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

  • J. Renwick Beattie
  • Antonia Sophocleous
  • M. Clare Caraher
  • Olive O’Driscoll
  • Niamh M. Cummins
  • Steven E. J. Bell
  • Mark TowlerEmail author
  • Alireza Rahimnejad Yazdi
  • Stuart H. Ralston
  • Aymen I. Idris
Biocompatibility Studies Original Research
Part of the following topical collections:
  1. Biocompatibility Studies

Abstract

Pharmacological therapy of osteoporosis reduces bone loss and risk of fracture in patients. Modulation of bone mineral density cannot explain all effects. Other aspects of bone quality affecting fragility and ways to monitor them need to be better understood. Keratinous tissue acts as surrogate marker for bone protein deterioration caused by oestrogen deficiency in rats. Ovariectomised rats were treated with alendronate (ALN), parathyroid hormone (PTH) or estrogen (E2). MicroCT assessed macro structural changes. Raman spectroscopy assessed biochemical changes. Micro CT confirmed that all treatments prevented ovariectomy-induced macro structural bone loss in rats. PTH induced macro structural changes unrelated to ovariectomy. Raman analysis revealed ALN and PTH partially protect against molecular level changes to bone collagen (80% protection) and mineral (50% protection) phases. E2 failed to prevent biochemical change. The treatments induced alterations unassociated with the ovariectomy; increased beta sheet with E2, globular alpha helices with PTH and fibrous alpha helices with both ALN and PTH. ALN is closest to maintaining physiological status of the animals, while PTH (comparable protective effect) induces side effects. E2 is unable to prevent molecular level changes associated with ovariectomy. Raman spectroscopy can act as predictive tool for monitoring pharmacological therapy of osteoporosis in rodents. Keratinous tissue is a useful surrogate marker for the protein related impact of these therapies.The results demonstrate utility of surrogates where a clear systemic causation connects the surrogate to the target tissue. It demonstrates the need to assess broader biomolecular impact of interventions to examine side effects.

Highlights

  • Osteoporotic treatments exhibit substantial differences in biochemical impact.

  • Alendronate preserved the bone tissue in the state closest to the sham group.

  • Parathyroid hormone prevents ovariectomy changes, induces different changes.

  • Estrogen preserves tissue macro structure, but unable to prevent biochemical changes.

  • Systemic conditions affect structural proteins in both bone and claw.

Abbreviations

ALN

alendronate

PTH

parathyroid hormone

E2

estrogen

OVX

ovariectomised (untreated)

OVXA

ovariectomised treated with alendronate

OVXE

ovariectomised treated with estrogen

OVXP

ovariectomised treated with parathyroid hormone

SEM

standard error of the mean

BMD

bone mineral density

DXA

Dual energy X-ray Absorptiometry

microCT

micro computed tomography

PCA

Principle Component Analysis

LDA

linear discriminant analysis

AUCROC

area under the curve for the receiver operator characteristics

ROI

region of interest

Notes

Funding

This work was supported by Crescent Diagnostics Ltd. and Intertrade Ireland (FUSION programme 2012).

Compliance with ethical standards

Conflict of interest

RB and MCC are former employees of Crescent Ops Ltd, a company which owns intellectual property on the relationship between Raman spectroscopy, nail structure and fracture risk. MT and RB are shareholders in Crescent Ops Ltd. MT, NC, OOD and RB have served as consultants for Crescent Ops Ltd. Crescent Diagnostics Ltd funded the work carried out by MCC, JRB, (OD), NMC, MT and SHR. AI and AS declare no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • J. Renwick Beattie
    • 1
  • Antonia Sophocleous
    • 2
  • M. Clare Caraher
    • 3
    • 4
  • Olive O’Driscoll
    • 5
  • Niamh M. Cummins
    • 6
  • Steven E. J. Bell
    • 4
  • Mark Towler
    • 7
    Email author
  • Alireza Rahimnejad Yazdi
    • 7
  • Stuart H. Ralston
    • 8
  • Aymen I. Idris
    • 9
  1. 1.J Renwick Beattie ConsultingCauseway Enterprise AgencyBallycastleUK
  2. 2.Department of Life SciencesEuropean University CyprusNicosiaCyprus
  3. 3.ICON plcDublinIreland
  4. 4.School of Chemistry and Chemical EngineeringQueen’s University BelfastBelfastUK
  5. 5.AventaMedCorkIreland
  6. 6.Centre for Interventions in Infection, Inflammation and Immunity, Graduate Entry Medical SchoolUniversity of LimerickLimerickIreland
  7. 7.Department of Mechanical and Industrial EngineeringRyerson UniversityTorontoCanada
  8. 8.Rheumatology and Bone Diseases Unit, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, Western General HospitalUniversity of EdinburghEdinburghUK
  9. 9.Department of Oncology and Metabolism, Medical SchoolUniversity of SheffieldSheffieldUK

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