Soluble TNF Receptors and Kidney Dysfunction in the Elderly

The importance of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in the development of kidney disease is being unraveled. Yet, community-based data regarding the role of sTNFRs are lacking. We assessed serum sTNFRs and aspects of kidney damage cross-sectionally in two independent community-based cohorts of elderly participants: Prospective Investigation of the Vasculature in Uppsala Seniors (n=815; mean age, 75 years; 51% women) and Uppsala Longitudinal Study of Adult Men (n=778; mean age, 78 years). Serum sTNFR1 correlated substantially with different aspects of kidney pathology in the Uppsala Longitudinal Study of Adult Men cohort (R=−0.52 for estimated GFR, R=0.22 for urinary albumin-to-creatinine ratio, and R=0.17 for urinary kidney injury molecule-1; P<0.001 for all), with similar correlations in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. These associations remained significant after adjustment for age, sex, inflammatory markers, and cardiovascular risk factors and were also evident in participants without diabetes. Serum sTNFR2 was associated with all three markers in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort (P<0.001 for all). Our findings from two independent community-based cohorts confirm and extend results of previous studies supporting circulating sTNFRs as relevant biomarkers for kidney damage and dysfunction in elderly individuals, even in the absence of diabetes.     

Finite element analysis of the initial stability of ankle arthrodesis with internal fixation: flat cut versus intact joint contours

OBJECTIVE: Qualitative comparison of the initial stability provided by two joint preparation techniques and various screw configurations in ankle arthrodesis, using the finite element method.Design. A three-dimensional model of a healthy ankle was developed from computed tomography images. Two groups of models were built, one with the joint contours resected to produce flat surfaces, and the second with the joint contours preserved. In each case, a variety of screw orientations were examined. BACKGROUND: Despite the improved results of ankle arthrodesis, failure rates due to non-union are still reported. The initial stability of the arthrodesis construct seems important in the final outcome of the fusion. METHODS: Non-linear contact finite element analyses were performed in the arthrodesis constructs subjected to internal/external torsion and dorsiflexion. Micromotions at the bone-to-bone interface were calculated for frictionless and Coulomb friction contact, and compared for the two joint preparation techniques and screw configurations. RESULTS: Overall lower peak micromotions were predicted when preserving the joint contours both in torsion and dorsiflexion. For both preparation techniques, the lowest micromotions tended to occur with the screws inserted at 30 degrees with respect to the long axis of the tibia, crossing above the fusion site. Inclusion of friction in the models caused a general decrease on the magnitude of the micromotions as compared to the frictionless case, but did not affect the ranking of the models. CONCLUSIONS: The finite element method can be used as a qualitative tool to study the initial stability of ankle arthrodesis, overcoming the difficulties of measuring bone-to-bone interface micromotions experimentally. Better initial stability was predicted for ankle arthrodesis when the joint contours were preserved rather than resected. Crossing the screws above the fusion site at a steeper angle also tended to increase the stability at the fusion site. RELEVANCE: Finite element analyses can help during the pre-operative planning of ankle arthrodesis. When bone density is not compromised, preserving the joint contour and inserting the screws at less than 45 degrees to the long axis of the tibia, crossing over the arthrodesis site, may offer better initial stability.     

Increased Trabecular Volumetric Bone Mass Density in Familial Hypocalciuric Hypercalcemia (FHH) Type 1: A Cross-Sectional Study

Familial Hypocalciuric Hypercalcaemia (FHH) Type 1 is caused by an inactivating mutation in the calcium-sensing receptor (CASR) gene resulting in elevated plasma calcium levels. We investigated whether FHH is associated with change in bone density and structure. We compared 50 FHH patients with age- and gender-matched population-based controls (mean age 56 years, 69 % females). We assessed areal BMD (aBMD) by DXA-scans and total, cortical, and trabecular volumetric BMD (vBMD) as well as bone geometry by quantitative computed tomography (QCT) and High-Resolution peripheral-QCT (HR-pQCT). Compared with controls, FHH females had a higher total and trabecular hip vBMD and a lower cortical vBMD and hip bone volume. Areal BMD and HRpQCT indices did not differ except an increased trabecular thickness and an increased vBMD at the transition zone between cancellous and cortical bone in of the tibia in FHH. Finite element analyses showed no differences in bone strength. Multiple regression analyses revealed correlations between vBMD and P-Ca²⁺ levels but not with P-PTH. Overall, bone health does not seem to be impaired in patients with FHH. In FHH females, bone volume is decreased, with a lower trabecular volume but a higher vBMD, whereas cortical vBMD is decreased in the hip. This may be due to either an impaired endosteal resorption or corticalization of trabecular bone. The smaller total bone volume suggests an impaired periosteal accrual, but bone strength is not impaired. The findings of more pronounced changes in females may suggest an interaction between sex hormones and the activity of the CaSR on bone.