Pentosidine correlates with nanomechanical properties of human jaw bone

doi:10.1016/j.jmbbm.2019.06.002

Journal of the Mechanical Behavior of Biomedical Materials

Volume 98, October 2019, Pages 20-25

https://doi.org/10.1016/j.jmbbm.2019.06.002 Get rights and content

Highlights

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High pentosidine causes less creep deformation resistance and reduced creep recovery.
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Viscoelasticity is associated with the relative intensity of pentosidine in the jaw.
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The bone pentosidine level could serve as an index to assess jaw bone quality.
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Bone pentosidine levels may be able to be predicted from plasma pentosidine levels.

Abstract

Initial intimate apposition between implant fixtures and host bone at the surgical site is a critical factor for osseointegration of dental implants. The advanced glycation end products accumulated in the jaw bone could lead to potential failure of a dental implant during the initial integration stage, because of the inferior bone mechanical property associated with the abnormal collagen cross-linking at the material level. Here, we demonstrate the lowered creep deformation resistance and reduced dimensional recovery of jaw bone in line with high levels of pentosidine accumulation in the bone matrix which likely correlate with the pentosidine level in blood plasma. Peripheral blood samples and cortical bone samples at the surgical site were obtained from patients scheduled for dental implants in the mandible. The pentosidine levels in blood plasma were assessed. Subsequently, the relative pentosidine levels and the mechanical properties of the jaw bone were quantified by Raman microspectroscopy and nanoindentation, respectively. The nanoindentation tests revealed less creep deformation resistance and reduced time-dependent dimensional recovery of bone samples with the increase in the relative pentosidine level in the bone matrix. Higher tan δ values at the various frequencies during the dynamic indentation tests also suggested that viscoelasticity is associated with the relative intensity of pentosidine in the jaw bone matrix. We found a positive correlation between the pentosidine levels in blood plasma and the bone matrix, which in turn reduced the mechanical property of the jaw bone at the material level. Increased creep and reduced dimensional recovery of the jaw bone may diminish the mechanical interlocking of dental implants during the initial integration stage. Given the likely correlation between the plasma pentosidine level and the mechanical properties of bone, measurement of the plasma pentosidine level could serve as a new index to assess jaw bone matrix quality in advance of implant surgery.

Graphical abstract

Introduction

When dental implants are placed into bone at the surgical site, intimate apposition between the implant fixture and the host bone is an important prerequisite for stabilizing the bone-implant interface (Lin et al., 2009). During this initial integration stage, the lack of mechanical property of the human jaw bone often generates micro-motion of implant fixtures and the development of unfavorable fibrous bone that is not replaced by mature lamellar bone on the implant surface (Shibata et al., 2015). To date, it is nearly impossible to predict the mechanical property of the host bone before implant surgery, because of the inherent donor-site limitations of the human jaw bone and the potential difficulty of assessing the mechanical properties of bone.

The importance of bone matrix quality has been widely recognized. Bone matrix quality based on densitometry was defined in the NIH Consensus Development Conference Statement (2001). Currently, the Hounsfield Unit is used as a clinical index for measuring bone mineral density before implant treatment (Gabet et al., 2010). However, there may be a considerable discrepancy between the Hounsfield Unit and bone matrix quality (Ganeko et al., 2015; Lettry et al., 2003). Bone matrix quality may be more precisely determined by an in-situ characterization at the smallest hierarchical level (Ebenstein and Pruitt, 2006). Specifically, the minimum structural unit across the bone hierarchical structure, such as nanoscale crystalline hydroxyapatite isotropically oriented in the collagen matrix, has a vital role in mechanical property at the material level (Maruyama et al., 2014, 2015).

About 90% of the bone matrix is collagen, and the functions of collagen cross-links have recently been attracting attention as co-factors in the mechanical properties of bone (Garnero, 2015; McNerny et al., 2015). Non-enzymatic collagen cross-linking mediated by advanced glycation end-products (AGEs) during the aging process and defective bone metabolism in patients with type-II diabetes have been frequently reported (Saito and Marumo, 2010; Viguet-Carrin et al., 2006). Such advanced glycations diminish creep deformation resistance and dimensional recovery of calcified tissues including bone and tooth (Rodriguez et al., 2017; Tobe et al., 2019). Moreover, inferior stress relaxation related to AGEs was reported as being unlikely to have been induced by ovariectomy (OVX) and administration of methionine in a New Zealand rabbit model (Ganeko et al., 2015). It is reported high levels of pentosidine in urine or blood which suggest bone collagen abnormalities, might be used as surrogate markers for evaluating bone matrix quality, assessing the risk of bone fracture (Saito and Marumo, 2010). Because of the likely concomitant increase in the pentosidine level in human blood, further consideration of the correlation between the mechanical properties of bone at the nanoscale (i.e., material) level and the results of blood tests can help us to predict the mechanical property of bone before surgery.

In the present study, human jaw bone was subjected to a series of nanoindentation tests to measure the time-dependent mechanical properties of bone at the material level. Raman microspectroscopy was also performed to evaluate the correlation between local accumulation of pentosidine at the indentation region in the jaw bone and the pentosidine level in blood plasma. The possible correlations revealed through this study could establish a new clinical index of bone matrix quality for pre-implant diagnosis via blood test.

Section snippets

Human subjects

Mandibular cortical bone and peripheral blood samples were extracted from 14 patients (9 male and 5 female donors, aged 54–66 years, 61.6 ± 5.1 years). The subjects agreed to the protocol approved by the ethics committee of Kyushu Dental University, Japan (Ref: 2013-13-4).

Sample collection and preparation

Peripheral blood was collected with a hypodermic needle from the subjects before surgery, and the plasma pentosidine level was measured by high-performance liquid chromatography (LSI Medience Corporation, Tokyo).

Cortical bone

Bone pentosidine level

The Raman microspectroscopy showed various spectra attributable to bone tissue such as υ₁ phosphate at 960 cm⁻¹, and pentosidine at 1495 cm⁻¹(Salehi et al., 2013; Rubin et al., 2016). Pentosidine peak intensity was normalized to the maximum height of the υ₁ phosphate band at 960 cm⁻¹ (Jang et al., 2014; Tobe et al., 2019). For example, the relative peak intensity ratio was 1495/960 cm⁻¹, which indicates the level of pentosidine (Rodriguez et al., 2017).

The maximum, minimum, mean, and median

Discussion

In this study, we explored the possible correlation between time-dependent creep deformation resistance and the dimensional recovery of target regions in human mandibular cortical bone at the material level in line with the pentosidine level in blood plasma. The high pentosidine level in blood plasma caused elevated pentosidine accumulation in human jaw bone. In this context, the reduced mechanical properties of bone likely associated with a concomitant increase in the relative intensity of

Conclusion

Elevated pentosidine levels resulted in a lower level of creep deformation resistance and reduced time-dependent dimensional recovery. The viscoelastic behavior of the jaw bone measured in this study may also affect integration with the implant surface. Measurement of the bone pentosidine level could serve as an index to assess jaw bone matrix quality in implant surgery, and bone pentosidine levels may be able to be predicted from plasma pentosidine levels.

Author contributions

The authors contributed equally.

Disclosures

Drs. Kawamura, Masaki, Shibata, Kondo, Mukaibo, Miyazaki, and Hosokawa report no conflicts of interest related to this study.

Acknowledgments

This study was supported by the Ministry of Education, Culture, Sports, Science and Technology, Grant-in-Aid for Scientific Research (B), no. 18H02995. We thank Helen Jeays, BDSc AE, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

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Aging is a physiological process with profound impact on the biology and function of biosystems, including the human dentition. While resilient, human teeth undergo wear and disease, affecting overall physical, psychological, and social human health. However, the underlying mechanisms of tooth aging remain largely unknown. Root dentin is integral to tooth function in that it anchors and dissipates mechanical load stresses of the tooth-bone system. Here, we assess the viscoelastic behavior, composition, and ultrastructure of young and old root dentin using nano-dynamic mechanical analysis, micro-Raman spectroscopy, small angle X-ray scattering, atomic force and transmission electron microscopies. We find that the root dentin overall stiffness increases with age. Unlike other mineralized tissues and even coronal dentin, however, the ability of root dentin to dissipate energy during deformation does not decay with age. Using a deconstruction method to dissect the contribution of mineral and organic matrix, we find that the damping factor of the organic matrix does deteriorate. Compositional and ultrastructural analyses revealed higher mineral-to-matrix ratio, altered enzymatic and non-enzymatic collagen cross-linking, increased collagen d-spacing and fibril diameter, and decreased abundance of proteoglycans and sulfation pattern of glycosaminoglycans . Therefore, even in the absence of remodeling, the extracellular matrix of root dentin shares traits of aging with other tissues. To explain this discrepancy, we propose that altered matrix-mineral interactions, possibly mediated by carbonate ions sequestered at the mineral interface and/or altered glycosaminoglycans counteract the deleterious effects of aging on the structural components of the extracellular matrix.
Globally, a quarter of the population will be over 65 years old by 2050. Because many will retain their dentition, it will become increasingly important to understand and manage how aging affects teeth. Dentin is integral to the protective, biomechanical, and regenerative features of teeth. Here, we demonstrate that older root dentin not only has altered mechanical properties, but shows characteristic shifts in mineralization, composition, and post-translational modifications of the matrix. This strongly suggests that there is a mechanistic link between mineral and matrix components to the biomechanical performance of aging dentin with implications for efforts to slow or even reverse the aging process.

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Pentosidine correlates with nanomechanical properties of human jaw bone

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Human subjects

Sample collection and preparation

Bone pentosidine level

Discussion

Conclusion

Author contributions

Disclosures

Acknowledgments

Nano Today

Acta Biomater.

J. Biomech.

Nanomedicine

J. Biomech.

Bone

J. Mech. Behav. Biomed. Mater.

Biomaterials

Bone

J. Mech. Behav. Biomed. Mater.

Nanomedicine

Nanomedicine

J. Prosthodont. Res.

J. Mech. Behav. Biomed. Mater.