Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus

Saito, Mitsuru; Marumo, Keishi

doi:10.1007/s00198-009-1066-z

Cited by 772 publications

(616 citation statements)

References 155 publications

(332 reference statements)

Supporting

Mentioning

574

Contrasting

Unclassified

Order By: Relevance

“…(14,17) In DM, high glucose levels cause the accumulation of advanced glycation end products (AGEs) that have been associated with an increased risk of fracture. (18) In vitro (19) and in vivo studies (20,21) demonstrate that AGE accumulation increases the brittleness of bone.…”

Section: Insights Into the Pathogenesis Of Atypical Femoral Fracturesmentioning

confidence: 99%

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Shane

Burr

Ebeling

et al. 2010

Journal of Bone and Mineral Research

998

679

View full text Add to dashboard Cite

Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address key questions related to this problem. A multidisciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. A case definition was developed so that subsequent studies report on the same condition. The task force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids, and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross-linking and maturation, accumulation of microdamage and advanced glycation end products, mineralization, remodeling, vascularity, and angiogenesis lend biologic plausibility to a potential association with long-term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared with the number of vertebral, hip, and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure, and there is concern that lack of awareness and underreporting may mask the true incidence of the problem. Given the relative rarity of atypical femoral fractures, the task force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance, and additional epidemiologic and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopedic and medical management. ß

show abstract

Section: Insights Into the Pathogenesis Of Atypical Femoral Fracturesmentioning

confidence: 99%

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Shane

Burr

Ebeling

et al. 2010

Journal of Bone and Mineral Research

998

679

View full text Add to dashboard Cite

show abstract

“…184 Endogenous collagen cross-links are mediated by both non-enzymatic and enzymatic reactions. Non-enzymatic collagen cross-links are mediated by oxidation and glycation processes, 185 while enzymatic reactions happen between the telopeptide and adjacent triple helical chains, 186 which is mediated by chemical reactions through lysyl oxidase covalent bonding. 187,188 This results in the formation of inter and intra-molecular and inter-microfibrillar cross-links.…”

Section: Cross-linkersmentioning

confidence: 99%

Bonding efficiency and durability: current possibilities

et al. 2017

View full text Add to dashboard Cite

Bonding plays a major role in dentistry nowadays. Dental adhesives are used in association with composites to solve many restorative issues. However, the wide variety of bonding agents currently available makes it difficult for clinicians to choose the best alternative in terms of material and technique, especially when different clinical situations are considered. Moreover, although bonding agents allow for a more conservative restorative approach, achieving a durable adhesive interface remains a matter of concern, and this mainly due to degradation of the bonding complex in the challenging oral environment. This review aims to present strategies that are being used or those still in development which may help to prevent degradation. It is fundamental that professionals are aware of these strategies to counteract degradation as much as possible. None of them are efficient to completely solve this problem, but they certainly represent reasonable alternatives to increase the lifetime of adhesive restorations.

show abstract

“…In these tissues, the mechanical strength is primarily provided by strong and elastic molecules such as collagen and elastin [4,5], which arrange into highly organized hierarchical structures [1][2][3]6] where the formation of intermolecular covalent cross-links is important in enhancing the mechanical stability of the resulting tissues. However, when the cross-link density increases, as found in elderly individuals, effects such as skin wrinkling, cartilage impairment or bone embrittlement as in osteoporosis and diabetes can occur [7,8]. This illustrates the role of cross-links in the alteration of material properties in disease states, which eventually leads to a breakdown of key material components of biological systems [5].…”

Section: Introductionmentioning

confidence: 99%

Molecular structure, mechanical behavior and failure mechanism of the C-terminal cross-link domain in type I collagen

Uzel

Buehler

2011

Journal of the Mechanical Behavior of Biomedical Materials

View full text Add to dashboard Cite

ABSTRACT:Collagen is a key constituent in structural materials found in biology, including bone, tendon, skin and blood vessels. Here we report a first molecular level model of an entire overlap region of a C-terminal cross-linked type I collagen assembly and carry out a nanomechanical characterization based on large-scale molecular dynamics simulation in explicit water solvent. Our results show that the deformation mechanism and strength of the structure is greatly affected by the presence of the cross-link, and by the specific loading condition of how the stretching is applied. We find that the presence of a cross-link results in greater strength during deformation as complete intermolecular slip is prevented, and thereby particularly affects larger deformation levels. Conversely, the lack of a cross-link results in the onset of intermolecular sliding during deformation and as a result an overall weaker structure. Through a detailed analysis of the distribution of deformation by calculating the molecular strain we show that the location of largest strains does not occur around the covalent bonding region, but is found in regions further away from this location. The insight developed from understanding collagenous materials from a fundamental molecular level upwards could play a role in advancing our understanding of physiological and disease states of connective tissues, and also enable the development of new scaffolding material for applications in regenerative medicine and biologically inspired materials. Keywords

show abstract

Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus

Cited by 772 publications

References 155 publications

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Bonding efficiency and durability: current possibilities

Molecular structure, mechanical behavior and failure mechanism of the C-terminal cross-link domain in type I collagen

Contact Info

Product

Resources

About