Le ranelate de strontium (RS) est un traitement anti-ostéoporotique agissant sur la formation osseuse via les ostéoblastes et la résorption osseuse via les ostéoclastes grâce au Calcium Sensing Receptor (CaSR). L’activité physique (EXE) est bien connue pour améliorer les propriétés osseuses. Dans ce travail, nous avons étudié ① l’effet de différentes activités physiques (tapis roulant et impact). Nous avons observé que 10 impacts par jour pendant 8 semaines à 45cm de hauteur ont eu des effets bénéfiques sur l’os (paramètres de microarchitecture et biomécanique, marqueurs du remodelage). ② L’étude du RS et de l’EXE sur l’os de rate ovariectomisée a montré que le RS a des effets comparables à l’EXE et que le RS+EXE ont des effets cumulatifs sur l’os (paramètres de microarchitecture et biomécanique, marqueurs du remodelage). ③ Enfin, une étude in vivo sur des MLO-Y4 a montré la présence des CaSR sur la membrane des ostéocytes et leur nombre est modulé en fonction de la concentration en RS. De plus, le RS a un effet sur la différenciation des CSM lors d’une différenciation ostéogénique en favorisant la différenciation ostéocytaire et elle est modulée par la concentration en RS. En conclusion, ce travail a démontré l’importance d’une pratique d’un exercice physique et du traitement du RS contre l’ostéoporose : maintien de la balance du remodelage osseux du côté de la formation. L’effet cumulatif du RS+EXE s’explique par le fait que le RS agit sur les ostéoblastes, ostéocytes et ostéoclastes via les CaSR et l’EXE sur les mécanorécepteurs des ostéocytes. / Strontium ranelate (SR) is an anti-osteoroporotic treatment acting on bone formation via osteoblasts and bone resorption via osteoclasts thanks to Calcium Sensing Receptor (CaSR). Physical activity is well known to improve bone properties. In this work, we studied ① different physical acticities (treadmill and impact). We observed that 10 impacts per day during 8 weeks from 45cm of height had beneficial effects on bone (microarchitecture and biomechanical parameters, bone remodeling markers). ② The study of SR and EXE effects on bone ovariectomized rats showed that RS had similar effects to EXE and SR+EXE had cumulative effects on bone (microarchitecture and biomechanical parameters, bone remodeling markers). ③ Finally, an in vivo study on MLO-Y4 showed CaSR presence on osteocyte with their number depending on SR concentration. Moreover, RS had positive effects on CSM differentiation in favor of osteocyte differentiation and it is modulated by SR concentration. In conclusion, this work has demonstrated the importance of taking physical exercise as well as SR treatment for osteoporosis: maintaining the bone remodeling in favor of bone formation. The cumulative effect of SR+EXE is explained by the fact the SR acts on osteoblasts, osteocytes and osteoclasts via CaSR and the EXE on osteocyte mechanoreceptors.

O ranelato de estrôncio (RS) diminui a reabsorção óssea e ao mesmo tempo age como um agente anabólico deste tecido. Este estudo foi realizado para avaliar os efeitos da ovariectomia e do tratamento com RS na reparação de defeitos ósseos em fêmures e nos componentes moleculares do osso em ratas. Vinte e sete ratas adultas foram submetidas a ovariectomia ou cirurgia Sham e, após trinta dias, defeitos ósseos em fêmures foram confeccionados e os animais divididos em três grupos: ovariectomizadas (OVZ), cirurgia Sham (SHAM) e ovariectomizadas + tratamento com 625 mg/kg/dia de RS (RS). A eutanásia foi realizada quatro semanas após a cirurgia do defeito ósseo. A reparação do defeito ósseo foi analisada por microtomografia computadorizada (?CT) e a composição química do tecido ósseo foi verificada por espectroscopia de infravermelho com transformada de Fourier (FTIR) e espectroscopia de energia dispersiva de raios-X (EDS). O grupo SHAM apresentou em média volume ósseo (BV) superior ao grupo OVZ (p=0,014) e o volume ósseo relativo (BV/TV) foi cerca de 8% superior ao grupo OVZ. A comparação entre SHAM e RS apresentou valores limítrofes para essas variáveis. A espessura trabecular (Tb.Th) no grupo RS foi significativamente maior que no grupo OVZ cerca de 1,8% (p = 0,049) e não diferiu em média do grupo SHAM. Não houve diferenças significativas nas relações que avaliam compostos inorgânicos sobre orgânicos nos grupos. A razão das áreas das bandas em 1057 e 1023 cm-1 para o cálculo do IC foi 1.024 no grupo SHAM, 1.015 no grupo RS e 1.108 no grupo OVZ. No estudo da banda de amida III foi observado nos animais ovariectomizados uma possível mudança na estrutura secundária das proteínas da matriz devido a uma diminuição das estruturas ?-hélice e random coil (RC) e aumento de ?-sheet. A maturidade do colágeno estimada pela relação de sub-bandas de amida I (1660/1690) foi menor no grupo RS. Neste grupo houve um aumento significativo de estrôncio (Sr) incorporado ao tecido ósseo e uma diminuição de cálcio (Ca) avaliados pela técnica do EDS. Os resultados demonstram que o tratamento sistêmico com RS promoveu a reparação óssea e melhorou a microarquitetura do osso neoformado no interior do defeito. No entanto, os resultados das análises com FTIR sugerem que o RS não reverteu as alterações na matriz orgânica ocasionadas pela ovariectomia e diminuiu as ligações cruzadas de colágeno maturas. / Strontium ranelate (SR) decreases bone resorption and at the same time acts as an anabolic agent in this tissue. This study was conducted to evaluate the effects of ovariectomy and treatment with SR on the repair of bone defects and molecular components of bones in femurs. Adult female rats (n=27) were subjected to ovariectomy or Sham surgery. Thirty days after surgery, a defect was made in the femur and the animals were divided into three groups: ovariectomy (OVZ), Sham surgery (SHAM) and ovariectomy plus treatment with SR, 625 mg / kg / day (SR). Euthanasia was performed four weeks after surgery to cause the bone defect. Repair in bone defect was assessed by computed microtomography (?CT) and the chemical composition of bone tissue was analyzed by Fourier transform infrared (FTIR) spectroscopy and energy dispersive X-ray spectroscopy (EDS). The SHAM group showed mean values for bone volume (BV) higher than those of the OVZ group (p = 0.014) and the relative bone volume (BV / TV) was about 8% higher than that of the OVZ group. Comparison between SHAM and SR showed borderline values for these variables. In the SR group, the average value for trabecular thickness (Tb.Th) was significantly higher (~1.8%) than that in the OVZ (p = 0.049) group and did not differ from that of the SHAM group. Significant difference was not observed in the relation between inorganic and organic compounds in the three groups. The ratio of the areas of the bands in 1057 and 1023 cm-1 for the calculation of IC was 1,024 in the SHAM group, 1,015 in the RS group and 1,108 in OVZ group. In the study of the amide III band, a change in the proportion of secondary structure of matrix proteins was observed in ovariectomized animals, possibly a decrease in of ?-helical and random coil (RC) and an increase in ?-sheet structures. The collagen cross-linking network maturity estimated by the relation between amide I subbands (1660/1690) showed the smaller number in the SR group. In this group, a significant increase in the amount of strontium (Sr) and a decrease in the amount of calcium (Ca) embedded to bone tissue, as assessed by the EDS technique, were also observed. The results demonstrate that systemic treatment with SR promoted bone repair and improved microarchitecture of the newly formed bone within the defect. However, results of analyses with FTIR suggest that the SR has not reversed the alterations caused by ovariectomy in the organic matrix and decreased cross-linking of collagen mature.

O ranelato de estrôncio (RS) diminui a reabsorção óssea e ao mesmo tempo age como um agente anabólico deste tecido. Este estudo foi realizado para avaliar os efeitos da ovariectomia e do tratamento com RS na reparação de defeitos ósseos em fêmures e nos componentes moleculares do osso em ratas. Vinte e sete ratas adultas foram submetidas a ovariectomia ou cirurgia Sham e, após trinta dias, defeitos ósseos em fêmures foram confeccionados e os animais divididos em três grupos: ovariectomizadas (OVZ), cirurgia Sham (SHAM) e ovariectomizadas + tratamento com 625 mg/kg/dia de RS (RS). A eutanásia foi realizada quatro semanas após a cirurgia do defeito ósseo. A reparação do defeito ósseo foi analisada por microtomografia computadorizada (?CT) e a composição química do tecido ósseo foi verificada por espectroscopia de infravermelho com transformada de Fourier (FTIR) e espectroscopia de energia dispersiva de raios-X (EDS). O grupo SHAM apresentou em média volume ósseo (BV) superior ao grupo OVZ (p=0,014) e o volume ósseo relativo (BV/TV) foi cerca de 8% superior ao grupo OVZ. A comparação entre SHAM e RS apresentou valores limítrofes para essas variáveis. A espessura trabecular (Tb.Th) no grupo RS foi significativamente maior que no grupo OVZ cerca de 1,8% (p = 0,049) e não diferiu em média do grupo SHAM. Não houve diferenças significativas nas relações que avaliam compostos inorgânicos sobre orgânicos nos grupos. A razão das áreas das bandas em 1057 e 1023 cm-1 para o cálculo do IC foi 1.024 no grupo SHAM, 1.015 no grupo RS e 1.108 no grupo OVZ. No estudo da banda de amida III foi observado nos animais ovariectomizados uma possível mudança na estrutura secundária das proteínas da matriz devido a uma diminuição das estruturas ?-hélice e random coil (RC) e aumento de ?-sheet. A maturidade do colágeno estimada pela relação de sub-bandas de amida I (1660/1690) foi menor no grupo RS. Neste grupo houve um aumento significativo de estrôncio (Sr) incorporado ao tecido ósseo e uma diminuição de cálcio (Ca) avaliados pela técnica do EDS. Os resultados demonstram que o tratamento sistêmico com RS promoveu a reparação óssea e melhorou a microarquitetura do osso neoformado no interior do defeito. No entanto, os resultados das análises com FTIR sugerem que o RS não reverteu as alterações na matriz orgânica ocasionadas pela ovariectomia e diminuiu as ligações cruzadas de colágeno maturas. / Strontium ranelate (SR) decreases bone resorption and at the same time acts as an anabolic agent in this tissue. This study was conducted to evaluate the effects of ovariectomy and treatment with SR on the repair of bone defects and molecular components of bones in femurs. Adult female rats (n=27) were subjected to ovariectomy or Sham surgery. Thirty days after surgery, a defect was made in the femur and the animals were divided into three groups: ovariectomy (OVZ), Sham surgery (SHAM) and ovariectomy plus treatment with SR, 625 mg / kg / day (SR). Euthanasia was performed four weeks after surgery to cause the bone defect. Repair in bone defect was assessed by computed microtomography (?CT) and the chemical composition of bone tissue was analyzed by Fourier transform infrared (FTIR) spectroscopy and energy dispersive X-ray spectroscopy (EDS). The SHAM group showed mean values for bone volume (BV) higher than those of the OVZ group (p = 0.014) and the relative bone volume (BV / TV) was about 8% higher than that of the OVZ group. Comparison between SHAM and SR showed borderline values for these variables. In the SR group, the average value for trabecular thickness (Tb.Th) was significantly higher (~1.8%) than that in the OVZ (p = 0.049) group and did not differ from that of the SHAM group. Significant difference was not observed in the relation between inorganic and organic compounds in the three groups. The ratio of the areas of the bands in 1057 and 1023 cm-1 for the calculation of IC was 1,024 in the SHAM group, 1,015 in the RS group and 1,108 in OVZ group. In the study of the amide III band, a change in the proportion of secondary structure of matrix proteins was observed in ovariectomized animals, possibly a decrease in of ?-helical and random coil (RC) and an increase in ?-sheet structures. The collagen cross-linking network maturity estimated by the relation between amide I subbands (1660/1690) showed the smaller number in the SR group. In this group, a significant increase in the amount of strontium (Sr) and a decrease in the amount of calcium (Ca) embedded to bone tissue, as assessed by the EDS technique, were also observed. The results demonstrate that systemic treatment with SR promoted bone repair and improved microarchitecture of the newly formed bone within the defect. However, results of analyses with FTIR suggest that the SR has not reversed the alterations caused by ovariectomy in the organic matrix and decreased cross-linking of collagen mature.