• 23
    Dec
  • FTIR microspectroscopic analysis: future perspectives. Infrared microspectroscopy, bone strength & osteoporosis

Infrared microspectroscopic analysis of bone tissue from ani­mal models and humans at equivalent anatomical locations gave great insight to the role of bone quality in determining bone strength. It became feasible to conclusively show differences in bone mineral maturity between normal and osteoporotic bone at equivalent anatomical locations. Even more revealing was the analysis of the spatial variation in pyr and deH-DHLNL collagen cross-links in the same bones. It was shown that the ratio between these two major collagen cross-links was very different when osteoporotic and normal bones were compared in the area of trabecular bone with ac­tively bone forming surfaces. These data are in ex­cellent agreement with recently published clinical observations that homocysteine blood serum level were elevated in patients with increased fracture risk. It is interesting to note that these differences were also observed between normal, and bone biopsies obtained from pre-menopausal women sus­taining spontaneous fractures while having normal BMD and biochemical markers, suggesting that this might be a common factor / cause of fragile bone.

The effect of therapeutic protocols on bone quality has also been investigated. During these studies, it was discovered that when fracture risk and BMD were divergent, both mineral maturity and pyr / deH- DHLNL collagen cross-link ratio was correlating with fracture risk rather than BMD, further emphasizing the contri­bution of bone quality to its mechanical performance.

Future directions

Since the introduction of the Infrared Microspectroscopic analy­sis in the early 1990’s, the debate rages whether it is a diag­nostic tool. Although it provides a plethora of useful outcomes, it is our opinion that it is not well suited to be employed as a mass-screening tool, for the simple reason that it is an invasive technique as a bone biopsy is required. On the other hand, it is ideally suited for cases of fracturing patients whose “classical” risk indicators such as BMD and biochemical markers are nor­mal.

On the other hand, it is a powerful research tool, affording unique insights into the pathophysiology of musculoskeletal diseases such as osteoporosis, osteogenesis imperfecta, Paget’s disease, osteomalacia, ostepetrosis, osteosclerosis, etc. Its outcomes complement ones obtained through analyses such as histology, histomorphometry, biochemical markers, blood analysis, and BMD measurements, to provide detailed information on the mechanisms that result in healthy and dis­eased bone.

It is also a useful technique in deducing the changes in the spatial distribution variation of the mineral crystallite maturity and pyr and deH-DHLNL collagen cross-link ratio induced by various therapeutic protocols, therefore it may be used in the future not only for evaluating the various therapeutic protocols but also assist in the design of more targeted ones.

Despite that both bone mineral crystallite maturity and pyr / deH-DHLNL collagen cross-link ratio have been shown to cor­relate well with bone strength, no calibration curve exists as all the cases reported thus far in the literature involved normal (100%) and diseased / fragile bone (0%). Since both mineral maturity and collagen cross-links do change long after they have been synthesized and deposited by the osteoblast as a consequence of tissue aging, establishing the threshold in the change in these two outcomes that results in mechanically in­ferior bone will be important as it will provide the calibration curve upon which bone strength may be predicted (when com­bined with the outcomes of other analyses), and help us dis­cern between aging and disease.

One of the major advantages of Infrared Microspectroscopy is that it can describe the spatial variation of pyr and deH-DHLNL collagen cross-links in mineralized thin tissue sections. These are only two of the major collagen cross-links and as a result only a partial understanding of the spatial and temporal distrib­ution of collagen properties has been achieved. In the future, spectral and mathematical methods should be combined so as to derive spectroscopic parameters that describe all of the known collagen cross-links, as they are important both in the mineralization initiation cascade of events, and in determining bone strength. You can afford your pills. Buy cialis professional 20 mg

The main outcomes of Infrared Microspectroscopic analysis correlate well with bone strength but are not the sole determi­nants. Moreover, a review of the literature reveals that the vari­ation in material and structural properties of bone is in the 1-10 |jm range. It is necessary then in the future to combine Infrared Microspectroscopic analysis with other techniques capable of analyzing thin bone tissue sections with similar spatial resolu­tion such as quantitative backscatter electron imaging (provid­ing information on the bone mineral density distribution at the mm level), small angle x-ray scattering (proving precise information on the mineral crystallite size, shape, and alignment to the collagen fibers), and nanoidentation (providing information on the bone mechanical properties at discrete anatomical location with a spatial resolution ~ 1 jim), at carefully selected (based on histology / histomorphometry to include cellular ac­tivity as a selection criterion) identical anatomical locations so that the contribution of each outcome to bone strength may be calculated.

In conclusion, Infrared Microspectroscopy has proven to be a powerful tool in the establishment of parameters contributing to bone quality and thus bone strength. Nevertheless, more spectroscopic parameters describing the organic matrix should be derived in the future, and quantitation of these against bone strength should be achieved.

 

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