FasL is a catabolic factor in alveolar bone homeostasis.

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 Faslgld 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 Faslgld 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 Faslgld mice were found to have more periodontal bone than their WT littermates. Faslgld 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.

The effect of osteocyte-derived RANKL on bone graft remodeling: An in vivo experimental study.

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 Tnfsf11fl/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, Tnfsf11fl/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 Tnfsf11fl/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 Tnfsf11fl/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.

Transglutaminase Activity Is Conserved in Stratified Epithelia and Skin Appendages of Mammals and Birds.

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.

Preoperative buccal bone volume predicts long-term graft retention following augmentation in the esthetic zone: A retrospective case series.

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 (V0 ) showed a moderate correlation to final buccal bone volume (Vt , rs  = .43) but a strong correlation to the absolute volumetric change (ΔV = Vt -V0 , rs  = -.80). A linear mixed model for Vt had a large intercept of 91.39 (p < .001) and a rather small slope of .11 for V0 (p = .11). Observed differences between treatments were not statistically significant in the mixed model. V0 above 105 mm3 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 V0 and point to a cutoff V0 above which the augmented volume is not retained long-term.

Resonance frequency analysis of implants placed in condensed bone.

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.

Bone healing around titanium implants in a preclinical model of bile duct ligation-induced liver injury.

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.

A volumetric prediction model for postoperative cyst shrinkage.

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) = V0 · e-ɑt] and one model with a patient-specific decay rate [Vk(t) = V0 · e-ßt + 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) = V0 · e-0.0035t where V(t) is the residual cyst volume after time t elapsed since surgery, V0 is the initial cyst volume, and e is the base of the natural logarithm. Considering a patient-specific decay rate, the model is Vk(t) = V0 · e-0.0049t + γkt where γk 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.

Angular changes in implants placed in the anterior maxillae of adults: a cephalometric pilot study.

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.

An advanced prediction model for postoperative complications and early implant failure.

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.

DBBM shows no signs of resorption under inflammatory conditions. An experimental study in the mouse calvaria.

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.

How old is old for implant therapy in terms of early implant losses?

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.

Bone-conditioned medium modulates the osteoconductive properties of collagen membranes in a rat calvaria defect model.

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.

Development of Implant Stability Quotient values of implants placed with simultaneous sinus floor elevation - results of a prospective study with 109 implants.

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 (ISQBL ) and after 8 weeks of healing (ISQ8 wk ). Patients showing ISQ8 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 ISQ8 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.

Immediate implant placement with simultaneous guided bone regeneration in the esthetic zone: 10-year clinical and radiographic outcomes.

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.

Human bone chips release of sclerostin and FGF-23 into the culture medium: an in vitro pilot study.

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.

Dimethyloxalylglycine lyophilized onto bone substitutes increase vessel area in rat calvarial defects.

AIM: Pharmacological inhibitors of prolyl hydroxylases, also termed hypoxia-mimetic agents (HMAs), when repeatedly injected can support angiogenesis and bone regeneration. However, the possible role of HMA loaded onto bone substitutes to support angiogenesis and bone regeneration under diabetic condition is unknown. The capacity of HMA loaded onto deproteinized bovine bone mineral (DBBM) to support angiogenesis and bone formation was examined in diabetic Wistar rats. METHODS: Diabetes was induced by intraperitoneal injection of streptozotocin. The HMA dimethyloxalylglycine (DMOG) and desferrioxamine (DFO) were lyophilized onto DBBM. Calvarial defects were created with a trephine drill and filled with the respective bone substitutes. After 4 weeks of healing, the animals were subjected to histological and histomorphometric analysis. RESULTS: In this report, we provide evidence that DMOG loaded onto DBBM can support angiogenesis in vivo. Specifically, we show that DMOG increased the vessel area in the defect site to 2.4% ± 1.3% compared with controls 1.1% ± 0.48% (P = 0.012). There was a trend toward an increased vessel number in the defect site with 38.6 ± 17.4 and 31.0 ± 10.3 in the DMOG and the control group (P = 0.231). The increase in angiogenesis, however, did not translate into enhanced bone formation in the defect area with 9.2% ± 7.1% and 8.4% ± 5.6% in DMOG and control group, respectively. No significant changes were caused by DFO. CONCLUSIONS: The results suggest that DMOG loaded onto DBBM can support angiogenesis, but bone formation does not increase accordingly in a type 1 diabetic rat calvarial defect model at the indicated time point.

The Effect of Parathyroid Hormone on Osseointegration in Insulin-Treated Diabetic Rats.

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.

Active and Passive Mineralization of Bio-Gide® Membranes in Rat Calvaria Defects.

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 mm3) compared with the minced group (0.4 mm3), 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.

Human versus Rat PRF on Collagen Membranes: A Pilot Study of Mineralization in Rat Calvaria Defect Model.

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 mm3 (range: 0.9; 5.3 mm3). 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 mm3 (range: 0.3-3.3 mm3), which was significantly lower than what was observed with rat PRF (r-PRF), with a BV median of 1.2 mm3 (range: 0.3-5.9 mm3). 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.

[Osteoporosis-Definition, risk assessment, diagnosis, prevention and treatment (update 2024) : Guidelines of the Austrian Society for Bone and Mineral Research]. / Osteoporose ­ Definition, Risikoerfassung, Diagnose, Prävention und Therapie (Update 2024) : Leitlinie der Österreichischen Gesellschaft für Knochen- und Mineralstoffwechsel.

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.