The Impact of Glucagon-Like Peptide-1 on Bone Metabolism and Its Possible Mechanisms

Zhao, Chengcheng; Liang, Jing; Yang, Yibing; Yu, Mi; Qu, Xinhua

doi:10.3389/fendo.2017.00098

Cited by 61 publications

(43 citation statements)

References 59 publications

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“…The effects of GLP‐1 on CT secretion appear to be prominent in rodents as the concentration of the GLP‐1R is higher in thyroid C cells from rodents compared with thyroid C cells from humans. In fact, human C cells have been shown to be less responsive to GLP‐1‐mediated CT release …”

Section: Drugs and Bonementioning

confidence: 99%

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: 99%

Diabetes pharmacotherapy and effects on the musculoskeletal system

Kalaitzoglou

Fowlkes

Popescu

et al. 2018

Diabetes Metabolism Res

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“…In obesity, GLP-1 and other protective gut molecules decrease and the process of osteopenia and/or osteoporosis intensifies progression to osteosarcopenia [91]. Insulin resistance increases, advanced glycation end-products are produced, and reactive oxygen species are formed, and these negatively affect the skeletal muscle causing sarcopenia [92][93][94].…”

Section: Osteosarcopenic Obesitymentioning

confidence: 99%

Chronic stress and body composition disorders: implications for health and disease

Stefanaki

Pervanidou

Boschiero³

et al. 2018

Hormones

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Recent studies have suggested that body composition is key to health and disease. First, fat tissue is a complex, essential, and highly active metabolic and endocrine organ that responds to afferent signals from traditional hormone systems and the central nervous system but also expresses and secretes factors with important endocrine, metabolic, and immune functions. Second, skeletal muscle mass is an important predictor of health in adult life, while severe mass loss has been associated with the frailty of old age. Studies have shown that skeletal muscle is also an important endocrine organ that secretes factors with autocrine, paracrine, or endocrine actions, which have been associated with inflammatory processes. Third, the bone is also a systemic endocrine regulator playing a pivotal role in health and disease. Finally, proper hydration in humans has been neglected as a health factor, especially in adults. Chronic stress and stress hormone hypersecretion alone or associated with distinct disorders, such as anxiety, depression, obesity, metabolic syndrome, autoimmune disorders, type 2 diabetes mellitus, and polycystic ovary syndrome (PCOS), have been associated with psychological and somatic manifestations, typically, increased fat mass, osteosarcopenia/frailty, cellular dehydration, and chronic systemic inflammation. This review aims to provide new insights into the newly developed concept of stress-related osteosarcopenic obesity and its prevention.

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“…Glucagon‐like peptide 1 (GLP‐1) is a 30‐amino acid peptide hormone secreted from L cells of the gastrointestinal mucosa, which acts as a key determinant of blood glucose homeostasis owing to its capabilities to slow gastric emptying, enhance pancreatic insulin secretion, and suppress pancreatic glucagon secretion . Moreover, it was reported that GLP‐1 might enhance bone mineral density and improve bone quality by promoting bone formation and inhibiting bone resorption . GLP‐1 RAs are a new class of anti‐diabetic drugs that mimic the effects of native GLP‐1, lead to robust glycemic control and weight loss, and different GLP‐1 RAs differ in several aspects owing to the difference in molecular structures .…”

Section: Introductionmentioning

confidence: 99%

“…11 Moreover, it was reported that GLP-1 might enhance bone mineral density and improve bone quality by promoting bone formation and inhibiting bone resorption. 12,13 GLP-1 RAs are a new class of anti-diabetic drugs that mimic the effects of native GLP-1, lead to robust glycemic control and weight loss, and different GLP-1 RAs differ in several aspects owing to the difference in molecular structures. 14 However, the effects of GLP-1 RAs on bone fracture remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Glucagon‐like peptide‐1 receptor agonists and risk of bone fracture in patients with type 2 diabetes: A meta‐analysis of randomized controlled trials

Liu

et al. 2019

Diabetes Metabolism Res

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Aims To evaluate the association between glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and the risk of bone fracture in patients with type 2 diabetes mellitus (T2DM). Materials and methods We conducted a systematic literature search in PubMed, Embase, the Cochrane Library, and Web of Science from inception to 28 February 2018 and identified eligible randomized controlled trials. The following data were extracted from each study: first author, year of publication, sample size, patient characteristics, study design, intervention drug, control drug, follow‐up time, and incident bone fracture events. A meta‐analysis was conducted using Review Manager 5.3 software to calculate the odds ratio (OR) and 95% confidence intervals (CI) for dichotomous variables. Results A total of 38 studies with 39 795 patients with T2DM were included. There were 241 incident bone fracture cases (107 in the GLP‐1 RAs group and 134 in the control group). Compared with patients who received placebo and other anti‐diabetic drugs, those who received GLP‐1 RAs treatment showed a pooled OR of 0.71 (95% CI, 0.56‐0.91) for bone fracture. Subgroup analysis showed that treatments with liraglutide and lixisenatide were associated with significantly reduced risk of bone fractures (ORs, 0.56; 95% CI, 0.38‐0.81 and 0.55; 95% CI, 0.31‐0.97, respectively). However, other GLP‐1 RAs did not show superiority to placebo or other anti‐diabetic drugs. Moreover, these beneficial effects were dependent on the duration of GLP‐1 RAs treatment, only a GLP‐1 RAs treatment period of more than 52 weeks could significantly lower the risk of bone fracture in patients with T2DM (OR, 0.71; 95% CI, 0.56‐0.91). Conclusions Compared with placebo and other anti‐diabetic drugs, liraglutide and lixisenatide were associated with a significant reduction in the risk of bone fractures, and the beneficial effects were dependent on the duration of treatment.

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The Impact of Glucagon-Like Peptide-1 on Bone Metabolism and Its Possible Mechanisms

Cited by 61 publications

References 59 publications

Diabetes pharmacotherapy and effects on the musculoskeletal system

Diabetes pharmacotherapy and effects on the musculoskeletal system

Chronic stress and body composition disorders: implications for health and disease

Glucagon‐like peptide‐1 receptor agonists and risk of bone fracture in patients with type 2 diabetes: A meta‐analysis of randomized controlled trials

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