Abstract

Raloxifene is an antiresorptive drug, selective estrogen receptor modulator (SERM) used in the treatment of osteoporosis.ObjectiveTo evaluate proteins related to bone repair at the peri-implant bone in a rat model of osteoporosis treated with raloxifene.Material and Methods72 rats were divided into three groups: SHAM (healthy animals), OVX (ovariectomized animals), and RLX (ovariectomized animals treated with raloxifene). Raloxifene was administered by gavage (1 mg/kg/day). Tibial implantation was performed 30 days after ovariectomy, and animals were euthanized at 14, 42, and 60 days postoperatively. Samples were collected and analyzed by immunohistochemical reactions, molecular analysis, and microtomographic parameters.ResultsRLX showed intense staining of all investigated proteins at both time points except for RUNX2. These results were similar to SHAM and opposite to OVX, showing mild staining. The PCR gene expression of OC and ALP values for RLX (P<0.05) followed by SHAM and OVX groups. For BSP data, the highest expression was observed in the RLX groups and the lowest expression was observed in the OVX groups (P<0.05). For RUNX2 data, RLX and SHAM groups showed greater values compared to OVX (P<0.05). At 60 days postoperatively, microtomography parameters, related to closed porosity, showed higher values for (Po.N), (Po.V), and (Po) in RLX and SHAM groups, whereas OVX groups showed lower results (P<0.05); (BV) values (P=0.009); regarding total porosity (Po.tot), RLX group had statistically significant lower values than OVX and SHAM groups (P=0.009). Regarding the open porosity (Po.V and Po), the SHAM group presented the highest values, followed by OVX and RLX groups (P<0.05). The Structural Model Index (SMI), RLX group showed a value closer to zero than SHAM group (P<0.05).ConclusionsRaloxifene had a positive effect on the expression of osteoblastogenesis/mineralization-related proteins and on micro-CT parameters related to peri-implant bone healing.

Highlights

  • Post-menopausal osteoporosis is the main skeletal disorder with high incidence found in society, being characterized by reduced bone mass due to estrogen deficiency and decreased intestinal absorption of calcium, resulting in increased bone fragility and fracture susceptibility19

  • Raloxifene had a positive effect on the expression of osteoblastogenesis/mineralization-related proteins and on micro-CT parameters related to peri-implant bone healing

  • The animals were divided into three groups: SHAM – rats submitted to sham surgery and fed a balanced diet; OVX – rats submitted to bilateral ovariectomy and fed a low calcium diet without medical treatment; RLX – rats submitted to bilateral ovariectomy and fed a low calcium diet with raloxifene treatment

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Summary

Introduction

Post-menopausal osteoporosis is the main skeletal disorder with high incidence found in society, being characterized by reduced bone mass due to estrogen deficiency and decreased intestinal absorption of calcium, resulting in increased bone fragility and fracture susceptibility. We highlight raloxifene, a second generation Selective Estrogen Receptor Modulator (SERM) approved for use in the prevention and treatment of osteoporosis in postmenopausal women. Bisphosphonates are the most commonly used drugs for osteoporosis treatment, mainly alendronate, and have shown great results by increasing bone mineral density and decreasing the risk of bone fracture in post-menopausal women the long-term use of these drugs is associated with the emergence of medication-related osteonecrosis of the jaw (MRONJ), increasingly common in patients who underwent oral surgeries, such as implants placement

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