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Objectives: Comparison of the impact of bisphopshonates and of denosumab, 2 popular treatment therapies in osteoporosis, on oral implant osseointegration, based on scientific evidence. Material and Methods: The PubMed (Medline) database was searched for articles published up until April 1st, 2018. The search was used to compile evidence on the mechanisms of both types of drugs and their impact on oral implant osseointegration. To do so, mesh terms, keywords and filters were applied. Results: The searches resulted in 947 articles for bisphosphonate and 295 articles for denosumab respectively. After selection according to the eligibility criteria, 21 studies were included. 18 of these studies discussed the role of bisphosphonates in implant dentistry. To the authors’ knowledge, there is little evidence yet on the effect of denosumab on oral implant osseointegration. Conclusion: Reports providing information related to titanium implant osseointegration in patients taking denosumab is currently lacking. It is anticipated that this knowledge gap will be bridged in the near future, given the increasing use of the drug in the treatment of osteoporosis.

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Context: Obesity is the main cause of type 2 diabetes mellitus (T2DM) and Roux-en-Y gastric bypass (RYGB) surgery is considered to be an effective treatment. The adverse effects of T2DM on bone tissue however remain or are even aggravated after this surgical procedure. While studies on the mandibular condyle are scarce, the aim of the present study is to assess its compositional characteristics in both T2DM and RYGB treated conditions. Design: Thirty-two C57BL/6 mice were randomly assigned after 8 weeks of age to receive either a high-fat or low-fat diet. After 14 weeks of high-fat diet intake, 7 obese mice were randomly subjected to RYGB surgery. All animals were euthanized at the age of 30 weeks. Mandibular bones were removed and the condylar region was further assessed using Raman microspectroscopy. Results: Statistically significant lower mineralization is evinced for both high-fat diet and RYGB treated trabecular condyle bones, with elevated carbonate substitutions within RYGB treated mice. Crystallinity and AGE pentosidine reached no significance, in contrary to the increased AGE CML after RYGB surgery. Site-dependency revealed a non-uniform composition with increasing mineralization and carbonate substitutions towards the centre. Conclusion: With a deteriorated bone composition in T2DM, RYGB surgery appears to weaken the oral condylar bone even more. Adverse effects are assumed to initiate from the outer trabecular bone. More studies, in particular histological ones, on the mandibular condyle bone are required.

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Aim: Diabetes is a metabolic disease that is becoming increasingly important and widespread all over the world. One of the complications of T2DM is an impaired vascularization. In this master thesis, we have attempted finding an answer on the following question: Is T2DM bone tissue poorly vascularized? What are the factors that cause a possible impaired vascularization in T2DM bone tissue? Materials and methods: Using the PubMed search engine, we selected appropriate information relative to the blood flow in diabetic bone. The following keywords were used to search relevant articles to answer our questions: bone perfusion, bone vascularization, bone vasculature, bone vessel calcification, vessel calcification, vessel stiffening, bone vascular calcification, bone atherosclerosis. Each keyword was also used to search in combination with ‘diabetes type 2’. When diabetes type 2 was not involved in the articles but only diabetes type 1 was found, those articles were excluded. Only articles that reported in vivo studies were judged as appropriate, either animal studies, clinical studies or reviews of the latter. Results: Using the keywords as mentioned above, we obtained 203 results. After applying the exclusion criteria, thus eliminating all articles concerning type 1 diabetes and in vitro studies as well as duplicates, 14 articles (4 animal studies, 8 clinical studies and 2 review articles) remained relevant. Conclusion: In T2DM, evidence is clear that the vascularization is impaired. BMP-2 and OPG are increased in T2DM patients. The BMP-2 level is increased in the endothelial cells, causing vascular calcification by promoting differentiation of VSMCs in cells with an osteoblast-like phenotype. The OPG level is increased in T2DM patients, especially in those with microvascular complications. OPG plays a protective role in bone tissue by inhibition of maturation and activity of osteoclasts. In the vasculature, OPG inhibits atherosclerosis and vascular inflammation and promotes the survival of vascular cells. The increase of OPG in T2DM patients could be explained by the fact that OPG production is upregulated as a protective compensatory mechanism in conditions were vascular calcification is increased. Insulin plays a protective role by improving osteoblast function and bone formation. The vascular calcification in T2DM is associated with a reduced bone health, bone turnover and BMD and an increased bone loss and osteoporotic fractures. More research on the vascularization of T2DM bone is urgently needed.

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Mastication is an intricate biomechanical process depending on many intra-oral (such as number of occluding units, periodontal status, salivary flow rate) and extra-oral (such as ageing, bite force, gender and general health) features. Does masticatory efficiency influences the oral health related quality of life (OHRQoL)? This research tries to find the answer to this question. The primary aim of the present study was to assess the potential correlation of chewing efficiency and quality of life. Secondary aim of the study was to explore the influencing potential of other factors, namely gender, age, dietary habits, dietary status, history data, morbidity, allocation of level of care I-III, dental status, prosthetic status, periodontal status and occlusal parameters, on the masticatory efficiency. A chewing test made use of standardized test units made from commercially available gelatin mass formed in cylindrical standard shape (1 cm x 2 cm). The test units were available in three different degrees of hardness, soft, medium and hard. A complete chewing function test consisted of 9 chewing sequences: 3 consistencies (soft – medium – hard) x 3 chewing locations (right – left – bilateral, each for 30 seconds. The ground test units were spit out into a sieve, collected and scanned. The actual clinical trial will start in Summer 2020. In the framework of this Master thesis, a pilot study was conducted in UZ Leuven by using volunteer students as subjects. The aim of the pilot study was to assess and optimize the feasibility and standardization of all procedures related to the actual study. The students were on average 28 years old with 28 occluding units and without underlying medical conditions. The analysis was limited to counting visually (instead of automated in the actual study) the number of ground particles. There were 3 test units per hardness as described earlier. Soft test units showed on average 29.08 (± 20.89) ground particles, medium test units 6.20 (± 7.78) particles and hard ones 14.56 (± 14.73). Although the study population was homogenous, the results showed great variations as illustrated by the large standard deviations. The results were also paradoxical as chewing on medium test units resulted in a smaller number of ground particles as compared to the hard test units. The latter finding may be explained by different reasons, e.g the gelatin test units were not individually packed and they might be dried up resulting in change in hardness; the test units were not placed in the fridge in-between the different tests so temperature variation might have affected a specific hardness. In conclusion, this pilot study offers a sound base to start the final study. Study shortcomings will first be discussed with the principal investigator of this multicenter multinational study prior to the start of the actual study. This pilot provides us evidence-based knowledge in order to conduct the final study in an optimal way.

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The impact of diabetes mellitus on bone fracture healing is an important problem for patients suffering from this disease, since they are prone to experiencing delayed fracture healing and even non-union. Even though efforts have been made to understand the detrimental effects of T2DM on the fracture healing process, the exact mechanisms involved and pathophysiological events still remain unclear. The aim of this study was to assess alterations in tibial fracture healing of diet-induced obese (DIO) mice, and to corroborate our in vivo findings by assessing the properties of osteoprogenitors derived from the diabetic micro-environment in vitro. To achieve the first, high-resolution contrast-enhanced microfocus X-ray computed tomography (CE-CT) was used, as it allowed to evaluate both soft (unmineralized cartilage and adipocytes) and hard (mineralized cartilage and newly-formed bone) tissues. For the first time, CE-CT enabled simultaneous 3D assessment of the amount and spatial distribution of the regenerated soft and hard tissues during fracture healing, and revealed that not only osteogenesis but also chondrogenesis is altered in DIO mice. Compared to aged-matched lean controls, DIO mice presented a decreased bone volume fraction and increased callus volume, adiposity and cartilaginous tissue volume at day 14 post-fracture. The in vitro data revealed that not only the osteogenic and adipogenic differentiation of periosteum-derived cells (PDCs) were altered by hyperglycemic (HG) conditions, but also the chondrogenic differentiation, supporting the in vivo results. In addition, elevated PPARγ expression in HG conditions confirmed the observed increase in differentiated adipocytes in vitro and in vivo. Finally, chondrogenesis-related genes SOX9 and COL2 were downregulated for PDCs treated with HG medium, further confirming the compromised chondrogenic differentiation in vitro and suggesting that chondroprogenitor functionality is altered during the fracture healing process in vivo. Altogether, these results provide novel insights into the alterations of bone repair, and reveal a link between HG-induced dysfunctionality of osteoprogenitors and fracture healing impairment under T2DM conditions.