancer in active treatment. However, methodological limitations in the studies conducted so far prevent firm conclusions.

Point-of-Care Phalangeal Bone Mineral Density Measurement Can Reduce the Need of Dual-Energy X-Ray Absorptiometry Scanning in Danish Women at Risk of Fracture.

Identifying persons with a high risk of osteoporotic fractures remains a challenge. DXA uptake in women with elevated risk of osteoporosis seems to be depending on distance to scanning facilities. This study aimed to investigate the ability of a small portable scanner in identifying women with reduced bone mineral density (BMD), and to define triage thresholds for pre-selection. Total hip and lumbar spine BMD was measured by dual-energy X-ray absorptiometry and phalangeal BMD by radiographic absorptiometry in 121 Danish women with intermediate or high 10-year fracture probability (aged 61-81 years). Correlation between the two methods was estimated using correlation coefficient (r) and Bland-Altman plots. A moderate correlation between phalangeal BMD versus total hip (r = 0.47) and lumbar spine (r = 0.51), and an AUC on 0.80 was found. The mean difference between phalangeal T score and total hip T score/lumbar spine T score was low, and ranged from -0.26 SD to -0.31 SD depending on site and reference database used for calculation of T scores, but, large variation was seen at an individual level. When applying a triage approach approx. one-third of all DXA scan could be avoided and only 6 % of women in the low-risk group would be false negatives.

Bone Structural Changes and Estimated Strength After Gastric Bypass Surgery Evaluated by HR-pQCT.

Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment of morbid obesity, with positive effects on obesity-related complications. The treatment is associated with bone loss, which in turn might increase fracture risk. The aim of this study was to evaluate changes in bone mineral density (BMD) and bone architecture assessed using dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT), 6 and 12 months after RYGB, and correlate them to changes in selected biochemical markers. A prospective cohort study included 25 morbidly obese patients (10 males, 15 females). Patients were examined with DXA of the hip and spine, HR-pQCT of radius and tibia, and blood sampling before and 6 and 12 months after RYGB. Patients lost in average 33.5 ± 12.1 kg (25.8 ± 8.5 %) in 12 months. In tibia, we found significant loss of total, cortical and trabecular volumetric BMD after 12 months (all p < 0.001). Microarchitectural changes involved lower trabecular number, increased trabecular separation, and network inhomogeneity along with thinning of the cortex. Estimated bone failure load was decreased after 12 months (p = 0.005). We found only minor changes in radius. Results demonstrate significant alterations of bone microarchitecture suggesting an accelerated endosteal resorption along with disintegration of the trabecular structure which resulted in a loss of estimated bone strength in tibia. Such changes may underlie the recently reported increased risk of fracture in bariatric patients after surgery. We only observed bone structural changes in the weight-bearing bone, which indicates that mechanical un-loading is the primary mediator.

The risk-stratified osteoporosis strategy evaluation study (ROSE): a randomized prospective population-based study. Design and baseline characteristics.

The risk-stratified osteoporosis strategy evaluation study (ROSE) is a randomized prospective population-based study investigating the effectiveness of a two-step screening program for osteoporosis in women. This paper reports the study design and baseline characteristics of the study population. 35,000 women aged 65-80 years were selected at random from the population in the Region of Southern Denmark and-before inclusion-randomized to either a screening group or a control group. As first step, a self-administered questionnaire regarding risk factors for osteoporosis based on FRAX(®) was issued to both groups. As second step, subjects in the screening group with a 10-year probability of major osteoporotic fractures ≥15% were offered a DXA scan. Patients diagnosed with osteoporosis from the DXA scan were advised to see their GP and discuss pharmaceutical treatment according to Danish National guidelines. The primary outcome is incident clinical fractures as evaluated through annual follow-up using the Danish National Patient Registry. The secondary outcomes are cost-effectiveness, participation rate, and patient preferences. 20,904 (60%) women participated and included in the baseline analyses (10,411 in screening and 10,949 in control group). The mean age was 71 years. As expected by randomization, the screening and control groups had similar baseline characteristics. Screening for osteoporosis is at present not evidence based according to the WHO screening criteria. The ROSE study is expected to provide knowledge of the effectiveness of a screening strategy that may be implemented in health care systems to prevent fractures.

Bone structure and estimated bone strength in obese patients evaluated by high-resolution peripheral quantitative computed tomography.

Obesity is associated with high bone mineral density (BMD), but whether obesity-related higher bone mass increases bone strength and thereby protect against fractures is uncertain. We estimated effects of obesity on bone microarchitecture and estimated strength in 36 patients (12 males and 24 females, age 25-56 years and BMI 33.2-57.6 kg/m(2)) matched with healthy controls (age 25-54 years and BMI 19.5-24.8 kg/m(2)) in regard to gender, menopausal status, age (±6 years) and height (±6 cm) using high resolution peripheral quantitative computed tomography and dual energy X-ray absorptiometry. In radius, total bone area and trabecular area were significantly higher in obese patients (both p < 0.04). In tibia, cortical area was larger in obese patients (p < 0.001) compared with controls. Total BMD was higher in tibia (p = 0.03) but not in radius. Trabecular integrity was strengthened in obese patients compared with controls in radius and tibia with higher trabecular number (p = 0.002 and p < 0.001) and lower trabecular spacing (p = 0.01 and p < 0.001). Finite element analysis estimated failure load (FL) was higher in tibia (p < 0.001), but not in radius in obese patients. FL was significantly lower per kg body weight in radius and tibia in obese patients compared with controls (p = 0.007 and p < 0.001). Furthermore, the ratios of FLs between groups were comparable in both sites. These findings suggest that mechanical loading is not the primary mediator of the effects of obesity on estimated FL, and suggest that bone strength adaptations in morbid obesity may be inadequate with respect to the increased mechanical demands.

The incidence of hip fractures in Norway -accuracy of the national Norwegian patient registry.

BACKGROUND: Hip fractures incur the greatest medical costs of any fracture. Valid epidemiological data are important to monitor for time-dependent changes. In Norway, hip fractures are registered in the Norwegian Patient Registry (NPR), but no published national validation exists. The aim of the present study was a national validation of NPR as a register for hip fractures using diagnostic codes (ICD-10 S 72.0-2) and/or procedure codes (NOMESCO version 1.14 NFBxy (x=0-9, y=0-2) or NFJxy (x=0-9, y=0-2). METHOD: A nationwide, population-based cohort comprising a random sub-sample of 1,000 hip fracture-related entries for the years 2008-09 was drawn from the NPR. 200 entries were defined by a combination of diagnostic and procedure codes (subsample 1), 400 entries were defined by diagnostic codes only (subsample 2) and 400 entries were defined by procedure codes only (subsample 3). Accuracy was ascertained through comparison with discharge summaries, procedure notes and X-ray reports requested from 40 health institutions. Comparisons between groups were done by chi2 for categorical and t-test for continuous variables. RESULTS: 792 health records from 32 institutions were reviewed. High accuracy (98.2%, 95% C.I. 96.5-99.9%) was found for subsample 1, a combination of diagnostic and procedure codes. Coding errors were prominent in other subsamples. Defining fractures by a combination of diagnostic and procedure codes, annual average hip fracture incidence in Norway was 9,092 (95% C.I. 8,934 -9,249), excluding only 6.5% of all hip fractures defined by wider definitions. CONCLUSIONS: Based on current coding practice in Norway, a reliable national estimate of hip fracture incidences is found by a combination of relevant ICD-10 and NOMESCO codes in the NPR. This method may be used for monitoring epidemiological changes.

Ten-year follow-up of fracture risk in a systematic population-based screening program: the risk-stratified osteoporosis strategy evaluation (ROSE) randomised trial.

Background: Osteoporotic fractures pose a growing public health concern. Osteoporosis is underdiagnosed and undertreated, highlighting the necessity of systematic screening programs. We aimed to evaluate the effectiveness of a two-step population-based osteoporotic screening program. Methods: This ten-year follow-up of the Risk-stratified Osteoporosis Strategy Evaluation (ROSE) randomized trial tested the effectiveness of a screening program utilizing the Fracture Risk Assessment Tool (FRAX) for major osteoporotic fractures (MOF) to select women for dual-energy x-ray absorptiometry (DXA) scan following standard osteoporosis treatment. Women residing in the Region of Southern Denmark, aged 65-80, were randomised (single masked) into a screening or a control group by a computer program prior to inclusion and subsequently approached with a mailed questionnaire. Based on the questionnaire data, women in the screening group with a FRAX value ≥15% were invited for DXA scanning. The primary outcome was MOF derived from nationwide registers. ClinicalTrials.gov: NCT01388244, status: Completed. Findings: All randomised women were included February 4, 2010-January 8, 2011, the same day as approached to participate. During follow-up, 7355 MOFs were observed. No differences in incidences of MOF were identified, comparing the 17,072 women in the screening group with the 17,157 controls in the intention-to-treat analysis (IRR 1.01, 0.95; 1.06). However, per-protocol, women DXA-scanned exhibited a 14% lower incidence of MOF (IRR 0.86, 0.78; 0.94) than controls with a FRAX value ≥15%. Similar trends were observed for hip fractures, all fractures, and mortality. Interpretation: While the ROSE program had no overall effect on osteoporotic fracture incidence or mortality it showed a preventive effect for women at moderate to high risk who underwent DXA scans. Hence the overall effect might have been diluted by those who were not at an intervention level threshold risk or those who did not show up for DXA. Using self-administered questionnaires as screening tools may be inefficient for systematic screening due to the low and differential screening uptake. Funding: INTERREG and the Region of Southern Denmark.

Selenium supplementation and placebo are equally effective in improving quality of life in patients with hypothyroidism.

PURPOSE: We investigated whether selenium supplementation improves quality-of-life (QoL) in patients with autoimmune thyroiditis (ID:NCT02013479). METHODS: We included 412 patients ≥18 years with serum thyroid peroxidase antibody (TPOAb) level ≥100 IU/mL in a multicentre double-blinded randomised clinical trial. The patients were allocated 1:1 to daily supplementation with either 200 µg selenium as selenium-enriched yeast or matching placebo tablets for 12 months, as add-on to levothyroxine (LT4) treatment. QoL, assessed by the Thyroid-related Patient-Reported-Outcome questionnaire (ThyPRO-39), was measured at baseline, after six weeks, three, six, 12, and 18 months. RESULTS: In total, 332 patients (81%) completed the intervention period, of whom 82% were women. Although QoL improved during the trial, no difference in any of the ThyPRO-39 scales was found between the selenium group and the placebo group after 12 months of intervention. In addition, employing linear mixed model regression no difference between the two groups was observed in the ThyPRO-39 composite score (28.8 [95%CI:24.5-33.6] and 28.0 [24.5-33.1], respectively; P=0.602). Stratifying the patients according to duration of the disease at inclusion, ThyPRO-39 composite score, TPOAb level, or selenium status at baseline did not significantly change the results. TPOAb levels after 12 months of intervention were lower in the selenium group than in the placebo group (1995 [95%CI:1512-2512] vs. 2344 kIU/L [1862-2951]; P=0.016) but did not influence LT4 dosage or free triiodothyronine/free thyroxin ratio. CONCLUSION: In hypothyroid patients on LT4 therapy due to autoimmune thyroiditis, daily supplementation with 200 µg selenium or placebo for 12 months improved QoL to the same extent.

Combined vertebral assessment and bone densitometry increases the prevalence and severity of osteoporosis in patients referred to DXA scanning.

We performed a retrospective study to assess if vertebral fracture assessment (VFA) after routine bone mineral density (BMD) measurement on a dual-energy X-ray absorptiometry (DXA) machine had increased the number of patients diagnosed with osteoporosis and revealed previous unknown incident vertebral fractures. A total of 3275 patients were referred to bone densitometry by DXA to be screened for osteoporosis or evaluation of ongoing antiosteoporotic treatment. All spine X-rays obtained at our hospital from the same patients in the period from 3 mo before to 3 mo after the date of DXA scans were reviewed. Among the 3275 patients, 85% were females and 15% were males. In total, 68% of the patients had normal BMD, and 32% had osteoporosis. Vertebral fractures diagnosed by VFA were seen in 7.9% patients, of which 3.2% had normal BMD and 4.8% had osteoporosis assessed by BMD. The relative number of patients diagnosed with osteoporosis increased 9.79% and in absolute terms from 32.4% to 35.6% of patients referred to DXA. Addition of VFA to routine BMD measurement increased clinically significant the number of patients diagnosed with osteoporosis as well as the number of patients with fractures and thereby altered the severity and prognosis.

Mutational analysis of PHEX, FGF23, DMP1, SLC34A3 and CLCN5 in patients with hypophosphatemic rickets.

This study aimed to identify the underlying genetic mutation in patients with hypophosphatemic rickets (HR). Genomic DNA was analysed for mutations in PHEX, FGF23 and CLCN5 by polymerase chain reaction (PCR) followed by denaturing high-performance liquid chromatography (dHPLC). Bi-directional sequencing was performed in samples with deviating chromatographic profiles. DMP1 and SLC34A3 were sequenced, only. In addition, a multiplex ligation-dependent probe amplification (MLPA) analysis was performed to detect larger deletions/duplications in PHEX or FGF23. Familial cases accounted for 12 probands while 12 cases were sporadic. In 20 probands, mutations were detected in PHEX of which 12 were novel, and one novel frameshift mutation was found in DMP1. Three PHEX mutations were identified by the MLPA analysis only; that is, two large deletions and one duplication. No mutations were identified in FGF23, SLC34A3 or CLCN5. By the methods used, a disease causing mutation was identified in 83% of the familial and 92% of the sporadic cases, thereby in 88% of the tested probands. Genetic analysis performed in HR patients by PCR, dHPLC, sequencing and in addition by MLPA analysis revealed a high identification rate of gene mutations causing HR, including 12 novel PHEX and one novel DMP1 mutation.

Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy.

BACKGROUND: Treatment of patients with perioxisome proliferator-activated receptor-γ full agonists are associated with weight gain, heart failure, peripheral oedema, and bone loss. However, the safety of partial perioxisome proliferator-activated receptor-γ agonists has not been established in a clinical trial. The BALaglitazone glucose Lowering Efficacy Trial aimed to establish the glucose-lowering effects and safety parameters of the perioxisome proliferator-activated receptor-γ partial agonist balaglitazone in diabetic patients on stable insulin therapy. METHODS: Four hundred and nine subjects from three countries with type 2 diabetes on stable insulin therapy were randomized to 26 weeks of double-blind treatment with once daily doses of 10 or 20 mg balaglitazone, 45 mg pioglitazone, or matching placebo (n ≥ 99 in each group). The primary endpoint was the efficacy of balaglitazone 10 and 20 mg versus placebo on the absolute change in haemoglobin A(1c) . Secondary endpoints included levels of fasting serum glucose, and changes in body composition and bone mineral density as measured by dual energy X-ray absorptiometry, in comparison to pioglitazone 45 mg. This study is registered with Clinicaltrials.gov identifier: NCT00515632. RESULTS: In the 10- and 20-mg balaglitazone groups, and in the 45-mg pioglitazone group, significant reductions in haemoglobin A(1c) levels were observed (−0.99, −1.11, and −1.22%, respectively; p < 0.0001) versus placebo. Fasting serum glucose was similarly reduced in all treatment arms. Dual energy X-ray absorptiometry analyses showed that, while balaglitazone at 10 mg caused weight gain and fluid retention compared to placebo, the magnitude of these effects was significantly smaller than that of pioglitazone 45 mg and balaglitazone 20mg. Balaglitazone at either dose did not appear to reduce bone mineral density, while Pioglitazone showed a trend towards a reduction. CONCLUSION: Patients treated with balaglitazone at 10 mg and 20 mg and pioglitazone at 45 mg showed clinically meaningful improvements in glucose levels and HbA(1c) . With the 10 mg dose, the benefits (glucose & HgA(1c) lowering) and untoward effects (fluid and fat accumulation) were less, results that encourage further studies of this drug candidate.

Fracture risk assessed by Fracture Risk Assessment Tool (FRAX) compared with fracture risk derived from population fracture rates.

PURPOSE: To evaluate the performance of the Swedish version of Fracture Risk Assessment Tool (FRAX)) without bone mass density (BMD) in a Danish population to examine the possibility of applying this version to Danish women. METHODS: From the Danish National Register of social security numbers, we randomly selected 5000 women living in the region of Southern Denmark aged 40-90 years to receive a mailed questionnaire concerning risk factors for osteoporosis based on FRAX. The predicted 10-year probability of hip fractures was calculated for each woman returning a complete questionnaire using the Swedish version of FRAX. The observed 10-year hip fracture risk was also calculated for each woman using age-specific hip fracture rates from the National Hospital Discharge Register and National survival tables. RESULTS: A total of 4194 (84%) women responded to the questionnaire and 3636 (73%) gave complete information and were included in the analysis. Using FRAX, the predicted 10-year fracture risk was 7.6%, ranging from 0.3 to 25.0% at the age of 41-50 and 81-90, respectively, while the corresponding observed fracture risk was 7.6%, ranging from 0.4 to 24.0%, respectively and not significantly different from the predicted risk (p = 0.92). CONCLUSIONS: The Swedish version of FRAX without BMD is applicable to Danish women.

Effects of Patient-Initiated Visits on Patient Satisfaction and Clinical Outcomes in a Type 1 Diabetes Outpatient Clinic: A 2-Year Randomized Controlled Study.

OBJECTIVE: We investigated the effects of replacing regular outpatient follow-up through prescheduled visits with patient-initiated visits on patient satisfaction and clinical variables of type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: A 24-month randomized controlled trial in which adults with T1D were allocated to either patient-initiated unlimited access to outpatient visits or usual care through regular prescheduled visits. The primary outcome was seven patient-reported experience measures of patient satisfaction focused on benefit of consultation and accessibility of the outpatient clinic. Secondary outcomes included clinical variables of diabetes and use of staff resources. RESULTS: We enrolled 357 outpatients (intervention, n = 178; control, n = 179). After 24 months, participants in the intervention group experienced more benefit from consultations compared with baseline within groups (P < 0.05) and fewer unnecessary visits compared with control subjects (P < 0.05). Patient needs covered and satisfaction with the outpatient clinic were high and unchanged in both groups, and accessibility was increased (three questions, all P < 0.05). A calculated seven-item patient satisfaction sum score favored the intervention group over control subjects (P < 0.001). There were no significant changes in glycated hemoglobin (HbA1c), LDL, blood pressure, and complication status. The mean number of outpatient visits over 24 months (± SD) was lower in the intervention group compared with control subjects (4.4 ± 2.8 vs. 6.3 ± 2.7; P < 0.001), while the number of telephone contacts was higher (3.1 ±3.4 vs. 2.5 ± 3.2; P < 0.001). CONCLUSIONS: Patient satisfaction remained high or improved with patient-initiated on-demand use of the diabetes outpatient clinic, with no decline in the quality of diabetes care, and a reduction in the use of staff resources.

Phenotype presentation of hypophosphatemic rickets in adults.

Hypophosphatemic rickets (HR) is a group of rare disorders caused by excessive renal phosphate wasting. The purpose of this cross-sectional study of 38 HR patients was to characterize the phenotype of adult HR patients. Moreover, skeletal and endodontic severity scores were defined to assess possible gender differences in disease severity in patients with genetically verified X-linked HR. Compared to normal reference data, i.e., z = 0, HR patients had significantly lower final height, with a mean difference in z-score of -1.9 (95% CI -2.4 to -1.4, P < 0.001). Compared to paired z-scores of final height, z-scores of leg length were significantly lower and those of sitting height were significantly higher (P < 0.001), resulting in disproportion as indicated by the significantly elevated sitting height ratio, mean difference in z-score of 2.6 (95% CI 2.1-3.1, P < 0.001). Z-scores of head circumference (median 1.4, range -0.4 to 5.5, P < 0.001) and z-scores of bone mineral density (BMD) of the lumbar spine (median 1.9, range -1.5 to 8.6, P < 0.001) were significantly elevated compared to normal reference data. The relative risk (RR) of fracture was reduced (RR = 0.34, 95% CI 0.20-0.57, P < 0.001). The skeletal severity score tended to be higher in males compared to females (P = 0.07), and no gender difference in endodontic severity was found. In conclusion, adult HR patients were characterized by short stature and were disproportioned. They had elevated BMD of the lumbar spine and a reduced risk of fractures. We found a tendency for males to be more severely affected than females.

Effects of nordic walking and exercise in type 2 diabetes mellitus: a randomized controlled trial.

OBJECTIVE: Both Nordic walking and Exercise on Prescription have potential as elements in the management of type 2 diabetes mellitus. These programs are recommended, but their effectiveness has not yet been established. The aim was to evaluate the efficacy of these 2 interventions compared with standard information on physical activity. DESIGN: Single-blinded, randomized, controlled intervention study. SETTING: Sixty-eight patients (37 men and 31 women) were randomized into 3 groups: Nordic walking (NW; n = 22), Exercise on Prescription (EP; n = 24), and control (CG; n = 22). PATIENTS: : Patients were recruited from a diabetes outpatient clinic and via newspaper advertisement. INTERVENTIONS: Consisted of a 4-month intervention period followed by an 8-month follow-up, during which the participants were recommended to train on their own. MAIN OUTCOME MEASURES: : HbA1c. RESULTS: : There was no difference in HbA1c when comparing the intervention groups relative to the control group: DeltaNW = -0.4% [95% confidence intervals (CI), -0.9% to 0.1%] and DeltaEP = -0.2% (95% CI, -0.6% to 0.2%) after 4 months; DeltaNW = 0.0% (95% CI, -0.6% to 0.5%) and DeltaEP = 0.3% (95% CI, -0.3% to 0.9%) after 12 months. However, fat mass assessed by dual energy X-ray absorptiometry (DXA) decreased significantly in the NW group after 4 months [-1.0 kg (95% CI, -1.7 to 0.1)] and after 12 months in both NW [-1.8 kg (95% CI, -3.2 to -0.4)] and EP [-1.5 kg (95% CI, -2.9 to -0.05)] groups. No significant changes in other variables. CONCLUSIONS: Four-month exercise programs at moderate intensity of either Nordic walking or Exercise on Prescription did not significantly improve HbA1c in patients with type 2 diabetes either at the end of the program or at the follow-up.

Coronary flow impairment in asymptomatic patients with early stage type-2 diabetes: Detection by FFRCT.

PURPOSE: To determine the occurrence of physiological significant coronary artery disease (CAD) by coronary CT angiography (CTA) derived fractional flow reserve (FFRCT) in asymptomatic patients with a new diagnosis (<1 year) of type-2 diabetes mellitus (T2DM). METHODS: FFRCT-analysis was performed from standard acquired coronary CTA data sets. The per-patient minimum distal FFRCT-value (d-FFRCT) in coronary vessels (diameter ⩾1.8 mm) was registered. The threshold for categorizing FFRCT-analysis as abnormal was a d-FFRCT ⩽0.75. Total plaque volume and volumes of calcified plaque, non-calcified plaque, and low-density non-calcified plaque (LD-NCP) were assessed by quantitative plaque analysis. RESULTS: Overall, 76 patients; age, mean (SD): 56 (11) years; males, n (%): 49(65), were studied. A total of 57% of patients had plaques. The d-FFRCT was ⩽0.75 in 12 (16%) patients. The d-FFRCT, median (IQR), was 0.84 (0.79-0.87). Median (range) d-FFRCT in patients with d-FFRCT ⩽0.75 was 0.70 (0.6-0.74). Patients with d-FFRCT⩽0.75 versus d-FFRCT >0.75 had numerically higher plaque volumes for all plaques components, although only significant for the LD-NCP component. CONCLUSION: Every sixth asymptomatic patient with a new diagnosis of T2DM has hemodynamic significant CAD as evaluated by FFRCT. Flow impairment by FFRCT was associated with coronary plaque characteristics.

Characterization of acid flux in osteoclasts from patients harboring a G215R mutation in ClC-7.

The chloride-proton antiporter ClC-7 has been speculated to be involved in acidification of the lysosomes and the resorption lacunae in osteoclasts; however, neither direct measurements of chloride transport nor acidification have been performed. Human osteoclasts harboring a dominant negative mutation in ClC-7 (G215R) were isolated, and used these to investigate bone resorption measured by CTX-I, calcium release and pit scoring. The actin cytoskeleton of the osteoclasts was also investigated. ClC-7 enriched membranes from the osteoclasts were isolated, and used to test acidification rates in the presence of a V-ATPase and a chloride channel inhibitor, using a H(+) and Cl(-) driven approach. Finally, acidification rates in ClC-7 enriched membranes from ADOII osteoclasts and their corresponding controls were compared. Resorption by the G215R osteoclasts was reduced by 60% when measured by both CTX-I, calcium release, and pit area when comparing to age and sex matched controls. In addition, the ADOII osteoclasts showed no differences in actin ring formation. Finally, V-ATPase and chloride channel inhibitors completely abrogated the H(+) and Cl(-) driven acidification. Finally, the acid influx was reduced by maximally 50% in the ClC-7 deficient membrane fractions when comparing to controls. These data demonstrate that ClC-7 is essential for bone resorption, via its role in acidification of the lysosomes and resorption lacunae in osteoclasts.

Nutritional rickets in Denmark: a retrospective review of children's medical records from 1985 to 2005.

INTRODUCTION: This study describes clinical and biochemical characteristics of nutritional rickets and risk factors at diagnosis among children living in Denmark. All medical records from patients with rickets referred to or discharged from hospitals in Southern Denmark from 1985 to 2005 were identified by register search. MATERIALS AND METHODS: Patients included were younger than 15 years of age and fulfilled the diagnostic criteria of primary, nutritional rickets. A total of 112 patients with nutritional rickets were included: 29 were of ethnic Danish origin, and 83 were immigrants. RESULTS: Patients diagnosed before the age of 4 (median 1.4) years displayed the classic clinical signs of rickets, whereas patients diagnosed after the age of 4 (median 12.5) years had few clinical signs and unspecific symptoms. Ethnic Danish patients were only diagnosed before age 24 months, and they accounted for 73% of all cases presenting with hypocalcemic seizures, but biochemically, they did not have more severe rickets. Of patients diagnosed before the age of 4 years, 45% were ethnic Danish. In early childhood, insufficient or no vitamin D supplementation was given in 88% of all cases. Among immigrant girls older than 4 years of age, 78% were veiled. DISCUSSION: Nutritional rickets in Denmark is predominantly a disease among immigrants, but ethnic Danish patients comprised nearly half of all patients diagnosed before the age of 4 years, and they presented more frequently with hypocalcemic seizures. The main risk factors were omitted, such as vitamin D prophylaxis among the youngest patients and veiling among older children/teenagers.