Effect of Metformin on Periimplant Wound Healing in a Rat Model of Type 2 Diabetes

K, Inouye; Bisch, Frederick C.; Elsalanty, Mohammed; Zakhary, Ibrahim; Khashaba, Rania M.; Borke, James L.

doi:10.1097/id.0000000000000069

Cited by 23 publications

(27 citation statements)

References 29 publications

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“…These findings, however, may be indirectly mediated by the insulin‐sensitizing and/or glucose‐lowering efficacy of metformin in these studies. As shown by Inouye et al, in Goto‐Kakizaki (GK) spontaneously diabetic rats treated with metformin, the peri‐implant wound healing around oral titanium implants was directly related to the glucose lowering success of the treatment …”

Section: Drugs and Bonementioning

confidence: 97%

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: 97%

Diabetes pharmacotherapy and effects on the musculoskeletal system

Kalaitzoglou

Fowlkes

Popescu

et al. 2018

Diabetes Metabolism Res

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“…Previous animal studies also support this conclusion. in vivo studies have reported unfavorable socket healing and alveolar bone destruction in diabetic rodent models . Decreased osteoblast differentiation and mineral deposition rates contributing to delayed healing have been observed in diabetic rodent models .…”

Section: Discussionmentioning

confidence: 99%

“…T2DM is characterized by hyperglycemia due to either the relative lack of insulin or resistance to insulin, which is associated with a series of skeletal complications, including poor osseous healing and impaired bone regeneration . Reports based on diabetic animal models have suggested that the delayed healing of postextraction sockets is associated with unfavorable socket dimensions postextraction . However, reports based on observations in humans (ie, diabetic patients and/or diabetic patients under glycemic management) indicate controversial effects of diabetes on the postextraction socket and ridge .…”

Section: Introductionmentioning

confidence: 99%

Type 2 diabetes affects postextraction socket healing and influences first‐stage implant surgery: A study based on clinical and animal evidence

Zhang

Song

Wang

et al. 2019

Clin Implant Dent Rel Res

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AIM To verify the influence of type 2 diabetes mellitus (T2DM) on postextraction socket healing and subsequent first‐stage implant surgery. Materials and Methods We analyzed pre‐extraction and postextraction cone beam computed tomography images of T2DM patients (n = 75) and paired nondiabetic controls to investigate changes in postextraction socket and ridge dimensions. The types of guided bone regeneration (GBR) surgeries were also compared. Three T2DM pig models were established to compare their postextraction socket healing with that of nondiabetic controls. Healing was quantitatively verified by microcomputed tomography. The osteogenic differentiation of mesenchymal stem cells (MSCs) was also compared. Results Compared to nondiabetic controls, T2DM patients had higher socket width/depth values postextraction across all groups with different healing times. Among the T2DM patients, 62.7% could not receive first‐stage implant surgery within 6 months postextraction, and 54.7% received GBR surgery during first‐stage surgery. Ossification was not achieved in the socket center of the T2DM pig models after 3 months of healing. A decrease in osteogenic differentiation was observed in T2DM‐MSCs. Conclusions T2DM interferes with the healing of the extraction socket and thus delays first‐stage implant surgery. This phenomenon may be due to the reduced osteogenic differentiation of MSCs in the sockets.

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“…Further, while metformin was shown to have no effect on bone mass and fracture healing time in young rodents (Jeyabalan and others 2013) or surgical stress in humans (Duncan and others 2007), it was found to reduce prolonged tracheal intubation and overall morbidities following surgery (Duncan and others 2007). However, conflicting reports regarding the effects of metformin on wound healing exist and should be investigated further (Inouye and others 2014; Jian and others 2013; Ochoa-Gonzalez and others 2016). Overall, early indications suggest that metformin has either proven beneficial or at least without negative consequences against a host of common challenges to robustness making it a promising agent to target many aspects of human aging.…”

Section: Pharmacologic Strategiesmentioning

confidence: 99%

Energetic interventions for healthspan and resiliency with aging

Huffman

Schafer

LeBrasseur

2016

Experimental Gerontology

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Several behavioral and pharmacological strategies improve longevity, which is indicative of delayed organismal aging, with the most effective interventions extending both life- and healthspan. In free living creatures, maintaining health and function into old age requires resilience against a multitude of stressors. Conversely, in experimental settings, conventional housing of rodents limits exposure to such challenges, thereby obscuring an accurate assessment of resilience. Caloric restriction (CR) and exercise, as well as pharmacologic strategies (resveratrol, rapamycin, metformin, senolytics), are well established to improve indices of health and aging, but some paradoxical effects have been observed on resilience. For instance, CR potently retards the onset of age-related diseases, and improves lifespan to a greater extent than exercise in a variety of models. However, exercise has proven more consistently beneficial to organismal resilience against a broad array of stressors, including infections, surgery, wound healing and frailty. CR can improve cellular stress defenses and protect from frailty, but also impairs the response to infections, bed rest and healing. How an intervention will impact not only longevity, health and function, but also resiliency, is critical to better understanding translational implications. Thus, organismal robustness represents a critical, albeit understudied aspect of aging, which needs more careful attention in order to better inform on how putative age-delaying strategies will impact preservation of health and function in response to stressors with aging in humans.

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Effect of Metformin on Periimplant Wound Healing in a Rat Model of Type 2 Diabetes

Abstract: Hyperglycemic GK type 2 diabetic rats showed improved blood glucose and wound healing around oral implants after metformin administration.

Cited by 23 publications

References 29 publications

Diabetes pharmacotherapy and effects on the musculoskeletal system

Diabetes pharmacotherapy and effects on the musculoskeletal system

Type 2 diabetes affects postextraction socket healing and influences first‐stage implant surgery: A study based on clinical and animal evidence

Energetic interventions for healthspan and resiliency with aging

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