Serum levels of bone resorption markers are decreased in patients with type 2 diabetes

Reyes-García, Rebeca; Rozas-Moreno, Pedro; López-Gallardo, Gema; García-Martín, Antonia; Varsavsky, Mariela; Avilés-Pérez, María Dolores; Muñóz-Torres, Manuel

doi:10.1007/s00592-011-0347-0

Cited by 71 publications

(65 citation statements)

References 22 publications

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“…Previous studies in type 2 diabetes have shown the decreased levels of bone turnover markers in type 2 diabetic patients compared to nondiabetic control subjects [15,16]. And some studies indicated that improved glycemic control in diabetic patients resulted in change in bone turnover markers [17][18][19], which is not found in the present study.…”

Section: Discussioncontrasting

confidence: 81%

“…It is still not clear what factors induce these controversial results. What should be addressed is that bone turnover markers levels were shown to be correlated with diabetes duration [15]. The subjects in our study are patients with newly diagnosed type 2 diabetes and were treated with monotherapy of hypoglycemic agents for 6 months, who are quite different with those patients enrolled in other studies.…”

Section: Discussionmentioning

confidence: 99%

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Effect of exenatide, insulin and pioglitazone on bone metabolism in patients with newly diagnosed type 2 diabetes

Luo

et al. 2015

Acta Diabetol

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Aim Preclinical studies suggested that insulin, incretin and thiazolidinediones had effect on regulation of bone metabolism. But clinical evidence is limited. We assessed the effects of these antihyperglycemic agents on bone metabolism in patients with newly diagnosed type 2 diabetes. Methods The present study was a two-center, randomized, parallel-group clinical trial. Sixty-two newly diagnosed and drug-naïve patients with type 2 diabetes were randomized to exenatide (EXE, n = 20), mixed protamine zinc recombinant human insulin lispro injection (25R; INS, n = 21) or pioglitazone (PIO, n = 21) group for a 24-week treatment. Glycosylated hemoglobin A1c (HbA1c), body weight, body mineral density (BMD) and fasting serum concentration of bone turnover markers including osteocalcin (OC), C-telopeptide of type I collagen (CTX) and tartrate-resistant alkaline phosphatase 5b (TRAcP5b) were assessed at baseline and week 24. Results Baseline characteristics were similar among groups. At week 24, HbA1c improved in all patients (EXE:-2.4 ± 0.3 %, INS:-2.4 ± 0.3 %, PIO:-2.0 ± 0.2 %; p [ 0.05 among groups). Patients treated with exenatide lost body weight remarkably (-4.7 ± 0.8 kg). In spite of the amelioration of glucose control, no significant improvement of OC, CTX or TRAcP5b was observed at week 24 (EXE: OC -0.619 ± 0.728 ng/ml, CTX 0.147 ± 0.046 ng/ml, TRAcP5b 0.302 ± 0.149 U/L;INS: OC 0.637 ± 0.787 ng/ml, CTX -0.012 ± 0.074 ng/ml, TRAc P5b 0.124 ± 0.395 U/L; PIO: OC -0.150 ± 0.691 ng/ml, CTX 0.073 ± 0.094 ng/ml, TRAcP5b 0.586 ± 0.183 U/L; p [ 0.05), as well as BMD measurement, regardless of the treatments.Conclusions Twenty-four-week treatment with exenatide, insulin and pioglitazone improved glucose control in patients with newly diagnosed type 2 diabetes, but had no impact on bone turnover markers or BMD.

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Section: Discussioncontrasting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Effect of exenatide, insulin and pioglitazone on bone metabolism in patients with newly diagnosed type 2 diabetes

Luo

et al. 2015

Acta Diabetol

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“…Moreover, higher levels of sclerostin correlate positively with duration of T2DM and levels of glycated hemoglobin, while negatively with levels of bone turnover markers. Another study from the same group reported decreased levels of both serum bone resorption markers (CTX and TRAPc) and intact PTH in patients with T2DM as compared to nondiabetic control (18). Decrease in levels of bone resorption markers and PTH correlated with increased BMD and duration of disease.…”

Section: Skeletal Status and Fracture Risk In T2dmmentioning

confidence: 87%

“…As a result, insulin increases bone turnover and production of undercarboxylated osteocalcin, which in endocrine fashion regulates insulin release from β-cells in pancreas and production of adiponectin in fat tissue (13)(14)(15)(16). Although it is not clear whether this regulatory circuit is affected in diabetes, several studies suggest that patients with T2DM have decreased bone turnover (17)(18)(19). If so, it would result in the decrease in osteocalcin production, especially its undercarboxylated form, which would lead to the attenuation of signaling responsible for increasing of insulin release from the pancreas and increasing fat sensitivity to insulin.…”

Section: Bone As An Integral Part Of Energy Metabolism Systemmentioning

confidence: 99%

Safety of Antidiabetic Therapies on Bone

Lecka‐Czernik

Schwartz

2016

Diabetic Bone Disease

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Osteoporosis and diabetic disease have reached epidemic proportion and create significant public health concerns. The prevalence of these diseases is alarming, and indicates that in the US, 50% of elderly individuals are osteoporotic and almost 20% of population has either diabetic or prediabetic conditions (Centers for Disease Control and Prevention; http://www.cdc.gov). Osteoporosis and diabetes share many features including genetic predispositions and molecular mechanisms. The linkage between these two chronic diseases, which stems from overlapping molecular controls involved in bone homeostasis and energy metabolism, creates a possibility that certain anti-diabetic therapies may affect bone. This concurs with recent findings indicating that bone status is closely linked to regulation of energy metabolism and insulin sensitivity. Indeed, bone and energy homeostasis are under the control of the same regulatory factors, including insulin, peroxisome proliferator activated receptor gamma (PPARγ), gastrointestinal hormones such as glucose inhibitory protein (GIP) and glucagon inhibitory peptide (GLP), and bone derived hormone osteocalcin. These factors and related mechanisms control glucose homeostasis and fatty acids metabolism in fat tissue, pancreas and intestine, which are pharmacological targets for antidiabetic therapies. The same factors contribute to the bone quality by their effect on bone cell differentiation and bone remodeling process. This implies that bone should be considered as a vital target for therapies which modulate energy metabolism. This review is summarizing available data on the skeletal effects of clinically approved anti-diabetic therapies. Keywords bone; BMD; fractures; anti-diabetic therapy; TZDs; metformin; insulin; glyburide; incretins; DPP-4 inhibitors; PPAR Bone remodelingMaintenance of bone homeostasis throughout life relies on the bone remodeling process, which continually replaces old and damaged bone with new bone in order to maintain strength and elasticity (1). In a healthy state, bone resorption is balanced with bone formation. Changes in the milieu of local and systemic factors may alter this balance leading to changes in the bone mass and/or bone biomechanical properties. Aging, estrogen deficiency, and metabolic diseases negatively affect bone mass and/or bone quality leading to the development of osteoporosis and increased fracture rate.Two types of cells are involved in bone remodeling: osteoclasts resorb damaged bone, and osteoblasts form new bone at the site of the resorpted cavity. Osteoclasts and osteoblasts Address to correspondence: Beata Lecka-Czernik, PhD; Dept. Orthopaedic Surgery, University of Toledo Health Sciences Campus, 3000 Arlington Ave, Mail Stop 1008, Toledo OH 43614; Phone: 419-383-4041; Fax: 419-383-2871; beata.leckaczernik@utoledo Bone as an integral part of energy metabolism systemIntegration of bone metabolism with energy metabolism has been presented recently as a model which links anabolic effect of insulin signaling in osteoblasts wi...

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“…This suggests poorer structural integrity of bone may play a role in the increased rate of fragility fractures in patients with T2DM. This is thought to be linked with reduced bone activity, as evidenced by lower levels of biochemical measures of bone turnover and parathormone in patients with T2DM [16]. There are several proposed mechanisms for this reduced bone activity.…”

Section: Mechanismsmentioning

confidence: 99%

A Review of the Mechanisms, Diagnosis and Preventative Treatment of Osteoporotic Fragility Fractures in Patients With Type 2 Diabetes Mellitus

2015

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The primary association of both type 2 diabetes mellitus (T2DM) and fragility fractures with age has become cause for concern in the developed world, with T2DM now considered an independent risk factor for an increased risk of fragility fracture. The increased susceptibility to fragility fracture associated with T2DM has wide ranging and increasing socioeconomic, morbidity and mortality effects. As the incidence of T2DM increases, understanding the mechanisms behind why T2DM is a causative risk factor to decreased bone health is an important step. These may be split into two broad categories: those that involve an increased risk of falling, and those mechanisms that make fragility fracture after falling more likely due to detrimental changes to bone strength. The latter is not definitively understood making diagnosis in T2DM populations difficult. Current diagnostic methods do not sufficiently account for the unique endocrinological effects of T2DM on bone. New markers for identifying fragility fracture risk in patients with T2DM are required to overcome the paradoxical increase in bone mineral density (BMD) in these populations, and the shortcomings of predictive algorithms and dual energy X-ray absorptiometry (DXA) in identifying fracture risk in T2DM populations. Earlier identification of patients with T2DM who are at risk of fragility fracture is important, as these patients are not as responsive to current preventative medical interventions as those without T2DM, although there are also adoptive lifestyle changes that can help.

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Serum levels of bone resorption markers are decreased in patients with type 2 diabetes

Cited by 71 publications

References 22 publications

Effect of exenatide, insulin and pioglitazone on bone metabolism in patients with newly diagnosed type 2 diabetes

Effect of exenatide, insulin and pioglitazone on bone metabolism in patients with newly diagnosed type 2 diabetes

Safety of Antidiabetic Therapies on Bone

A Review of the Mechanisms, Diagnosis and Preventative Treatment of Osteoporotic Fragility Fractures in Patients With Type 2 Diabetes Mellitus

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