Pentosidine correlates with nanomechanical properties of human jaw bone
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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