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Introduction: Cortical bone thinning and a rarefaction of the trabecular architecture represent possible causes of increased femoral neck (FN) fracture risk. Due to X-ray exposure limits, the bone microstructure is rarely measurable in the FN of subjects but can be assessed at the tibia. Here, we studied whether changes of the tibial cortical microstructure, which were previously reported to be associated with femur strength, are also associated with structural deteriorations of the femoral neck., Methods: The cortical and trabecular architectures in the FN of 19 humans were analyzed ex vivo on 3D microcomputed tomography images with 30.3 μm voxel size. Cortical thickness (Ct.Th tibia ), porosity (Ct.Po tibia ) and pore size distribution in the tibiae of the same subjects were measured using scanning acoustic microscopy (12 μm pixel size). Femur strength during sideways falls was simulated with homogenized voxel finite element models., Results: Femur strength was associated with the total (vBMD tot ; R 2  = 0.23, p < 0.01) and trabecular (vBMD trab ; R 2  = 0.26, p < 0.01) volumetric bone mineral density (vBMD), with the cortical thickness (Ct.Th FN ; R 2  = 0.29, p < 0.001) and with the trabecular bone volume fraction (Tb.BV/TV FN ; R 2  = 0.34, p < 0.001), separation (Tb.Sp FN ; R 2  = 0.25, p < 0.01) and number (Tb.N FN ; R 2  = 0.32, p < 0.001) of the femoral neck. Moreover, smaller Ct.Th tibia was associated with smaller Ct.Th FN (R 2  = 0.31, p < 0.05), lower Tb.BV/TV FN (R 2  = 0.29, p < 0.05), higher Tb.Sp FN (R 2  = 0.33, p < 0.05) and lower Tb.N FN (R 2  = 0.42, p < 0.01). A higher prevalence of pores with diameter > 100 μm in tibial cortical bone (relCt.Po 100μm-tibia ) indicated higher Tb.Sp FN (R 2  = 0.36, p < 0.01) and lower Tb.N FN (R 2  = 0.45, p < 0.01)., Conclusion: Bone resorption and structural decline of the femoral neck may be identified in vivo by measuring cortical bone thickness and large pores in the tibia., Competing Interests: Declaration of competing interest KR and GI have the patent application “CortBS: Ultrasonic method for determining pore dimensions in cortical bone” pending. JS, AR, FH, LP, CW, CCG and DP have nothing to disclose. JB reports grants and personal fees from Eli Lilly, grants and personal fees from Amgen, grants from Will Pharma, outside the submitted work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Identifying determinants of long-term functional outcome after a distal radius fracture is challenging. Previously, we reported on the association between early HR-pQCT measurements and clinical outcome 12 weeks after a conservatively treated distal radius fracture. We extended the follow-up and assessed functional outcome after two years in relation to early HR-pQCT derived bone parameters. HR-pQCT scans of the fracture region were performed in 15 postmenopausal women with a distal radius fracture at 1-2 (baseline), 3-4 weeks and 26 months post-fracture. Additionally, the contralateral distal radius was scanned at baseline. Bone density, micro-architecture parameters and bone stiffness using micro-finite element analysis (μFEA) were evaluated. During all visits, wrist pain and function were assessed using the patient-rated wrist evaluation questionnaire (PRWE), quantifying functional outcome with a score between 0 and 100. Two-year PRWE was associated with torsional and bending stiffness 3-4 weeks post-fracture (R 2 : 0.49, p = 0.006 and R 2 : 0.54, p = 0.003, respectively). In contrast, early micro-architecture parameters of the fracture region or contralateral bone parameters did not show any association with long-term outcome. This exploratory study indicates that HR-pQCT with μFEA performed within four weeks after a distal radius fracture captures biomechanical fracture characteristics that are associated with long-term functional outcome and therefore could be a valuable early outcome measure in clinical trials and clinical practice., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cortical pores are determinants of the elastic properties and of the ultimate strength of bone tissue. An increase of the overall cortical porosity (Ct.Po) as well as the local coalescence of large pores cause an impairment of the mechanical competence of bone. Therefore, Ct.Po represents a relevant target for identifying patients with high fracture risk. However, given their small size, the in vivo imaging of cortical pores remains challenging. The advent of modern high-resolution peripheral quantitative computed tomography (HR-pQCT) triggered new methods for the clinical assessment of Ct.Po at the peripheral skeleton, either by pore segmentation or by exploiting local bone mineral density (BMD). In this work, we compared BMD-based Ct.Po estimates with high-resolution reference values measured by scanning acoustic microscopy. A calibration rule to estimate local Ct.Po from BMD as assessed by HR-pQCT was derived experimentally. Within areas of interest smaller than 0.5 mm 2 , our model was able to estimate the local Ct.Po with an error of 3.4%. The incorporation of the BMD inhomogeneity and of one parameter from the BMD distribution of the entire scan volume led to a relative reduction of the estimate error of 30%, if compared to an estimate based on the average BMD. When applied to the assessment of Ct.Po within entire cortical bone cross-sections, the proposed BMD-based method had better accuracy than measurements performed with a conventional threshold-based approach., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Between 5% and 10% of all fractures fail to heal adequately resulting in nonunion of the fracture fragments. This can significantly decrease a patient's quality of life and create associated psychosocial and socio-economic problems. Nitric oxide (NO) and nitric oxide synthases (NOS) have been found to be involved in fracture healing, but until now it is not known if disturbances in these mechanisms play a role in nonunion and delayed union development. In this study, we explored the role of endothelial and inducible NOS deficiency in a delayed union model in mice., Materials and Methods: A 0.45mm femur osteotomy with periosteal cauterization followed by plate-screw osteosynthesis was performed in the left leg of 20-24week old wild type, Nos2(-/-) and Nos3(-/-) mice. Contralateral unfractured legs were used as a control. Callus volume was measured using micro-computed tomography (μCT) after 28 and 42days of fracture healing. Immuno histochemical myeloperoxidase (MPO) staining was performed on paraffin embedded sections to assess neutrophil influx in callus tissue and surrounding proximal and distal marrow cavities of the femur. After 7 and 28days of fracture healing, femurs were collected for amino acid and RNA analysis to study arginine-NO metabolism., Results: With μCT, delayed union was observed in wild type animals, whereas in both Nos2(-/-) and Nos3(-/-) mice nonunion development was evident. Both knock-out strains also showed a significantly increased influx of MPO when compared with wild type mice. Concentrations of amino acids and expression of enzymes related to the arginine-NO metabolism were aberrant in NOS deficient mice when compared to contralateral control femurs and wild type samples., Discussion and Conclusion: In the present study we show for the first time that the absence of nitric oxide synthases results in a disturbed arginine-NO metabolism and inadequate fracture healing with the transition of delayed union into a nonunion in mice after a femur osteotomy. Based on these data we suggest that the arginine-NO metabolism may play a role in the prevention of delayed unions and nonunions., (Copyright © 2015 Elsevier Inc. All rights reserved.)