Mechanisms of altered bone remodeling in children with type 1 diabetes

Brunetti, Giacomina; Damato, G.; Santis, Stefania De; Grano, Maria; Faienza, Maria Felicia

doi:10.4239/wjd.v12.i7.997

“…Many childhood chronic diseases have impact on bone health, such as type 1 diabetes mellitus [ 3 ], chronic kidney disease [ 4 ], rheumatic arthritis [ 2 ], and SLE [ 1 ], involving bone remodeling degeneration. GC can contribute to bone deterioration through the suppression of bone formation and osteoclast activity.…”

Section: Indroductionmentioning

confidence: 99%

Bone remodeling serum markers in children with systemic lupus erythematosus

Hao

¹

,

Zhang

²

,

Huang

³

et al. 2022

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Indroduction SLE is an autoimmune multisystem disease. Glucocorticoid is an irreplaceable medication for SLE. Glucocorticoid and inflammatory mediators impact bone remodeling by OPG/RANKL/RANK signal system, which could lead to osteoporosis. Our aim is to detect the expression of RANKL/OPG in children with SLE, and to preliminarily explore the changes of bone remodeling serum markers in children with SLE. Methods Serum RANKL and OPG of 40 children with SLE and healthy children were detected by ELISA, while 25(OH)VitD3 was detected routinely. Clinical data of children with SLE were recorded, including gender, age, height, weight, BMI, SLEDAI, duration of the disease, cumulative dose of glucocorticoid, and correlation analysis was conducted with RANKL, OPG and 25(OH)VitD3. Results Serum RANKL concentrations in SLE group were significantly higher than health group (9.82 ± 7.20 vs. 6.80 ± 4.35 pg/ml and 0.081 ± 0.072 vs. 0.042 ± 0.034, P < 0.05) respectively, and the concentrations of OPG and 25(OH)VitD3 in serum were significantly lower than health group (156.34 ± 57.33 vs. 189.16 ± 68.70 pg/ml and 43.66 ± 31.27 vs. 59.04 ± 21.56 mmol/L, P < 0.05). Serum RANKL in children with SLE was positively correlated with the duration of SLE, cumulative dose of GC(r = 0.593, 0.727, P < 0.05). And it was negatively correlated with serum OPG and 25(OH)VitD3 (r = -0.601, -0.469, P < 0.05). In addition, serum OPG and 25(OH)VitD3 concentrations were inversely correlated with cumulative dose of GC (r = -0.66, -0.508, P < 0.05). Conclusion Low levels of vitamin D3 and bone metabolic abnormalities still persist in children with SLE even if the disease is in remission, while serum RANKL level was elevated, OPG expression was reduced. In the case of disease remission, GC is involved in the occurrence and development of abnormal bone remodeling through RANKL/OPG.

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“…Glucose metabolism disorders and vitamin D deficiency could change the bone microstructure and matrix [ 22 ]. Diabetes damages bone microstructure by inducing abnormal osteocyte function and matrix structure, increasing osteoblast apoptosis, reducing osteoblast differentiation, and enhancing osteoclast-mediated bone resorption [ 23 , 24 ]. The increased bone density due to obesity does not necessarily provide better protection for bone.…”

Section: Discussionmentioning

confidence: 99%

The association of diabetes status and bone mineral density among US adults: evidence from NHANES 2005–2018

Liu

¹

,

Liu

²

,

Pan

³

et al. 2023

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Backgrounds We aimed to explore the relationship between diabetes status and bone mineral density (BMD) among adults with pre-diabetes and diabetes. Methods We collected and analyzed five cycles (2005–2006, 2007–2008, 2009–2010, 2013–2014, and 2017–2018) data from NHANES. We removed the individuals containing missing values. The linear regression models were used to explore the relationship between diabetes status and bone mineral density. Finally, we performed subgroup analyzes by age, sex and race to find special populations. Result Finally, 9661 participants with complete data were involved in the study. 944 were diagnosed with pre-diabetes, and 2043 were with diabetes. We found that bone mineral density in the hip, femoral neck, and lumbar spine showed an upward trend in both prediabetic and diabetic patients in the three linear regression models. Further, after subgroup analysis, we found that this trend was more prominent in whites race, women, and those over 50 years old. Conclusion Using NHANES data from 2005 to 2018, we found that patients with abnormal glucose metabolism had increased bone mineral density.

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“…The effect concerns not only bone mass, density, and fracture risk [ 6 – 9 ] but also may involve the linear growth of long bones [ 10 ]. Possible mechanisms involve hyperglycaemia, insulin deficiency, GH/IGF-1 axis disturbance, Wnt/ β -catenin pathway alteration, decreased irisin secretion, and, probably, RANKL/RANK/OPG pathway perturbation [ 3 – 5 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Bone Density, Geometry, and Mass by Peripheral Quantitative Computed Tomography and Bone Turnover Markers in Children with Diabetes Mellitus Type 1

Jaworski

¹

,

Wierzbicka

²

,

Czekuc-Kryskiewicz

³

et al. 2022

Journal of Diabetes Research

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Background. The type 1 diabetes mellitus (T1DM) is a chronic systemic autoimmune-mediated disease characterised by the insulin deficiency and hyperglycaemia. Its deleterious effect on bones concerns not only bone mass, density, and fracture risk but also may involve the linear growth of long bones. Studies on the lower leg in children with T1DM by pQCT have generated conflicting results, and most of the studies published so far focused only on a selected features of the bone. An additional information about growth, modelling, and remodelling processes can be gathered by the bone turnover marker measurement. The objective of the study was to evaluate bone mineral density, mass, and geometry using peripheral quantitative computed tomography as well as bone turnover markers in the patients with type 1 diabetes mellitus. Material and Methods. Bone mineral density, mass, and geometry on the lower leg using peripheral quantitative computed tomography and serum osteocalcin (OC) and carboxyterminal cross-linked telopeptide of type 1 collagen (CTx) were measured in 35 adolescents with T1DM (15 girls) aged 12.3-17.9 yrs. The results were compared to age- and sex-adjusted reference values for healthy controls. Results. Both sexes reveal lower than zero Z -scores for lower leg 66% total cortical bone cross-sectional area to muscle cross-sectional area ratio ( − 0.97 ± 1.02 , p = 0.002517 and − 0.98 ± 1.40 , p = 0.007050 , respectively) while tibia 4% trabecular bone density Z -score was lowered in boys ( − 0.67 ± 1.20 , p = 0.02259 ). In boys in Tanner stage 5 bone mass and dimensions were diminished in comparison to Tanner stages 3 and 4, while in girls, such a phenomenon was not observed. Similarly, bone formation and resorption were decreased in boys but not in girls. Consistently, bone turnover markers correlated positively with bone size, dimensions, and strength in boys only. Conclusions. T1DM patients revealed a decreased ratio of cortical bone area/muscle area, reflecting disturbed adaptation of the cortical shaft to the muscle force. When analyzing bone mass and dimensions, boys in Tanner stage 5 diverged from “less-mature” individuals, which may suggest that bone development in these individuals was impaired, affecting all three: mass, size, and strength. Noted in boys, suppressed bone metabolism may result in impairment of bone strength because of inadequate repair of microdamage and accumulation of microfractures.

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Mechanisms of altered bone remodeling in children with type 1 diabetes

Cited by 13 publications

References 107 publications

Bone remodeling serum markers in children with systemic lupus erythematosus

Bone remodeling serum markers in children with systemic lupus erythematosus

The association of diabetes status and bone mineral density among US adults: evidence from NHANES 2005–2018

Bone Density, Geometry, and Mass by Peripheral Quantitative Computed Tomography and Bone Turnover Markers in Children with Diabetes Mellitus Type 1

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