Long-term effects of aromatase inhibitor withdrawal on bone mineral density in early breast cancer patients: 10-year follow-up results of the BREX study.

PURPOSE: We aimed to provide long-term bone mineral density (BMD) data on early breast cancer patients of the BREX (Breast Cancer and Exercise) study. The effects of exercise and adjuvant endocrine treatment 10 years after randomization were analyzed, with special emphasis on aromatase inhibitor (AI) therapy discontinuation at 5 years. METHODS: The BREX study randomized 573 pre- and postmenopausal breast cancer patients into a 1-year supervised exercise program or a control group. 372 patients were included into the current follow-up analysis. BMD (g/cm2) was measured by dual-energy X-ray absorptiometry at lumbar spine (LS), left femoral neck (FN), and the total hip. Separate groups were displayed according to baseline menopausal status, and whether the patient had discontinued AI therapy at 5 years or not. RESULTS: The BMD change from 5 to 10 years did not significantly differ between the two randomized arms. AI discontinuation at 5 years had statistically significant BMD effects. The FN BMD continued to decrease in patients who discontinued AI therapy during the first 5-year off-treatment, but the decrease was three-fold less than in patients without AI withdrawal (- 1.4% v. - 3.8%). The LS BMD increased (+ 2.6%) in patients with AI withdrawal during the first 5 years following treatment discontinuation, while a BMD decrease (-1.3%) was seen in patients without AI withdrawal. CONCLUSION: This study is to our knowledge the first to quantify the long-term impact of AI withdrawal on BMD. Bone loss associated with AI therapy seems partially reversible after stopping treatment. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov/ (Identifier Number NCT00639210).

Elective Cardiac Procedure Patients Have Low Preoperative Cardiorespiratory Fitness.

Preoperative cardiorespiratory fitness may influence the recovery after cardiac procedure. The aim of this study was to investigate the cardiorespiratory fitness of patients scheduled for elective cardiac procedures, using a six-minute walk test, and compare the results with a population-based sample of Finnish adults. Patients (n=234) awaiting percutaneous coronary intervention or coronary angiography, coronary artery bypass grafting, aortic valve replacement or mitral valve surgery performed the six-minute walk test. VO2max was calculated based on the walk test. The patients were compared to a population-based sample of 60-69-year-old Finnish adults from the FinFit2017 study. The mean six-minute walk test distances (meters) and VO2max (ml/kg/min) of the patient groups were: 452±73 and 24.3±6.9 (coronary artery bypass grafting), 499±84 and 27.6±7.2 (aortic valve replacement), 496±85 and 27.4±7.3 (mitral valve surgery), and 519±90 and 27.3±6.9 (percutaneous coronary intervention or coronary angiography). The population-based sample had significantly greater walk test distance (623±81) and VO2max (31.7±6.1) than the four patient groups (all p-values<0.001). All patient groups had lower cardiorespiratory fitness than the reference population of 60-69-year-old Finnish adults. Particularly the coronary artery bypass grafting group had a low cardiorespiratory fitness, and therefore might be prone to complications and challenging rehabilitation after the operation.

Success and complications in lumbar punctures of pediatric patients with leukemia: a study protocol for a randomized clinical crossover trial of a bioimpedance needle system versus conventional procedure.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children. At present, the long-term survival from pediatric ALL is well over 90%. However, the probability of event-free survival is reduced if the lumbar puncture (LP) procedures at the beginning of the patient's intrathecal therapy cause blood leakage into the spinal canal and blast cells contaminate the cerebrospinal fluid. According to the literature, such traumatic LP procedures concern one out of five pediatric patients with ALL. Recently, a novel medical device measuring the tissue bioimpedance at the tip of a spinal needle was found feasible in pediatric patients with ALL. The LP procedure was successful at the first attempt in 80% of procedures, and the incidence of traumatic LPs was then 11%. The purpose of the present study is to compare the bioimpedance spinal needle system with the standard clinical practice resting on a conventional spinal needle and investigate its efficacy in clinical practice. METHODS: The study is a multicenter, randomized, two-arm crossover noninferiority trial of pediatric hemato-oncology patients that will be conducted within the usual clinical workflow. Patients' LP procedures will be performed alternately either with the IQ-Tip system (study arm A) or a conventional Quincke-type 22G spinal needle (study arm B). For each enrolled patient, the order of procedures is randomly assigned either as ABAB or BABA. The total number of LP procedures will be at least 300, and the number of procedures per patient between two and four. After each study LP procedure, the performance will be recorded immediately, and 1-week diary-based and 4-week record-based follow-ups on symptoms, complications, and adverse events will be conducted thereafter. The main outcomes are the incidence of traumatic LP, first puncture success rate, and incidence of post-dural puncture headache. DISCUSSION: The present study will provide sound scientific evidence on the clinical benefit, performance, and safety of the novel bioimpedance spinal needle compared with the standard clinical practice of using conventional spinal needles in the LP procedures of pediatric patients with leukemia. TRIAL REGISTRATION: ISRCTN ISRCTN16161453. Registered on 8 July 2022.

Objectively measured preoperative physical activity and sedentary behaviour among Finnish patients scheduled for elective cardiac procedures: baseline results from randomized controlled trial.

BACKGROUND: We investigated preoperative physical activity (PA) and sedentary behaviour (SB) in patients scheduled for elective cardiac procedures and compared them with population-based sample of Finnish adults. METHODS: Cardiac patients (n = 139) undergoing cardiac operations carried a triaxial accelerometer for seven days during the month before the procedure. Patients were categorised into four groups according to the procedure: percutaneous coronary intervention or coronary angiography (PCI-CA), coronary artery bypass grafting (CABG), aortic valve replacement (AVR) and mitral valve surgery (MVS). The raw accelerometer data was analyzed with dedicated algorithms to determine metabolic equivalents (METs, 3.5 mL/kg/min of oxygen consumption) of PA. The intensity of PA was divided into two categories: light (LPA, 1.5-2.9 METs) and moderate-to-vigorous (MVPA, ≥ 3.0 METs), while SB represented intensity < 1.5 MET without movements. SB and PA were described as daily means and accumulation from different bout lengths. Daily standing, steps and mean and peak MET-values were calculated. The results were compared between the patient groups and against the reference group from a population-based study FinFit2017. RESULTS: Cardiac patients had fewer daily steps than the FinFit population (p = 0.01), and less SB accumulating from < 20 min bouts (p = 0.002) but more from 20 to 60 min bouts (p = 0.002). Particularly, CABG group had less daily MVPA (p = 0.002) and MVPA accumulating from > 10 min bouts (p < 0.001) than the FinFit population. CONCLUSIONS: We found large differences in PA and SB between the patient groups and the FitFit population, CABG group having the worst activity profile. Also, the variation within the patient groups was wide, which should be considered to individualise the rehabilitation programs postoperatively. Trial registration clinicaltrials.gov (NCT03470246). Registered 19 March 2018, https://clinicaltrials.gov/ct2/show/NCT03470246.

Traumatic lumbar punctures in diagnostic and intrathecal treatment punctures of pediatric hemato-oncology patients.

Successful first diagnostic lumbar puncture (LP) is crucial because intrathecal chemotherapy has not yet protected the central nervous system against cancer cells. If blood contaminates the cerebrospinal fluid (CSF) with blasts, they may enter the central neural system and compromise the patient's health. We retrospectively determined the incidence of traumatic lumbar punctures (TLP) in 2,507 LPs of 250 pediatric hemato-oncology patients aged from one to 18 years, including both diagnostic and intrathecal treatment procedures, and 2,617 LPs of 1,525 other age-matched pediatric patients. We used ≥10 erythrocytes/µL in the CSF sample as the criterion of TLP. TLPs were less frequent in hemato-oncology patients than in other patients (31.6% vs. 48.5%, p < 0.0001). The incidence of TLP was significantly lower in the first diagnostic LP than in subsequent intrathecal treatment LPs (20.5% vs. 31.6%, p = 0.0046). According to logistic regression analysis, the odds of TLP was 1.6-fold if the LP procedure was not performed in the hemato-oncology department. The odds of the patient's next LP being traumatic were threefold if the previous first LP was traumatic. A week or less time between the first and next LP tripled the odds of TLP as well. The patient's age category was not significantly associated with the incidence of TLP. Given the risks of TLP, hemato-oncology patients' first diagnostic LP should include administration of chemotherapy, as generally recommended, and be performed under general anesthesia or deep sedation by an experienced physician to optimize not only the success of the first LP procedure but also following procedures.

Bioimpedance spinal needle provides high success and low complication rate in lumbar punctures of pediatric patients with acute lymphoblastic leukemia.

In this prospective single-arm study of 50 pediatric patients with acute lymphoblastic leukemia (ALL), we evaluated the clinical performance of a novel bioimpedance spinal needle system in 152 intrathecal treatment lumbar punctures (LP) of these patients. The system detects in real-time when the needle tip reaches the cerebrospinal fluid (CSF) in the spinal canal. The success was defined as getting a CSF sample and/or administering the intrathecal treatment with one needle insertion. Incidence of traumatic LP (TLP) was defined as ≥ 10 erythrocytes/µL of CSF. Post-procedural complications were monitored with a one-week diary and one-month register follow-up. The success of the first attempt was 79.5%, with the CSF detection sensitivity of 86.1%. The incidence of TLP was 17.3%. A successful first attempt was associated with a significantly lower incidence of TLP (10% vs 40%, p = 0.0015). During the week after the procedure, the incidence of post-dural puncture headache was 6%. During the follow-up, no major complications were observed. In conclusion, the novel bioimpedance spinal needle system achieved a high success rate and low incidence of TLP and other complications in pediatric patients with ALL in a real-world clinical setting, indicating clinical utility for this system in pediatric hemato-oncology.

Humanin vivoliver and tumor bioimpedance measured with biopsy needle.

Objective.Liver biopsy is an essential procedure in cancer diagnostics but targeting the biopsy to the actual tumor tissue is challenging. Aim of this study was to evaluate the clinical feasibility of a novel bioimpedance biopsy needle system in liver biopsy and simultaneously to gatherin vivobioimpedance data from human liver and tumor tissues.Approach.We measured human liver and tumor impedance datain vivofrom 26 patients who underwent diagnostic ultrasound-guided liver biopsy. Our novel 18 G core biopsy needle tip forms a bipolar electrode that was used to measure bioimpedance during the biopsy in real-time with frequencies from 1 kHz to 349 kHz. The needle tip location was determined by ultrasound. Also, the sampled tissue type was determined histologically.Main results.The bioimpedance values showed substantial variation between individual cases, and liver and tumor data overlapped each other. However, Mann-Whitney U test showed that the median bioimpedance values of liver and tumor tissue are significantly (p < 0.05) different concerning the impedance magnitude at frequencies below 25 kHz and the phase angle at frequencies below 3 kHz and above 30 kHz.Significance.This study uniquely employed a real-time bioimpedance biopsy needle in clinical liver biopsies and reported the measured humanin vivoliver and tumor impedance data. Impedance is always device-dependent and therefore not directly comparable to measurements with other devices. Although the variation in tumor types prevented coherent tumor identification, our study provides preliminary evidence that tumor tissue differs from liver tissuein vivo,and this association is frequency-dependent.

Uncovering the shared lipidomic markers of subclinical osteoporosis-atherosclerosis comorbidity: The Young Finns Study.

BACKGROUND: Osteoporosis and atherosclerosis are complex multifactorial diseases sharing common risk factors and pathophysiological mechanisms suggesting that these are comorbidities. Omics studies identifying joint molecular markers associated with these diseases are sparse. SUBJECTS AND METHODS: Using liquid chromatography-tandem mass spectrometry, we quantified 437 molecular lipid species from the Young Finns Study cohort (aged 30-45 years and 57% women) and performed lipidome-wide multivariate analysis of variance (MANOVA) with early markers for both diseases. Carotid intima-media thickness for atherosclerosis measured with ultrasound and bone mineral density from distal radius and tibia for osteoporosis measured with peripheral quantitative computed tomography were used as early markers of the diseases. RESULTS: MANOVA adjusted with age, sex and body mass index, identified eight statistically significant (adjusted p-value (padj) < 0.05) and 15 suggestively significant (padj < 0.25) molecular lipid species associated with the studied markers. Similar analysis adjusted additionally for smoking habit, physical activity and alcohol consumption identified four significant and six suggestively significant molecular lipid species. These most significant lipid classes/species jointly associated with the studied markers were glycerolipid/TAG(18:0/18:0/18:1), glycerophospholipid/PC(40:3), sphingolipid/Gb3(d18:1/22:0), and sphingolipid/Gb3(d18:1/24:0). CONCLUSION: Our results support the osteoporosis-atherosclerosis comorbidity hypothesis and present potential new joint lipid biomarkers for these diseases.

Modular genome-wide gene expression architecture shared by early traits of osteoporosis and atherosclerosis in the Young Finns Study.

We analysed whole blood genome-wide expression data to identify gene co-expression modules shared by early traits of osteoporosis and atherosclerosis. Gene expression was profiled for the Young Finns Study participants. Bone mineral density and content were measured as early traits of osteoporosis. Carotid and bulbus intima media thickness were measured as early traits of atherosclerosis. Joint association of the modules, identified with weighted co-expression analysis, with early traits of the diseases was tested with multivariate analysis. Among the six modules significantly correlated with early traits of both the diseases, two had significant (adjusted p-values (p.adj) < 0.05) and another two had suggestively significant (p.adj < 0.25) joint association with the two diseases after adjusting for age, sex, body mass index, smoking habit, alcohol consumption, and physical activity. The three most significant member genes from the significant modules were NOSIP, GXYLT2, and TRIM63 (p.adj ≤ 0.18). Genes in the modules were enriched with biological processes that have separately been found to be involved in either bone metabolism or atherosclerosis. The gene modules and their most significant member genes identified in this study support the osteoporosis-atherosclerosis comorbidity hypothesis and can provide new joint biomarkers for both diseases and their dual prevention.

Personalised eHealth intervention to increase physical activity and reduce sedentary behaviour in rehabilitation after cardiac operations: study protocol for the PACO randomised controlled trial (NCT03470246).

INTRODUCTION: Personalized intervention to increase physical Activity and reduce sedentary behaviour in rehabilitation after Cardiac Operations (PACO) is a smartphone-based and accelerometer-based eHealth intervention to increase physical activity (PA) and reduce sedentary behaviour (SB) among patients recovering from cardiac surgery. DESIGN: Prospective randomised controlled trial. METHODS AND ANALYSIS: The present protocol describes a randomised controlled clinical trial to be conducted in the Heart Centres of Kuopio and Turku university hospitals. The trial comprises 540 patients scheduled for elective coronary artery bypass grafting, aortic valve replacement or mitral valve repair. The patients will be randomised into two groups. The control group will receive standard postsurgical rehabilitation guidance. The eHealth intervention group will be given the same guidance together with personalised PA guidance during 90 days after discharge. These patients will receive personalised daily goals to increase PA and reduce SB via the ExSedapplication. Triaxial accelerometers will be exploited to record patients' daily accumulated PA and SB, and transmit them to the application. Using the accelerometer data, the application will provide online guidance to the patients and feedback of accomplishing their activity goals. The data will also be transmitted to the cloud, where a physiotherapist can monitor individual activity profiles and customise the subsequent PA and SB goals online. The postoperative improvement in patients' step count, PA, exercise capacity, quality of sleep, laboratory markers, transthoracic echocardiography (TTE) parameters and quality of life, and reduction in SB and incidence of major cardiac events are investigated as outcomes. CONCLUSIONS: The PACO intervention aims to build a personalised eHealth tool for the online tutoring of cardiac surgery patients. TRIAL REGISTRATION NUMBER: NCT03470246.

Effectiveness of a 12-month Exercise Intervention on Physical Activity and Quality of Life of Breast Cancer Survivors; Five-year Results of the BREX-study.

BACKGROUND/AIM: This is a report of the 5-year quality of life (QoL) findings of the BREX-study (n=444). PATIENTS AND METHODS: A 12-month exercise intervention was arranged shortly after adjuvant treatments. Physical activity (PA) was assessed by PA diary, physical performance by a 2- km walking test, QoL by the EORTC QLQC30 and BR-23 questionnaires, fatigue by the FACIT-Fatigue scale and depression by the Beck's 13-item depression scale (BDI). RESULTS: Participants who improved their PA from baseline to 5-year follow-up were more likely to improve their global health score (RRR=1.02, p=0.016), physical (RRR=1.02, p=0.009), social (RRR=1.03, p=0.013), role functioning (RRR=1.03, p=0.005), and fatigue (RRR=1.02, p=0.002). An improved 2-km walking test was associated to improved global health, physical and role functioning, body image, future perspectives, and fatigue (p=0.011, p<0.001, p=0.001, p=0.021, p=0.012 and p=0.003). No significant difference between the groups was found. CONCLUSION: Improvement in PA or physical performance yields a positive change in QoL of breast cancer patients.

Childhood Exposure to Passive Smoking and Bone Health in Adulthood: The Cardiovascular Risk in Young Finns Study.

CONTEXT: Passive smoke exposure has been linked to the risk of osteoporosis in adults. OBJECTIVE: We examined the independent effects of childhood passive smoke exposure on adult bone health. DESIGN/SETTING: Longitudinal, the Cardiovascular Risk in Young Finns Study. PARTICIPANTS: The study cohort included 1422 individuals followed for 28 years since baseline in 1980 (age 3 to 18 years). Exposure to passive smoking was determined in childhood. In adulthood, peripheral bone traits were assessed with peripheral quantitative CT (pQCT) at the tibia and radius, and calcaneal mineral density was estimated with quantitative ultrasound. Fracture data were gathered by questionnaires. RESULTS: Parental smoking in childhood was associated with lower pQCT-derived bone sum index in adulthood (ß± SE, -0.064 ± 0.023 per smoking parent; P = 0.004) in multivariate models adjusted for age, sex, active smoking, body mass index, serum 25-OH vitamin D concentration, physical activity, and parental socioeconomic position. Similarly, parental smoking was associated with lower heel ultrasound estimated bone mineral density in adulthood (ß± SE, -0.097 ± 0.041 per smoking parent; P = 0.02). Parental smoking was also associated with the incidence of low-energy fractures (OR, 1.28; 95% CI, 1.01 to 1.62). Individuals with elevated cotinine levels (3 to 20 ng/mL) in childhood had lower bone sum index with pQCT (ß± SE, -0.206 ± 0.057; P = 0.0003). Children whose parents smoked and had high cotinine levels (3 to 20 ng/mL) had significantly lower pQCT-derived bone sum index compared with those with smoking parents but had low cotinine levels (<3 ng/mL) (ß± SE, -0.192 ± 0.072; P = 0.008). CONCLUSIONS AND RELEVANCE: Children of parents who smoke have evidence of impaired bone health in adulthood.

Long-term leisure-time physical activity and other health habits as predictors of objectively monitored late-life physical activity - A 40-year twin study.

Moderate-to-vigorous physical activity (MVPA) in old age is an important indicator of good health and functional capacity enabling independent living. In our prospective twin cohort study with 616 individuals we investigated whether long-term physical activity assessed three times, in 1975, 1982 and 1990 (mean age 48 years in 1990), and other self-reported health habits predict objectively measured MVPA measured with a hip-worn triaxial accelerometer (at least 10 hours per day for at least 4 days) 25 years later (mean age of 73 years). Low leisure-time physical activity at younger age, higher relative weight, smoking, low socioeconomic status, and health problems predicted low MVPA in old age in individual-based analyses (altogether explaining 20.3% of the variation in MVPA). However, quantitative trait modeling indicated that shared genetic factors explained 82% of the correlation between baseline and follow-up physical activity. Pairwise analyses within monozygotic twin pairs showed that only baseline smoking was a statistically significant predictor of later-life MVPA. The results imply that younger-age physical activity is associated with later-life MVPA, but shared genetic factors underlies this association. Of the other predictors mid-life smoking predicted less physical activity at older age independent of genetic factors.

Dietary phosphorus intake is negatively associated with bone formation among women and positively associated with some bone traits among men-a cross-sectional study in middle-aged Caucasians.

High dietary phosphorus (P) intake has acute negative effects on calcium (Ca) and bone metabolism, but long-term clinical data are contradictory. We hypothesized that high P intake is associated with impaired bone health as suggested by earlier short-term studies on bone metabolism. In this cross-sectional study, we investigated associations between dietary P intake, bone traits in the radius and tibia, and bone turnover in a population-based sample of 37- to 47-year-old Caucasian premenopausal women (n=333) and men (n=179) living in Southern Finland (60°N). We used various regression models in an "elaboration approach" to elucidate the role of P intake in bone traits and turnover. The addition of relevant covariates to the models mainly removed the significance of P intake as a determinant of bone traits. In the final regression model (P intake, weight, height, age, Ca intake, serum 25-hydroxyvitamin D, physical activity, smoking, contraceptive use in women), P intake was slightly positively associated only with bone mineral content and cross-sectional cortical bone area in the tibia of men. Among women, inclusion of Ca removed all existing significance in the crude models for any bone trait. In women P intake was negatively associated with the bone formation marker serum intact pro-collagen type I amino-terminal propeptide, whereas no association was present between P intake and bone turnover in men. In conclusion, these findings disagree with the hypothesis; P intake was not deleteriously associated with bone traits; however, P intake may negatively contribute to bone formation among women.

Clinical Characteristics and the Dietary Response in Celiac Disease Patients Presenting With or Without Anemia.

BACKGROUND AND AIMS: It remains unclear as to what are the clinical characteristics associated with the presence of anemia at celiac disease diagnosis, and how these are affected by a gluten-free diet. We investigated these issues in a prospective study. METHODS: Clinical and demographic data, small-bowel mucosal histology, serology, and laboratory parameters, body mass index (BMI), and bone mineral density (BMD) both at diagnosis and after 1 year on a gluten-free diet were investigated in 163 adults with celiac disease. Gastrointestinal symptoms and psychological well-being were evaluated by validated Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires. All study variables were compared between participants with and without anemia at celiac disease diagnosis. RESULTS: Altogether, 23% of the patients had anemia at diagnosis. Anemic patients were more often women (P=0.001) and had more gastrointestinal symptoms (P=0.004) and were less often screen detected (P=0.009). Further, they had higher celiac antibody values (P=0.007) and a lower total iron (P<0.001), BMI (P=0.003), and density of mucosal γδ+ intraepithelial lymphocytes (P=0.033). After 1 year on a gluten-free diet, the anemia group had a lower mucosal villous height-crypt depth ratio (P=0.008) and BMI (P=0.050), and higher antibody values (P=0.012) and densities of CD3 (P=0.008) and αß+ intraepithelial lymphocytes (P=0.022). There was no significant difference between the groups in their bone mineral density, Gastrointestinal Symptom Rating Scale and Psychological General Well-Being. CONCLUSIONS: Celiac patients with anemia had more severe disease than nonanemic patients in terms of the serology and a lower BMI. Further, they evinced a slower histologic response to the dietary treatment. An early diagnosis and careful follow-up are important in these patients.

Declining incidence of fall-induced ankle fractures in elderly adults: Finnish statistics between 1970 and 2014.

BACKGROUND: Fall-induced fractures of older adults are a major public health concern. However, nationwide information on recent fracture trends is sparse. METHODS: We determined the trend in the number and incidence (per 100,000 persons) of fall-induced ankle fractures among older adults in Finland by taking into account all persons 60 years of age or older who were admitted to Finnish hospitals for primary treatment of such fracture in 1970-2014. RESULTS: The number of fall-induced ankle fractures among 60-year-old or older Finnish persons increased steadily and sharply between 1970 (369 fractures) and 1997 (1668 fractures), but since then, the increase has slowed down (1835 fractures in 2014). The raw incidence of ankle fracture, showing a clear rise from 57 fractures per 100,000 persons in 1970 to 169 fractures in 1997, declined steadily between 1997 and 2014 (to 126 fractures in 2014). Observations on the age-adjusted fracture incidence were similar. During 1970-1997, the age-adjusted incidence of fall-induced ankle fracture clearly rose in both women and men, but thereafter, the incidence declined; in women, from 199 in 1997 to 158 in 2014, and in men, from 123 in 1997 to 80 in 2014. CONCLUSIONS: The sharp rise in the incidence of fall-induced ankle fracture in Finnish older adults from early 1970s until late 1990s has been followed by a declining fracture rate. Despite this welcome development, the rapid aging of our population is likely to increase the absolute number of these fractures in the near future, and therefore, large-scale fracture-preventing intervention studies are urgently needed.

Predictors and Significance of Incomplete Mucosal Recovery in Celiac Disease After 1 Year on a Gluten-Free Diet.

OBJECTIVES: In celiac disease, a follow-up biopsy taken 1 year after diagnosis is considered important in monitoring histological recovery. In many cases, recovery is incomplete, and the clinical significance of this is poorly understood. We now investigated associated factors and the significance of imperfect histological recovery in patients in whom the follow-up had been completed. METHODS: Two hundred sixty-three biopsy-proven patients were divided into two groups: histological recovery and incomplete recovery after 1 year on gluten-free diet. Serology, laboratory values, bone mineral density, and different clinical variables were measured at diagnosis and after 1 year. Gastrointestinal symptoms and quality of life were assessed by validated questionnaires. Further, long-term follow-up data on mortality, malignancies, and other severe complications were collected. RESULTS: The incomplete recovery group had more severe mucosal damage (P=0.003), higher antibody values (P=0.017), and more signs of malabsorption (P<0.001) at diagnosis. There was no difference in gender, symptoms or quality of life, family history of celiac disease, or comorbidities. At follow-up, there was still a difference in antibodies (P=0.018) and femoral T-scores (P=0.024). Histologically recovered patients showed better dietary adherence, although it was excellent in both groups (97% vs. 87%, P<0.001). There was no difference in long-term outcomes between groups. CONCLUSIONS: The presence of more severe disease in terms of histology, serology, and signs of malabsorption was associated with histological non-response. In patients with high dietary adherence, incomplete villous recovery after 1 year does not affect the clinical response or long-term prognosis. A personalized approach is required to decide the optimal timing of the follow-up biopsy.

Influence of exercise loading on magnetic resonance image texture of thigh soft tissues.

Adaptation to exercise training can affect bone marrow adiposity; muscle-fat distribution; and muscle volume, strength and architecture. The objective of this study was to identify exercise-load-associated differences in magnetic resonance image textures of thigh soft tissues between various athlete groups and non-athletes. Ninety female athletes representing five differently loading sport types (high impact, odd impact, high magnitude, repetitive low impact and repetitive non-impact), and 20 non-athletic clinically healthy female controls underwent magnetic resonance imaging. Five thigh muscles, subcutaneous fat and femoral bone marrow were analysed with co-occurrence matrix-based quantitative texture analysis at two anatomical levels of the dominant leg. Compared with the controls thigh muscle textures differed especially in high-impact and odd-impact exercise-loading groups. However, all sports appeared to modulate muscle textures to some extent. Fat tissue was found different among the low-impact group, and bone marrow was different in the high-impact group when compared to the controls. Exercise loading was associated with textural variation in magnetic resonance images of thigh soft tissues. Texture analysis proved a potential method for detecting apparent structural differences in the muscle, fat and bone marrow.

Does bone resorption stimulate periosteal expansion? A cross-sectional analysis of ß-C-telopeptides of type I collagen (CTX), genetic markers of the RANKL pathway, and periosteal circumference as measured by pQCT.

We hypothesized that bone resorption acts to increase bone strength through stimulation of periosteal expansion. Hence, we examined whether bone resorption, as reflected by serum ß-C-telopeptides of type I collagen (CTX), is positively associated with periosteal circumference (PC), in contrast to inverse associations with parameters related to bone remodeling such as cortical bone mineral density (BMDC ). CTX and mid-tibial peripheral quantitative computed tomography (pQCT) scans were available in 1130 adolescents (mean age 15.5 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass, and height. CTX was positively related to PC (ß=0.19 [0.13, 0.24]) (coefficient=SD change per SD increase in CTX, 95% confidence interval)] but inversely associated with BMDC (ß=-0.46 [-0.52,-0.40]) and cortical thickness [ß=-0.11 (-0.18, -0.03)]. CTX was positively related to bone strength as reflected by the strength-strain index (SSI) (ß=0.09 [0.03, 0.14]). To examine the causal nature of this relationship, we then analyzed whether single-nucleotide polymorphisms (SNPs) within key osteoclast regulatory genes, known to reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants within or proximal to genes encoding receptor activator of NF-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) were identified by literature search. Six of the 15 alleles that were inversely related to BMD were positively related to CTX (p<0.05 cut-off) (n=2379). Subsequently, we performed a meta-analysis of associations between these SNPs and PC in ALSPAC (n=3382), Gothenburg Osteoporosis and Obesity Determinants (GOOD) (n=938), and the Young Finns Study (YFS) (n=1558). Five of the 15 alleles that were inversely related to BMD were positively related to PC (p<0.05 cut-off). We conclude that despite having lower BMD, individuals with a genetic predisposition to higher bone resorption have greater bone size, suggesting that higher bone resorption is permissive for greater periosteal expansion.

Differential effects of exercise on tibial shaft marrow density in young female athletes.

CONTEXT: Increased mechanical loading can promote the preferential differentiation of bone marrow mesenchymal stem cells to osteoblastogenesis, but it is not known whether long-term bone strength-enhancing exercise in humans can reduce marrow adiposity. OBJECTIVE: Our objective was to examine whether bone marrow density (MaD), as an estimate of marrow adiposity 1) differs between young female athletes with contrasting loading histories and bone strengths and 2) is an independent predictor of bone strength at the weight-bearing tibia. DESIGN: Mid-tibial MaD, cortical area (CoA), total area, medullary area, strength strain index (SSI), and cortical volumetric bone mineral density (vBMD) (total, endocortical, midcortical, and pericortical) was assessed using peripheral quantitative computed tomography in 179 female athletes involved in both impact and nonimpact loading sports and 41 controls aged 17-40 years. RESULTS: As we have previously reported CoA, total area, and SSI were 16% to 24% greater in the impact group compared with the controls (all P < .001) and 12% to 18% greater than in the nonimpact group (all P < .001). The impact group also had 0.5% higher MaD than the nonimpact and control groups (both P < .05). Regression analysis further showed that midtibial MaD was significantly associated with SSI, CoA, endocortical vBMD, and pericortical vBMD (P < .05) in all women combined, after adjusting for age, bone length, loading groups, medullary area, muscle cross-sectional area, and percent fat. CONCLUSION: In young female athletes, tibial bone MaD was associated with loading history and was an independent predictor of tibial bone strength. These findings suggest that an exercise-induced increase in bone strength may be mediated via reduced bone marrow adiposity and consequently increased osteoblastogenesis.