Influence of an Antidiabetic Drug on Biomechanical and Histological Parameters Around Implants in Type 2 Diabetic Rats

Hashiguchi, Chikoto; Kawamoto, Shinichiro; Kasai, Takayuki; Nishi, Yasuhiro; Nagaoka, Eiichi

doi:10.1097/id.0000000000000021

Cited by 18 publications

(15 citation statements)

References 40 publications

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“…A more recent study utilizing the GK rat model of T2D found that treatment with voglibose, one of the newest α‐GI drugs (approved for use in Asia), was insufficient to reverse the negative effects of diabetes on osteo‐integration of dental implants . From this study, the authors inferred a detrimental effect of α‐GI treatment on bone repair, although incomplete glycemic control could also account for their findings . Considering the longevity of this drug class, it is reasonable to assume that post‐marketing surveillance would identify a serious musculoskeletal safety concern, although teasing out a class‐specific contribution from these drugs could be difficult, considering that they are used less often and typically only in select multi‐component therapy.…”

Section: Drugs and Bonementioning

confidence: 83%

“…Moreover, when similar alpha‐glucosidase inhibitory plant phenol extracts have been investigated in rodent models, we could not identify reports of skeletal toxicity or skeletal malformation in these preclinical studies . A more recent study utilizing the GK rat model of T2D found that treatment with voglibose, one of the newest α‐GI drugs (approved for use in Asia), was insufficient to reverse the negative effects of diabetes on osteo‐integration of dental implants . From this study, the authors inferred a detrimental effect of α‐GI treatment on bone repair, although incomplete glycemic control could also account for their findings .…”

Section: Drugs and Bonementioning

confidence: 89%

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Diabetes pharmacotherapy and effects on the musculoskeletal system

Kalaitzoglou

Fowlkes

Popescu

et al. 2018

Diabetes Metabolism Res

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Summary Persons with type 1 or type 2 diabetes have a significantly higher fracture risk than age‐matched persons without diabetes, attributed to disease‐specific deficits in the microarchitecture and material properties of bone tissue. Therefore, independent effects of diabetes drugs on skeletal integrity are vitally important. Studies of incretin‐based therapies have shown divergent effects of different agents on fracture risk, including detrimental, beneficial, and neutral effects. The sulfonylurea class of drugs, owing to its hypoglycemic potential, is thought to amplify the risk of fall‐related fractures, particularly in the elderly. Other agents such as the biguanides may, in fact, be osteo‐anabolic. In contrast, despite similarly expected anabolic properties of insulin, data suggests that insulin pharmacotherapy itself, particularly in type 2 diabetes, may be a risk factor for fracture, negatively associated with determinants of bone quality and bone strength. Finally, sodium‐dependent glucose co‐transporter 2 inhibitors have been associated with an increased risk of atypical fractures in select populations, and possibly with an increase in lower extremity amputation with specific SGLT2I drugs. The role of skeletal muscle, as a potential mediator and determinant of bone quality, is also a relevant area of exploration. Currently, data regarding the impact of glucose lowering medications on diabetes‐related muscle atrophy is more limited, although preclinical studies suggest that various hypoglycemic agents may have either aggravating (sulfonylureas, glinides) or repairing (thiazolidinediones, biguanides, incretins) effects on skeletal muscle atrophy, thereby influencing bone quality. Hence, the therapeutic efficacy of each hypoglycemic agent must also be evaluated in light of its impact, alone or in combination, on musculoskeletal health, when determining an individualized treatment approach. Moreover, the effect of newer medications (potentially seeking expanded clinical indication into the pediatric age range) on the growing skeleton is largely unknown. Herein, we review the available literature regarding effects of diabetes pharmacotherapy, by drug class and/or by clinical indication, on the musculoskeletal health of persons with diabetes.

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Section: Drugs and Bonementioning

confidence: 83%

Section: Drugs and Bonementioning

confidence: 89%

Diabetes pharmacotherapy and effects on the musculoskeletal system

Kalaitzoglou

Fowlkes

Popescu

et al. 2018

Diabetes Metabolism Res

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“…1, 2 The successful healing of bone grafts in these sites of implantation is based on the supply of oxygen and nutrients to the grafted tissue. In non-vascularized bone grafts, revascularization originating from the recipient site is the key process for bone graft survival and successful repair.…”

Section: Introductionmentioning

confidence: 99%

Supportive angiogenic and osteogenic differentiation of mesenchymal stromal cells and endothelial cells in monolayer and co-cultures

Böhrnsen

Schliephake

2016

Int J Oral Sci

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Sites of implantation with compromised biology may be unable to achieve the required level of angiogenic and osteogenic regeneration. The specific function and contribution of different cell types to the formation of prevascularized, osteogenic networks in co-culture remains unclear. To determine how bone marrow-derived mesenchymal stromal cells (BMSCs) and endothelial cells (ECs) contribute to cellular proangiogenic differentiation, we analysed the differentiation of BMSCs and ECs in standardized monolayer, Transwell and co-cultures. BMSCs were derived from the iliac bone marrow of five patients, characterized and differentiated in standardized monolayers, permeable Transwells and co-cultures with human umbilical vein ECs (HUVECs). The expression levels of CD31, von Willebrand factor, osteonectin (ON) and Runx2 were assessed by quantitative reverse transcriptase polymerase chain reaction. The protein expression of alkaline phosphatase, ON and CD31 was demonstrated via histochemical and immunofluorescence analysis. The results showed that BMSCs and HUVECs were able to retain their lineage-specific osteogenic and angiogenic differentiation in direct and indirect co-cultures. In addition, BMSCs demonstrated a supportive expression of angiogenic function in co-culture, while HUVEC was able to improve the expression of osteogenic marker molecules in BMSCs.

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“…To create a clinically compatible rat model for implantation, we have done a comprehensive literature review of rat dental implant models. Implants placed out of oral cavity such as the femur [9][10][11] and the tibia [12,13], or not on the ridge of alveolar bone, i.e., the ramus of mandibular [14] is not considered in the present experiment Fig. 1 a) Time course of the experiment.…”

Section: Introductionmentioning

confidence: 99%

Is maxillary diastema an appropriate site for implantation in rats?

et al. 2020

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Background: Implantology or implant dentistry is growing fast during last four decades. Facing the growing demand of implant treatment, there are extreme challenges to clinicians and researchers. First is peri-implantitis with remarkable prevalence. Though investigators have revealed that the etiology of the peri-implant infection is similar to periodontitis, clinically there is no effective treatment. Second, implantation in patients with severe systemic conditions, i.e., severe diabetes, lupus, osteoporosis, organ transplant, and cancer with intensive radiotherapy and/or chemotherapy, is another challenge to implant treatment for lack of scientific research data. Animal models are crucial to help investigators reveal the mechanisms underlying these disorders. Murine models are used most commonly. Rats are the better subject in dental implant research, due to mice could not provide clinical compatible and macro-level measurable data for implant osseointegration and peri-implantitis in oral cavity for lacking enough cancellous bone to support an implant more than 1 mm in length. Objective: Our aim of this research is to find a clinical comparable rat dental implant model. Methods: Six male Sprague-Dawley rats with body weight more than 500 g were used in the experiment. Each rat received two implants. One implant was placed at maxillary diastema in each side. Seven weeks after the implantation, only one implant successfully osseointegrated without movement and inflammation. Implant success and failure rate is analyzed by using Clopper-Pearson's exact method at 95% confidence interval. Results: The present data indicate that the true success rate of implantation in maxillary natural diastema in rat is less than 38.4% at a confident level of 95%. Meanwhile, Micro-CT indicates maxillary first molar position will be a promising site for implantation. Conclusion: Maxillary nature diastema may not be an appropriate site for implantation research for its low successful rate, but maxillary first molar position could be a candidate for implantation research. Further researches are required to illustrate the details.

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Influence of an Antidiabetic Drug on Biomechanical and Histological Parameters Around Implants in Type 2 Diabetic Rats

Abstract: Despite controlling blood glucose, voglibose was unable to reverse the bone metabolic effects of DM.

Cited by 18 publications

References 40 publications

Diabetes pharmacotherapy and effects on the musculoskeletal system

Diabetes pharmacotherapy and effects on the musculoskeletal system

Supportive angiogenic and osteogenic differentiation of mesenchymal stromal cells and endothelial cells in monolayer and co-cultures

Is maxillary diastema an appropriate site for implantation in rats?

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