Search

Purpose: Osteoporosis and diabetes are physiologic determinants that affect the process of osseointegration. The demand for dental implants is high in these patients, who have benefited from progress in preclinical research. Osseointegration has been extensively studied in rat models of osteoporosis and diabetes. The aim of this study is to present an assessment of the published data and provide consideration for future studies. Materials and Methods: The present study summarizes information through a systematic review of the literature from 1997 to 2008 available through PUBMED. The authors found 20 and 13 articles that report on osseointegration of implants in osteoporotic and diabetic rats, respectively. The survey was extended to recent publications on relevant aspects related to species, strains, and quality of endpoint data. Results: Differences in experimental variables such as timing of implant insertion, location of implants, or duration of disease prior to implant placement were reported and can be justified based on the experimental questions. Moreover, heterogeneity was further caused by variations in the age of rats and in reporting of the main parameters of osseointegration in the cortical and medullary compartments. Regardless of these differences, the evidence indicates consistently that ovariectomy results in reduced osseointegration, while there is only moderate evidence for impaired osseointegration in diabetic rats. Conclusions: Selection of the appropriate protocol is critical when studying implant osseointegration in rats. This overview highlights the demand for quality endpoint data related to animal numbers, data collection, and the way to establish osseointegration. Because of the differences in research questions, general recommendations for uniform models for osteoporosis and diabetes cannot be made. Int J Oral Maxillofac Implants 2010;25:516-524. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the accuracy of crown diameter measurements by dental CT as a tool for preoperative diagnosis before tooth transplantations. Fifty-eight patients underwent clinically indicated dental CT. The diameter of the crowns were measured by CT using a standard protocol (1.5-mm slice thickness, 1-mm table feed, 120 kV, 25-75 mA/s, 2-s scan time/slice, 512 matrix) and a standard dental software package. Postoperatively, the same distances were clinically measured using a sliding gauge. The degree of the deviation between CT measurements and clinical measurements was in the sub-millimeter range. According to the regression analysis, the correlation coefficient equals 0.98 and 0.97, indicating a strong relationship between the CT and the manual measurement of the crown diameter in the bucco-lingual and the mesio-distal direction. The mean deviation of CT measurements with regard to the bucco-lingual diameter of the crown was +0.08 mm (SD: +/-0.38 mm). For the mesio-distal diameter, the mean deviation of CT measurements was -0.24 mm (SD: +/-0.53 mm). These results demonstrate that dental CT promises to be a valuable tool for the evaluation of the potential and optimal size and site for tooth transplantations. [ABSTRACT FROM AUTHOR]

Background: Austria is among the countries with the highest incidence and prevalence of osteoporotic fractures worldwide. Guidelines for the prevention and management of osteoporosis were first published in 2010 under the auspices of the then Federation of Austrian Social Security Institutions and updated in 2017. The present comprehensively updated guidelines of the Austrian Society for Bone and Mineral Research are aimed at physicians of all specialties as well as decision makers and institutions in the Austrian healthcare system. The aim of these guidelines is to strengthen and improve the quality of medical care of patients with osteoporosis and osteoporotic fractures in Austria., Methods: These evidence-based recommendations were compiled taking randomized controlled trials, systematic reviews and meta-analyses as well as European and international reference guidelines published before 1 June 2023 into consideration. The grading of recommendations used ("conditional" and "strong") are based on the strength of the evidence. The evidence levels used mutual conversions of SIGN (1++ to 3) to NOGG criteria (Ia to IV)., Results: The guidelines include all aspects associated with osteoporosis and osteoporotic fractures, such as secondary causes, prevention, diagnosis, estimation of the 10-year fracture risk using FRAX®, determination of Austria-specific FRAX®-based intervention thresholds, drug-based and non-drug-based treatment options and treatment monitoring. Recommendations for the office-based setting and decision makers and institutions in the Austrian healthcare system consider structured care models and options for osteoporosis-specific screening., Conclusion: The guidelines present comprehensive, evidence-based information and instructions for the treatment of osteoporosis. It is expected that the quality of medical care for patients with this clinical picture will be substantially improved at all levels of the Austrian healthcare system., (© 2024. The Author(s).)

Platelet-rich fibrin, the coagulated plasma fraction of blood, is commonly used to support natural healing in clinical applications. The rat calvaria defect is a standardized model to study bone regeneration. It remains, however, unclear if the rat calvaria defect is appropriate to investigate the impact of human PRF (Platelet-Rich Fibrin) on bone regeneration. To this end, we soaked Bio-Gide ® collagen membranes in human or rat liquid concentrated PRF before placing them onto 5 mm calvarial defects in Sprague Dawley rats. Three weeks later, histology and micro-computed tomography (μCT) were performed. We observed that the collagen membranes soaked with rat PRF show the characteristic features of new bone and areas of mineralized collagen matrix, indicated by a median mineralized volume of 1.5 mm 3 (range: 0.9; 5.3 mm 3 ). Histology revealed new bone growing underneath the membrane and hybrid bone where collagen fibers are embedded in the new bone. Moreover, areas of passive mineralization were observed. The collagen membranes soaked with human PRF, however, were devoid of histological features of new bone formation in the center of the defect; only occasionally, new bone formed at the defect margins. Human PRF (h-PRF) caused a median bone volume of 0.9 mm 3 (range: 0.3-3.3 mm 3 ), which was significantly lower than what was observed with rat PRF (r-PRF), with a BV median of 1.2 mm 3 (range: 0.3-5.9 mm 3 ). Our findings indicate that the rat calvaria defect model is suitable for assessing the effects of rat PRF on bone formation, but caution is warranted when extrapolating conclusions regarding the efficacy of human PRF.

Bio-Gide ® is a collagen membrane routinely used in guided bone regeneration. Recent studies have shown that this collagen membrane has osteoconductive properties, meaning that it can support the growth of new bone. However, it has also been observed that the collagen membrane has areas of mineralized fibers which can occur spontaneously and independently of osteoblasts. To better understand how this works, we established a model using minced collagen membranes to reduce the active mineralization of intact collagen membranes in favor of passive mineralization. We thus compared the original intact membrane with a minced collagen membrane in a 5 mm calvarial defect model in Sprague Dawley rats. After three weeks of healing, histology and microcomputed tomography (μCT) were performed. Histological analysis confirmed the osteoconductive properties, with new bone growing inside the intact collagen membrane. However, in minced collagen membranes, the osteoconductive properties were restricted to the defect margins. Interestingly, histology revealed large mineralized areas indicating passive mineralization with no signs of bone formation. In the μCT analysis, the intact collagen membranes caused a higher median mineralized volume (1.5 mm 3 ) compared with the minced group (0.4 mm 3 ), but this lacked significance ( p = 0.09). The μCT analysis needs to be interpreted carefully, particularly in defects filled with minced membranes, considering that the mineralized tissue may not necessarily be bone but also the result of passive mineralization. Taken together, the findings suggest that Bio-Gide ® collagen membranes support bone formation while also exhibiting potential for passive mineralization.

Objectives: Autologous bone is considered the gold standard for grafting, yet it suffers from a tendency to undergo resorption over time. While the exact mechanisms of this resorption remain elusive, osteocytes have been shown to play an important role in stimulating osteoclastic activity through their expression of receptor activator of NF-κB (RANK) ligand (RANKL). The aim of this study was to assess the function of osteocyte-derived RANKL in bone graft remodeling., Materials and Methods: In Tnfsf11 fl/fl ;Dmp1-Cre mice without osteocyte-specific RANKL as well as in Dmp1-Cre control mice, 2.6 mm calvarial bone disks were harvested and transplanted into mice with matching genetic backgrounds either subcutaneously or subperiosteally, creating 4 groups in total. Histology and micro-computed tomography of the grafts and the donor regions were performed 28 days after grafting., Results: Histology revealed marked resorption of subcutaneous control Dmp1-Cre grafts and new bone formation around subperiosteal Dmp1-Cre grafts. In contrast, Tnfsf11 fl/fl ;Dmp1-Cre grafts showed effectively neither signs of bone resorption nor formation. Quantitative micro-computed tomography revealed a significant difference in residual graft area between subcutaneous and subperiosteal Dmp1-Cre grafts (p < .01). This difference was not observed between subcutaneous and subperiosteal Tnfsf11 fl/fl ;Dmp1-Cre grafts (p = .17). Residual graft volume (p = .08) and thickness (p = .13) did not differ significantly among the groups. Donor area regeneration was comparable between Tnfsf11 fl/fl ;Dmp1-Cre and Dmp1-Cre mice and restricted to the defect margins., Conclusions: The results suggest an active function of osteocyte-derived RANKL in bone graft remodeling., (© 2023 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Aim: Fas ligand (FasL) belongs to the tumour necrosis factor superfamily regulating bone turnover, inflammation, and apoptosis. The appendicular and axial skeleton phenotype of mature Fasl gld mice has been reported. The impact of FasL on the alveolar bone providing support for the teeth at mature stages under healthy and induced inflammatory conditions remains unknown., Materials and Methods: We performed a phenotypical analysis of mice carrying the homozygous Fasl gld mutation and wild-type (WT) mice (C57BL/6) under healthy conditions and upon ligature-induced periodontitis. After 12 days, micro-computed tomography analysis revealed the distance between the cement enamel junction and the alveolar bone crest. Additional structural parameters, such as the bone volume fraction (BV/TV) and the periodontal ligament space volume, were measured. Histological analyses were performed to visualize the catabolic changes at the defect site., Results: Healthy Fasl gld mice were found to have more periodontal bone than their WT littermates. Fasl gld had no significant effect on inflammatory osteolysis compared to WT controls with ligatures. Histology revealed eroded surfaces at the root and in the inter-proximal bone in both strains., Conclusions: Our findings suggest that FasL is a catabolic factor in alveolar bone homeostasis but it does not affect the inflammatory osteolysis., (© 2022 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

The cross-linking of structural proteins is critical for establishing the mechanical stability of the epithelial compartments of the skin and skin appendages. The introduction of isopeptide bonds between glutamine and lysine residues depends on catalysis by transglutaminases and represents the main protein cross-linking mechanism besides the formation of disulfide bonds. Here, we used a fluorescent labeling protocol to localize the activity of transglutaminases on thin sections of the integument and its appendages in mammals and birds. In human tissues, transglutaminase activity was detected in the granular layer of the epidermis, suprabasal layers of the gingival epithelium, the duct of sweat glands, hair follicles and the nail matrix. In the skin appendages of chickens, transglutaminase activity was present in the claw matrix, the feather follicle sheath, the feather sheath and in differentiating keratinocytes of feather barb ridges. During chicken embryogenesis, active transglutaminase was found in the cornifying epidermis, the periderm and the subperiderm. Transglutaminase activity was also detected in the filiform papillae on the tongue of mice and in conical papillae on the tongue of chickens. In summary, our study reveals that transglutaminase activities are widely distributed in integumentary structures and suggests that transglutamination contributes to the cornification of hard skin appendages such as nails and feathers.

The detection and classification of cystic lesions of the jaw is of high clinical relevance and represents a topic of interest in medical artificial intelligence research. The human clinical diagnostic reasoning process uses contextual information, including the spatial relation of the detected lesion to other anatomical structures, to establish a preliminary classification. Here, we aimed to emulate clinical diagnostic reasoning step by step by using a combined object detection and image segmentation approach on panoramic radiographs (OPGs). We used a multicenter training dataset of 855 OPGs (all positives) and an evaluation set of 384 OPGs (240 negatives). We further compared our models to an international human control group of ten dental professionals from seven countries. The object detection model achieved an average precision of 0.42 (intersection over union (IoU): 0.50, maximal detections: 100) and an average recall of 0.394 (IoU: 0.50-0.95, maximal detections: 100). The classification model achieved a sensitivity of 0.84 for odontogenic cysts and 0.56 for non-odontogenic cysts as well as a specificity of 0.59 for odontogenic cysts and 0.84 for non-odontogenic cysts (IoU: 0.30). The human control group achieved a sensitivity of 0.70 for odontogenic cysts, 0.44 for non-odontogenic cysts, and 0.56 for OPGs without cysts as well as a specificity of 0.62 for odontogenic cysts, 0.95 for non-odontogenic cysts, and 0.76 for OPGs without cysts. Taken together, our results show that a combined object detection and image segmentation approach is feasible in emulating the human clinical diagnostic reasoning process in classifying cystic lesions of the jaw.

Objectives: Buccal bone augmentation in the esthetic zone is routinely used to achieve optimal clinical outcomes. Nonetheless, long-term data are sparse, and it is unknown how baseline buccal bone volume affects the retention of the augmented volume over time., Material and Methods: This is a long-term follow-up retrospective case series. After a preoperative computed tomography scan, implants were placed in the anterior maxilla following guided bone regeneration, autogenous block grafting, or both. At the follow-up, patients received a computed tomography scan and a clinical examination. Buccal bone volume was the primary outcome. Buccal bone thickness, peri-implant, and esthetic parameters were secondary outcomes., Results: After a median follow-up of 6.7 years (interquartile range: 4.9-9.4), 28 implants in 19 patients (median age at augmentation: 43.3 years, interquartile range: 34.4-56.7, 53% female) were followed up. Preoperative buccal bone volume at baseline (V 0 ) showed a moderate correlation to final buccal bone volume (V t , r s  = .43) but a strong correlation to the absolute volumetric change (ΔV = V t -V 0 , r s  = -.80). A linear mixed model for V t had a large intercept of 91.39 (p < .001) and a rather small slope of .11 for V 0 (p = .11). Observed differences between treatments were not statistically significant in the mixed model. V 0 above 105 mm 3 predicted a negative volume change (ΔV < 0) with a specificity of 100% and a sensitivity of 96%., Conclusions: The results suggest higher gains in sites with lower V 0 and point to a cutoff V 0 above which the augmented volume is not retained long-term., (© 2022 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

During the coronavirus disease 2019 (COVID-19) pandemic, aerosol-generating procedures, including dental implant treatments, are considered high-risk. With dental implant treatment mostly an elective procedure, we aimed to assess whether the pandemic influenced patient selection, surgical procedures, and postoperative complications. We compared dental implant treatments during (March to December 2020) and before (December 2018 to February 2020) the COVID-19 pandemic based on patient and implant parameters, as well as postoperative complications. For analysis, we used the Chi-squared test with the Holm-Sidak correction for multiple comparisons. The number of implants placed during the COVID-19 pandemic (696 implants in 406 patients, 70 implants per month) was comparable to pre-pandemic levels (1204 implants in 616 patients, 80 implants per month). Regarding patient parameters, there were no significant differences in respiratory ( p = 0.69) and cardiovascular conditions ( p = 0.06), diabetes ( p = 0.69), and smoking ( p = 0.68). Regarding implant parameters, there was a significant difference in the distribution of augmentative procedures (no augmentation, guided bone regeneration, and sinus floor elevation, p = 0.01), but no significant differences in the types of edentulous spaces ( p = 0.19) and the timing of implant placement ( p = 0.52). Regarding complications, there were significantly fewer minor complications ( p < 0.001) and early (i.e., before loading) implant failures ( p = 0.02) compared with pre-pandemic levels. Our results suggest that the COVID-19 pandemic had no effect on patient selection and only a slight effect on the surgical procedures. However, postoperative complications, including early failures, were significantly less prevalent during the pandemic.

Objectives: The extraction of impacted mandibular third molars is a common surgical procedure often associated with complications including post-traumatic neuropathy. Previous work has focused on identifying confounding factors, but a robust preoperative risk prediction model remains elusive., Methods: Using a dataset of 648 patients and 812 impacted mandibular third molars, we used least absolute shrinkage and selection operator (LASSO) to fit prediction models based on risk factors assessed at both the tooth and patient levels. In addition, we fitted multivariable logistic regression models with the Firth correction for generalized estimating equations (GEE)., Results: The LASSO model for post-traumatic neuropathy identified distoangular impaction of ≥ 45° (odds ratio [OR] = 2.9), proximity to the inferior alveolar nerve of ≤ 3 mm (OR = 1.9), disadvantageous curving (OR = 1.4), and psychiatric conditions (OR = 2.1) as predictors [area under the receiving operator characteristic curve (AUC) = 0.75]. Among other complications analyzed, the LASSO model for bleeding identified deep embedding or full impaction (OR = 1.8), psychiatric conditions (OR = 1.3), and age (OR = 0.9) as predictors (AUC = 0.64). These associations between predictors and postoperative complications were fundamentally reinforced by the corresponding GEE models., Conclusions: Our findings point to the predictability of post-traumatic neuropathy and bleeding based on tooth anatomy and patient characteristics, overall suggesting that preoperatively identifiable factors can predict the risk of adverse outcomes in the extraction of impacted mandibular third molars., Clinical Significance: Mandibular third molar extraction is both a routine procedure and a leading cause of trigeminal neuropathy. Prevention of post-traumatic neuropathy, aided by individualized preoperative risk prediction, is of high clinical relevance., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: With only limited information available on dimensional changes after jaw cyst surgery, postoperative cyst shrinkage remains largely unpredictable. We aimed to propose a model for volumetric shrinkage based on time elapsed since cyst surgery., Material and Methods: We used data from patients that underwent cyst enucleation or decompression between 2007 and 2017 and had at least three computed tomography (CT) scans per patient. We fitted one simple exponential decay model [V(t) = V 0 · e -ɑt ] and one model with a patient-specific decay rate [V k (t) = V 0 · e -βt + γkt ]., Results: Based on 108 CT scans from 36 patients (median age at surgery: 45.5 years, IQR: 32.3-55.3, 44% female), our simple exponential decay model is V(t) = V 0 · e -0.0035t where V(t) is the residual cyst volume after time t elapsed since surgery, V 0 is the initial cyst volume, and e is the base of the natural logarithm. Considering a patient-specific decay rate, the model is V k (t) = V 0 · e -0.0049t + γkt where γ k is normally distributed, with expectation 0 and standard deviation 0.0041., Conclusions: Using an exponential regression model, we were able to reliably estimate volumetric shrinkage after jaw cyst surgery. The patient-specific decay rate substantially improved the fit of the model, whereas adding specific covariates as interaction effects to model the decay rate did not provide any significant improvement., Clinical Relevance: Estimating postoperative cyst shrinkage is relevant for both treatment planning of jaw cyst surgery as well as evaluating the clinical success of the surgical approach., (© 2021. The Author(s).)

Objectives: Resonance frequency analysis (RFA) is used to monitor implant stability. Its output, the Implant Stability Quotient (ISQ), supposedly correlates with insertion torque, a common measurement of primary stability. However, the reliability of RFA in condensed bone remains unclear., Material and Methods: In this human cadaver study in edentulous jaws and fresh extraction sockets, implants were inserted using a split-mouth approach into condensed or untreated bone. Mean ISQ, peak insertion torque, and pre- and postoperative bone volume fractions (BV/TV) were assessed., Results: In edentulous jaws, insertion torque and ISQ correlated both in untreated (r = 0.63, p = 0.02) and in condensed (r = 0.82, p  < 0.01) bone. In extraction sockets, insertion torque and ISQ only correlated in untreated (r = 0.78, p < 0.01), but not in condensed bone (r = 0.15, p = 0.58). In all edentulous jaws, preoperative BV/TV correlated with insertion torque (r = 0.90, p < 0.0001), ISQ (r = 0.64, p < 0.001), and changes in BV/TV (r = -0.71, p < 0.01). In all extraction sockets, preoperative BV/TV did not correlate with either insertion torque (r = 0.33, p = 0.15), ISQ (r = 0.38, p = 0.09), or changes in BV/TV (r = -0.41, p = 0.09). Joint analysis identified preoperative BV/TV as a predictor of postoperative BV/TV (p < 0.001), insertion torque (p < 0.001), and ISQ (p < 0.001)., Conclusions: RFA is feasible for monitoring stability after late implant placement into condensed bone, but not after immediate placement into condensed fresh extraction sites., (© 2021 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Objectives: Chronic liver disease increases the risk for periodontal disease and osteoporotic fractures, but its impacts on bone regeneration remain unknown. Herein, we studied the impact of liver cirrhosis on peri-implant bone formation., Material and Methods: A total of 20 male Wistar rats were randomly divided into two groups: one with the common bile duct ligated (BDL) and the respective sham-treated control group (SHAM). After four weeks of disease induction, titanium mini-screws were inserted into the tibia. Successful induction of liver cirrhosis was confirmed by the presence of clinical symptoms. Another four weeks later, peri-implant bone volume per tissue volume (BV/TV) and bone-to-implant contact (BIC) were determined by histomorphometric analysis., Results: Peri-implant bone formation was not significantly different between the SHAM and BDL groups. In the cortical compartment, the median percentage of peri-implant new bone was 10.1% (95% CI of mean 4.0-35.7) and 22.5% (13.8-30.6) in the SHAM and BDL groups, respectively (p = .26). Consistently, the new bone in direct contact with the implant was 18.1% (0.4-37.8) and 23.3% (9.2-32.8) in SHAM and BDL groups, respectively (p = .38). When measuring the medullary compartment, the new bone area was 7.1% (4.8-10.4) and 10.4% (7.2-13.5) in the SHAM and BDL groups, respectively (p = .17). Medullary new bone in direct contact with the implant was 10.0% (1.2-50.4) and 20.6% (16.8-35.3) in SHAM and BDL groups, respectively, and thus comparable between the two groups (p = .46)., Conclusions: Bile duct ligation has no significant impact on the early stages of peri-implant bone formation., (© 2021 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Volume-stable collagen matrices (VSCM) are conductive for the connective tissue upon soft tissue augmentation. Considering that collagen has osteoconductive properties, we have investigated the possibility that the VSCM also consolidates with the newly formed bone. To this end, we covered nine rat calvaria circular defects with a VSCM. After four weeks, histology, histomorphometry, quantitative backscattered electron imaging, and microcomputed tomography were performed. We report that the overall pattern of mineralization inside the VSCM was heterogeneous. Histology revealed, apart from the characteristic woven bone formation, areas of round-shaped hypertrophic chondrocyte-like cells surrounded by a mineralized extracellular matrix. Quantitative backscattered electron imaging confirmed the heterogenous mineralization occurring within the VSCM. Histomorphometry found new bone to be 0.7 mm 2 (0.01 min; 2.4 max), similar to the chondrogenic mineralized extracellular matrix with 0.7 mm 2 (0.0 min; 4.2 max). Microcomputed tomography showed the overall mineralized tissue in the defect to be 1.6 mm 3 (min 0.0; max 13.3). These findings suggest that in a rat cranial defect, VSCM has a limited and heterogeneous capacity to support intramembranous bone formation but may allow the formation of bone via the endochondral route.

Background: Bilayer collagen membranes are routinely used in guided bone/tissue regeneration to serve as osteoconductive scaffolds and prevent the invasion of soft tissues. It is recommended to place the membranes with their dense layer towards the soft tissue and their porous layer towards the bony defect area. However, evidence supporting this recommendation is lacking. This study aimed to determine whether the alignment of bilayer collagen membranes has an effect on bone regeneration., Methods: In two groups of ten male Sprague-Dawley rats each, a 5-mm calvarial defect was created. Thereafter, the defect was randomly covered with a bilayer, resorbable, pure type I and III collagen membrane placed either regularly or upside-down (i.e., dense layer towards bone defect). After 4 weeks of healing, micro-computed tomography (μCT), histology, and histomorphometry of the inner cylindrical region of interest (4.5 mm in diameter) were performed to assess new bone formation and the consolidation of the collagen membrane in the defect area., Results: Quantitative μCT showed similar bone volume (median 8.0 mm 3 , interquartile range 7.0-10.0 vs. 6.2 mm 3 , 4.3-9.4, p = 0.06) and trabecular thickness (0.21 mm, 0.19-0.23 vs. 0.18 mm, 0.17-0.20, p = 0.03) between upside-down and regular placement, both leading to an almost complete bony coverage. Histomorphometry showed comparable new bone areas between the upside-down and regularly placed membranes, 3.9 mm 2 (2.7-5.4) vs. 3.8 mm 2 (2.2-4.0, p = 0.31), respectively. Both treatment groups revealed the same regeneration patterns and spatial distribution of bone with and without collagen fibers, as well as residual collagen fibers., Conclusions: Our data support the osteoconductive properties of collagen membranes and suggest that bone regeneration is facilitated regardless of membrane layer alignment.

Purpose: This study was conducted to determine how the distance of the near insertion points in a vertical mattress suture from the wound margin influences the pattern of primary closure in an in vitro experimental model., Methods: Pairs of 180 porcine gingival and alveolar mucosa samples were harvested from 90 pig jaws and fixed to a specially designed model. A vertical mattress suture was performed with the near insertion point at 3 different distances from the wound margin (1-, 3-, and 5-mm) on both the gingival and mucosal samples (6 groups; n=30 for each group). The margin discrepancy and the presence of epithelium between the wound margins were measured on histologic slides., Results: The margin discrepancy decreased significantly as the near insertion point became closer to the wound margin both in mucosal tissue (0.241±0.169 mm, 0.945±0.497 mm, and 1.306±0.773 mm for the 1-, 3-, and 5-mm groups, respectively) and in gingival tissue (0.373±0.304 mm, 0.698±0.431 mm, and 0.713±0.691 mm, respectively). The frequency of complications of wound margin adaptation reduced as the distance of the near insertion point from the wound margin decreased both in the mucosal and gingival tissues., Conclusions: Placing the near insertion point close to the wound margin enhances the precision of wound margin approximation/adaptation using a vertical mattress suture., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2021. Korean Academy of Periodontology.)

Acid bone lysates (ABLs) represent the growth factors and other molecules released during autologous graft resorption. However, the impact of these bone-derived growth factors on the healing of bone defects has not yet been investigated. The aim of the present study was, therefore, to examine the impact of ABLs adsorbed to collagen membranes on bone regeneration. To this end, in 16 female Sprague Dawley rats, a standardized 5-mm-diameter critical size defect on the calvarial bone was created. The defects were covered with collagen membranes that had been soaked either in serum-free media or ABLs followed by lyophilization. After a healing period of 4 weeks, micro-computed tomography (μCT) and histological analyses by means of undecalcified thin ground sections were performed. μCT analysis of the inner 4 mm of the calvaria defect showed a greater bone defect coverage in the control group when compared to ABL group, 29.8% (confidence interval [CI]: 17.7-50.3) versus 5.6% (CI: 1.0-29.8, p = .03), respectively. Moreover, we found significantly more absolute bone volume (BV) in the control group when compared to ABL group, 0.59 mm 3 (CI: 0.27-1.25) versus 0.07 mm 3 (CI: 0.06-0.59, p = .04), respectively. Histomorphometry confirmed these findings with a relative BV in the central compartment of 14.1% (CI: 8.4-20.6) versus 5.6% (CI: 3.4-7.9, p = .004), respectively. These findings indicate that bone-derived growth factors contained in ABLs are able to attenuate bone regeneration within collagen membranes., (© 2020 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Autogenous tooth roots are increasingly applied as a grafting material in alveolar bone augmentation. Since tooth roots undergo creeping substitution similar to bone grafts, it can be hypothesized that osteoclasts release the growth factors stored in the dentin thereby influencing bone formation. To test this hypothesis, collagen membranes were either soaked in acid dentin lysates (ADL) from extracted porcine teeth or serum-free medium followed by lyophilization. Thereafter, these membranes covered standardized 5-mm-diameter critical-size defects in calvarial bone on rats. After four weeks of healing, micro-computed tomography and histological analyses using undecalcified thin ground sections were performed. Micro-computed tomography of the inner 4.5 mm calvaria defects revealed a median bone defect coverage of 91% (CI: 87-95) in the ADL group and 94% (CI: 65-100) in the control group, without significant differences between the groups (intergroup p > 0.05). Furthermore, bone volume (BV) was similar between ADL group (5.7 mm 3 , CI: 3.4-7.1) and control group (5.7 mm 3 , CI: 2.9-9.7). Histomorphometry of the defect area confirmed these findings with bone area values amounting to 2.1 mm 2 (CI: 1.2-2.6) in the ADL group and 2.0 mm 2 (CI: 1.1-3.0) in the control group. Together, these data suggest that acid dentin lysate lyophilized onto collagen membranes failed to modulate the robust bone formation when placed onto calvarial defects.

Objectives: Completion of adolescent growth represents the earliest time point for implant placement, yet craniofacial growth persists into adulthood and may affect implant position. We aimed to assess whether implants placed in the anterior maxillae of adults show angular changes over time., Material and Methods: We conducted a cephalometric pilot study in postpubertal patients with no growth disorders, skeletal malformations, or parafunctions. The patients received a single implant in the anterior maxilla and no orthodontic or orthognathic treatment afterwards. We measured angular changes of implants and central incisors on cephalograms taken immediately and after at least 5 years postoperatively with the Sella-Nasion line (SNL) and the nasal line (NL) as references. Changes in implant-SNL angles were the primary outcome., Results: In 21 patients (30.2 ± 11.5 years at surgery) after a mean follow-up of 8.6 ± 1.3 years, implant-SNL angles and implant-NL angles changed in 81% and 57% of implants, respectively. Implant-SNL changes ranged from 3° counterclockwise to 4° clockwise and were more prevalent in males (100% vs. 58%) and patients under 30 at surgery (85% vs. 63%); mean absolute differences were larger in males (1.8 ± 1.0° vs. 1.3 ± 1.4°) and patients under 30 at surgery (1.5 ± 1.4° vs. 1.1 ± 1.4°). Incisor-SNL angles and incisor-NL angles changed in 89% and 32% of incisors, respectively., Conclusions: Implants placed in the anterior maxillae of adults show modest angular changes over time., Clinical Relevance: Changes in implant angles have potential functional and esthetic consequences.

Deproteinized bovine bone mineral (DBBM) is brittle and can break into fragments. Here, we examined whether DBBM fragments have an impact on mice calvarial bone during bone augmentation. DBBM was either randomly crushed (DBBM fragments) or left undisturbed (DBBM granules). Then, DBBM fragments or original DBBM granules were placed onto calvarial bone in 20 BALB/c mice. Following random allocation, ten mice received DBBM fragments and ten mice received original DBBM granules. After fourteen days of healing, micro computed tomography (micro-CT) and histological analysis of the augmented sites were performed. The primary outcome was the porosity of the calvarial bone. The micro-CT analysis revealed that DBBM fragments failed to significantly change the porosity of the calvarial bone as compared with original DBBM granules, despite the slightly higher bone resorption in the DBBM fragment group, 10.3% (CI 6.3-11.6) versus 6.1% (CI 4.1-7.8, p = 0.355), respectively. The cortical bone volume was not altered by DBBM fragments as compared with original DBBM granules, i.e., 79.0% (CI 78.9-81.2) versus 81.5% (CI 80.1-83.3, p = 0.357), respectively. The DBBM fragment group revealed similar bone thickness values as compared with the DBBM granules group, i.e., 0.26 mm (CI 0.23-0.29) versus 0.25 mm (CI 0.22-0.27, p = 0.641), respectively. The histological evaluation supported the micro-CT observations, displaying minor signs of porosity and resorption. The particle-size distribution analysis confirmed a shift towards smaller particle sizes in the DBBM fragment group. These findings suggest that DBBM fragments behave similarly to original DBBM granules in terms of bone morphological changes at augmented sites.

Objectives: Risk prediction in implant dentistry presents specific challenges including the dependence of observations from patients with multiple implants and rare outcome events. The aim of this study was to use advanced statistical methods based on penalized regression to assess risk factors in implant dentistry., Material and Methods: We conducted a retrospective study from January 2016 to November 2018 recording postoperative complications including bleeding, hematoma, local infection, and nerve damage, as well as early implant failure. We further assessed patient- and implant-related risk factors including smoking and diabetes, as well as treatment parameters including types of gaps and surgical procedures. Univariable and multivariable generalized estimating equation (GEE) models were estimated to assess predictor effects, and a prediction model was fitted using L1 penalized estimation (lasso)., Results: In a total of 1,132 patients (mean age: 50.6 ± 16.5 years, 55.4% female) and 2,413 implants, postoperative complications occurred in 71 patients. Sixteen implants were lost prior to loading. Multivariable GEE models showed a higher risk of any complication for diabetes mellitus (p = .006) and bone augmentation (p = .039). The models further revealed a higher risk of local infection for bone augmentation (p = .003), and a higher risk of hematoma formation for diabetes mellitus (p = .007) and edentulous jaws (p = .024). The lasso model did not select any risk factors into the prediction model., Conclusions: Using novel methodology well-suited to tackle the specific challenges of risk prediction in implant dentistry, we were able to reliably estimate associations of risk factors with outcomes., (© 2020 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation.

Objectives: Deproteinized bovine bone mineral (DBBM) is not resorbable. However, the behavior of DBBM under inflammatory conditions remains unclear. Aim of the study was therefore to evaluate the resorption of DBBM under local inflammatory conditions in vivo using the calvarial osteolysis model., Methods: In thirty adult BALB/c mice, DBBM was implanted into the space between the elevated soft tissue and the calvarial bone. Inflammation was induced either by lipopolysaccharides (LPS) injection or by polyethylene particles (Ceridust) mixed with DBBM. Three modalities were randomly applied (n = 10 each): (a) DBBM alone (control), (b) DBBM + LPS, and (c) DBBM + polyethylene particles (Ceridust). Mice were euthanized on day fourteen, and each calvarium was subjected to histological and µCT analysis. Primary outcome was the size distribution of the DBBM particles. Secondary outcome was the surface erosion of the calvarial bone., Results: Histological and µCT analysis revealed that the size distribution and the volume of DBBM particles in the augmented site were similar between DBBM alone and the combinations with LPS or polyethylene particles. Moreover, histological evaluation showed no signs of erosions of DBBM particles under inflammatory conditions. µCT analysis and histology further revealed that LPS and the polyethylene particles, but not the DBBM alone, caused severe erosions of the calvarial bone as indicated by large voids representing the massive compensatory new immature woven bone formation on the endosteal surface., Conclusions: Local calvarial bone but not the DBBM particles undergo severe resorption and subsequent new bone formation under inflammatory conditions in a mouse model., (© 2019 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Objectives: To assess, retrospectively, whether older age has an impact on implant osseointegration when compared with younger age., Methods: All patients ≥65 years old at implant installation, in an university setting over a time-period of 11.5 years, with complete anamnestic data and follow-up until prosthetic restoration were included, and any early implant loss (EIL; i.e. lack of osseointegration prior to or at the time-point of prosthetic restoration) was recorded. Further, one implant, from each of the elderly patients, was attempted matched to one implant in a younger patient (35 to <55 years old at implant installation) from the same clinic based on (a) gender, (b) implant region, (c) smoking status and (d) bone grafting prior to/simultaneously with implant installation. The potential impact of various local and systemic factors on EIL in the entire elderly population, and in the matched elderly and younger patient group was statistically assessed., Results: Four hundred forty-four patients ≥65 years old (range 65.1-91.3; 56.8% female) receiving 1,517 implants were identified; 10 patients had one EIL each (implant/patient level: 0.66/2.25%). Splitting this patient cohort additionally into four age groups [65-69.9 (n = 213), 70-74.9 (n = 111), 75-79.9 (n = 80) and ≥80 (n = 40)], EIL was on the implant level 0.41, 0.83, 0.34 and 2.26%, respectively, (p = .102) and on the patient level 1.41, 2.70, 1.25 and 7.50%, respectively, (p = .104); multilevel analysis showed weak evidence of association of increasing age with higher EIL rate (p = .090). Matching was possible in 347 cases, and 5 (1.44%) and 9 (2.59%) EIL in the elderly and younger patients, respectively, were observed (p = .280). EIL could not be associated with any systemic condition or medication intake., Conclusions: Elderly patients ≥65 years old presented a similarly low EIL rate as younger patients 35 to <55 years old, while patients ≥80 years old may have a slight tendency for a higher EIL rate. Hence, ageing does not seem to compromise osseointegration, and if at all, then only slightly and at a later stage of life., (© 2019 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Cornifelin (CNFN) has been identified as a protein component of epidermal corneocytes. Here, we investigated the tissue distribution of CNFN and potential consequences of CNFN deficiency on epithelial function in in vitro models of human skin and oral mucosa. Our detailed bioinformatics and immunostaining analysis revealed that CNFN is not only expressed in human epidermis but also in noncornifying oral mucosa. In normal epidermis, CNFN was confined to the upper granular layer and the stratum corneum. By contrast, in both partly cornifying and noncornifying oral mucosa, CNFN was expressed in a cell membrane-associated pattern over several suprabasal layers. Small interfering RNA-mediated knockdown of CNFN in epidermal keratinocytes (KCs) was associated with only subtle alterations of the overall epidermal architecture in skin models in vitro but led to altered morphology of corneodesmosomes, as detected by electron microscopy. Using dispase treatment followed by mechanical stress, epithelial sheets of CNFN-deficient epidermal KCs were easily disrupted, whereas their CNFN-competent counterparts remained intact. In contrast to the epidermal KCs, CNFN knockdown in oral KCs had a more severe effect and caused pronounced acantholysis in organotypic models of oral mucosa. Together, these findings indicate that CNFN is a structural component of the cell adhesion system of differentiated KCs in both epidermis and oral mucosa., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Collagen membranes are not limited to be occlusive barriers as they actively support bone regeneration. However, the impact of bone-derived growth factors on their osteoconductive competence has not been examined., Methods: Twenty adult Sprague Dawley rats were included in the study. Calvaria defects with a diameter of five millimeter were created. The defect was covered with one layer of a collagen membrane previously soaked in conditioned medium of porcine bone chips or in culture medium alone. After 4 weeks, microcomputed tomography was performed. Undecalcified thin-ground sections were subjected to light and scanning electron microscopy. Primary outcome parameter was the bone volume in the defect. Unit of analysis was the bone-conditioned medium (BCM)., Results: In the central defect area of the control and the BCM group, median new bone connected to the host bone was 0.54 and 0.32 mm³, respectively (p = .10). In the ectocranial defect area, the control group showed significantly more bone than the BCM group (0.90 and 0.26 mm³; p = .02). Based on an exploratory interpretation, the control group had smaller bony islands than the BCM group. Scanning electron microscopy and histology indicate the formation of bone but also the collagen membrane to be mineralized in the defect site., Conclusions: These results demonstrate that the commercial collagen membrane holds an osteoconductive competence in a rat calvaria defect model. Soaking collagen membranes with BCM shifts bone formation toward the formation of bony islands rather than new bone connected to the host bone., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Recombinant human bone morphogenetic protein 2 (rhBMP-2) together with an absorbable collagen carrier (ACS) was approved for augmentation of the maxillary sinus prior to implant placement. The original registration trial was based on a lateral window approach. Clinical outcomes of crestal sinus augmentation with rhBMP-2 have not been reported so far., Materials and Methods: An uncontrolled pilot trial in which seven patients with a residual maxillary height below 5 mm were enrolled to receive crestal sinus augmentation with rhBMP-2/ACS was conducted. Elevation of the sinus mucosa was performed by gel pressure. Primary endpoints were the gain in augmentation height and volume measured by computed tomography after 6 months. Evaluation of bone quality at the time of implant placement was based on histology. Secondary endpoints were the clinical and radiologic evaluation of the implants and patient satisfaction by visual analog scale (VAS) at the 2-year follow-up., Results: Median gain in augmentation height was 7.2 mm (range 0.0 to 17.5 mm). Five patients gained at least 5 mm of bone height. Two patients with a perforation of the sinus mucosa failed to respond to rhBMP-2/ACS and underwent lateral window augmentation. The median gain in augmentation volume of the five patients was 781.3 mm³ (range 426.9 to 1,242.8 mm³). Biopsy specimens showed a cancellous network consisting of primary plexiform bone with little secondary lamellar bone. After 2 years, implants were in function with no signs of inflammation or peri-implant bone loss. Patients were satisfied with the esthetic outcomes and chewing function., Conclusion: This pilot clinical trial supports the original concept that rhBMP-2/ACS supports bone formation, also in crestal sinus augmentation, and emphasizes the relevance of the integrity of the sinus mucosa to predict the bone gain.

Objectives: In patients with implant placement and simultaneous sinus floor elevation (SFE), healing periods of 6 months have been the standard of care for more than 25 years. The primary objective of this prospective case series study was to determine what percentage of implants placed with SFE reach a threshold Implant Stability Quotient (ISQ) of ≥70 after 8 weeks of healing using Resonance Frequency Analysis (RFA)., Material and Methods: A total of 109 dental implants were placed in 97 patients. SFE was carried out with a lateral window approach and a mixture of autogenous bone chips and deproteinized bovine bone mineral (DBBM). Titanium screw-type, tissue-level implants with a chemically modified SLA surface were used. ISQ values were measured after implant insertion (ISQ BL ) and after 8 weeks of healing (ISQ 8 wk ). Patients showing ISQ 8 wk  ≥ 70 subsequently underwent restoration. Implants with an ISQ value < 70 were recalled at 2-week intervals., Results: The ISQ at baseline had a mean value of 68.3 (SD ± 9.8). At 8 weeks, the mean ISQ value was 73.6 (SD ± 6.4). This increase was statistically significant (P < 0.001). An ISQ 8 wk value ≥70 was observed for 91 implants (83%). One implant (0.9%) with a peri-implant infection and severe bone loss at 8 weeks was considered an early failure., Conclusions: This study showed that 83% of implants reached the threshold level of ISQ ≥ 70 after 8 weeks, allowing an early loading protocol. The early failure rate was considered low with 0.9%. The RFA technology is a suitable method to objectively monitor implant stability longitudinally., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Current strategies to reduce medical device-associated infections propose zirconia as a potential implant material which may limit bacterial adhesion. Because multinucleated giant cells (MNGCs) have been detected on these implant surfaces, concerns have been raised regarding tissue integration., Purpose: The present study examined the presence of MNGCs and their subsequent effect upon tissue integration. Surface-modified implants made of yttria-stabilized (TZP) and alumina-toughened zirconia (ATZ) were compared with commercially pure titanium (Ti)., Materials and Methods: Seven miniature pigs received three implants on either side of the maxilla. After healing periods of 4 and 8 weeks, the tissue response at the implant surfaces was characterized according to three specific parameters: bone-to-implant contact (BIC), MNGC-to-implant contact (MIC), and the peri-implant bone density (BD)., Results: Despite being present on all tested implant surfaces, MNGCs were not associated with an inflammatory cell infiltrate or with fibrous encapsulation. MNGCs were less numerous on the Ti implants (range: 3.9-5.2%) compared with the ceramic implants (range: 17.6-30.3%, p < .0001). Even though the values of newly formed bone and pristine bone in direct contact with the implant surfaces were high at 4 weeks (tBIC: Ti = 82.3%, TZP = 64.3%, ATZ = 70%), a negative correlation was observed between the presence of MNGCs and newly formed bone at the implant surface (p < .001). Interestingly, the newly formed peri-implant bone density, defined as the percentage of new bone area inside the screw threads (nBD), was not diminished by the presence of MNGCs., Conclusions: Differences in the presence of MNGCs and the BIC parameters between Ti and the ceramic implants appear to be a local cellular phenomenon which is restricted to the implant-bone marrow interface and do not affect the peri-implant bone formation. Factors triggering MNGC differentiation and their persistence in response to biomaterial surface need to be investigated in future studies., (© 2015 Wiley Periodicals, Inc.)

Aim: To associate the dimension of the facial bone wall with clinical, radiological, and patient-centered outcomes at least 10 years after immediate implant placement with simultaneous guided bone regeneration in a retrospective study., Material and Methods: Primary endpoint was the distance from the implant shoulder (IS) to the first bone-to-implant contact (IS-BIC10y ). Secondary endpoints included the facial bone thickness (BT10y ) 2, 4, and 6 mm apical to the IS, and the implant position. At baseline, the horizontal defect width (HDWBL ) from the implant surface to the alveolar wall was recorded. At recall, distance from the IS to the mucosal margin (IS-MM10y ), degree of soft tissue coverage of the mesial and distal aspects of the implants (PISm10y , PISd10y ; Papilla Index), pocket probing depth (PPD10y ), and patient-centered outcomes were determined. Width of the keratinized mucosa (KM), Full-Mouth Plaque and Bleeding Score (FMPS, FMBS) were available for both time points., Results: Of the 20 patients who underwent immediate implant placement with simultaneous guided bone regeneration and transmucosal healing, nine males and eight females with a median age of 62 years (42 min, 84 max) were followed up for a median period of 10.5 y (min 10.1 max 11.5). The 10-year implant survival rate was 100%. Multivariate regression analysis revealed a correlation of the IS-BIC10y , controlled for age and gender, with four parameters: HDWBL (P = 0.03), KMBL -10 (P = 0.02), BT10 4 mm (P = 0.01), and BT10 6 mm (P = 0.01)., Conclusion: Within the conditions of the present study, the horizontal defect width was the main indicator for the vertical dimension of the facial bone. The facial bone dimension was further associated with a reduction in the width of the keratinized mucosa and the dimension of the buccal bone., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Signaling molecules derived from osteocytes have been proposed as a mechanism by which autografts contribute to bone regeneration. However, there have been no studies that determined the role of osteocytes in bone grafts., Material and Method: Herein, it was examined whether bone chips and demineralized bone matrix release sclerostin and FGF-23, both of which are highly expressed by osteocytes., Results: Bone grafts from seven donors were placed in culture medium. Immunoassay showed that bone chips released sclerostin (median 1.0 ng/ml) and FGF-23 (median 9.8 relative units/ml) within the first day, with declining levels overtime. Demineralized bone matrix also released detectable amounts of sclerostin into culture medium, while FGF-23 remained close to the detection limit. In vitro expanded isolated bone cells failed to release detectable amounts of sclerostin and FGF-23., Conclusion: These results suggest that autografts but also demineralized bone matrix can release signaling molecules that are characteristically produced by osteocytes., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To analyze the indications and frequency for three-dimensional (3D) imaging for implant treatment planning in a pool of patients referred to a specialty clinic over a 3-year period., Materials and Methods: All patients who received dental implants between 2008 and 2010 at the Department of Oral Surgery and Stomatology at the University of Bern were included in the study. The influence of age, gender, and time of treatment (2008 to 2010) on the frequency of use of two-dimensional (2D) radiographic imaging modalities alone or in combination with 3D cone beam computed tomography (CBCT) scans was analyzed. Furthermore, the influence of the indication, location, and need for bone augmentation on the frequency of use of 2D imaging modalities alone or in combination with CBCT was evaluated., Results: In all, 1,568 patients (792 women and 776 men) received 2,279 implants. Overall, 633 patients (40.4%) were analyzed with 2D imaging procedures alone. CBCT was performed in 935 patients (59.6%). There was a statistically significant increase in CBCT between 2008 and 2010. Patients older than 55 years received a CBCT scan in addition to 2D radiographic imaging statistically significantly more often. Additional 3D imaging was most frequently performed in the posterior maxilla, whereas 2D radiographs alone exhibited the highest frequency in the anterior mandible. The combination of 2D with CBCT was used predominantly for implant placement with simultaneous or staged guided bone regeneration or sinus elevation., Conclusion: Based on these findings from a specialty clinic, the use of additional CBCT imaging for implant treatment planning is influenced by the indication, location, local anatomy (including the need for bone augmentation), and the age of the patient.

Objectives: Uncontrolled diabetes mellitus is associated with impaired osseointegration. Diabetic individuals might benefit from bone anabolic therapies. Intermittent administration of 1-34 parathyroid hormone (PTH) stimulates bone formation in rodent models. However, this anabolic effect fails in diabetic rats. Whether the anabolic effect of PTH can be achieved in insulin-controlled diabetic rats has not been investigated yet., Materials and Methods: After diabetes induction with streptozotocin in 40 female Wistar rats, the animals were randomly divided into 4 groups: diabetes, diabetes plus PTH, insulin-treated diabetes, and insulin-treated diabetes plus PTH. After 1 week, miniscrews were inserted in the tibiae. Osmotic pumps with insulin or saline solution were implanted. Animals received 60 mg/kg PTH or saline solution. Histomorphometric analysis was performed., Results: In diabetic rats, no changes of medullary periimplant bone area or bone-to-implant contacts (BICs) were achieved with or without treatment with PTH. However, also animals treated with insulin failed to response significantly to PTH regarding bone area (7.4 ± 4.1% and 8.1 ± 4.1%) and BICs (33.7 ± 16.9% and 49.9 ± 11.9%)., Conclusion: These results demonstrate that the metabolic characteristics of the diabetic rats produced a condition unable to respond to PTH treatment, even when hyperglycemia was controlled with insulin.