Raman spectroscopy as a predictive tool for monitoring osteoporosis therapy in a rat model of postmenopausal osteoporosis

Sequential Treatment of Estrogen Deficient, Osteopenic Rats with Alendronate, Parathyroid Hormone (1–34), or Raloxifene Alters Cortical Bone Mineral and Matrix Composition

“…measures. Our design and general type of measurements bear some similarity to recent publications [27,28]. We treated osteopenic, OVX rats in three consecutive periods of three months each with different sequences of single osteoporosis treatment agents.…”

Raman spectroscopy as a tool for monitoring osteoporosis therapy in postmenopausal osteoporosis

“…Three of the models are from a rat-based study (PREQUEST) involving the surgically triggered development of osteoporosis ('Rat Claw Osteoporosis', N = 20) and its prevention using alendronate ('Rat Claw Alendronate', N = 20) or parathyroid hormone ('Rat Claw Parathyroid', N = 20). 22,23 Two models are of osteoporosis status ('NHS Osteoporosis', N = 179) and prospective fracture status ('NHS Fracture', N = 50) within the Nurse's Health Study cohort, [28][29][30] and two are osteoporosis ('FRAN Osteoporosis', N = 116) and current fracture status ('FRAN Fracture', N = 628) within the FRAN study cohort. 28,29 Because each model contains unique variation and errors, a combined model was made in two iterations.…”

“…22,29,30 The treatment model is positively correlated with an independent rat-based alendronate treatment model (r = 0.46, p < 10 À9 ); this correlation is stronger than a rat-based model of parathyroid treatment (r = 0.30, p < 10 À4 ). 23 A combined model of the influence of osteoporosis on Raman spectra of nail (to average out random variations between datasets) was correlated against each individual model and gave uniformly higher correlations. Fifty per cent of the variation in the current treatment model (R 2 = 0.50) is shared with this mean model, despite the initial iteration not involving this model.…”

“…Research on matched rat bone and claw samples established that directly parallel changes to protein structure occur in bone collagen and claw keratin, in response to a systemic perturbation known to impact bone health, both in terms of pathological progression and intervention. 22,23 The data suggest that, in the absence of intervention, over time, there is a progressive rearrangement of the secondary structure in the controls with the accumulation of nonfibrous structures as the proteins reorganise. It is noteworthy that bands assigned to disulphide vibrational modes also play a role in the spectroscopic changes observed as disulphide bonds are critical in imposing and maintaining a protein's higher order structure and their ability to form is affected by local changes in secondary structure.…”

“…21 Recent studies by the authors in ovariectomised rats have shown that bone collagens become disordered relative to shamtreated animals 22 and subsequent alendronate administration can prevent this disordering. 23 Raman spectroscopy is a sensitive, non-invasive, optical technique that is commonly used in forensic and pharmaceutical studies and is a potential tool for evaluating bone proteins, where nail keratin is used as a surrogate marker. [24][25][26][27] The authors have previously shown that Raman spectroscopy is effective at both screening and predicting fracture based on assessment of nail keratin.…”