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

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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.

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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

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Funding

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

Author information

Authors and Affiliations

  1. J Renwick Beattie Consulting, Causeway Enterprise Agency, Ballycastle, UK

    J. Renwick Beattie

  2. Department of Life Sciences, European University Cyprus, Nicosia, Cyprus

    Antonia Sophocleous

  3. ICON plc, South County Business Park, Leopardstown, Dublin, Ireland

    M. Clare Caraher

  4. School of Chemistry and Chemical Engineering, Queen’s University Belfast, Stranmillis Road, Belfast, UK

    M. Clare Caraher & Steven E. J. Bell

  5. AventaMed, Rubicon Centre, Rossa Avenue, Bishopstown, Cork, Ireland

    Olive O’Driscoll

  6. Centre for Interventions in Infection, Inflammation and Immunity, Graduate Entry Medical School, University of Limerick, Limerick, Ireland

    Niamh M. Cummins

  7. Department of Mechanical and Industrial Engineering, Ryerson University, Toronto, ON, Canada

    Mark Towler & Alireza Rahimnejad Yazdi

  8. Rheumatology and Bone Diseases Unit, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK

    Stuart H. Ralston

  9. Department of Oncology and Metabolism, Medical School, University of Sheffield, Beech Hill Road, Sheffield, UK

    Aymen I. Idris

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  1. J. Renwick Beattie
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Correspondence to Mark Towler.

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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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Beattie, J.R., Sophocleous, A., Caraher, M.C. et al. Raman spectroscopy as a predictive tool for monitoring osteoporosis therapy in a rat model of postmenopausal osteoporosis. J Mater Sci: Mater Med 30, 25 (2019). https://doi.org/10.1007/s10856-019-6226-x

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