Three-dimensional confocal images of microdamage in cancellous bone

Fazzalari, N.L.; Forwood, Mark R.; Manthey, Beverley A.; Smith, Kenneth T.; Kolesik, Peter

doi:10.1016/s8756-3282(98)00111-2

Cited by 118 publications

(84 citation statements)

References 21 publications

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“…8,47 Several factors may explain, in part, the disagreement between Wenzel et al and the current study, including the age range of subjects (greater in Wenzel et al than in current study), and the vertebral body examined (T12 vs. L2), and the location of the trabecular core within the vertebral body. 6 Regarding our finding that microdamage was not associated with trabecular bone mechanical properties, Fazzalari et al 8 also found no relationship between the amount of microdamage and the ultimate failure stress in trabecular bone specimens from human femurs. Furthermore, our data are also consistent with findings from Allen and Burr, who found no relationship between microdamage levels and compressive mechanical properties in vertebral bodies of dogs treated with vehicle, alendronate or risedronate.…”

Section: Discussioncontrasting

confidence: 77%

“…Microdamage has been largely studied in animal models and in human cortical bone, with only a few studies reporting microdamage in human trabecular bone either naturally occurring [6][7][8][9][10][11] or due to loading ex-vivo. 12 In cortical bone, microdamage accumulation leads to decreased mechanical properties, 13,14 and therefore has been implicated in skeletal fragility and stress fractures.…”

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confidence: 99%

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Effects of preexisting microdamage, collagen cross‐links, degree of mineralization, age, and architecture on compressive mechanical properties of elderly human vertebral trabecular bone

Follet

Viguet-Carrin

Burt‐Pichat

et al. 2010

Journal Orthopaedic Research

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Previous studies have shown that the mechanical properties of trabecular bone are determined by bone volume fraction (BV/ TV) and microarchitecture. The purpose of this study was to explore other possible determinants of the mechanical properties of vertebral trabecular bone, namely collagen cross-link content, microdamage, and mineralization. Trabecular bone cores were collected from human L2 vertebrae (n ¼ 49) from recently deceased donors 54-95 years of age (21 men and 27 women). Two trabecular cores were obtained from each vertebra, one for preexisting microdamage and mineralization measurements, and one for BV/TV and quasi-static compression tests. Collagen cross-link content (PYD, DPD, and PEN) was measured on surrounding trabecular bone. Advancing age was associated with impaired mechanical properties, and with increased microdamage, even after adjustment by BV/TV. BV/TV was the strongest determinant of elastic modulus and ultimate strength (r 2 ¼ 0.44 and 0.55, respectively). Microdamage, mineralization parameters, and collagen cross-link content were not associated with mechanical properties. These data indicate that the compressive strength of human vertebral trabecular bone is primarily determined by the amount of trabecular bone, and notably unaffected by normal variation in other factors, such as crosslink profile, microdamage and mineralization. Keywords: bone strength; microdamage; microarchitecture; mineralization; collagen cross-links; vertebral trabecular bone Several studies have shown that the mechanical properties of trabecular bone are influenced by bone volume fraction (BV/TV) and microarchitecture. 1,2 However, additional factors, such as degree of mineralization, preexisting microdamage, and collagen cross-link profile may also play a role, yet the contribution of these factors to human trabecular bone mechanical properties remains incompletely understood.Increased mineralization of cortical bone is exponentially related to increased stiffness, but decreased energy absorption. 3 A similar trend was seen in human trabecular bone from the calcaneus, with a positive relationship between mineralization and elastic modulus, after adjusting for BV/TV. 4 It has also been suggested that a reduction in the heterogeneity of mineralization density distribution leads to increased bone fragility, 5 but there are few data to support this assertion.Microdamage has been largely studied in animal models and in human cortical bone, with only a few studies reporting microdamage in human trabecular bone either naturally occurring 6-11 or due to loading ex-vivo. 12 In cortical bone, microdamage accumulation leads to decreased mechanical properties, 13,14 and therefore has been implicated in skeletal fragility and stress fractures. 15 However, the association between microdamage and cortical bone fracture toughness was weak, 16 raising questions as to the role of microdamage in cortical bone. Increased microdamage has also been associated with decreased strength in human vertebral cancellous bone; 1...

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Section: Discussioncontrasting

confidence: 77%

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confidence: 99%

Effects of preexisting microdamage, collagen cross‐links, degree of mineralization, age, and architecture on compressive mechanical properties of elderly human vertebral trabecular bone

Follet

Viguet-Carrin

Burt‐Pichat

et al. 2010

Journal Orthopaedic Research

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“…2 B and C) of bone fracture in controlled crack propagation studies show the presence of diffuse damage on the crack path and within the uncracked ligament. Diffuse damage (DD), as we and others have previously reported (9,(24)(25)(26)(27), forms under tensile loading and is characterized by several submicroscopic cracks. Unlike linear microcracks (LM), examination of diffuse damage patches under high-resolution laser confocal, atomic force, and scanning electron microscopy shows the formation of dilatational bands (Fig.…”

Section: Resultsmentioning

confidence: 95%

Dilatational band formation in bone

Poundarik

Diab

Sroga

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

238

274

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Toughening in hierarchically structured materials like bone arises from the arrangement of constituent material elements and their interactions. Unlike microcracking, which entails micrometer-level separation, there is no known evidence of fracture at the level of bone's nanostructure. Here, we show that the initiation of fracture occurs in bone at the nanometer scale by dilatational bands. Through fatigue and indentation tests and laser confocal, scanning electron, and atomic force microscopies on human and bovine bone specimens, we established that dilatational bands of the order of 100 nm form as ellipsoidal voids in between fused mineral aggregates and two adjacent proteins, osteocalcin (OC) and osteopontin (OPN). Laser microdissection and ELISA of bone microdamage support our claim that OC and OPN colocalize with dilatational bands. Fracture tests on bones from OC and/or OPN knockout mice (OC −/− , OPN −/− , OC-OPN −/−;−/− ) confirm that these two proteins regulate dilatational band formation and bone matrix toughness. On the basis of these observations, we propose molecular deformation and fracture mechanics models, illustrating the role of OC and OPN in dilatational band formation, and predict that the nanometer scale of tissue organization, associated with dilatational bands, affects fracture at higher scales and determines fracture toughness of bone.noncollagenous proteins | diffuse damage | energy dissipation I n hierarchically structured materials, the composition and spatial arrangement of nanoscale elements are the key determinants of toughness (1, 2). In comparison with many man-made materials, cortical bone is well known for its superior toughness (3, 4). Bone's ability to resist crack propagation originates from its highly complex hierarchical material structure ( Fig. 1). At the highest level of material structure in adult human bone lie the osteons (0.1-0.2 mm in diameter) that contribute to toughness by trapping microcracks (5, 6) and participate in the formation of "uncracked ligaments" (7). Osteons are made of multiple 3-to 7-μm-thick sheets (lamellae) of mineralized matrix. Individual lamellae have the ability to slide past each other (8, 9), forming 60-to 130-μm-long linear microcracks (9) that provide resistance to fracture through microcrack toughening (10). Individual mineralized collagen fibrils <1μm thick, which make up the lamellae, bridge the crack surfaces and toughen the bone (7). Bone's ability to crack, and not fracture by propagating that crack, is therefore a key fundamental aspect of the toughening mechanisms at the microstructural level (10).Recent evidence suggests that bone's nanostructure contributes to bone toughness (11). The nonfibrillar and ductile extrafibrillar matrix components in bone can serve as a "glue" between stiffened mineralized collagen fibrils (11) and between fibrils and mineral platelets (12). Fibril matrix shearing (13) has been proposed to enhance bone toughness through mineral interparticle friction (14) and "sacrificial bonds," a nanoscale mechanism...

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“…Since the first application in studying human cranial bone microstructure by Alan Boyde in 1990, 3 confocal microscopy has become a powerful tool in research related to the skeletal system, such as assessment of bone microdamage under physiological and pathological conditions. [4][5][6] Confocal microscopy has also provided opportunities to investigate bone cell-to-cell interactions in three-dimension, which is particular important for research involving osteocytes and osteoblasts. [7][8][9][10][11] More recently using revised and improved bone processing strategy, a significant progress has been made in the imaging of the bone marrow microenvironment and particularly the vasculature in bone.…”

Section: Introductionmentioning

confidence: 99%

Confocal/two-photon microscopy in studying colonisation of cancer cells in bone using xenograft mouse models

Allocca¹,

Kusumbe²,

Ramasamy³

et al. 2016

BoneKEy Reports

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Confocal and two-photon microscopy has been widely used in bone research to not only produce high quality, three-dimensional images but also to provide valuable structural and quantitative information. In this article, we describe step-by-step protocols for confocal and two-photon microscopy to investigate earlier cellular events during colonisation of cancer cells in bone using xenograft mouse models. This includes confocal/two-photon microscopy imaging of paraformaldehyde fixed thick bone sections and frozen bone samples.

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Three-dimensional confocal images of microdamage in cancellous bone

Cited by 118 publications

References 21 publications

Effects of preexisting microdamage, collagen cross‐links, degree of mineralization, age, and architecture on compressive mechanical properties of elderly human vertebral trabecular bone

Effects of preexisting microdamage, collagen cross‐links, degree of mineralization, age, and architecture on compressive mechanical properties of elderly human vertebral trabecular bone

Dilatational band formation in bone

Confocal/two-photon microscopy in studying colonisation of cancer cells in bone using xenograft mouse models

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