Serum bone formation marker correlation with improved osseointegration in osteoporotic rats treated with simvastatin. Long-term results and survival rate of implants treated with guided bone regeneration: a 5-year case series prospective study. Immunolocalization of markers for bone formation during guided bone regeneration in osteopenic rats The RANK/ RANKL/ OPG interaction in the repair of autogenous bone grafts in female rats with estrogen deficiency. TGF-beta1 as a marker of delayed fracture healing. Hyperbaric oxygen stimulates vascularization and bone formation in rat calvarial defects. Porous titanium granules promote bone healing and growth in rabbit tibia peri-implant osseous defects. Plasma rich in growth factors in human extraction sockets: a radiographic and histomorphometric study on early bone deposition. Release of Bone Markers in Immediately Loaded and Nonloaded Dental Implants Salivary biomarkers of periodontal disease in response to treatment. Guided tissue regeneration may modulate gene expression in periodontal intrabony defects: a human study.
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 staining score throughout the study , when compared with control group . CONCLUSIONS Plasma rich in growth factors-treated group did not show any enhancement in early ( 4 and 8 weeks ) bone deposition compared with control group The aim of this study was to compare the release of bone markers during osseointegration of immediately loaded and nonloaded implants . Forty patients who were indicated for rehabilitation with dental implants r and omly received either implant and prosthesis placement within 72 hours ( group IM ) or implant insertion and no prosthesis placement ( group NL ) . Peri-implant crevicular fluid was collected immediately after implant insertion and 7 , 15 , 30 , 60 , 90 , and 120 days after surgery and levels of osteoprotegerin , transforming growth factors , osteocalcin , osteopontin , and parathyroid hormone were evaluated using Luminex assay . Bleeding index and peri-implantar sulcus depth were also evaluated . The data were compared using statistical tests ( α = 5 % ) . No statistical difference was found regarding demographic and clinical parameters ( p > .05 ) . Transforming growth factors , osteoprotegerin , osteopontin , and parathyroid hormone presented an earlier release peak in group IM than in NL group ( p < .05 ) . Osteocalcin achieved higher levels in group IM versus group NL between 7 and 30 days of evaluation ( p < .05 ) . It may be concluded that earlier loading positively modulates bone mediators release around immediately loaded implants when compared with nonloaded dental implants ( Clinical Trials.gov NCT01909999 ) BACKGROUND Salivary biomarkers of periodontitis were assessed longitudinally to determine response to therapy . METHODS A 6-month case-controlled study of adults with chronic periodontitis was performed , with 33 participants receiving oral hygiene instructions ( OHI ) alone and 35 with scaling and root planing ( SRP ) combined with OHI .  Saliva sample s collected at week 0 , 16 and 28 were analysed for interleukin (IL)-1β , IL-8 , macrophage inflammatory protein (MIP)-1α , matrix metalloproteinase-8 ( MMP-8 ) , osteoprotegerin ( OPG ) , and tumour necrosis factor-α (TNF)-α . Clinical measures of periodontal disease were recorded at each visit . RESULTS All parameters of periodontal health improved significantly in both groups by week 16 ( p<0.0001 ) with the SRP group demonstrating greater benefit at week 16 and 28 . Baseline OPG and TNF-α levels changed significantly at both follow-up visits ( p<0.03 ) , regardless of treatment group . IL-1β and MMP-8 levels decreased significantly from baseline ( p<0.04 ) in the SRP group only . OPG , MMP-8 , and MIP-1α were significantly reduced in responders compared with non-responders ( p=0.04 , 0.01 , 0.05 , respectively ) . In receiver-operating characteristic analyses , MMP-8 produced the highest area under the curve ( 0.7 ; p=0.01 ) . CONCLUSION Salivary levels of IL-1β , MMP-8 , OPG , and MIP-1α reflected disease severity and response to therapy suggesting their potential utility for monitoring periodontal disease status BACKGROUND AND OBJECTIVE Guided tissue regeneration has been shown to lead to periodontal regeneration , however , the mechanisms involved remain to be clarified . The present study was carried out to assess the expression of genes involved in the healing process of periodontal tissues in membrane-protected vs. nonprotected intrabony defects in humans . MATERIAL AND METHODS Thirty patients with deep intrabony defects ( > or = 5 mm , two or three walls ) around teeth that were scheduled for extraction were selected and r and omly assigned to receive one of the following treatments : flap surgery alone ( control group ) or flap surgery plus guided tissue regeneration ( exp and ed polytetrafluorethylene ( e-PTFE ) membrane ) ( test group ) . Twenty-one days later , the newly formed tissue was harvested and quantitatively assessed using the polymerase chain reaction assay for the expression of the following genes : alkaline phosphatase , receptor activator of nuclear factor-kappa B lig and , osteoprotegerin , osteopontin , osteocalcin , bone sialoprotein , basic fibroblast growth factor , interleukin-1 , interleukin-4 , interleukin-6 , matrix metalloproteinase-2 and matrix metalloproteinase-9 . RESULTS Data analysis demonstrated that mRNA levels for alkaline phosphatase , receptor activator of nuclear factor-kappa B lig and , osteoprotegerin , osteopontin , bone sialoprotein , basic fibroblast growth factor , interleukin-1 , interleukin-6 , matrix metalloproteinase-2 and matrix metalloproteinase -9 were higher in the sites where guided tissue regeneration was applied compared with the control sites ( p < 0.05 ) , whereas osteocalcin mRNA levels were lower ( p < 0.05 ) . No difference was observed in interleukin-4 mRNA levels between control and test groups . CONCLUSION Within the limits of this study , it can be concluded that genes are differentially expressed in membrane barrier-led periodontal healing when compared with flap surgery alone , and this may account for the clinical outcome achieved by guided tissue regeneration
BACKGROUND Biomarkers are detected during bone formation and resorption associated with the dynamics of bone metabolism and are gaining importance as preferential indicators of bone healing in comparison with conventional method ologies .
Current literature suggests that the usage of bone turnover markers for monitoring bone regeneration in association with bio material s is limited .