Low bone mineral density is associated to poor glycemic control and increased OPG expression in children and adolescents with type 1 diabetes

Loureiro, Melina Bezerra; Ururahy, Marcela Abbott Galvão; Freire-Neto, Francisco Paulo; Oliveira, G. H. M.; Duarte, Valéria M.G.; Luchessi, André Ducati; Brandão-Neto, José; Hirata, Rosário Dominguez Crespo; Hirata, Mario H.; Maciel-Neto, José J.; Arrais, Ricardo Fernando; Almeida, M. Gabriela; Rezende, Adriana Augusto de

doi:10.1016/j.diabres.2013.12.018

Cited by 52 publications

(60 citation statements)

References 19 publications

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“…Data on bone density in T1DM are controversial. Although the present findings are in agreement with a few previous studies (Gunczler et al, 1998;Gogas Yavuz et al, 2011;Loureiro et al, 2014;Souza et al, 2016), others found no significant decrease in BMD in individuals with T1DM when compared to controls (Bechtold et al, 2006;Brandao et al, 2007;Amorim et al, 2008;Maggio et al, 2010;Simmons et al, 2011). Some of these studies had limitations, such as sample sizes not sufficient to draw definitive conclusions regarding BMD.…”

Section: Discussionsupporting

confidence: 82%

“…This is consistent with previous studies which demonstrated that prolonged exposure to hyperglycemia can promote changes in bone turnover, primarily in bone formation, leading to a decrease in bone mass, which can in turn result in short-term bone fragility and osteopenia/ osteoporosis (Gunczler et al, 1998;Gogas Yavuz et al, 2011;Loureiro et al, 2014).…”

Section: Discussionsupporting

confidence: 81%

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Relationship between glycemic control and OPG gene polymorphisms with lower bone mineral density in patients with type 1 Diabetes mellitus

Loureiro

Ururahy

Souza

et al. 2018

Braz. J. Pharm. Sci.

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The aim of the present study was to investigate the bone mineral density (BMD) of patients with type 1 Diabetes mellitus (T1DM). We also assessed the association between osteoprotegerin (OPG) genetic polymorphisms and BMD. Genotyping was performed for 1181G>C and 163A>G OPG polymorphisms by allelic discrimination in 119 patients with T1DM and 161 normoglycemic (NG) individuals, aged 6 to 20 years old. Glycemic control, serum parameters of bone metabolism and BMD were evaluated. T1DM patients showed low BMD, poor glycemic control and decreased total calcium values when compared to controls (p < 0.05). For all the polymorphisms studied, the genotype and allele frequencies in patients with T1DM were not significantly different from the controls. In patients with T1DM, carriers of OPG 1181CC showed higher concentrations of ionized calcium compared to patients with GG+GC genotypes. These results suggest that low BMD is associated with poor glycemic control in T1DM. Despite the lack of a detected association between OPG polymorphisms and BMD in these patients, the increased ionized calcium in those carrying OPG 1181CC suggests a possible increase in osteoclastogenesis, a conclusion that may be supported by the lower BMD observed in these subjects.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 81%

Relationship between glycemic control and OPG gene polymorphisms with lower bone mineral density in patients with type 1 Diabetes mellitus

Loureiro

Ururahy

Souza

et al. 2018

Braz. J. Pharm. Sci.

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“…In the study by Loureiro, BMD was lower in diabetic patients and there was an inverse relationship between BMD and blood glucose levels and HbA1c (24); this relationship was observed only with HbA1c, and not with blood glucose levels in our study.…”

Section: Discussionmentioning

confidence: 41%

Status of Bone Mineral Density in Children with Type 1 Diabetes Mellitus and Its Related Factors

et al. 2017

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Background: Type 1 Diabetes mellitus (DM) causes changes in bone mineral density (BMD). Objectives: The aim of this study was to evaluate BMD in children with type 1 DM and predictive factors of BMD loss in these patients. Methods: This cross-sectional study was conducted on 112 children with type 1 DM referrtd to children's medical center in Tehran, Iran during 2015 and 2016. Serum levels of hemoglobin A1c (HbA1c), Insulin-like growth factor 1 (IGF-1), 25-hydroxy vitamin D (25(OH) D), calcium, phosphorus, parathyroid hormone (PTH), alkaline phosphates (ALP), Fasting blood sugar (FBS) was recorded. Lumbar

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“…Genes coding for the RANKL/RANK/OPG system and the corresponding markers were found to be altered in humans with T1D and insulinopenic animal models. Some studies found increased OPG gene expression in young patients with T1D [2] and in chronic hyperglycemic conditions in vivo [11] and in vitro [37], which suggests a decreased osteoclast differentiation and a possible adaptive protection against excessive bone resorption in diabetes. Others found downregulation of OPG expression in STZ-induced diabetes in mice [46].…”

Section: Effects Of T1d On Osteoclastsmentioning

confidence: 99%

“…Long-standing T1D is associated with a variety of complications such as nephropathy, neuropathy and retinopathy, especially when glycemic control is poor. In addition to these complications, studies have shown an increase in the risk of bone fractures and low bone mineral density in patients with T1D, even in early stages of the disease [1], and particularly in the presence of uncontrolled hyperglycemia [2]. This insult to the skeleton involves impairments in bone metabolism, both in terms of formation and resorption of bone which depends on normal function and communication of bone cells.…”

Section: Introductionmentioning

confidence: 99%

Effects of Type 1 Diabetes on Osteoblasts, Osteocytes, and Osteoclasts

Kalaitzoglou

Popescu

Bunn

et al. 2016

Curr Osteoporos Rep

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Purpose of review To describe the effects of Type 1 diabetes on bone cells. Recent findings Type 1 diabetes (T1D) is associated with low bone mineral density, increased risk of fractures and poor fracture healing. Its effects on the skeleton were primarily attributed to impaired bone formation, but recent data suggests that bone remodeling and resorption are also compromised. The hyperglycemic and inflammatory environment associated with T1D impacts osteoblasts, osteocytes and osteoclasts. The mechanisms involved are complex; insulinopenia, pro-inflammatory cytokine production and alterations in gene expression are a few of the contributing factors leading to poor osteoblast activity and survival and, therefore, poor bone formation. In addition, the observed sclerostin level increase accompanied by decreased osteocyte number and enhanced osteoclast activity in T1D results in uncoupling of bone remodeling. Summary T1D negatively impacts osteoblasts and osteocytes whereas its effects on osteoclasts are not well characterized, although the limited studies available indicate increased osteoclast activity, favoring bone resorption.

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Low bone mineral density is associated to poor glycemic control and increased OPG expression in children and adolescents with type 1 diabetes

Cited by 52 publications

References 19 publications

Relationship between glycemic control and OPG gene polymorphisms with lower bone mineral density in patients with type 1 Diabetes mellitus

Relationship between glycemic control and OPG gene polymorphisms with lower bone mineral density in patients with type 1 Diabetes mellitus

Status of Bone Mineral Density in Children with Type 1 Diabetes Mellitus and Its Related Factors

Effects of Type 1 Diabetes on Osteoblasts, Osteocytes, and Osteoclasts

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