Multi-Scale Approach for the Evaluation of Bone Mineralization in Strontium Ranelate-Treated Diabetic Rats

  • Pedro Álvarez-Lloret
  • Juan Manuel Fernández
  • María Silvina Molinuevo
  • Agustina Berenice Lino
  • José Luis Ferretti
  • Ricardo Francisco Capozza
  • Ana María Cortizo
  • Antonio Desmond McCarthy


Long-term diabetes mellitus can induce osteopenia and osteoporosis, an increase in the incidence of low-stress fractures, and/or delayed fracture healing. Strontium ranelate (SrR) is a dual-action anti-osteoporotic agent whose use in individuals with diabetic osteopathy has not been adequately evaluated. In this study, we studied the effects of an oral treatment with SrR and/or experimental diabetes on bone composition and biomechanics. Young male Wistar rats (half non-diabetic, half with streptozotocin/nicotinamide-induced diabetes) were either untreated or orally administered 625 mg/kg/day of SrR for 6 weeks. After sacrifice, femora from all animals were evaluated by a multi-scale approach (X-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma optical-emission spectrometry, static histomorphometry, pQCT, and mechanical testing) to determine chemical, crystalline, and biomechanical properties. Untreated diabetic animals (versus untreated non-diabetic) showed a decrease in femoral mineral carbonate content, in cortical thickness and BMC, in trabecular osteocyte density, in maximum load supported at rupture and at yield point, and in overall toughness at mid-shaft. Treatment of diabetic animals with SrR further affected several parameters of bone (some already impaired by diabetes): crystallinity index (indicating less mature apatite crystals); trabecular area, BMC, and vBMD; maximum load at yield point; and structural elastic rigidity. However, SrR was also able to prevent the diabetes-induced decreases in trabecular osteocyte density (completely) and in bone ultimate strength at rupture (partially). Our results indicate that SrR treatment can partially but significantly prevent some bone structural mechanical properties as previously affected by diabetes, but not others (which may even be worsened).


Diabetes mellitus Strontium ranelate Bone mineralization Microstructural properties Bone biomechanics 



P.A-LL is an Ad Interim Assistant Professor of Crystallography and Mineralogy (UNIOVI), University of Oviedo, Spain. JMF, JLF, RC, and MSM are Members of Carrera del Investigador Científico (CONICET), Argentina. AMC is a Member of Carrera del Investigador Científico (CICPBA), Argentina. ABL is a Fellow of ANPCyT, Argentina. ADM is full Professor of Clinical Chemistry at National University of La Plata (UNLP). Financial support for this study was provided by Santander Foundation JPI-2014, CGL2015-64683-P, UNOV-13-EMERG-08, Agencia Nacional de Promoción Científica y Tecnológica (PICT 2012-0053), and grants from CONICET, CICPBA, and UNLP. We thank Dr. L.P. Olivar-Pérez (Osakidetza) for her valuable comments in preparing the manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Pedro Álvarez-Lloret
    • 1
  • Juan Manuel Fernández
    • 2
  • María Silvina Molinuevo
    • 2
  • Agustina Berenice Lino
    • 2
  • José Luis Ferretti
    • 3
  • Ricardo Francisco Capozza
    • 3
  • Ana María Cortizo
    • 2
  • Antonio Desmond McCarthy
    • 2
  1. 1.Departament of GeologyUniversity of OviedoOviedoSpain
  2. 2.Laboratorio de Investigaciones en Osteopatías y Metabolismo Mineral (LIOMM), Facultad de Ciencias ExactasUniversidad Nacional de La PlataLa PlataArgentina
  3. 3.Centro de Estudios del Metabolismo Fosfocálcico (CeMFoC), Facultad de MedicinaUniversidad Nacional de RosarioRosarioArgentina

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