Femoral Neck Trabecular Bone: Loss With Aging and Role in Preventing Fracture

Hip fracture risk rises 100‐ to 1000‐fold over six decades of age, but only a minor part of this increase is explained by declining BMD. A potentially independent cause of fragility is cortical thinning predisposing to local crushing, in which bone tissue's material disintegrates at the microscopic level when compressed beyond its capacity to maintain integrity. Elastic instability or buckling of a much thinned cortex might alternatively occur under compression. In a buckle, the cortex moves approximately at right angles to the direction of load, thereby distorting its microstructure, eventually to the point of disintegration. By resisting buckling movement, trabecular buttressing would protect the femoral neck cortex against this type of failure but not against crushing. We quantified the effect of aging on trabecular BMD in the femoral neck and assessed its contribution to cortical elastic stability, which determines resistance to buckling. Using CT, we measured ex vivo the distribution of bone in the midfemoral necks of 35 female and 33 male proximal femurs from cases of sudden death in those 20–95 yr of age. We calculated the critical stress σ_cr, at which the cortex was predicted to buckle locally, from the geometric properties and density of the cortical zone most highly loaded in a sideways fall. Using long‐established engineering principles, we estimated the amount by which stability or buckling resistance was increased by the trabecular bone supporting the most stressed cortical sector in each femoral neck. We repeated these measurements and calculations in an age‐ and sex‐matched series of femoral necks donated by women who had suffered intracapsular hip fracture and controls, using histological measurements of cortical thickness to improve accuracy. With normal aging, trabecular BMD declined asymmetrically, fastest in the supero‐lateral one‐half (in antero‐posterior projection) of the trabecular compartment. When viewed axially with respect to the femoral neck, the most rapid loss of trabecular bone occurred in the posterior part of this region (supero‐posterior [S‐P]), amounting to a 42% reduction in women (34% in men) over five decades of adult age. Because local cortical bone thickness declined comparably, age had no significant effect on the relative contributions of cortical and trabecular bone to elastic stability, and trabecular bone was calculated to contribute 40% (in men) and 43% (in women) to the S‐P cortex of its overall elastic stability. Hip fracture cases had reduced elastic stability compared with age‐matched controls, with a median reduction of 49% or 37%, depending on whether thickness was measured histologically or by CT (pQCT; p < 0.002 for both). This effect was because of reduced cortical thickness and density. Trabecular BMD was similar in hip fracture cases and controls. The capacity of the femur to resist fracture in a sideways fall becomes compromised with normal aging because cortical thickness and trabecular BMD in the most compressed part of the femoral neck both decline substantially. This decline is relatively more rapid than that of femoral neck areal BMD. If elastic instability rather than cortical crushing initiates the fracture event, interventions that increase trabecular bone in the proximal femur have great potential to reduce fracture risk because the gradient defining the increase in elastic stability with increasing trabecular BMD is steep, and most hip fracture cases have sufficient trabecular bone for anabolic therapies to build on.     

Foxp3 expression in lesions of the different clinical forms of American tegumentary leishmaniasis

As the diversity in clinical presentation of American tegumentary leishmaniasis (ATL) is determined mainly by the immune response of host, our aim was to evaluate the in situ expression of Foxp3 [marker of regulatory T (Treg) cell] in lesions of the different clinical forms of ATL. Foxp3⁺ cells were observed in 39·5% (32/81) of the samples and the number of positive cells was low in all the clinical forms. Even presenting a significantly lower number of CD4⁺ T cells, diffuse cutaneous leishmaniasis (DCL) showed a higher expression of Foxp3 when compared with localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). In LCL and MCL, the number of Foxp3⁺ cells correlated positively with the number of apoptotic cells (active caspase-3⁺ cells). A positive correlation was also observed between the expression of active caspase-3 and FasL in these clinical forms. Our data suggest that increased number of Treg cells may be associated to the hyporesponsiveness observed in DCL and also indicate that the apoptosis may be a possible mechanism of action of Foxp3⁺ Treg cell in LCL and MCL. However, further studies are required to better understand the mechanism of action of Treg cell.     

Continent urinary diversions: review of current surgical procedures and radiologic imaging

Continent urinary diversions are currently gaining wide acceptance as alternatives to the ileal conduit following cystectomy for neoplasm or bladder dysfunction. Clean, intermittent catheterization of the reservoir (pouch) at regular intervals obviates the inconvenience of wearing an external stomal appliance. A variety of surgical techniques have been described for continent pouches. These techniques make use of the small bowel alone (Camey and Kock techniques) or a combination of cecum and terminal ileum (Indiana, Mainz, Penn, and King techniques). The optimum pouch protects the upper tracts by prevention of reflux, provides urinary continence, and has sufficient capacity to require catheterization no more frequently than every 3-6 hours. Simplified construction techniques for the commonly encountered pouches are graphically presented, and a method is suggested for the study of continent diversions.     

Increased IL-10 production by stimulated whole blood cultures in primary IgA nephropathy

Most patients with primary IgA nephropathy (IgAN) have a significantly higher memory repertoire of IgA1-producing B lymphocytes in their bone marrow together with high plasma levels of IgA1. The connection between the mucosal immune system and the bone marrow compartment is probably based on traffic of either antigen-presenting cells (APC) or antigen-specific lymphocytes. Cytokines play an important role in the proliferation and differentiation of lymphoid cells. In order to mimic the in vivo situation as much as possible, we assessed cytokine production profiles ex vivo in 23 IgAN patients and matched controls, using lipopolysaccharide (LPS)- or phytohaemagglutinin (PHA)-stimulated whole blood (WB) cultures. Interferon-gamma (IFN-γ), IL-2, IL-6, IL-10 and tumour necrosis factor-alpha (TNF-α) production in culture supernatants were determined by cytokine-specific ELISAs. Compared with controls, PHA-stimulated cultures resulted in significantly higher IL-10 (P < 0.001), IL-2 (P < 0.005) and IFN-γ (P < 0.001) levels in IgAN patients, but no significant differences in TNF-α or IL-6 levels were found. In LPS-stimulated cultures, the only significant difference (P < 0.001) between the two groups was the increased IL-10 production in IgAN patients. The enhanced cytokine production in stimulated WB cultures suggests altered monocyte-related T cell responses in patients with IgAN. Increased IL-10 production may eventually result in an increased number of IgA-producing B lymphocytes in the bone marrow. In addition, high levels of endogenous IL-10 may down-regulate the effector functions of monocytes, or possibly APC in general, and consequently the IgA response at the mucosal level.     

Bisphosphonate associated osteomyelitis of the jaw in patients with bony exposure: prevention,a new way of thinking

Objective

There is strong evidence of a link between the use of systemic bisphosphonates (BPs) and osteonecrosis of the jaw, especially in cancer patients. Among risk factors for BRONJ, tooth extraction and immune suppressive drugs seem to have significant role on bone healing. Therefore, the importance of these parameters in development of BRONJ was reviewed in this retrospective study in two maxillofacial surgery units.

Material and Methods

From 2007 to 2012, 46 patients on bisphosphonate who had developed oral bony lesions participated in this study. The pharmacological exposure, comorbidities, maxillofacial findings, types of treatment and outcome data were collected from clinical and radiological records.

Results

The most frequently used BP was alendronate (67%). Tooth extraction was reported in 61% of patients with BRONJ. Systemic corticosteroids were prescribed in 35 cases (76%) as an adjuvant for BP. Patients on corticosteroids had a lower probability of bony lesion healing (p<0.05) than patients without corticosteroids. Of the 46 patients who underwent conservative treatments, only ten were completely healed (21%).

Conclusions

Beside tooth extraction, corticosteroids were shown to be an implant risk factor for low rate of bone healing and hence the development of BRONJ. The outcome of conservative treatment was uncertain and this emphasizes the importance of prevention.     

Treatment effects in Trichuris dysentery syndrome

Heavy infection with the geohelminth Trichuris trichiura causes the Trichuris dysentery syndrome (TDS). Growth retardation and anaemia are characteristic of TDS and both are associated with poor development. We have examined the growth and developmental responses to treatment in 19 children aged 27–84 months with TDS. Developmental levels (DQ) were measured with the Griffiths mental development scales. Compared with a control group matched for age, gender and neighbourhood, the TDS children initially had serious deficits in DQ (24 points, p < 0.001). After a year of anthelmintic treatment, the TDS children showed improvement in locomotor development (p < 0.001) compared with the controls. The TDS children also had initial deficits in height-for-age, weight-for-height, mid-upper arm circumference and haemoglobin levels. They caught up rapidly in indices of wasting (weight-for-height and mid-upper arm circumference) and showed steady improvement in height-for-age and haemoglobin levels. Catch-up in height was comparable to that of children recovering from coeliac disease. The importance of continuing prevention after initial treatment is highlighted.     

胎-母输血综合征对围产儿的影响--附2例报告

胎－母输血综合征对围产儿的影响——附２例报告丁新黄醒华胎－母输血综合征，即胎儿血液由胎盘的绒毛间隙进入母体血循环，引起胎儿不同程度的失血及母体溶血性输血反应的一组症候群。大量胎－母输血可导致胎儿贫血、休克、死胎、死产；新生儿贫血、休克、死亡。我院在近...