title: Raloxifene but not alendronate can compensate the impaired osseointegration in osteoporotic rats.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings suggest that raloxifene but not alendronate can compensate for the impaired osseointegration in osteoporotic rats.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery and Integrated Clinic, Division of Oral and Maxillofacial Surgery, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, 16015-050, Brazil. leobucomaxilo@gmail.com.
authors.forename: Leonardo Perez
authors.initials: LP
authors.lastname: Faverani
authors.affiliation: Department of Surgery and Integrated Clinic, Division of Oral and Maxillofacial Surgery, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, 16015-050, Brazil.
authors.forename: Tárik Ocon Braga
authors.initials: TOB
authors.lastname: Polo
authors.affiliation: Department of Surgery and Integrated Clinic, Division of Oral and Maxillofacial Surgery, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, 16015-050, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Ramalho-Ferreira
authors.affiliation: Department of Surgery and Integrated Clinic, Division of Oral and Maxillofacial Surgery, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, 16015-050, Brazil.
authors.forename: Gustavo Antonio Correa
authors.initials: GAC
authors.lastname: Momesso
authors.affiliation: Department of Surgery and Integrated Clinic, Division of Oral and Maxillofacial Surgery, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, 16015-050, Brazil.|Department of Basic Sciences, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, 16015-050, Brazil.
authors.forename: Jaqueline Suemi
authors.initials: JS
authors.lastname: Hassumi
authors.affiliation: Department of Morphology, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba, SP, Brazil.
authors.forename: Ana Cláudia
authors.initials: AC
authors.lastname: Rossi
authors.affiliation: Department of Morphology, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba, SP, Brazil.
authors.forename: Alexandre Rodrigues
authors.initials: AR
authors.lastname: Freire
authors.affiliation: Department of Morphology, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba, SP, Brazil.
authors.forename: Felippe Bevilacqua
authors.initials: FB
authors.lastname: Prado
authors.affiliation: Department of Surgery and Integrated Clinic, Division of Integrated Clinic, São Paulo State University UNESP), School of Dentistry, Araçatuba, São Paulo, 16015-050, Brazil.
authors.forename: Eloá Rodrigues
authors.initials: ER
authors.lastname: Luvizuto
authors.affiliation: Department of Oral Biology, Medical University of Vienna, Wien, Austria.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Gruber
authors.affiliation: Department of Basic Sciences, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, 16015-050, Brazil.
authors.forename: Roberta
authors.initials: R
authors.lastname: Okamoto
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D015921:Dental Implants; D004195:Disease Models, Animal; D005260:Female; D007124:Immunoenzyme Techniques; D020007:Implants, Experimental; D018613:Microscopy, Confocal; D016348:Osseointegration / Q000187:drug effects*; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013977:Tibia / Q000601:surgery; D055114:X-Ray Microtomography
chemical_list: D015921:Dental Implants; D020849:Raloxifene Hydrochloride; D019386:Alendronate
keywords: Alendronate; Dental implants; Microscopy; Osteoporosis; Raloxifene