ReviewStudies on bone metabolism by using isotope microscopy, FTIR imaging, and micro-Raman spectroscopy
Introduction
Osteoporosis leads to an increase risk of fracture caused by reduced bone mineral density (BMD), deteriorates the bone microarchitecture, and alters collagen and other proteins. Primary osteoporosis is caused by age-related bone loss and occurs commonly in older women [1]. Secondary osteoporosis arises regardless of age or gender and is caused by an underlying specific disease or disorder, such as chronic kidney disease (CKD) or diabetes [2]. Osteopenia is a condition when your bone density is lower than normal, but not low enough to be considered osteoporosis. An estimated 11 million people in Japan and 52 million people in the United States suffer from osteoporosis, and it has been estimated that the number of people with osteopenia/osteoporosis in the US will increase to 61 million by the year 2020.
Bone is a composite material consisting of about 60 wt% mineral formed mostly from carbonate-containing hydroxylapatite, 8–10 wt% water, and organic materials consisting primarily of type I collagen and smaller amounts of noncollagenous proteins and lipids. By volume, these proportions are approximately 40%, 25%, and 35% [3]. Bone is normally evaluated by its strength, which reflects the integration of 70% BMD and 30% bone quality. Bone quality is defined by at least 4 factors as follows: (1) the rate of bone turnover, (2) the properties of the mineral/collagen matrix, (3) accumulation of microdamage, and (4) the architectures of trabecula and cortical bone [4]. Bone is continuously replaced through modeling or remodeling generated by the coordinated actions of osteoblast and osteoclasts. The rate of bone turnover is reflected by mineral balance in the body and is commonly determined using markers such as osteocalcin, bone-specific alkaline phosphatase, pyridinoline, and deoxypyridinoline. However, measurements of bone turnover by using these markers are time consuming. Therefore, establishing analytical methods without such markers will enhance the determination of bone turnover. Recently, natural stable calcium isotopes, such as 40Ca, 42Ca, and 44Ca have been employed to measure bone mineral balance [5]. Isotopes are useful tracers in cosmo- and geochemistry to determine the origin and circulation of elements in nature [6].
Vibrational spectroscopic techniques, including infrared (IR) and Raman spectroscopy are powerful tools for characterizing the chemical compositions of materials, because they can provide both qualitative and quantitative information on molecular structure. Research in the laboratories of Boskey [7], [8], [9], [10], [11], [12], [13], [14] and Morris [15], [16], [17], [18], [19], [20] has succeeded in determining bone quality using noninvasive techniques, such as FTIR microspectroscopy, FTIR imaging, and Raman spectroscopy. Boskey and collaborators focused on collagen cross-links in bone and characterized the nonreducible:reducible collagen cross-link ratio in diseased bone matrix using FTIR microspectroscopy and FTIR imaging [13], and Morris and colleagues characterized microcracks in bone mineral using a newly developed Raman system [16]. However, further detailed studies on the various bones are required to better understand bone quality. In this review, we describe recent advances in the analysis of bone metabolism using isotope microscopy, FTIR imaging, and micro-Raman spectroscopy.
Section snippets
Overview of vibrational spectroscopy
Vibrational spectroscopies using FTIR and Raman techniques have been used frequently to identify molecular structures and specific molecular functional groups within them [21]. Molecules constantly vibrate and can absorb energy received from photons to increase vibrational frequency, which is detected by these techniques. In FTIR analysis, molecular targets absorb photons in the mid-infrared range (2.5–25 μm) causing their vibrations to increase. This is associated with symmetrical stretching,
Isotope microscopy
Analysis of the distribution of isotopes and trace elements in heterogeneous microstructures has become increasingly crucial for identifying natural and biological materials [31]. However, isotope microscopy has not become a standard technique, because isotopic variations that occur in nature are very small. Recently, several technical developments in secondary ion mass spectrometry have been employed that have achieved an approximate lateral resolution of approximately 1 μm with a precision of
Conclusion
Isotope microscopy, FTIR imaging, and micro-Raman spectroscopy are non-destructive tools to characterize bone quality and do not require the use of stains. Such nondestructive analyses are suitable for evaluating heterogeneous tissues and provide information about the distribution of molecules. Comprehensive analysis using isotope microscopy, FTIR imaging, and micro-Raman spectroscopy may provide more information on bone quality compared with using a single technique. It now becomes important
Conflict of interest
Authors declare no conflict of interest.
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