Peri-implant bone loss of dental implants with platform-switching design after 5 years of loading: a cross-sectional study

OBJECTIVE The aim of this cross-sectional study was to estimate bone loss of implants with platform-switching design and analyze possible risk indicators after 5 years of loading in a multi-centered private practice network. METHOD AND MATERIALS Peri-implant bone loss was measured radiographically as the distance from the implant shoulder to the mesial and distal alveolar crest, respectively. Risk factor analysis for marginal bone loss included type of implant prosthetic treatment concept and dental status of the opposite arch. RESULTS A total of 316 implants in 98 study patients after 5 years of loading were examined. The overall mean value for radiographic bone loss was 1.02 mm (SD ± 1.25 mm, 95% CI 0.90- 1.14). Correlation analyses indicated a strong association of peri-implant bone loss > 2 mm for removable implant-retained prostheses with an odds ratio of 53.8. CONCLUSION The 5-year-results of the study show clinically acceptable values of mean bone loss after 5 years of loading. Implant-supported removable prostheses seem to be a strong co-factor for extensive bone level changes compared to fixed reconstructions. However, these results have to be considered for evaluation of the included special cohort under private dental office conditions.

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.

Anterior superior alveolar nerve (ASAN): A morphometric-anatomical Analysis

The anterior superior alveolar nerve (ASAN) is a branch of the infraorbital nerve. Only few studies have morphometrically evaluated the course of the ASAN. Midfacial segments of ten hemisectioned fresh adult cadaver heads were dissected to uncover the anterior wall of the maxilla. Specimens were subsequently decalcified and the bone overlying the ASAN was removed under a microscope to expose the ASAN. Its branching pattern from the infraorbital nerve was recorded, and the course of the ASAN within the anterior wall of the maxillary sinus was morphometrically assessed measuring distances to predefined landmarks using a digital caliper. A distinct ASAN was observed in all specimens. It arose lateral (six cases) or inferior (four cases) from the infraorbital nerve. The point of origin was located at a mean distance of 12.2 ± 5.79 mm posterior to the infraorbital foramen. The ASAN was located on average 2.8 ± 5.13 mm lateral to the infraorbital foramen. After coursing medially, the ASAN ran inferior to the foramen at a mean distance of 5.5 ± 3.07 mm. When approaching the nasal aperture, the loop of the ASAN was on average 13.6 ± 3.07 mm above the nasal floor. The horizontal mean distance from the ASAN to the nasal aperture was 4.3 ± 2.74 mm halfway down from the loop, and 3.3 ± 2.60 mm at the floor of the nose, respectively. In conclusion, the present study evaluated the course of the ASAN relative to the infraorbital foramen and nasal aperture. This information is helpful to avoid damage to this anatomical structure during interventions in the infraobrital region of the maxilla. Further, knowledge of the course of the ASAN and of its bony correlate (canalis sinuosus) may be valuable in interpreting anesthetic or radiologic findings in the anterior maxilla.

Bone metabolic and hormonal characteristics of Australian Antarctic expeditioners

Summary: Serum 25(OH)D levels decline without sunlight exposure. We studied 120 expeditioners to Antarctica to determine the skeletal and hormonal responses to sunlight deprivation. With emerging vitamin D insufficiency, serum calcium decreased, PTH increased, and bone loss at the proximal femur was observed. Baseline serum 25(OH)D levels >100 nmol/L prevented vitamin D insufficiency. Introduction: Vitamin D stores deplete without adequate sunlight exposure unless supplementation is provided. We studied 120 healthy adults who spent a year in Antarctica as a model for sunlight deprivation to define the timing and magnitude of the skeletal and hormonal responses to emerging vitamin D insufficiency. Methods: Fasting blood samples were assessed at baseline, 6 and 12 months for serum 25-hydroxyvitamin D (25(OH)D), osteocalcin (OC), bone formation (P1NP) and resorption (CTx), PTH and calcium. Lumbar spine and proximal femur BMD was measured using DXA. Differences over time were determined using repeated measures ANOVA. Percent changes were expressed as (Delta value/(value A +value B)/2)x100. Relationships between outcome measures were determined using Spearman's correlations. Results: Vitamin D insufficiency (<50 nmol/L) was observed in 85% of expeditioners by 6 months when serum calcium decreased and PTH increased (p<0.01). By 12 months, OC increased by 7.4±3.0% (p<0.05), and BMD decreased by 1.0±2.0% at the total proximal femur (p<0.05). For those with vitamin D sufficiency at baseline (>50 nmol/L), sunlight deprivation produced vitamin D insufficiency within 4 months unless baseline values were >100 nmol/L. Conclusion: Supplementation may be necessary for expeditioners with limited access to UV light.

Regulation of osteoclast activation and autophagy through altered protein kinase pathways in Paget's disease of bone

Résumé : La maladie osseuse de Paget (MP) est un désordre squelettique caractérisé par une augmentation focale et désorganisée du remodelage osseux. Les ostéoclastes (OCs) de MP sont plus larges, actifs et nombreux, en plus d’être résistants à l’apoptose. Même si la cause précise de la MP demeure inconnue, des mutations du gène SQSTM1, codant pour la protéine p62, ont été décrites dans une proportion importante de patients avec MP. Parmi ces mutations, la substitution P392L est la plus fréquente, et la surexpression de p62P392L dans les OCs génère un phénotype pagétique partiel. La protéine p62 est impliquée dans de multiples processus, allant du contrôle de la signalisation NF-κB à l’autophagie. Dans les OCs humains, un complexe multiprotéique composé de p62 et des kinases PKCζ et PDK1 est formé en réponse à une stimulation par Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL), principale cytokine impliquée dans la formation et l'activation des OCs. Nous avons démontré que PKCζ est impliquée dans l’activation de NF-κB induite par RANKL dans les OCs, et dans son activation constitutive en présence de p62P392L. Nous avons également observé une augmentation de phosphorylation de Ser536 de p65 par PKCζ, qui est indépendante d’IκB et qui pourrait représenter une voie alternative d'activation de NF-κB en présence de la mutation de p62. Nous avons démontré que les niveaux de phosphorylation des régulateurs de survie ERK et Akt sont augmentés dans les OCs MP, et réduits suite à l'inhibition de PDK1. La phosphorylation des substrats de mTOR, 4EBP1 et la protéine régulatrice Raptor, a été évaluée, et une augmentation des deux a été observée dans les OCs pagétiques, et est régulée par l'inhibition de PDK1. Également, l'augmentation des niveaux de base de LC3II (associée aux structures autophagiques) observée dans les OCs pagétiques a été associée à un défaut de dégradation des autophagosomes, indépendante de la mutation p62P392L. Il existe aussi une réduction de sensibilité à l’induction de l'autophagie dépendante de PDK1. De plus, l’inhibition de PDK1 induit l’apoptose autant dans les OCs contrôles que pagétiques, et mène à une réduction significative de la résorption osseuse. La signalisation PDK1/Akt pourrait donc représenter un point de contrôle important dans l’activation des OCs pagétiques. Ces résultats démontrent l’importance de plusieurs kinases associées à p62 dans la sur-activation des OCs pagétiques, dont la signalisation converge vers une augmentation de leur survie et de leur fonction de résorption, et affecte également le processus autophagique.

Molecular cloning and expression of leptin in gray and harbor seal blubber, bone marrow, and lung and its potential role in marine mammal respiratory physiology

Leptin is a multifunctional hormone, produced predominantly in adipocytes. It regulates energy balance through its impact on appetite and fat metabolism, and its concentration indicates the size of body fat reserves. Leptin also plays a vital role in stretch-induced surfactant production during alveolar development in the fetus. The structure, expression pattern, and role of leptin have not previously been explored in marine mammals. Phocid seals undergo cyclical changes in body composition as a result of prolonged fasting and intensive foraging bouts and experience rapid, dramatic, and repeated changes in lung volume during diving. Here, we report the tissue-specific expression pattern of leptin in these animals. This is the first demonstration of leptin expression in the lung tissue of a mature mammal, in addition to its expression in the blubber and bone marrow, in common with other animals. We propose a role for leptin in seal pulmonary surfactant production, in addition to its likely role in long-term energy balance. We identify substitutions in the phocine leptin sequence in regions normally highly conserved between widely distinct vertebrate groups, and, using a purified seal leptin antiserum, we confirm the presence of the leptin protein in gray seal lung and serum fractions. Finally, we report the substantial inadequacies of using heterologous antibodies to measure leptin in unextracted gray seal serum.

Characterization of bone pathologies in the ins2+/akita mouse, a new model for diabetes insulindependent: contribution for a better understanding of the disease in humans

Tese de Doutoramento, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016

Fresh-frozen vs irradiated allograft bone in orthopaedic reconstructive surgery

The use of allograft bone is increasingly common in orthopaedic reconstruction procedures. The optimal method of preparation of allograft bone is subject of great debate. Proponents of fresh-frozen graft cite improved biological and biomechanical characteristics relative to irradiated material, whereas fear of bacterial or viral transmission warrants some to favour irradiated graft. Careful review of the literature is necessary to appreciate the influence of processing techniques on bone quality. Whereas limited clinical trials are available to govern the selection of appropriate bone graft, this review presents the argument favouring the use of fresh-frozen bone allograft as compared to irradiated bone.

Lateral bone density variations in the scoliotic spine

Adolescent Idiopathic Scoliosis (AIS) is the most common deformity of the spine, affecting 2-4% of the population. Previous studies have shown that the vertebrae in scoliotic spines undergo abnormal shape changes, however there has been little exploration of how AIS affects bone density distribution within the vertebrae. Existing pre-operative CT scans of 53 female idiopathic scoliosis patients with right-sided main thoracic curves were used to measure the lateral (right to left) bone density profile at mid-height through each vertebral body. This study demonstrated that AIS patients have a marked convex/concave asymmetry in bone density for vertebral levels at or near the apex of the scoliotic curve. To the best of our knowledge, the only previous studies of bone density distribution in AIS are those of Périé et al [1,2], who reported a coronal plane ‘mechanical migration’ of 0.54mm toward the concavity of the scoliotic curve in the lumbar apical vertebrae of 11 scoliosis patients. This is comparable to the value of 0.8mm (4%) in our study, especially since our patients had more severe scoliotic curves. From a bone adaptation perspective, these results suggest that the axial loading on the scoliotic spine is strongly asymmetric.

Effect of bone graft type on fusion rates following endoscopic anterior scoliosis correction

Bone graft is generally considered fundamental in achieving solid fusion in scoliosis correction and pseudarthrosis following instrumentation may predispose to implant failure. In endoscopic anterior-instrumented scoliosis surgery, autologous rib or iliac crest graft has been utilised traditionally but both techniques increase operative duration and cause donor site morbidity. Allograft bone and bone- morphogenetic-protein alternatives may improve fusion rates but this remains controversial. This study's objective was to compare two-year postoperative fusion rates in a series of patients who underwent endoscopic anterior instrumentation for thoracic scoliosis utilising various bone graft types. Significantly better rates of fusion occurred in endoscopic anterior instrumented scoliosis correction using femoral allograft compared to autologous rib-heads and iliac crest graft. This may be partly explained by the difficulty obtaining sufficient quantities of autologous graft. Lower fusion rates in the autologous graft group appeared to predispose to rod fracture although the clinical consequence of implant failure is uncertain.

Implication of 3D culture system for study of prostate cancer (CaP) mediated bone metastasis

Introduction : For the past decade, three dimensional (3D) culture has served as a foundation for regenerative medicine study. With an increasing awareness of the importance of cell-cell and cell-extracellular matrix interactions which are lacking in 2D culture system, 3D culture system has been employed for many other applications namely cancer research. Through development of various biomaterials and utilization of tissue engineering technology, many in vivo physiological responses are now better understood. The cellular and molecular communication of cancer cells and their microenvironment, for instance can be studied in vitro in 3D culture system without relying on animal models alone. Predilection of prostate cancer (CaP) to bone remains obscure due to the complexity of the mechanisms and lack of proper model for the studies. In this study, we aim to investigate the interaction between CaP cells and osteoblasts simulating the natural bone metastasis. We also further investigate the invasiveness of CaP cells and response of androgen sensitve CaP cells, LNCaP to synthetic androgen.----- Method : Human osteoblast (hOB) scaffolds were prepared by seeding hOB on medical grade polycaprolactone-tricalcium phosphate (mPLC-TCP) scaffolds and induced to produce bone matrix. CaP cell lines namely wild type PC3 (PC3-N), overexpressed prostate specific antigen PC3 (PC3k3s5) and LNCaP were seeded on hOB scaffolds as co-cultures. Morphology of cells was examined by Phalloidin-DAPI and SEM imaging. Gelatin zymography was performed on the 48 hours conditioned media (CM) from co-cultures to determine matrix metalloproteinase (MMP) activity. Gene expression of hOB/LNCaP co-cultures which were treated for 48 hours with 1nM synthetic androgen R1881 were analysed by quantitative real time PCR (qRT-PCR).----- Results : Co-culture of PCC/hOB revealed that the morphology of PCCs on the tissue engineered bone matrix varied from homogenous to heterogenous clusters. Enzymatically inactive pro-MMP2 was detected in CM from hOBs and PCCs cultured on scaffolds. Elevation in MMP9 activity was found only in hOB/PC3N co-culture. hOB/LNCaP co-culture showed increase in expression of key enzymes associated with steroid production which also corresponded to an increase in prostate specific antigen (PSA) and MMP9.----- Conclusions : Upregulation of MMP9 indicates involvement of ECM degradation during cancer invasion and bone metastases. Expression of enzymes involved in CaP progression, PSA, which is not expressed in osteoblasts, demonstrates that crosstalk between PCCs and osteoblasts may play a part in the aggressiveness of CaP. The presence of steroidogenic enzymes, particularly, RDH5, in osteoblasts and stimulated expression in co-culture, may indicate osteoblast production of potent androgens, fuelling cancer cell proliferation. Based on these results, this practical 3D culture system may provide greater understanding into CaP mediated bone metastasis. This allows the role of the CaP/hOB interaction with regards to invasive property and steroidogenesis to be further explored.

Lateral bone density variations in the scoliotic spine

Adolescent Idiopathic Scoliosis (AIS) is the most common deformity of the spine, affecting 2-4% of the population. Previous studies have shown that the vertebrae in scoliotic spines undergo abnormal shape changes, however there has been little exploration of how scoliosis affects bone density distribution within the vertebrae. In this study, existing CT scans of 53 female idiopathic scoliosis patients with right-sided main thoracic curves were used to measure the lateral (right to left) bone density profile at mid-height through each vertebral body. Five key bone density profile measures were identified from each normalised bone density distribution, and multiple regression analysis was performed to explore the relationship between bone density distribution and patient demographics (age, height, weight, body mass index (BMI), skeletal maturity, time since Menarche, vertebral level, and scoliosis curve severity). Results showed a marked convex/concave asymmetry in bone density for vertebral levels at or near the apex of the scoliotic curve. At the apical vertebra, mean bone density at the left side (concave) cortical shell was 23.5% higher than for the right (convex) cortical shell, and cancellous bone density along the central 60% of the lateral path from convex to concave increased by 13.8%. The centre of mass of the bone density profile at the thoracic curve apex was located 53.8% of the distance along the lateral path, indicating a shift of nearly 4% toward the concavity of the deformity. These lateral bone density gradients tapered off when moving away from the apical vertebra. Multi-linear regressions showed that the right cortical shell peak bone density is significantly correlated with skeletal maturity, with each Risser increment corresponding to an increase in mineral equivalent bone density of 4-5%. There were also statistically significant relationships between patient height, weight and BMI, and the gradient of cancellous bone density along the central 60% of the lateral path. Bone density gradient is positively correlated with weight, and negatively correlated with height and BMI, such that at the apical vertebra, a unit decrease in BMI corresponds to an almost 100% increase in bone density gradient.

The effect of bone graft type on fusion rates following anterior thoracoscopic scoliosis correction

Bone graft is generally considered fundamental in achieving solid fusion in scoliosis correction and pseudarthrosis following instrumentation may predispose to implant failure. In thoracoscopic anterior-instrumented scoliosis surgery, autologous rib or iliac crest graft has been utilised traditionally but both techniques increase operative duration and cause donor site morbidity. Allograft bone and bone morphogenetic protein (BMP) alternatives may improve fusion rates but this remains controversial. This study's objective was to compare two-year postoperative fusion rates in a series of patients who underwent thoracoscopic anterior instrumentation for thoracic scoliosis utilising various bone graft types.