Sclerostin distribution in children and adolescents with type 1 diabetes mellitus and correlation with bone metabolism and bone mineral density

Tsentidis, Charalampos; Gourgiotis, Dimitrios; Kossiva, Lydia; Marmarinos, Antonios; Doulgeraki, Artemis; Karavanaki, Kyriaki

doi:10.1111/pedi.12288

Cited by 31 publications

(17 citation statements)

References 38 publications

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“…In a cross-sectional study of 106 T1DM subjects (12.2 ± 4 years), along with 80 controls, serum sclerostin and dickkopf-1 (DKK-1; another inhibitor of the Wnt/beta-catenin pathway) significantly increased (69). However, these findings were not confirmed in another cross-sectional study of 40 T1DM children (age 13.04 ± 3.53 yr) and 40 controls (70). In that study, T1DM patients had similar levels of sclerostin with controls.…”

Section: Introductionmentioning

confidence: 76%

Skeletal growth and bone mineral acquisition in type 1 diabetic children; abnormalities of the GH/IGF-1 axis

Raisingani

Preneet

Kohn

et al. 2017

Growth Hormone & IGF Research

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Type 1 Diabetes Mellitus (T1DM) is one of the most common chronic diseases diagnosed in childhood. Childhood and adolescent years are also the most important period for growth in height and acquisition of skeletal bone mineral density (BMD). The growth hormone (GH)/insulin like growth factor -1 (IGF-1) axis which regulates growth, is affected by T1DM, with studies showing increased GH and decreased IGF-1 levels in children with T1DM. There is conflicting data as to whether adolescents with TIDM are able to achieve their genetically-determined adult height. Furthermore, data support that adolescents with T1DM have decreased peak BMD, although the pathophysiology of which has not been completely defined. Various mechanisms have been proposed for the decrease in BMD including low osteocalcin levels, reflecting decreased bone formation; increased sclerostin, an inhibitor of bone anabolic pathways; and increased leptin, an adipocytokine which affects bone metabolism via central and peripheral mechanisms. Other factors implicated in the increased bone resorption in T1DM include upregulation of the osteoprotegerin/ receptor-activator of the nuclear factor-κB ligand pathway, elevated parathyroid hormone levels, and activation of other cytokines involved in chronic systemic inflammation. In this review, we summarize the clinical studies that address the alterations in the GH/IGF-I axis, linear growth velocity, and BMD in children and adolescents with T1DM; and we review the possible molecular mechanisms that may contribute to an attenuation of linear growth and to the reduction in the acquisition of peak bone mass in the child and adolescent with T1DM.

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Section: Introductionmentioning

confidence: 76%

Skeletal growth and bone mineral acquisition in type 1 diabetic children; abnormalities of the GH/IGF-1 axis

Raisingani

Preneet

Kohn

et al. 2017

Growth Hormone & IGF Research

View full text Add to dashboard Cite

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“…While several studies report that serum sclerostin levels are higher among males than females, both during childhood and puberty [39,40] and in adults [10,41], Amrein et al [42] did not find any sex differences in adults after adjustment for confounders. Our finding of no sex difference of serum sclerostin levels accords with the findings reported by Malluche et al [43] in dialysis patients.…”

Section: Discussionmentioning

confidence: 92%

Association of Serum Sclerostin with Bone Sclerostin in Chronic Kidney Disease is Lost in Glucocorticoid Treated Patients

et al. 2018

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The osteocytic protein sclerostin inhibits bone turnover. Serum sclerostin rises early in chronic kidney disease (CKD), but if this reflects osteocyte sclerostin production is unclear, since sclerostin is also expressed in extra-skeletal tissue. Glucocorticoid treatment impacts on serum sclerostin, but the effect on the association between serum and bone sclerostin is unknown. We sought to determine whether serum sclerostin reflects bone sclerostin in different CKD stages and how this association is influenced by glucocorticoid treatment. In a cross-sectional analysis, we investigated serum sclerostin, bone sclerostin by immunohistochemistry, and bone histomorphometry in iliac crest bone biopsies from 43 patients with CKD 3-5D, including 14 dialysis patients and 22 transplanted patients (18 kidney, 4 other). Thirty-one patients were on glucocorticoid treatment at time of biopsy. Patients with low bone turnover (bone formation rate < 97 µm²/mm²/day; N = 13) had higher median serum sclerostin levels (224.7 vs. 141.7 pg/ml; P = 0.004) and higher bone sclerostin, expressed as sclerostin positive osteocytes per bone area (12.1 vs. 5.0 Scl+ osteocytes/B.Ar; P = 0.008), than patients with non-low bone turnover (N = 28). In linear regression analyses, correcting for age, gender, dialysis status and PTH, serum sclerostin was only associated with bone sclerostin in patients not treated with glucocorticoids (r 2 = 0.6, P = 0.018). For the first time, we describe that female CKD patients have higher median bone sclerostin than males (11.7 vs. 5.7 Scl+ osteocytes/B.Ar, P = 0.046), despite similar serum sclerostin levels and bone histo-morphometric parameters. We conclude that glucocorticoid treatment appears to disrupt the association of serum sclerostin with bone sclerostin in CKD.

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“…Increased sclerostin levels have also been reported in some [70, 71] but not all [72] clinical studies of adults with longstanding T1D, but not in children [73], possibly indicative of an exaggerated age-related increase in sclerostin levels in T1D [70]. Interestingly, this is similar to studies in adult patients with T2D, and with prediabetes, which also demonstrate increased serum sclerostin levels [72] [74-77]; in T2D, specifically, sclerostin levels correlate positively with glycated hemoglobin levels and with measures of insulin resistance [74, 76, 77], but negatively with bone-specific alkaline phosphatase (BSAP) [74].…”

Section: Effects Of Type 1 Diabetes On Osteocytesmentioning

confidence: 94%

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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Sclerostin distribution in children and adolescents with type 1 diabetes mellitus and correlation with bone metabolism and bone mineral density

Cited by 31 publications

References 38 publications

Skeletal growth and bone mineral acquisition in type 1 diabetic children; abnormalities of the GH/IGF-1 axis

Skeletal growth and bone mineral acquisition in type 1 diabetic children; abnormalities of the GH/IGF-1 axis

Association of Serum Sclerostin with Bone Sclerostin in Chronic Kidney Disease is Lost in Glucocorticoid Treated Patients

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

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