The Role of Bone Biopsy in the Management of CKD-MBD

A bone biopsy is still considered the gold standard for diagnosis of renal osteodystrophy. It allows to measure both static and dynamic parameters of bone remodeling and is the only method able to evaluate mineralization and allows analysis of both cortical and trabecular bone. Although bone volume can be measured indirectly by dual-energy X-ray absorptiometry, mineralization defects, bone metal deposits, cellular number/activity, and even turnover abnormalities are difficult to determine by techniques other than qualitative bone histomorphometry. In this review, we evaluate the role of bone biopsy in the clinical practice.info:eu-repo/semantics/publishedVersio

The Role of Bone Biopsy in the Management of CKD-MBD: CKD-Related Osteoporosis or CKD-MBD/Osteoporosis?

info:eu-repo/semantics/publishedVersio

Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis

Osteoporosis is associated with chronic iron overload secondary to hereditary hemochromatosis (HH), but the causative mechanisms are incompletely understood. The main objective of this study was to investigate the role of dietary iron on osteoporosis, using as biological model the Hfe-KO mice, which have a systemic iron overload. We showed that these mice show an increased susceptibility for developing a bone loss phenotype compared to WT mice, which can be exacerbated by an iron rich diet. The dietary iron overload caused an increase in inflammation and iron incorporation within the trabecular bone in both WT and Hfe-KO mice. However, the osteoporotic phenotype was only evident in Hfe-KO mice fed the iron-enriched diet. This appeared to result from an imbalance between bone formation and bone resorption driven by iron toxicity associated to Hfe-KO and confirmed by a decrease in bone microarchitecture parameters (identified by micro-CT) and osteoblast number. These findings were supported by the observed downregulation of bone metabolism markers and upregulation of ferritin heavy polypeptide 1 (Fth1) and transferrin receptor-1 (Tfrc), which are associated with iron toxicity and bone loss phenotype. In WT mice the iron rich diet was not enough to promote a bone loss phenotype, essentially due to the concomitant depression of bone resorption observed in those animals. In conclusion the dietary challenge influences the development of osteoporosis in the HH mice model thus suggesting that the iron content in the diet may influence the osteoporotic phenotype in systemic iron overload conditions.National Funds through Foundation for Science and Technology (FCT) Norte-01-0145-FEDER-000012 Portuguese Foundation for Science and Technology (FCT) SFRH/BD/77056/2011 European Regional Development Fund (FEDER) Norte-01-0145-FEDER-000012info:eu-repo/semantics/publishedVersio

Vertebral fractures are associated with increased cortical porosity in iliac crest bone biopsy of men with idiopathic osteoporosis

In men, vertebral fractures are poorly associated with bone density, and both cortical and trabecular micro-architectural changes could contribute to bone fragility. Bone histomorphometry makes it possible to investigate both the thickness and porosity of cortical bone, which has been reported to have a major impact on the biomechanical properties of bone. We therefore conducted a cross sectional study using iliac crest biopsies to investigate the trabecular and cortical bone structure in men with or without vertebral fractures.We selected 93 bone biopsies from men with idiopathic osteoporosis (defined as a T-score <− 2.5), between 40 and 70 years of age. Patients were divided into two groups on the basis of the presence (n = 46) or absence (n = 47) of prevalent vertebral fracture (VFX). We measured micro-architectural indices in trabecular and cortical bone by histomorphometry at the iliac crest. Patients with VFX had lower trabecular bone volume (BV/TV: 12.4 ± 3.8 versus 14.7 ± 3.1 % (m ± SD)), p < 0.01), higher trabecular separation (Tb.Sp: 871 ± 279 versus 719 ± 151 μm, p < 0.01), and higher marrow star volume (V*m.space: 1.617 ± 1.257 versus 0.945 ± 0.466 mm3, p < 0.01). Cortical thickness (Ct.Th) was the same in patients with or without VFX, whereas cortical porosity (Ct.Po) was higher in patients with VFX (6.5 ± 2.6 versus 5.0 ± 2.0 %, p < 0.01), because their Haversian canals had higher mean areas (8291 ± 4135 versus 5438 ± 2809 μm2, p < 0.001). There was no correlation between any trabecular and cortical micro-architectural parameters. Using a logistic regression model, we evaluated the VFX as a function of the V⁎m.space and Ct.Po, adjusted for age. The odds-ratio of having a VFX was 3.89 (95% CI 1.19–12.7, p = 0.02) for the third tertile of V*m.space (adjusted on age and Ct.Po), and 4.07 (95% CI 1.25–13.3, p = 0.02) for the third tertile of Ct.Po (adjusted on age and V*m.space). Our data show that both trabecular and cortical bone microarchitecture contribute independently to vertebral fractures in men with idiopathic osteoporosis. In contrast to data reported in women, in men it is cortical porosity, and not cortical width, that is associated with vertebral fractures. This suggests that the cortical deficit is different in men and in women with fragility fractures

Performance evaluation of novel square-bordered position-sensitive silicon detectors with four-corner readout

We report on a recently developed novel type of large area (62 mm x 62 mm) position sensitive silicon detector with four-corner readout. It consists of a square-shaped ion-implanted resistive anode framed by additional low-resistivity strips with resistances smaller than the anode surface resistance by a factor of 2. The detector position linearity, position resolution, and energy resolution were measured with alpha-particles and heavy ions. In-beam experimental results reveal a position resolution below 1 mm (FWHM) and a very good non-linearity of less than 1% (rms). The energy resolution determined from 228Th alpha source measurements is around 2% (FWHM).Comment: 13 pages, 10 figures, submitted to Nucl. Instr. and Meth.

Longitudinal Bone Loss Occurs at the Radius in CKD.

Chronic kidney disease (CKD) exposes to an increased incidence of fragility fractures. International guidelines recommend performing bone mineral density (BMD) if the results will impact treatment decisions. It remains unknown where bone loss occurs and what would preclude the longitudinal loss in patients with CKD. Here, we aimed to investigate factors influencing BMD and to analyze the longitudinal BMD changes. In the NephroTest cohort, we measured BMD at the femoral neck, total hip, lumbar spine, and proximal radius, together with circulating biomarkers and standardized measured glomerular filtration rate (mGFR) by <sup>51</sup> Cr-EDTA in a subset of patients with CKD stage 1 to 5 followed during 4.3 ± 2.0 years. A linear mixed model explored the longitudinal bone loss and the relationship of associated factors with BMD changes. A total of 858 patients (mean age 58.9 ± 15.2 years) had at least 1 and 477 had at least 2 BMD measures. At baseline, cross-sectional analysis showed a significantly lower BMD at femoral neck and total hip and a significant higher serum parathyroid hormone (PTH) along with CKD stages. Baseline age, gender, tobacco, low body mass index (BMI), and high PTH levels were significantly associated with low BMD. Longitudinal analysis during the mean 4.3 years revealed a significant bone loss at the radius only. BMD changes at the femoral neck were associated with BMI, but not CKD stages or basal PTH levels. CKD is associated with low BMD and high PTH in the cross-sectional analysis. Longitudinal bone loss occurred at the proximal radius after 4.3 years

Metastatic Melanomas Express Inhibitory Low Affinity Fc Gamma Receptor and Escape Humoral Immunity

Our research, inspired by the pioneering works of Isaac Witz in the 1980s, established that 40% of human metastatic melanomas express ectopically inhibitory Fc gamma receptors (FcγRIIB), while they are detected on less than 5% of primary cutaneous melanoma and not on melanocytes. We demonstrated that these tumoral FcγRIIB act as decoy receptors that bind the Fc portion of antimelanoma IgG, which may prevent Fc recognition by the effector cells of the immune system and allow the metastatic melanoma to escape the humoral/natural immune response. The FcγRIIB is able to inhibit the ADCC (antibody dependent cell cytotoxicity) in vitro. Interestingly, the percentage of melanoma expressing the FcγRIIB is high (70%) in organs like the liver, which is rich in patrolling NK (natural killer) cells that exercise their antitumoral activity by ADCC. We found that this tumoral FcγRIIB is fully functional and that its inhibitory potential can be triggered depending on the specificity of the anti-tumor antibody with which it interacts. Together these observations elucidate how metastatic melanomas interact with and potentially evade humoral immunity and provide direction for the improvement of anti-melanoma monoclonal antibody therapy