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

Repair, regenerative and supportive therapies of the annulus fibrosus: achievements and challenges

Lumbar discectomy is a very effective therapy for neurological decompression in patients suffering from sciatica due to hernia nuclei pulposus. However, high recurrence rates and persisting post-operative low back pain in these patients require serious attention. In the past decade, tissue engineering strategies have been developed mainly targeted to the regeneration of the nucleus pulposus (NP) of the intervertebral disc. Accompanying techniques that deal with the damaged annulus fibrous are now increasingly recognised as mandatory in order to prevent re-herniation to increase the potential of NP repair and to confine NP replacement therapies. In the current review, the requirements, achievements and challenges in this quickly emerging field of research are discussed

Bone fracture and bone fracture repair

Fracture healing is a multistage repair process that involves complex, well-orchestrated steps initiated in response to tissue injury. The early upregulation of IL-6, osteoprotegerin (OPG), VEGF, and BMPs indicates a central role for these factors in the initiation of cartilage and periosteal woven bone formation. In both callus fracture repair and stress fracture repair, the RANKL/OPG ratio is initially reduced, but peaks earlier in stress fracture healing than callus fracture healing. Though the understanding of the biological processes and molecular signals that coordinate fracture repair has advanced, the cause of variability observed in fracture repair is poorly understood.N. L. Fazzalar

Bone remodeling: A review of the bone microenvironment perspective for fragility fracture (osteoporosis) of the hip

Crown copyright © 2008 Published by Elsevier Ltd.Bone remodeling is an active process throughout the skeleton. The concept of bone turnover surface has been developed and reported in the peer reviewed literature as the quotient of formation surface/resorption surface and is significantly lower in hip fracture. It is necessary to identify the molecular drivers of these changes in bone turnover. Factors that have been strongly implicated in bone metabolism are therefore divided into three categories, "Vascular", "Anabolic" and "Catabolic". Further data is required from the bone tissue-level microenvironment, of fragility fracture patients, on the variation in molecular signals, and the associated changes in bone structure and remodeling.Nicola L. Fazzalarihttp://www.elsevier.com/wps/find/journaldescription.cws_home/622944/description#descriptio

Fractal Properties of Cancellous Bone of the Iliac Crest in Vertebral Crush Fracture

Fractal analysis is a method for describing complex shapes, including the cancellous structure of bone. It describes the surface texture and form of individual trabecular profiles and the overall cancellous structure. Sixty-four postmenopausal women with symptoms of back pain were referred for investigation for osteoporosis. The patients were divided into two groups for comparison: vertebral crush fracture (n = 31, mean age 68.58 +/- 6.47 years), and no vertebral crush fracture (n = 33, mean age 63.36 +/- 7.21 years). Cores of cancellous bone, 3 mm in diameter, were taken from the iliac crest and sectioned. A box-counting method implemented on an image analyzer was used to measure the fractal dimension. Three fractal dimensions describing trabecular surface texture (fractal 1), trabecular shape (fractal 2), and trabecular arrangement (fractal 3) were measured, indicating that cancellous bone has sectional self-similarity. Conventional histomorphometry was also performed on the samples. The results show that fractal 2 is significantly lower in the vertebral crush fracture group than in the nonfracture group (1.15 +/- 0.10 < 1.23 +/- 0.090, p < 0.0013). The histomorphometric analysis shows that bone surface total volume (p < 0.0002), trabecular number (p < 0.0001), and osteoid surface bone surface (p < 0.028) are significantly lower in the fracture group than the nonfracture group. Eroded surface/bone surface (p < 0.056) follows this trend, whereas trabecular separation (p < 0.001) is significantly higher in the fracture group than in the nonfracture group. Fractal 1 and fractal 3 were not significantly different between study groups. The fractal dimension detects changes in the cancellous architecture and gives information about iliac bone transformation in postmenopausal women with vertebral fracture

Femoral Trabecular Bone of Osteoarthritic and Normal Subjects in an Age and Sex Matched Group

ObjectiveTo describe changes to the cancellous structure of femoral bone from patients with severe primary osteoarthritis by comparison with age and sex matched controls.MethodSpecimens were taken from 18 male and 18 female pairs. One of each pair was a normal control, the other having severe primary osteoarthritis which required hip arthroplasty. Undecalcified cancellous bone blocks were embedded in resin, sectioned and impregnated with silver. Histoquantitation was performed using image analysis. Using a plate model for the trabecular structure of bone, an estimate was made of bone volume, bone surface, trabecular thickness, trabecular separation and trabecular number.ResultsIn osteoarthritis, pooled male and female data show a significant decrease in trabecular number together with an increase in trabecular thickness and separation. The statistical variance in the histomorphometric variables for each of the study groups was calculated and expressed as the ratio of osteoarthritic to control. This ratio shows that the variance of the osteoarthritic groups is significantly increased for each variable in the pooled data. The same trend is evident in the male and female groups.ConclusionsThis quantitative study of cancellous bone architecture in the femoral head, infero-medial to the fovea, has found increased trabecular thickness and decreased trabecular number in patients with primary osteoarthritis. Increased morphometric variance has shown that severe osteoarthritis, contrary to osteoporosis, is associated with heterogeneous bone structures. These findings provide some basis for understanding how osteoarthritis may contribute to the prevention of osteoporotic fracture

Characterisation of trabecular bone structure

The characterisation of trabecular bone structure has until recently relied on morphometric analysis of histological sections although there is now wide availability of bench top non-destructive X-ray-based imaging with the ability to resolve trabecular elements at resolution on the order of ~10 microns. The advent of non-destructive X-ray-based imaging, such as micro-computed tomography (micro-CT) has enabled measurements from image datasets, representing the three-dimensional structure of trabecular bone. Ex vivo studies into trabecular bone structure in osteoporosis have mainly focused on clinically relevant skeletal sites, such as the proximal femur, the distal radius and vertebral bodies. In vivo, the iliac crest and the sternum have been used to obtain material for the diagnosis of metabolic bone diseases including osteoporosis. Metaphyseal bone structure is determined early in development as secondary trabeculae emerge from the primary spongiosa in the epiphyseal plates during endochondral bone growth. After closure of the epiphyseal growth plates at skeletal maturity, bone remodelling becomes the predominant means by which bone is added or removed from the trabecular compartment. From the time of attainment of peak bone mass, studies show that there is a decrease in trabecular bone volume through to older age in both sexes, although not at all sites and not uniformly for males and females. Gender specific changes in trabecular bone are most evident at and after the menopause in females, which is associated with decreased estrogen and associated with reduced androgen production in males. The consequence of menopausal or age-related bone loss for females and males, respectively, is a marked increase in fracture incidence, although the changes to the trabecular bone architecture are different between sexes.Ian H. Parkinson and Nicola L. Fazzalar