Clinical Oral Investigations

, Volume 22, Issue 1, pp 255–265 | Cite as

Raloxifene but not alendronate can compensate the impaired osseointegration in osteoporotic rats

  • Leonardo Perez Faverani
  • Tárik Ocon Braga Polo
  • Gabriel Ramalho-Ferreira
  • Gustavo Antonio Correa Momesso
  • Jaqueline Suemi Hassumi
  • Ana Cláudia Rossi
  • Alexandre Rodrigues Freire
  • Felippe Bevilacqua Prado
  • Eloá Rodrigues Luvizuto
  • Reinhard Gruber
  • Roberta Okamoto
Original Article



Alendronate and raloxifene, a bisphosphonate and a selective estrogen modulator, respectively, are established osteoporosis therapies. Current evidence suggests that simultaneous application of osteoporosis therapies modulates osseointegration. However, alendronate shows inconsistent findings and raloxifene has not been studied comprehensively. This study aimed to evaluate the bone dynamics and molecular and microstructural features at the peri-implant bone interface in osteoporotic rats.

Materials and methods

Thirty female rats underwent ovariectomy and were fed a diet low in calcium and phosphate and treated with alendronate or raloxifene for 30 days or underwent fictional ovariectomy surgery (SHAM) prior to implant insertion in the tibia; osteoporosis therapies continued thereafter. After 42 days, peri-implant bone was evaluated by histometric and micro-CT analysis. Fluorochrome incorporation and gene expression was determined to evaluate bone turnover.


We report here that alendronate had no impact on bone-to-implant contacts and the mineral apposition rate. The RANKL/OPG ratio and local bone volume, however, were increased compared to the untreated osteoporotic rats. Even though signaling to bone resorption activity through RANKL production was observed in the alendronate group, the blockade of bone resorption activity that occurs in decorrence to alendronate activity took place and resulted in an increase in bone volume. Raloxifene significantly increased osseointegration in osteoporotic rats, as indicated by bone-to-implant contacts, mineral apposition, and local bone volume. Raloxifene, however, had no considerable impact on the RANKL/OPG ratio compared to untreated osteoporotic rats. As expected, the SH group showed higher bone-to-implant contacts and mineral apposition rates than the untreated osteoporotic rats.


These findings suggest that raloxifene but not alendronate can compensate for the impaired osseointegration in osteoporotic rats.

Clinical relevance

Regarding the superiority of raloxifene observed in the improvement of bone dynamics response, this statement suggests that raloxifene could be a good option for osteoporosis patients in oral rehabilitation procedures.


Osteoporosis Dental implants Alendronate Raloxifene Microscopy 



The authors would like to thank the São Paulo Research Foundation—FAPESP (2012/15748-8 and 2012/15912-2), for financial support; Marcia Sirlene Zardin Graeff, from Bauru Dental School—USP, for help in obtaining confocal microscopy images, and Prof. Dr. Elcio Marcantonio Junior and laboratory technician Ana Claudia Gregolin Costa Miranda, from UNESP—Araraquara, for facilitating the laboratory processing of specimens with EXAKT. Also, we would like to thank the Implalife Biotechnology for providing the implants.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


This study was supported by the São Paulo Research Foundation—FAPESP (2012/15748-8 and 2012/15912-2).

Ethical approval

The procedures and protocol design described here were approved by the Ethics Committee in Animal Experimentation of Aracatuba Dental School, UNESP—Univ Estadual Paulista, Brazil (approval no. 2012-01096).

Informed consent

For this type of study, formal consent is not required.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Leonardo Perez Faverani
    • 1
  • Tárik Ocon Braga Polo
    • 1
  • Gabriel Ramalho-Ferreira
    • 1
  • Gustavo Antonio Correa Momesso
    • 1
  • Jaqueline Suemi Hassumi
    • 1
    • 2
  • Ana Cláudia Rossi
    • 3
  • Alexandre Rodrigues Freire
    • 3
  • Felippe Bevilacqua Prado
    • 3
  • Eloá Rodrigues Luvizuto
    • 4
  • Reinhard Gruber
    • 5
  • Roberta Okamoto
    • 2
  1. 1.Department of Surgery and Integrated Clinic, Division of Oral and Maxillofacial SurgerySão Paulo State University (UNESP), School of DentistryAraçatubaBrazil
  2. 2.Department of Basic SciencesSão Paulo State University (UNESP), School of DentistryAraçatubaBrazil
  3. 3.Department of Morphology, Piracicaba Dental SchoolUniversity of Campinas (UNICAMP)PiracicabaBrazil
  4. 4.Department of Surgery and Integrated Clinic, Division of Integrated ClinicSão Paulo State University UNESP), School of DentistryAraçatubaBrazil
  5. 5.Department of Oral BiologyMedical University of ViennaWienAustria

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