Higher levels of s-RANKL and osteoprotegerin in children and adolescents with type 1 diabetes mellitus may indicate increased osteoclast signaling and predisposition to lower bone mass: a multivariate cross-sectional analysis

Tsentidis, Charalampos; Gourgiotis, D; Kossiva, Lydia; Doulgeraki, Artemis; Marmarinos, Antonios; Galli-Tsinopoulou, Assimina; Karavanaki, Kyriaki

doi:10.1007/s00198-015-3422-5

Cited by 74 publications

(71 citation statements)

References 47 publications

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“…Our finding also showed no differences in P1NP levels between diabetes patients with or without micro-vascular complications [27]. In contrast to our study, Shanbhogue and colleagues have reported higher level of P1NP in T2DM with or without micro-vascular complications compared to respective controls [26].…”

Section: Discussioncontrasting

confidence: 83%

The association between bone turnover markers and microvascular complications of type 2 diabetes

Maghbooli

Shabani

Gorgani‐Firuzjaee

et al. 2016

J Diabetes Metab Disord

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BackgroundGlobal epidemic of diabetes is a serious health care concern because of its complications and consequently reduced life expectancy and increased morbidity. However, the bone turnover and thus bone health may be affected or even compromised by diabetes and its complications. The aim of this study was to assess whether bone turnover markers are associated with diabetes micro-vascular complications.MethodsA total of 204 type 2 diabetes patients (104 patients with diabetic micro-vascular complications (retinopathy and/or nephropathy) as a case group and 100 patients without retinopathy and/or nephropathy) as a control group were recruited in this case–control study. The biochemical and metabolic parameters and bone turnover markers were assessed in all patients.ResultsOur findings showed serum levels of osteocalcin (OC) (p = 0.0001) and, carboxy-terminal collagen crosslinks (CTX) (p = 0.006) were higher in diabetic patients with both diabetic retinopathy and nephropathy compared with control group. However, there was no significant difference in serum levels of procollagen I aminoterminal propeptide (P1NP) between diabetic patients with diabetic retinopathy (DR) and/or diabetic nephropathy (DN) compared with control.In diabetes patients with complications, there were significant negative correlation between OC and CTX with estimated-glomerular filtration rate (e-GFR) and also positive correlation between each bone marker (OC and CTX) and PTH levels (p = 0.0001) and BUN (p = 0.0001).In a general linear model, after adjusting for age, sex and BMI, and microvascular complications, there was not any significant association between three bone turnover markers and metabolic markers including fasting glucose, insulin, and lipid profile. Among kidney markers, there were significant positive associations between serum levels of CTX and OC with BUN (p < 0.05) as well as PTH (p < 0.0001).ConclusionsOur data suggest the possible role of PTH and BUN levels in modulating bone turnover markers in diabetic patients.

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Section: Discussioncontrasting

confidence: 83%

The association between bone turnover markers and microvascular complications of type 2 diabetes

Maghbooli

Shabani

Gorgani‐Firuzjaee

et al. 2016

J Diabetes Metab Disord

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“…In this mechanism, OPG appears to act as a negative regulator of osteoclastogenesis. Recent data suggest that increased bone turnover may be associated with increased soluble RANKL (s-RANKL) activity, as seen in children and adolescents with T1D, which would promote increased osteoclast activity and bone resorption [93]. In support of this theory, it has been shown that peripheral blood derived osteoclasts from humans with T1D are less sensitive to OPG than osteoclasts from control subjects, indicating a heightened sensitivity in RANKL/RANK signaling [94].…”

Section: Effects Of T1d On Osteoclastsmentioning

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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“…Few studies have investigated the effects of T1D on vitamin D metabolism in humans. One study in young adults with T1D found no relationship between HbA1c and either 25(OH) vitamin D, 1,25(OH) 2 vitamin D, or 24,25(OH) 2 vitamin D [79]. Urinary vitamin D binding protein excretion was higher in T1D patients compared to controls, and related to hyperglycemia and urinary microalbumin excretion [80], a finding which could contribute to low-vitamin D levels in patients with poorly controlled or long-standing disease.…”

Section: Introductionmentioning

confidence: 99%

Epidemiology of Skeletal Health in Type 1 Diabetes

Weber

Schwartz

2016

Curr Osteoporos Rep

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The skeleton is adversely affected by type 1 diabetes (T1D). Patients with T1D of both sexes have an increased risk of fracture that begins in childhood and extends across the entire lifespan. T1D is characterized by mild to modest deficits in bone density, structure, and microarchitecture. Current evidence suggests that the observed bone deficits in T1D are the result of impaired bone formation rather than increased bone resorption. There is emerging data that bone quality is impaired in T1D, which may explain the findings that fracture risk is elevated out of proportion to the degree of bone mineral deficit. In this review, we summarize the current knowledge regarding the epidemiology of skeletal health in T1D. Given the high individual and societal burden of osteoporotic fracture, there is an urgent need to better understand the etiology of T1D-related bone disease so that clinical strategies to prevent fracture can be developed.

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Higher levels of s-RANKL and osteoprotegerin in children and adolescents with type 1 diabetes mellitus may indicate increased osteoclast signaling and predisposition to lower bone mass: a multivariate cross-sectional analysis

Cited by 74 publications

References 47 publications

The association between bone turnover markers and microvascular complications of type 2 diabetes

The association between bone turnover markers and microvascular complications of type 2 diabetes

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

Epidemiology of Skeletal Health in Type 1 Diabetes

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