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Diabetes is a chronic, metabolic disease characterized by elevated levels of blood glucose, asso-ciated with premature mortality and morbidity. Lifestyle changes and/or bypass surgery increase quality of life. Recent studies have shown that skeletal fragility should also be considered among the complications associated with type 2 diabetes and following bypass surgery. Individ-uals with type 2 diabetes have increased fracture risk, despite normal to increased bone mineral density. The phenomenon of skeletal fragility in diabetes is not completely understood. In order to contribute to this lack in knowledge, the present study focused on the relationship between the microarchitecture of the bone structure and the parameters diet and age. The diet-induced obese diabetic mouse was used as animal model, in which a high fat diet was given for a period of 22 weeks. Micro-computed tomography analysis was performed to evaluate the micro-architecture of trabecular and cortical femur bone. A lower bone volume in a population sample of mice with diet-induced obesity and diabetic phenotype and of mice with bypass surgery, compared with young and age-matched controls, was found. In terms of cortical bone changes in response to high-fat diet and ageing, a decrease in the cortical bone volume was observed for both the diabetic obese and the bypass mice. Although this study is preclinical research per-formed in rodent animals, the observed overall significant catabolic changes in trabecular and cortical bone corroborate with the findings in human studies that diabetes and bypass surgery influence the bone architecture.

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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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Abstract: The aim of the study was to quantify the micro‐architectural changes of the jaw bone in response to ovariectomy, exposed or not to bisphosphonate treatment. A total of 47 Wistar rats were ovariectomized (OVX) or sham‐operated (shOVX) and exposed to osteoporosis preventive treatment for eight weeks either with bisphosphonates (alendronate, ALN; group OVX‐ALN) three days/week at a dose of 2 mg/kg or with saline solution (untreated control condition; group OVX). The bone morphometric parameters of the trabecular jaw bone were assessed using ex vivo microcomputed tomography. The regions of interest investigated in the maxilla were the inter‐radicular septum of the second molar and the tuber. The regions quantified in the mandible included the three molar regions and the condyle. A one‐way analysis of variance followed by pairwise comparison using Tukey’s HSD and the Games–Howell test was conducted to explore significant differences between the groups. In the maxilla, OVX decreased the bone volume in the inter‐radicular septum of the second molar. Bisphosphonate treatment was able to prevent this deterioration of the jaw bone. The other investigated maxillary regions were not affected by (un)treated ovariectomy. In the mandible, OVX had a significant negative impact on the jaw bone in the buccal region of the first molar and the inter‐radicular region of the third molar. Treatment with ALN was able to prevent this jaw bone loss. At the condyle site, OVX significantly deteriorated the trabecular connectivity and shape, whereas preventive bisphosphonate treatment showed a positive effect on this trabecular bone region. No significant results between the groups were observed for the remaining regions of interest. In summary, our results showed that the effects of ovariectomy‐induced osteoporosis are manifested at selected jaw bone regions and that bisphosphonate treatment is capable to prevent these oral bone changes.

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Inleiding: De incidentie van type 1 (T1DM) en 2 diabetes (T2DM) mellitus stijgt wereldwijd. De huidige gouden standaard voor screening, diagnose en monitoring van DM houdt bloedafname in. Recente onderzoeken dragen speeksel aan als alternatief. Afname is goedkoop, niet-invasief en pijnvrij. Bij vroege opsporing van (pre)DM kunnen complicaties en progressie van de ziekte voorkomen worden. Het objectief van deze literatuurstudie is om het potentieel van speeksel in de diagnose van (pre)DM type 1 en 2 na te gaan. Methode: In de PubMed en Embase werd gezocht op zoektermen: (DIABETES OR DM) and SALIVA. Er werden alleen artikels geselecteerd van de afgelopen 5 jaar. Studies met minder dan 30 patiënten en dierenstudies werden niet opgenomen in de selectie. Resultaten: In totaal werden er 35 studies opgenomen in deze literatuurstudie. Het glucosegehalte in speeksel is hoger bij (pre)DM en hoogst bij patiënten met ongecontroleerde DM, zowel bij T1DM als T2DM. Over het diagnostisch potentieel van andere speekselcomponenten kon op basis van deze resultaten nog geen uitspraak gedaan worden. Conclusie: Het glucosegehalte in speeksel kan mogelijk gebruikt worden voor de vroegtijdige screening en diagnose van preDM, T1DM en T2DM en monitoring van glycemietoestand bij diabetici. Om de klinische toepasbaarheid en het diagnostisch potentieel van het glucosegehalte en andere speekselcomponenten te bepalen voor (pre)DM zijn er meer studies met betere onderzoeksopzet vereist.