Abstract
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.
Highlights
Age-related bone fracture is a major health problem that can result in disability and substantial medical care costs [1]
Bone quality can be altered by several features including changes in the extracellular matrix (ECM) and microarchitecture, which interact under applied loading to influence microdamage formation that can contribute to bone’s mechanical properties [7,8]
We found that with increases in microdamage quantity, there was deterioration in microarchitecture on both the global level and region of minimum BV/TV (Table 2)
Summary
Age-related bone fracture is a major health problem that can result in disability and substantial medical care costs [1]. Studies demonstrate that decreased bone mass alone is not sufficient to cause a fracture [4,5,6] Other factors such as changes in bone quality [7] may be key determinants of fracture risk. Bone’s ECM components undergo numerous biochemical changes with aging Any changes in these constituents can detrimentally alter the mechanical behavior of bone and explain the increased fracture incidence in the aging population [5]. Type I collagen is susceptible to both enzymatic and non-enzymatic biochemical changes [9] Both pathways yield crosslinks, but they affect bone’s mechanical properties differently. Because turnover affects formation and removal of microdamage and the local microarchitecture, AGEs may act through reduced turnover and influence other measures of bone quality associated with bone fragility
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