human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE Simvastatin has been shown to enhance osseointegration of pure titanium implants in osteoporotic rats . This study aim ed to evaluate the relationship between the serum level of bone formation markers and the osseointegration of pure titanium implants in osteoporotic rats treated with simvastatin .  MATERIAL S AND METHODS Fifty-four female Sprague-Dawley rats , aged 3 months , were r and omly divided into three groups : Sham-operated group ( SHAM ; n = 18 ) , ovariectomized group ( OVX ; n = 18 ) , and ovariectomized with simvastatin treatment group ( OVX + SIM ; n = 18 ) . Fifty-six days after ovariectomy , screw-shaped titanium implants were inserted into the tibiae . Simvastatin was administered orally at 5 mg/kg each day after the placement of the implant in the OVX + SIM group . The animals were killed at either 28 or 84 days after implantation and the undecalcified tissue sections were processed for histological analysis . Total alkaline phosphatase ( ALP ) , bone-specific alkaline phosphatase ( BALP ) and bone Gla protein ( BGP ) were measured in all animal sera collected at the time of euthanasia and correlated with the histological assessment of osseointegration . RESULTS The level of ALP in the OVX group was higher than the SHAM group at day 28 , with no differences between the three groups at day 84 . The level of BALP in the OVX + SIM group was significantly higher than both OVX and SHAM groups at days 28 . Compared with day 28 , the BALP level of all three groups showed a significant decrease at day 84 . There were no significant differences in BGP levels between the three groups at day 28 , but at day 84 , the OVX + SIM group showed significantly higher levels than both the OVX and SHAM groups . There was a significant increase in BGP levels between days 28 and 84 in the OVX + SIM group . The serum bone marker levels correlated with the histological assessment showing reduced osseointegration in the OVX compared to the SHAM group which is subsequently reversed in the OVX + SIM group . CONCLUSION The results from this study indicate that the serum level of bone formation markers , especially BALP and BGP , could be correlated with the degree of osseointegration around titanium implants in osteoporotic rats treated with simvastatin One of the key factors for attaining osseointegration is the presence of an adequate osseous volume . In patients with inadequate osseous width or height , a bone augmentation using the guided bone regeneration ( GBR ) concept may be applied either with a simultaneous or a staged approach . The aim of this multicenter prospect i ve case series study was to evaluate the efficacy and predictability of the GBR technique ( simultaneous approach ) in patients with peri-implant osseous defects , both dehiscences and fenestrations . Results 5 years post-treatment ( survival rates and marginal bone level ) were assessed . A total of 19 consecutive patients with 26 peri-implant osseous defects ( 20 dehiscences and six fenestrations ) were treated during the period from September 1992 to June 1993 with a simultaneous GBR approach using non-resorbable membranes combined with autogenous bone grafts or decalcified freeze-dried bone allograft . The mean osseous augmentation was 94.8 % . Marginal bone levels at re-entry and 5 years after surgery were calculated from st and ardized periapical radiographs . One implant was lost 3 months after loading . Thus , the cumulative survival rate was 96.1 % after 5 years . The mean marginal bone level after 5 years was 2.03 mm ( SD=+/-0.5 ) , without a difference between mesial and distal sites . This study demonstrates that implants with peri-implant defects that are treated with GBR had similar survival rates and crestal bone levels compared with implants in native bone Objective The aim of this paper was to evaluate the repair of onlay autogenous bone grafts covered or not covered by an exp and ed polytetrafluoroethylene ( e-PTFE ) membrane using immunohistochemistry in rats with induced estrogen deficiency . Material and Methods Eighty female rats were r and omly divided into two groups : ovariectomized ( OVX ) and with a simulation of the surgical procedure ( SHAM ) . Each of these groups was again divided into groups with either placement of an autogenous bone graft alone ( BG ) or an autogenous bone graft associated with an e-PTFE membrane ( BGM ) . Animals were euthanized on days 0 , 7 , 21 , 45 , and 60 . The specimens were subjected to immunohistochemistry for bone sialoprotein ( BSP ) , osteonectin ( ONC ) , and osteocalcin ( OCC ) . Results All groups ( OVX+BG , OVX+BMG , SHAM+BG , and SHAM+BMG ) showed greater bone formation , observed between 7 and 21 days , when BSP and ONC staining were more intense . At the 45-day , the bone graft showed direct bonding to the recipient bed in all specimens . The ONC and OCC showed more expressed in granulation tissue , in the membrane groups , independently of estrogen deficiency . Conclusions The expression of bone forming markers was not negatively influenced by estrogen deficiency . However , the markers could be influenced by the presence of the e-PTFE membrane The aim of this study was to evaluate the resorption process during the repair of autogenous bone grafts with or without coverage by an exp and ed polytetrafluoroethylene ( e-PTFE ) membrane in female rats with estrogen deficiency using the immunohistochemical technique . Eighty female rats were r and omly divided into two groups ( OVX and SHAM ) . The 40 female rats in the OVX group were subjected to ovariectomy , and the 40 female rats in the SHAM group were subjected to simulated ovariectomy . The two groups were further divided in subgroup E , which was subjected to surgery for placement of autogenous bone graft ( ABG ) , and subgroup ME , in which the ABG was covered with an e-PTFE membrane . The animals were killed at 0 , 7 , 21 , 45 and 60 days . The specimens were analyzed using immunohistochemistry for the bone resorption markers RANK , RANK-L and Osteoprotegerin ( OPG ) . A higher remodeling rate was observed at 7 and 21 days after the autogenous bone grafts , when the markers were more intensely expressed . At the final time point , the specimens presented similar characteristics to those observed at the initial time point . The expression of immunohistochemical markers was not altered by the estrogen deficiency . The presence of the e-PTFE membrane delayed the bone resorption process , influencing the immunohistochemical expression of markers Mitogens of the TGF-beta superfamily have been shown to be crucial local and systemic regulatory molecules involved in fracture healing . However , there exists only little information about systemic regulation of bone regeneration by growth factors and no reports comparing serum levels of bone growth factors between normal and failed fracture healing have been published so far . We hypothesized that quality of fracture healing might be reflected by systemic alterations of key regulatory growth factors involved in bone formation and remodeling . Therefore , the aim of this study was to evaluate possible differences in serum levels of BMP-2 , BMP-4 , and TGF-beta1 in patients with normal and delayed fracture healing . 103 patients with diaphyseal fractures of long bones were recruited prospect ively .  Peripheral blood sample s were collected over a period of 6 months following a st and ardized time schedule . At the end of the individual investigation period ,  growth factor serum levels  were measured using commercially available enzyme immunoassays . For the elimination of disturbing influences , patients in both groups were matched by gender , age , fracture type , and localization as well as applied technique of osteo synthesis . During a study period of 1 year , 10 patients with an atrophic type of delayed union could be retrieved and matched to 10 patients with normal fracture healing . The diagnosis of delayed union was assumed in case of failed consolidation 4 months after trauma . We found an increase of TGF-beta1 serum levels up to 2 weeks after fracture in both groups with a following return to the reference value within 6 weeks after trauma . However , decline of serum concentration occurred earlier in patients with delayed fracture healing . At 4 weeks after trauma , serum levels of TGF-beta1 were significantly lower in patients of the delayed union group . Serum levels of BMP-2 and BMP-4 were below detection level in all patients , respectively . These findings support the critical role of TGF-beta1 in fracture healing . Events during the consolidation phase seem to be dependent on sufficient availability of TGF-beta1 Hyperbaric oxygen ( HBO ) therapy is used to treat or prevent tissue necrosis in patients undergoing irradiation . Many such patients require reconstructive surgery , but little is known of the effects of HBO on bone vascularization and regeneration . In this study , copolymer poly(l-lactide-co-1,5-dioxepan-2-one ) ( poly(LLA-co-DXO ) ) scaffolds were implanted into critical-sized calvarial defects in Wistar rats . The animals were r and omly allotted to hyperbaric or normobaric oxygen groups . The treatment group received five sessions weekly for 90 min at increased atmospheric pressure , for up to 4 weeks . Sample s were retrieved at weeks 2 and 8 , i.e. after a total of 10 and 20 sessions , respectively . The sample s were analyzed by real-time reverse transcriptase polymerase chain reaction ( RT-PCR ) and histology at week 2 , and radiographically and histologically at week 8 . At week 2 , defects treated with HBO exhibited greater numbers of cells positive for the endothelial marker CD31 , up-regulated gene expression of osteogenic markers , and down-regulated expression of pro-inflammatory cytokines . At week 8 , radiographic examination revealed that calvarial defects subjected to HBO exhibited a higher percentage of radiopacities than normobaric controls , and histological examination disclosed enhanced bone healing . These results confirmed that HBO treatment was effective in stimulating vascularization and bone formation in rat calvarial defects OBJECTIVES The aim of this study was to investigate the osteoconductive properties and biological performance of porous titanium granules used in osseous defects adjacent to titanium implants . MATERIAL AND METHODS In this animal experimental study , calibrated defects were prepared in the tibias of 24 New Zeal and rabbits . The defects were r and omized into two tests and one control group . The test defects were grafted with either metallic or oxidized porous titanium granules ( PTG or WPTG , respectively ) , whereas control defects were left empty ( sham ) . The defects were closed with a submerged coin shaped titanium implant . Defects were left for healing for 4 weeks . After healing , the implants were removed and the new bone tissue formed onto the implant surface was analyzed for run x 2 , osteocalcin , collagen-I , tartrate-resistant acid phosphatase , H(+)-ATPase , tumor necrosis factor-alpha , interleukin (IL)-6 and IL-10 gene expression using reverse transcriptase polymerase chain reaction . Wound fluid from the healed defects was analyzed for lactate dehydrogenase and alkaline phosphatase activity . Finally osteoconductivity was analyzed by micro-computed tomography and histology . RESULTS Significantly more new bone formed in PTG and WPTG grafted defects compared with sham . The new bone grew both through the porosities of the granules and onto the implant surfaces . The WPTG group showed significantly less expression of key inflammation markers , but with no significant difference in a marker for necrosis . The WPTG also showed a significant increase in collagen-I mRNA expression compared with PTG . CONCLUSION The results suggest that PTG and WPTG are both osteoconductive material s that can be used to promote bone formation in osseous defects adjacent to titanium implants without hampering implant osseointegration OBJECTIVES To determine whether and to what extent the additional application of plasma rich in growth factors ( PRGF ) to an extraction socket may influence the early bone deposition , as assessed by micro-computed tomography ( micro-CT ) scan as well as histomorphometric markers . MATERIAL AND METHODS Twenty-eight patients ( age range : 34 - 74 years ) contributing 36 extraction sockets were included in the study . Sockets were either treated with PRGF ( PRGF group ; 18 sites in 11 patients ) or left to spontaneous healing ( control group ; 18 sites in 17 patients ) . Radiographic and histomorphometric analysis was performed on bone cores trephined from each healing socket after 4 - 6 ( T1 ) or 7 - 10 ( T2 ) weeks of healing . RESULTS Patients treated with PRGF application showed ( i ) similar bone volume and tissue mineral content , ( ii ) a trend , although not statistically significant , toward a greater number of CD68 + cells ( at T1 and T2 ) and vVW+ cells ( at T1 ) , and ( iii ) a similar OCN st 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE Simvastatin has been shown to enhance osseointegration of pure titanium implants in osteoporotic rats . This study aim ed to evaluate the relationship between the serum level of bone formation markers and the osseointegration of pure titanium implants in osteoporotic rats treated with simvastatin .  MATERIAL S AND METHODS Fifty-four female Sprague-Dawley rats , aged 3 months , were r and omly divided into three groups : Sham-operated group ( SHAM ; n = 18 ) , ovariectomized group ( OVX ; n = 18 ) , and ovariectomized with simvastatin treatment group ( OVX + SIM ; n = 18 ) . Fifty-six days after ovariectomy , screw-shaped titanium implants were inserted into the tibiae . Simvastatin was administered orally at 5 mg/kg each day after the placement of the implant in the OVX + SIM group . The animals were killed at either 28 or 84 days after implantation and the undecalcified tissue sections were processed for histological analysis . Total alkaline phosphatase ( ALP ) , bone-specific alkaline phosphatase ( BALP ) and bone Gla protein ( BGP ) were measured in all animal sera collected at the time of euthanasia and correlated with the histological assessment of osseointegration . RESULTS The level of ALP in the OVX group was higher than the SHAM group at day 28 , with no differences between the three groups at day 84 . The level of BALP in the OVX + SIM group was significantly higher than both OVX and SHAM groups at days 28 . Compared with day 28 , the BALP level of all three groups showed a significant decrease at day 84 . There were no significant differences in BGP levels between the three groups at day 28 , but at day 84 , the OVX + SIM group showed significantly higher levels than both the OVX and SHAM groups . There was a significant increase in BGP levels between days 28 and 84 in the OVX + SIM group . The serum bone marker levels correlated with the histological assessment showing reduced osseointegration in the OVX compared to the SHAM group which is subsequently reversed in the OVX + SIM group . CONCLUSION The results from this study indicate that the serum level of bone formation markers , especially BALP and BGP , could be correlated with the degree of osseointegration around titanium implants in osteoporotic rats treated with simvastatin One of the key factors for attaining osseointegration is the presence of an adequate osseous volume . In patients with inadequate osseous width or height , a bone augmentation using the guided bone regeneration ( GBR ) concept may be applied either with a simultaneous or a staged approach . The aim of this multicenter prospect i ve case series study was to evaluate the efficacy and predictability of the GBR technique ( simultaneous approach ) in patients with peri-implant osseous defects , both dehiscences and fenestrations . Results 5 years post-treatment ( survival rates and marginal bone level ) were assessed . A total of 19 consecutive patients with 26 peri-implant osseous defects ( 20 dehiscences and six fenestrations ) were treated during the period from September 1992 to June 1993 with a simultaneous GBR approach using non-resorbable membranes combined with autogenous bone grafts or decalcified freeze-dried bone allograft . The mean osseous augmentation was 94.8 % . Marginal bone levels at re-entry and 5 years after surgery were calculated from st and ardized periapical radiographs . One implant was lost 3 months after loading . Thus , the cumulative survival rate was 96.1 % after 5 years . The mean marginal bone level after 5 years was 2.03 mm ( SD=+/-0.5 ) , without a difference between mesial and distal sites . This study demonstrates that implants with peri-implant defects that are treated with GBR had similar survival rates and crestal bone levels compared with implants in native bone Objective The aim of this paper was to evaluate the repair of onlay autogenous bone grafts covered or not covered by an exp and ed polytetrafluoroethylene ( e-PTFE ) membrane using immunohistochemistry in rats with induced estrogen deficiency . Material and Methods Eighty female rats were r and omly divided into two groups : ovariectomized ( OVX ) and with a simulation of the surgical procedure ( SHAM ) . Each of these groups was again divided into groups with either placement of an autogenous bone graft alone ( BG ) or an autogenous bone graft associated with an e-PTFE membrane ( BGM ) . Animals were euthanized on days 0 , 7 , 21 , 45 , and 60 . The specimens were subjected to immunohistochemistry for bone sialoprotein ( BSP ) , osteonectin ( ONC ) , and osteocalcin ( OCC ) . Results All groups ( OVX+BG , OVX+BMG , SHAM+BG , and SHAM+BMG ) showed greater bone formation , observed between 7 and 21 days , when BSP and ONC staining were more intense . At the 45-day , the bone graft showed direct bonding to the recipient bed in all specimens . The ONC and OCC showed more expressed in granulation tissue , in the membrane groups , independently of estrogen deficiency . Conclusions The expression of bone forming markers was not negatively influenced by estrogen deficiency . However , the markers could be influenced by the presence of the e-PTFE membrane The aim of this study was to evaluate the resorption process during the repair of autogenous bone grafts with or without coverage by an exp and ed polytetrafluoroethylene ( e-PTFE ) membrane in female rats with estrogen deficiency using the immunohistochemical technique . Eighty female rats were r and omly divided into two groups ( OVX and SHAM ) . The 40 female rats in the OVX group were subjected to ovariectomy , and the 40 female rats in the SHAM group were subjected to simulated ovariectomy . The two groups were further divided in subgroup E , which was subjected to surgery for placement of autogenous bone graft ( ABG ) , and subgroup ME , in which the ABG was covered with an e-PTFE membrane . The animals were killed at 0 , 7 , 21 , 45 and 60 days . The specimens were analyzed using immunohistochemistry for the bone resorption markers RANK , RANK-L and Osteoprotegerin ( OPG ) . A higher remodeling rate was observed at 7 and 21 days after the autogenous bone grafts , when the markers were more intensely expressed . At the final time point , the specimens presented similar characteristics to those observed at the initial time point . The expression of immunohistochemical markers was not altered by the estrogen deficiency . The presence of the e-PTFE membrane delayed the bone resorption process , influencing the immunohistochemical expression of markers Mitogens of the TGF-beta superfamily have been shown to be crucial local and systemic regulatory molecules involved in fracture healing . However , there exists only little information about systemic regulation of bone regeneration by growth factors and no reports comparing serum levels of bone growth factors between normal and failed fracture healing have been published so far . We hypothesized that quality of fracture healing might be reflected by systemic alterations of key regulatory growth factors involved in bone formation and remodeling . Therefore , the aim of this study was to evaluate possible differences in serum levels of BMP-2 , BMP-4 , and TGF-beta1 in patients with normal and delayed fracture healing . 103 patients with diaphyseal fractures of long bones were recruited prospect ively .  Peripheral blood sample s were collected over a period of 6 months following a st and ardized time schedule . At the end of the individual investigation period ,  growth factor serum levels  were measured using commercially available enzyme immunoassays . For the elimination of disturbing influences , patients in both groups were matched by gender , age , fracture type , and localization as well as applied technique of osteo synthesis . During a study period of 1 year , 10 patients with an atrophic type of delayed union could be retrieved and matched to 10 patients with normal fracture healing . The diagnosis of delayed union was assumed in case of failed consolidation 4 months after trauma . We found an increase of TGF-beta1 serum levels up to 2 weeks after fracture in both groups with a following return to the reference value within 6 weeks after trauma . However , decline of serum concentration occurred earlier in patients with delayed fracture healing . At 4 weeks after trauma , serum levels of TGF-beta1 were significantly lower in patients of the delayed union group . Serum levels of BMP-2 and BMP-4 were below detection level in all patients , respectively . These findings support the critical role of TGF-beta1 in fracture healing . Events during the consolidation phase seem to be dependent on sufficient availability of TGF-beta1 Hyperbaric oxygen ( HBO ) therapy is used to treat or prevent tissue necrosis in patients undergoing irradiation . Many such patients require reconstructive surgery , but little is known of the effects of HBO on bone vascularization and regeneration . In this study , copolymer poly(l-lactide-co-1,5-dioxepan-2-one ) ( poly(LLA-co-DXO ) ) scaffolds were implanted into critical-sized calvarial defects in Wistar rats . The animals were r and omly allotted to hyperbaric or normobaric oxygen groups . The treatment group received five sessions weekly for 90 min at increased atmospheric pressure , for up to 4 weeks . Sample s were retrieved at weeks 2 and 8 , i.e. after a total of 10 and 20 sessions , respectively . The sample s were analyzed by real-time reverse transcriptase polymerase chain reaction ( RT-PCR ) and histology at week 2 , and radiographically and histologically at week 8 . At week 2 , defects treated with HBO exhibited greater numbers of cells positive for the endothelial marker CD31 , up-regulated gene expression of osteogenic markers , and down-regulated expression of pro-inflammatory cytokines . At week 8 , radiographic examination revealed that calvarial defects subjected to HBO exhibited a higher percentage of radiopacities than normobaric controls , and histological examination disclosed enhanced bone healing . These results confirmed that HBO treatment was effective in stimulating vascularization and bone formation in rat calvarial defects OBJECTIVES The aim of this study was to investigate the osteoconductive properties and biological performance of porous titanium granules used in osseous defects adjacent to titanium implants . MATERIAL AND METHODS In this animal experimental study , calibrated defects were prepared in the tibias of 24 New Zeal and rabbits . The defects were r and omized into two tests and one control group . The test defects were grafted with either metallic or oxidized porous titanium granules ( PTG or WPTG , respectively ) , whereas control defects were left empty ( sham ) . The defects were closed with a submerged coin shaped titanium implant . Defects were left for healing for 4 weeks . After healing , the implants were removed and the new bone tissue formed onto the implant surface was analyzed for run x 2 , osteocalcin , collagen-I , tartrate-resistant acid phosphatase , H(+)-ATPase , tumor necrosis factor-alpha , interleukin (IL)-6 and IL-10 gene expression using reverse transcriptase polymerase chain reaction . Wound fluid from the healed defects was analyzed for lactate dehydrogenase and alkaline phosphatase activity . Finally osteoconductivity was analyzed by micro-computed tomography and histology . RESULTS Significantly more new bone formed in PTG and WPTG grafted defects compared with sham . The new bone grew both through the porosities of the granules and onto the implant surfaces . The WPTG group showed significantly less expression of key inflammation markers , but with no significant difference in a marker for necrosis . The WPTG also showed a significant increase in collagen-I mRNA expression compared with PTG . CONCLUSION The results suggest that PTG and WPTG are both osteoconductive material s that can be used to promote bone formation in osseous defects adjacent to titanium implants without hampering implant osseointegration OBJECTIVES To determine whether and to what extent the additional application of plasma rich in growth factors ( PRGF ) to an extraction socket may influence the early bone deposition , as assessed by micro-computed tomography ( micro-CT ) scan as well as histomorphometric markers . MATERIAL AND METHODS Twenty-eight patients ( age range : 34 - 74 years ) contributing 36 extraction sockets were included in the study . Sockets were either treated with PRGF ( PRGF group ; 18 sites in 11 patients ) or left to spontaneous healing ( control group ; 18 sites in 17 patients ) . Radiographic and histomorphometric analysis was performed on bone cores trephined from each healing socket after 4 - 6 ( T1 ) or 7 - 10 ( T2 ) weeks of healing . RESULTS Patients treated with PRGF application showed ( i ) similar bone volume and tissue mineral content , ( ii ) a trend , although not statistically significant , toward a greater number of CD68 + cells ( at T1 and T2 ) and vVW+ cells ( at T1 ) , and ( iii ) a similar OCN st 
    Output:
    