Bone Turnover Markers in Patients With Nonalcoholic Fatty Liver Disease and/or Type 2 Diabetes During Oral Glucose and Isoglycemic Intravenous Glucose

Maagensen, Henrik; Junker, Anders E; Jørgensen, Niklas Rye; Gluud, Lise Lotte; Knop, Filip K.; Vilsbøll, Tina

doi:10.1210/jc.2018-00176

Cited by 19 publications

(14 citation statements)

References 45 publications

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“…In addition, the relationship between bone turnover markers and FLD is controversial. (35,36). In our study, the BMD did not differ between the participants with and without FLD, in either sex (Table 2 and 3).…”

Section: Discussionmentioning

confidence: 99%

Association of Bone Metabolism with Fatty Liver Disease in the Elderly in Japan: A Community-based Study

et al. 2020

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Objective With the aging of society, both osteoporosis and fatty liver disease (FLD) are becoming important issues. However, the relationship between osteoporosis and FLD remains controversial. We investigated the association between bone metabolism and FLD in a Japanese community in a cross-sectional study. Methods A total of 1,020 participants were enrolled in a health survey. FLD was diagnosed by ultrasonography. Bone metabolism was evaluated based on bone mineral density (BMD), which was assessed using dual-energy X-ray absorptiometry, and with the bone formation index (total type I procollagen N-terminal propeptide/bone-alkaline phosphatase ratio; P1NP/BAP ratio) and the bone resorption index (crosslinked Ntelopeptide of type I collagen/tartrate-resistant acid phosphatase-5b ratio; NTx/TRACP-5b ratio) calculated from serum bone turnover markers. Results The BMD (percentage of the young adult mean) was the same level in both male and female participants with and without FLD. Both men and women showed an age-dependent decrease in their bone formation index and bone resorption index values. Men of ! 70 years of age and women of 60-69 years of age with FLD had significantly lower bone formation index values and higher bone resorption index values. However, similar findings were not seen in women of ! 70 years of age. Conclusion Although the BMD levels were the same, regardless of the presence or absence of FLD, elderly participants with FLD showed decreased bone formation and increased bone resorption, with sex differences. Because our results suggest that FLD in elderly individuals is detrimental for bone metabolism, and that it leads to bone loss and osteoporosis, further studies using a cohort population are warranted.

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Section: Discussionmentioning

confidence: 99%

Association of Bone Metabolism with Fatty Liver Disease in the Elderly in Japan: A Community-based Study

et al. 2020

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“…(38) There is accumulating evidence that the suppression of bone turnover in response to a glucose challenge is less robust with increased insulin resistance and the presence of type 2 diabetes. (8,39,40) The underlying mechanism for decreased osteoclast activity may be related to elevated OPG activity, because OPG inhibits osteoclastogenesis by acting as a decoy receptor for RANKL. Elevated circulating OPG has been reported in those with T1D as compared to healthy controls, but the contributors to OPG in circulation are not limited to bone.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Acute Hyperinsulinemia Alters Bone Turnover in Women and Men With Type 1 Diabetes

et al. 2020

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Type 1 diabetes (T1D) increases fracture risk across the lifespan. The low bone turnover associated with T1D is thought to be related to glycemic control, but it is unclear whether peripheral hyperinsulinemia due to dependence on exogenous insulin has an independent effect on suppressing bone turnover. The purpose of this study was to test the bone turnover marker (BTM) response to acute hyperinsulinemia. Fifty‐eight adults aged 18 to 65 years with T1D over 2 years were enrolled at seven T1D Exchange Clinic Network sites. Participants had T1D diagnosis between age 6 months to 45 years. Participants were stratified based on their residual endogenous insulin secretion measured as peak C‐peptide response to a mixed meal tolerance test. BTMs (CTX, P1NP, sclerostin [SCL], osteonectin [ON], alkaline phosphatase [ALP], osteocalcin [OCN], osteoprotegerin [OPG], osteopontin [OPN], and IGF‐1) were assessed before and at the end of a 2‐hour hyperinsulinemic‐euglycemic clamp (HEC). Baseline ON (r = −0.30, p = .022) and OCN (r = −0.41, p = .002) were negatively correlated with age at T1D diagnosis, but baseline BTMs were not associated with HbA1c. During the HEC, P1NP decreased significantly (−14.5 ± 44.3%; p = .020) from baseline. OCN, ON, and IGF‐1 all significantly increased (16.0 ± 13.1%, 29.7 ± 31.7%, 34.1 ± 71.2%, respectively; all p < .001) during the clamp. The increase in SCL was not significant (7.3 ± 32.9%, p = .098), but the decrease in CTX (−12.4 ± 48.9, p = .058) neared significance. ALP and OPG were not changed from baseline (p = .23 and p = .77, respectively). Baseline ON and SCL were higher in men, but OPG was higher in women (all p ≤ .029). SCL was the only BTM that changed differently in women than men. There were no differences in baseline BTMs or change in BTMs between C‐peptide groups. Exogenous hyperinsulinemia acutely alters bone turnover, suggesting a need to determine whether strategies to promote healthy remodeling may protect bone quality in T1D. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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“…Several studies reported lower levels of CTX or NTX in individuals with T2DM [26][27][28][29][30][31][32][33][34], those with diabetes-related retinal complications [35], or those with increasingly pathological levels of glycemic markers [31,36]. Other studies reported no association between these markers and diabetes [23,[36][37][38][39][40]. Zhou et al reported an increased urinary NTX secretion in individuals with T2DM [41], whereas Ardawi et al observed reduced urinary NTX secretion in these individuals [34].…”

Section: T2dm and Biochemical Markers Of Bone Healthmentioning

confidence: 99%

“…Rasul et al reported an association between prevalent polyneuropathy and higher levels of CTX, P1NP, and OC in men but not in women [50]. Maagensen et al and Chailurkit et al investigated the effect of an oral glucose load and reported that the suppression of CTX was attenuated in individuals with T2DM [37,40]. Moreover, Maagensen et al observed that the suppression of OC and P1NP was unaffected in individuals with T2DM, and Chailurkit et al observed the suppression of osteoprotegerin to be unaffected by T2DM [37,40].…”

Section: T2dm and Biochemical Markers Of Bone Healthmentioning

confidence: 99%

Bone Health in the Elderly with Type 2 Diabetes Mellitus–A Systematic Review

Al-Mashhadi¹,

Viggers²,

Fuglsang-Nielsen³

et al. 2020

OBM Geriatrics

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Bone Turnover Markers in Patients With Nonalcoholic Fatty Liver Disease and/or Type 2 Diabetes During Oral Glucose and Isoglycemic Intravenous Glucose

Abstract: OGTT-induced CTX suppression seems to be impaired in patients with NAFLD and T2D, but preserved in patients with either NAFLD or T2D, suggesting that coexistence of T2D and NAFLD may affect gut-bone axis.

Cited by 19 publications

References 45 publications

Association of Bone Metabolism with Fatty Liver Disease in the Elderly in Japan: A Community-based Study

Association of Bone Metabolism with Fatty Liver Disease in the Elderly in Japan: A Community-based Study

Acute Hyperinsulinemia Alters Bone Turnover in Women and Men With Type 1 Diabetes

Bone Health in the Elderly with Type 2 Diabetes Mellitus–A Systematic Review

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