Bone metabolism and risk of secondary hyperparathyroidism 12 months after gastric banding in obese pre-menopausal women.

OBJECTIVE: To evaluate, during the first postoperative year in obese pre-menopausal women, the effects of laparoscopic gastric banding on calcium and vitamin D metabolism, the potential modifications of bone mineral content and bone mineral density, and the risk of development of secondary hyperparathyroidism. SUBJECTS: Thirty-one obese pre-menopausal women aged between 25 and 52 y with a mean body mass index (BMI) of 43.6 kg/m(2), scheduled for gastric banding were included. Patients with renal, hepatic, metabolic and bone disease were excluded. METHODS: Body composition and bone mineral density (BMD) were measured at baseline, 6 and 12 months after gastric banding using dual-energy X-ray absorptiometry. Serum calcium, phosphate, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, bilirubin, urea, creatinine, uric acid, proteins, parathormone, vitamin D(3), IGF-1, IGF-BP3 and telopeptide, as well as urinary telopeptide, were measured at baseline and 1, 3, 6, 9 and 12 months after surgery. RESULTS: After 1 y vitamin D3 remained stable and PTH decreased by 12%, but the difference was not significant. Serum telopeptide C increased significantly by 100% (P<0.001). There was an initial drop of the IGF-BP3 during the first 6 months (P<0.05), but the reduction was no longer significant after 1 y. The BMD of cortical bone (femoral neck) decreased significantly and showed a trend of a positive correlation with the increase of telopeptides (P<0.06). The BMD of trabecular bone, at the lumbar spine, increased proportionally to the reduction of hip circumference and of body fat. CONCLUSION: There is no evidence of secondary hyperparathyroidism 1 y after gastric banding. Nevertheless biochemical bone markers show a negative remodelling balance, characterized by an increase of bone resorption. The serum telopeptide seems to be a reliable parameter, not affected by weight loss, to follow up bone turnover after gastroplasty.

Ponction biopsie medullaire [Bone marrow aspiration and biopsy]

Le diagnostic final des pathologies impliquant le système hématopoïétique tel que les leucémies, pancytopénies inexpliquées ou autres désordres médullaires, requiert une ponction biopsie de moelle. Cette procédure relativement invasive doit être maîtrisée non seulement par l'hématologue, mais également par l'interniste. Il est crucial d'en connaître les indications et contre-indications et de pouvoir prévenir les complications par une bonne connaissance de celles-ci. Cet article revoit ces différents éléments et apporte les détails pratiques de la procédure ainsi que le matériel nécessaire. The definitive diagnosis of several hematological diseases, as for instance leukaemias, unexplained pancytopenias and other bone marrow disorders, requires a bone marrow aspiration and biopsy. Not only haematologists, but also internists, need to master this rather invasive procedure. The knowledge of indications, contra-indications, potential complications and their prevention of its complications is of utmost importance. This article reviews these topics about bone marrow biopsy, giving some practical advices on this procedure

Early stage primary bone lymphoma - a retrospective, multicenter rare cancer network (rcn) study

Purpose: Primary bone lymphoma (PBL) accounts for less than 1% of all malignant lymphomas, and 4-5% of all extra-nodal lymphomas. In this study, the disease profile, outcome, and prognostic factors were assessed in patients with stage I and II PBL.Patients and Methods: Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Inclusion criteria were age > 16 years, stage I and II, minimum 6 months follow-up and a biopsy-proven confirmation of non-Hodgkin's lymphoma (NHL). Eighty-seven patients underwent chemoradiotherapy (CXRT), 15 radiotherapy (RT) without (13) or with (2) surgery, 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range: 4-60). The median number of CXT cycles was 6 (range: 2-8). Median follow-up was 41 months (range: 6-242).Results: The overall response rate at the end of treatment was 91% (CR 74%, PR 17%). Local recurrence or progression was observed in 12 (10%) patients, and systemic recurrence in 17 (15%). Causes of death included disease progression in 21, unrelated in 5, CXT-related toxicity in 1, and second primary cancer in 2 patients. The 5-yr overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78% and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS were age <50 years (P=0.008), international prognostic index (IPI) score ≤1 (P=0.009), high grade histology (P=0.04), CXRT (P=0.05), CXT (P=0,0004), complete response (CR) (P<0.0001), number of CXT cycles ( ≥6 ) (P=0.01), and RT dose > 40 Gy (P=0.005). All above-mentioned parameters were also significant for LSS except for age and number of chemotherapy cycles. For LC, only CR and stage I were favorable factors. In multivariate analysis, IPI score, RT dose, complete response, and chemotherapy were independently influencing the outcome (OS and LSS). Complete response at the end of treatment was the only predicting factor for LC. Six patients developed grade 3 or more toxicities, according to Common Terminology Criteria for Adverse Events (CTCAE) V3.0.Conclusion: This large multicenter study confirms the relatively good prognosis of early stage PBL treated with combined CXRT. Local control was excellent, while systemic failures were rare. An adequate dose of RT (40 Gy or more) and complete CXT regime (≥ 6 cycles) were associated with better outcome.

Augmentation of bone defect healing using a new biocomposite scaffold: an in vivo study in sheep.

Previous studies support resorbable biocomposites made of poly(L-lactic acid) (PLA) and beta-tricalcium phosphate (TCP) produced by supercritical gas foaming as a suitable scaffold for tissue engineering. The present study was undertaken to demonstrate the biocompatibility and osteoconductive properties of such a scaffold in a large animal cancellous bone model. The biocomposite (PLA/TCP) was compared with a currently used beta-TCP bone substitute (ChronOS, Dr. Robert Mathys Foundation), representing a positive control, and empty defects, representing a negative control. Ten defects were created in sheep cancellous bone, three in the distal femur and two in the proximal tibia of each hind limb, with diameters of 5 mm and depths of 15 mm. New bone in-growth (osteoconductivity) and biocompatibility were evaluated using microcomputed tomography and histology at 2, 4 and 12 months after surgery. The in vivo study was validated by the positive control (good bone formation with ChronOS) and the negative control (no healing with the empty defect). A major finding of this study was incorporation of the biocomposite in bone after 12 months. Bone in-growth was observed in the biocomposite scaffold, including its central part. Despite initial fibrous tissue formation observed at 2 and 4 months, but not at 12 months, this initial fibrous tissue does not preclude long-term application of the biocomposite, as demonstrated by its osteointegration after 12 months, as well as the absence of chronic or long-term inflammation at this time point.

Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis. Results of a 2-year study.

A Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (mu FEA), over 2 years, in postmenopausal osteoporotic women.Introduction Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk.Methods Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2 g/day) or alendronate (70 mg/week) for 2 years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers.Results In the intention-to-treat population (n = 83, age: 64 +/- 8 years; lumbar T-score: -2.8 +/- 0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P < 0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) (P < 0.05 for all above between-group differences). Difference for CTh evaluated with a distance transformation method was close to significance (P = 0.06). The estimated failure load increased with SrRan (+2.1%, P < 0.005), not with alendronate (-0.6%, NS) (between-group difference, P < 0.01). Cortical stress was lower with SrRan (P < 0.05); both treatments decreased trabecular stress. At distal radius, there was no between-group difference other than DCort (P < 0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (-1%) after 2 years of SrRan (between-group difference at each time point for both markers, P < 0.0001). Both treatments were well tolerated.Conclusions Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another method.

A retrospective case-control study assessing the role of trabecular bone score in postmenopausal Caucasian women with osteopenia: analyzing the odds of vertebral fracture.

This case-control study assessed whether the trabecular bone score (TBS), determined from gray-level analysis of DXA images, might be of any diagnostic value, either alone or combined with bone mineral density (BMD), in the assessment of vertebral fracture risk among postmenopausal women with osteopenia. Of 243 postmenopausal Caucasian women, 50-80 years old, with BMD T-scores between -1.0 and -2.5, we identified 81 with osteoporosis-related vertebral fractures and compared them with 162 age-matched controls without fractures. Primary outcomes were BMD and TBS. For BMD, each incremental decrease in BMD was associated with an OR = 1.54 (95% CI = 1.17-2.03), and the AUC was 0.614 (0.550-0.676). For TBS, corresponding values were 2.53 (1.82-3.53) and 0.721 (0.660-0.777). The difference in the AUC for TBS vs. BMD was statistically significant (p = 0.020). The OR for (TBS + BMD) was 2.54 (1.86-3.47) and the AUC 0.732 (0.672-0.787). In conclusion, the TBS warrants a closer look to see whether it may be of clinical usefulness in the determination of fracture risk in postmenopausal osteopenic women.

Clinical factors associated with trabecular bone score.

Dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) is the reference standard for diagnosing osteoporosis but does not directly reflect deterioration in bone microarchitecture. The trabecular bone score (TBS), a novel grey-level texture measurement that can be extracted from DXA images, predicts osteoporotic fractures independent of BMD. Our aim was to identify clinical factors that are associated with baseline lumbar spine TBS. In total, 29,407 women ≥50yr at the time of baseline hip and spine DXA were identified from a database containing all clinical results for the Province of Manitoba, Canada. Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Multiple linear regression and logistic regression (lowest vs highest tertile) was used to define the sensitivity of TBS to other risk factors associated with osteoporosis. Only a small component of the TBS measurement (7-11%) could be explained from BMD measurements. In multiple linear regression and logistic regression models, reduced lumbar spine TBS was associated with recent glucocorticoid use, prior major fracture, rheumatoid arthritis, chronic obstructive pulmonary disease, high alcohol intake, and higher body mass index. In contrast, recent osteoporosis therapy was associated with a significantly lower likelihood for reduced TBS. Similar findings were seen after adjustment for lumbar spine or femoral neck BMD. In conclusion, lumbar spine TBS is strongly associated with many of the risk factors that are predictive of osteoporotic fractures. Further work is needed to determine whether lumbar spine TBS can replace some of the clinical risk factors currently used in fracture risk assessment.

Identification of different heart tissues from MRI C-SENC images using an unsupervised multi-stage fuzzy clustering technique.

PURPOSE: To objectively characterize different heart tissues from functional and viability images provided by composite-strain-encoding (C-SENC) MRI. MATERIALS AND METHODS: C-SENC is a new MRI technique for simultaneously acquiring cardiac functional and viability images. In this work, an unsupervised multi-stage fuzzy clustering method is proposed to identify different heart tissues in the C-SENC images. The method is based on sequential application of the fuzzy c-means (FCM) and iterative self-organizing data (ISODATA) clustering algorithms. The proposed method is tested on simulated heart images and on images from nine patients with and without myocardial infarction (MI). The resulting clustered images are compared with MRI delayed-enhancement (DE) viability images for determining MI. Also, Bland-Altman analysis is conducted between the two methods. RESULTS: Normal myocardium, infarcted myocardium, and blood are correctly identified using the proposed method. The clustered images correctly identified 90 +/- 4% of the pixels defined as infarct in the DE images. In addition, 89 +/- 5% of the pixels defined as infarct in the clustered images were also defined as infarct in DE images. The Bland-Altman results show no bias between the two methods in identifying MI. CONCLUSION: The proposed technique allows for objectively identifying divergent heart tissues, which would be potentially important for clinical decision-making in patients with MI.

Retention half times in the skeleton of plutonium and Sr-90 from above-ground nuclear tests: A retrospective study of the Swiss population

Plutonium and Sr-90 are considered to be among the most radiotoxic nuclides produced by the nuclear fission process. In spite of numerous studies on mammals and humans there is still no general agreement on the retention half time of both radionuclides in the skeleton in the general population. Here we determined plutonium and Sr-90 in human vertebrae in individuals deceased between 1960 and 2004 in Switzerland. Plutonium was measured by sensitive SF-ICP-MS techniques and Sr-90 by radiometric methods. We compared our results to the ones obtained for other environmental compartments to reveal the retention half time of NBT fallout Pu-239 and Sr-90 in trabecular bones of the Swiss population. Results show that plutonium has a retention half time of 40 +/- 14 years. In contrast Sr-90 has a shorter retention half time of 13.5 +/- 1.0 years. Moreover Sr-90 retention half time in vertebrae is shown to be linked to the retention half time in food and other environmental compartments. These findings demonstrate that the renewal of the vertebrae through calcium homeostatic control is faster for Sr-90 excretion than for plutonium excretion. The precise determination of the retention half time of plutonium in the skeleton will improve the biokinetic model of plutonium metabolism in humans. (C) 2010 Elsevier Ltd. All rights reserved.

Testostérone et os: indications et limites [Testosterone and bone: indications and limitations].

Osteoporosis incidence increases exponentially with age in men and hypogonadism represents a risk factor. Sex steroids levels are correlated to bone mineral density and to fracture prevalence. Most studies demonstrate an improvement in bone mineral density in men with hypogonadism as a result of testosterone therapy. Nevertheless there are no data evaluating the effect of testosterone therapy on fractures in men. Approximately 20% of men older than 60 have a total testosterone level lower than the lower limit of the reference range but there is no true consensus on the definition of hypogonadism in older men. In older men we recommend to treat only if total morning testosterone levels are < 8 nmol/l or even < 6,9 nmol/l on several occasions in the absence of any reversible illness and if there is no contraindication for treatment.

Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial.

BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. RESULTS: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. CONCLUSIONS: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.

Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis.

Metabolites from intestinal microbiota are key determinants of host-microbe mutualism and, consequently, the health or disease of the intestinal tract. However, whether such host-microbe crosstalk influences inflammation in peripheral tissues, such as the lung, is poorly understood. We found that dietary fermentable fiber content changed the composition of the gut and lung microbiota, in particular by altering the ratio of Firmicutes to Bacteroidetes. The gut microbiota metabolized the fiber, consequently increasing the concentration of circulating short-chain fatty acids (SCFAs). Mice fed a high-fiber diet had increased circulating levels of SCFAs and were protected against allergic inflammation in the lung, whereas a low-fiber diet decreased levels of SCFAs and increased allergic airway disease. Treatment of mice with the SCFA propionate led to alterations in bone marrow hematopoiesis that were characterized by enhanced generation of macrophage and dendritic cell (DC) precursors and subsequent seeding of the lungs by DCs with high phagocytic capacity but an impaired ability to promote T helper type 2 (TH2) cell effector function. The effects of propionate on allergic inflammation were dependent on G protein-coupled receptor 41 (GPR41, also called free fatty acid receptor 3 or FFAR3), but not GPR43 (also called free fatty acid receptor 2 or FFAR2). Our results show that dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation.

Clinical consequences of sensitisation to minor histocompatibility antigens before allogeneic bone marrow transplantation.

To study sensitisation to minor histocompatibility antigens (mHag) before and after BMT, we measured antidonor CTL activity in five patients who had rejected their graft, and in a control group of 10 leukemic patients who engrafted without complications. All patients were transplanted with marrow from an HLA-identical sibling. Fourteen patients were conditioned with cyclophosphamide (120 mg/kg) and TBI (1350 cGy) and received a T cell-depleted graft, while one patient with aplastic anaemia received cyclophosphamide alone and unmanipulated marrow. Before transplantation, anti-donor CTL activity was detected in two of the 15 patients. These patients rejected their grafts at days 21 and 58, respectively. In the other three patients who rejected their grafts at days 41, 60 and 250, CTL activity was found only after transplantation. In contrast, no anti-donor CTLs could be detected at any time in the 10 patients who engrafted permanently. We have identified some of the mHags recognised during graft rejection by cloning and subsequent specificity analysis of the recipient CTLs. In the patient who rejected at day 41 without detectable immunisation before BMT, the response was directed against HA-1, a minor antigen known to play a role in GVHD. In the other combinations, a significant part of the CTL activity was directed against the male antigen H-Y. In the patient who rejected the marrow of her HLA-identical brother at day 250, two clones recognised H-Y, while five others recognised at least three distinct autosomal mHags. This patient had an HLA-identical sister who expressed only one autosomal mHag that had been recognised by one single T cell clone. After re-transplantation with the marrow of this second donor, the CTL activity could no longer be detected and the patient engrafted without further complications.