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  • br Conclusions The following is

    2019-07-30


    Conclusions The following is the supplementary data related to this article.
    Transparency document
    Acknowledgments and funding This study was supported by the Shanghai National Science Foundation (16ZR1421300) and the Biomedical Engineering Cross Foundation of Shanghai Jiaotong University (YG2013MS32).
    Conflicts of interest
    Introduction Postmenopausal osteoporosis is a common disease characterised by reduced bone mass and an increased risk of fragility fractures which increases dramatically in incidence with age [1]. The risk of osteoporosis is determined by a balance between levels of peak bone mass attained during skeletal growth and the amount of bone that is lost later on in life [2], [3], [4], [5]. At menopause, declining oestrogen levels trigger an increase in bone remodelling with uncoupling of osteoclastic bone resorption from osteoblastic bone formation [6]. Evidence from rodent and nonhuman primate studies indicates that enhanced bone remodelling associated with deficiency in sex hormone leads to bone loss [7], [8], [9], [10] (in humans this type of change increases risk of fragility fractures). The majority of osteoporotic fractures occur in patients with low bone mineral density (BMD), as assessed by Dual Elafibranor (GFT505) X-ray Absorptiometry (DXA) [11], [12], [13]. However, there is overlap in BMD between individuals with recurrent fractures and those who have not, inferring that low BMD is not the only cause of fragile bones [10], [14]. Degree of mineralization is another standard by which osteoporosis is diagnosed, however it is often unreliable in detecting bone fragility. This is mainly due to its inability to take into account, amongst other factors [15], changes in the bone matrix protein, primarily collagen. Studies have shown that collagen in osteotropic patients exhibits a different structure to normal collagen [16], [17], and have found a correlation between these structural changes in collagen and bone fracture [18], [19]. Ovariectomy in large rodents is a reproducible and widely accepted model of oestrogen deficiency and reflects many changes observed in postmenopausal women. For example, it leads to reduction in trabecular bone volume coupled with an increase in adipose tissues (in some rodents), phenotypes similar to those observed in aged human. Notwithstanding this the model does not account for factors such as genetic variability, life style, diet and other hormone levels that affect bone health. A key feature of this model is that the hormone deficiency is a systemic effect and as such would be expected to expose the whole body of the animal to the same risk factor. Raman spectroscopy is a sensitive and non-invasive optical technique in which the transfer of energy from light to matter gives ‘fingerprint’ information of a sample's chemical composition and physical state. The technique is commonly used in chemical analysis e.g. in forensic, and pharmaceutical science, however more recently it has been identified as a potential tool for evaluating bone. Using Raman spectroscopy, a comparison study of iliac crest biopsies and femoral head samples revealed that osteoporotic women with fractures had a greater carbonate/phosphate ratio in cortical bone and a higher carbonate/amide I ratio in femoral trabecular bone when compared to healthy women [20]. Other studies by Pillay et al., Towler et al. and Moran et al. used Raman spectroscopy to demonstrate that nails from osteoporotic patients had lower disulphide bonding compared to healthy controls [21], [22], [23]. A subsequent clinical study on 633 nail donors showed that Raman analysis of the fingernails was capable of discriminating between donors who had and who had not suffered a fragility fracture [24]. Detailed spectroscopic investigation revealed that the structural integrity of the keratin in the nail was different between the groups, with the fracture group exhibiting a more disordered protein structure than the non-fracture group [25]. Together, these findings led to the hypothesis that changes in composition and structure of keratin (nail) in osteoporotic models may act as a surrogate marker of systemic processes that affect the structural proteins in the bone matrix (collagen).