Heterogeneous Glycation of Cancellous Bone and Its Association with Bone Quality and Fragility

Non-enzymatic glycation (NEG) and enzymatic biochemical processes create crosslinks that modify the extracellular matrix (ECM) and affect the turnover of bone tissue. Because NEG affects turnover and turnover at the local level affects microarchitecture and formation and removal of microdamage, we hypothesized that NEG in cancellous bone is heterogeneous and accounts partly for the contribution of microarchitecture and microdamage on bone fragility. Human trabecular bone cores from 23 donors were subjected to compression tests. Mechanically tested cores as well as an additional 19 cores were stained with lead-uranyl acetate and imaged to determine microarchitecture and measure microdamage. Post-yield mechanical properties were measured and damaged trabeculae were extracted from a subset of specimens and characterized for the morphology of induced microdamage. Tested specimens and extracted trabeculae were quantified for enzymatic and non-enzymatic crosslink content using a colorimetric assay and Ultra-high Performance Liquid Chromatography (UPLC). Results show that an increase in enzymatic crosslinks was beneficial for bone where they were associated with increased toughness and decreased microdamage. Conversely, bone with increased NEG required less strain to reach failure and were less tough. NEG heterogeneously modified trabecular microarchitecture where high amounts of NEG crosslinks were found in trabecular rods and with the mechanically deleterious form of microdamage (linear microcracks). The extent of NEG in tibial cancellous bone was the dominant predictor of bone fragility and was associated with changes in microarchitecture and microdamage

Mechanical properties versus microarchitecture.

<p>Several microarchitectural properties were correlated with cancellous bone's mechanical parameters.</p

Schematic of UPLC chromatogram.

<p>Eluted peak areas were used for quantification of Pyd, Dpd, and pentosidine.</p

Relationships between crosslink content and mechanical properties, microarchitecture, and microdamage content.

<p>Data is presented as the Spearman correlation coefficient with the p-value in parentheses. NS = not significant. Variables showing significance (p<0.05 but <0.10) are shown in bold.</p

Mechanical properties versus NEG crosslinks.

<p>Graphical data for several mechanical parameters versus total fluorescent AGEs (top) and pentosidine (bottom) are shown.</p

Bone mechanical properties and changes with osteoporosis

This review will define the role of collagen and within-bone heterogeneity and elaborate the importance of trabecular and cortical architecture with regard to their effect on the mechanical strength of bone. For each of these factors, the changes seen with osteoporosis and ageing will be described and how they can compromise strength and eventually lead to bone fragility

Non-Multisystem Inflammatory Syndrome in Children—Postacute Sequelae of Paediatric COVID-19: Autoimmune or Autoinflammatory? A Systematic Review of the Reported Cases

Three years after its emergence, coronavirus disease 2019 (COVID-19) continues to be a leading cause of worldwide morbidity and mortality. This systematic review comprises relevant case reports that discuss non-multisystem inflammatory syndrome in children (non-MIS-C) and postacute sequalae of COVID-19 (PASC) in the paediatric population, also known as long COVID syndrome. The study aims to highlight the prevalent time interval between COVID-19 and the development of non-MIS-C post-infectious sequalae (PIS). Databases were searched for studies that met our inclusion and exclusion criteria. The final screening revealed an equal sex distribution where the commonest age intervals were school-age and adolescence, with 38% of the patients being older than six years. Interestingly, hospital admission during the course of COVID-19 was not a predictor of the subsequent PASC; forty-nine patients (44.9%) were hospitalized while sixty patients (55.1%) were not hospitalized. Moreover, the most predominant time interval between COVID-19 and the developing PASC was within 14 days from the start of COVID-19 infection (61%). These findings suggest a crucial link between COVID-19 and immune PIS in the paediatric population, especially those older than six years. Accordingly, follow-up and management are encouraged in case of unusual symptoms and signs following COVID-19 infection, regardless of the COVID-19 infection severity