The role of mineralization and organic matrix in the microhardness of bone tissue from controls and osteoporotic patients

Boivin, Georges; Bala, Yohann; Doublier, Audrey; Farlay, Delphine; Ste-Marie, Line; Meunier, Pierre J.; Delmas, Pierre D.

doi:10.1016/j.bone.2008.05.024

Cited by 168 publications

(173 citation statements)

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“…18 The mean degree of mineralization of vertebral trabecular bone was similar to that of human trabecular bone from the calcaneus, and slightly higher than that in human iliac crest. 35 Mineralization heterogeneity index (HI) values from the current study of vertebral trabecular bone (0.29 AE 0.09 g/cm 3 ) are higher than those measured on iliac crest biopsies from healthy control subjects (0.19 AE 0.05 g/cm 3 ) but, similar to values obtained from osteoporotic patients (0.23 AE 0.06 g/ cm 3 ). 35 Our lower range of HI overlapped values previously reported for bisphosphonate users (0.16 AE 0.03 g/cm 3 ).…”

Section: Discussionsupporting

confidence: 60%

“…35 Mineralization heterogeneity index (HI) values from the current study of vertebral trabecular bone (0.29 AE 0.09 g/cm 3 ) are higher than those measured on iliac crest biopsies from healthy control subjects (0.19 AE 0.05 g/cm 3 ) but, similar to values obtained from osteoporotic patients (0.23 AE 0.06 g/ cm 3 ). 35 Our lower range of HI overlapped values previously reported for bisphosphonate users (0.16 AE 0.03 g/cm 3 ). 52 In contrast to a previous report in human calcaneal trabecular bone, 4 we found no relationship between the mean degree of mineralization and mechanical properties.…”

Section: Discussionsupporting

confidence: 60%

“…The mean degree of mineralization and heterogeneity of mineralization were assessed using quantitative microradiography, as previously described. 35,36 Briefly, thick sections (about 150 mm) were cut from embedded bone samples with a precision diamond wire saw (Well, Escil, Chassieu, France), progressively ground to a thickness of 100 mm, and polished with a diamond paste (1 mm). The thickness of the section was measured with an accuracy of 1 mm using a precision micrometer (Compac, Geneva, Switzerland).…”

Section: Mineralization Measurementsmentioning

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: Discussionsupporting

confidence: 60%

Section: Discussionsupporting

confidence: 60%

Section: Mineralization Measurementsmentioning

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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“…The association of dilatational bands with damage at higher scales, including diffuse damage, explains their contribution to bone toughness. Thus, any changes in bone's nanostructure (i.e., mineral, collagen, and noncollagen proteins), reported in osteoporosis and metabolic bone diseases (45)(46)(47)(48)(49), will dramatically reduce bone toughness by altering toughening at from nano-to macro scales.…”

Section: Discussionmentioning

confidence: 99%

Dilatational band formation in bone

Poundarik

Diab

Sroga

et al. 2012

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

235

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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“…Contact microradiography of 100 mm-thick bone sections was performed using an x-ray diffraction unit PW 1830/40 (Philips, Limeil Brévannes, France) (24). The nickel-filtered copper Ka radiation was used under 25 kV and 25 mA.…”

Section: Quantitative Microradiographymentioning

confidence: 99%

Modifications of bone material properties in postmenopausal osteoporotic women long-term treated with alendronate

Bala

Farlay

Chapurlat³

et al. 2011

European Journal of Endocrinology

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Objective: Given recent concern about long-term safety of bisphosphonate (BP) therapy, the effects of long-term alendronate (ALN) therapy on intrinsic bone properties were studied among postmenopausal osteoporotic (PMOP) women. Design and methods: Transiliac bone biopsies were obtained from 32 outpatient clinic PMOP women treated with oral ALN for 6.4G2.0 years. Variables reflecting bone mineralization were measured both at tissue level using quantitative microradiography and at crystal level by Fourier transform infrared microspectroscopy. Bone microhardness was investigated by Vickers indentation tests. Results were compared with those from 22 age-matched untreated PMOP women. Results: Long-term treatment with ALN was associated with a 84% (P!0.001) lower remodeling activity compared with untreated PMOP women, leading to an increased degree of mineralization in both cortical and trabecular bone (C9 and C6%, respectively, P!0.05). Despite a more mature and more mineralized bone matrix, after treatment, cortical and trabecular microhardness and crystallinity were lower than that measured in untreated patients. None of the variables reflecting material properties were significantly correlated to the duration of the treatment. Conclusion: Increased degree of mineralization associated with lower crystallinity and microhardness in ALN long-term-treated PMOP women suggests that ALN could alter the quality of bone matrix. The study also suggested that after 3 years of treatment, the changes in material properties are not dependent on the duration of the treatment. Further studies are requested to assess the short-term (!3 years) effects of BPs on bone intrinsic properties.

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The role of mineralization and organic matrix in the microhardness of bone tissue from controls and osteoporotic patients

Cited by 168 publications

References 44 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

Modifications of bone material properties in postmenopausal osteoporotic women long-term treated with alendronate

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